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Trial record 12 of 4077 for:    colon cancer AND Intestinal Neoplasms

PK/PD Investigation of Modufolin® in Plasma, Tumor and Adjacent Mucosa Adjacent Mucosa in Patients With Colon Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01681472
Recruitment Status : Completed
First Posted : September 10, 2012
Results First Posted : July 17, 2015
Last Update Posted : July 10, 2019
Sponsor:
Information provided by (Responsible Party):
Isofol Medical AB

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Investigator);   Primary Purpose: Treatment
Condition Colonic Neoplasms
Interventions Drug: 6R-MTHF 200 mg/m2
Drug: Levoleucovorin 200 mg/m2
Drug: 6R-MTHF 60 mg/m2
Drug: Levoleucovorin 60 mg/m2
Enrollment 32
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Levoleucovorin 200 mg/m2 Levoleucovorin 60 mg/m2 6R-MTHF 200 mg/m2 6R-MTHF 60 mg/m2
Hide Arm/Group Description Levoleucovorin: i.v. bolus injection Levoleucovorin: i.v. bolus injection [6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection [6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection
Period Title: Overall Study
Started 8 8 8 8
Completed 8 7 8 8
Not Completed 0 1 0 0
Reason Not Completed
Adverse Event             0             1             0             0
Arm/Group Title Levoleucovorin 200 mg/m2 Levoleucovorin 60 mg/m2 Modufolin 200 mg/m2 Modufolin 60 mg/m2 Total
Hide Arm/Group Description Levoleucovorin: i.v. bolus injection Levoleucovorin: i.v. bolus injection [6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection [6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection Total of all reporting groups
Overall Number of Baseline Participants 8 8 8 8 32
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 8 participants 8 participants 8 participants 32 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
0
   0.0%
3
  37.5%
2
  25.0%
2
  25.0%
7
  21.9%
>=65 years
8
 100.0%
5
  62.5%
6
  75.0%
6
  75.0%
25
  78.1%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 8 participants 8 participants 8 participants 8 participants 32 participants
80.5  (9.15) 66.71  (16.89) 72  (15) 71.75  (11.25) 72.74  (13.07)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 8 participants 8 participants 8 participants 32 participants
Female
4
  50.0%
5
  62.5%
3
  37.5%
4
  50.0%
16
  50.0%
Male
4
  50.0%
3
  37.5%
5
  62.5%
4
  50.0%
16
  50.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Sweden Number Analyzed 8 participants 8 participants 8 participants 8 participants 32 participants
8
 100.0%
8
 100.0%
8
 100.0%
8
 100.0%
32
 100.0%
1.Primary Outcome
Title Concentration of [6R]-5,10-methylene-THF in Tumor Tissue
Hide Description Comparison of concentration of the active substance in Modufolin: [6R]-5,10-methylene-THF in tumor tissue after the different treatments.
Time Frame Sample taken Day 1 (Day of surgery) at 0 min (before anesthetics) and 5, 10, 20, 40, 60, 90, 120, 180, 240, 360 min after study drug administration, and 24 h after study drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure.
Arm/Group Title Levoleucovorin 200 mg/m2 Levoleucovorin 60 mg/m2 Modufolin 200 mg/m2 Modufolin 60 mg/m2
Hide Arm/Group Description:
Levoleucovorin: i.v. bolus injection
Levoleucovorin: i.v. bolus injection
[6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection
[6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection
Overall Number of Participants Analyzed 8 6 8 7
Mean (Standard Deviation)
Unit of Measure: pmol/g
1871  (1159) 959  (417) 4725  (2210) 2393  (1920)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Modufolin 200 mg/m2, Modufolin 60 mg/m2
Comments The exploratory evaluation of [6R]-5,10-methylene-THF concentration in tumor tissue was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0323
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Levoleucovorin 60 mg/m2, Modufolin 60 mg/m2
Comments The exploratory evaluation of [6R]-5,10-methylene-THF concentration in tumor tissue was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1336
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Levoleucovorin 200 mg/m2, Modufolin 60 mg/m2
Comments The exploratory evaluation of [6R]-5,10-methylene-THF concentration in tumor tissue was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8622
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Levoleucovorin 60 mg/m2, Modufolin 200 mg/m2
Comments The exploratory evaluation of [6R]-5,10-methylene-THF concentration in tumor tissue was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0024
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Levoleucovorin 200 mg/m2, Modufolin 200 mg/m2
Comments The exploratory evaluation of [6R]-5,10-methylene-THF concentration in tumor tissue was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0074
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Levoleucovorin 200 mg/m2, Levoleucovorin 60 mg/m2
Comments The exploratory evaluation of [6R]-5,10-methylene-THF concentration in tumor tissue was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1752
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
2.Primary Outcome
Title Concentration of [6R]-5,10-methylene-THF in Adjacent Mucosa Tissue
Hide Description Comparison of concentration of the active substance in Modufolin: [6R]-5,10-methylene-THF in mucosa adjacent to the tumor after the different treatments.
Time Frame Sample taken Day 1 (Day of surgery) at 0 min (before anesthetics) and 5, 10, 20, 40, 60, 90, 120, 180, 240, 360 min after study drug administration, and 24 h after study drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure.
Arm/Group Title Levoleucovorin 200 mg/m2 Levoleucovorin 60 mg/m2 Modufolin 200 mg/m2 Modufolin 60 mg/m2
Hide Arm/Group Description:
Levoleucovorin: i.v. bolus injection
Levoleucovorin: i.v. bolus injection
[6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection
[6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection
Overall Number of Participants Analyzed 8 6 8 7
Mean (Standard Deviation)
Unit of Measure: pmol/g
1333  (852) 626  (439) 5099  (3927) 3481  (3926)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Modufolin 200 mg/m2, Modufolin 60 mg/m2
Comments The exploratory evaluation of [6R]-5,10-methylene-THF concentration in mucosa adjacent to the tumor was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1480
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Levoleucovorin 60 mg/m2, Modufolin 60 mg/m2
Comments The exploratory evaluation of [6R]-5,10-methylene-THF concentration in mucosa adjacent to the tumor was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0034
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Levoleucovorin 200 mg/m2, Modufolin 60 mg/m2
Comments The exploratory evaluation of [6R]-5,10-methylene-THF concentration in mucosa adjacent to the tumor was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0177
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Levoleucovorin 60 mg/m2, Modufolin 200 mg/m2
Comments The exploratory evaluation of [6R]-5,10-methylene-THF concentration in mucosa adjacent to the tumor was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Levoleucovorin 200 mg/m2, Modufolin 200 mg/m2
Comments The exploratory evaluation of [6R]-5,10-methylene-THF concentration in mucosa adjacent to the tumor was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0019
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Levoleucovorin 200 mg/m2, Levoleucovorin 60 mg/m2
Comments The exploratory evaluation of [6R]-5,10-methylene-THF concentration in mucosa adjacent to the tumor was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0118
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
3.Primary Outcome
Title Concentration of [6S]-5-THF in Tumor Tissue
Hide Description Comparison of concentration of the metabolite [6S]-5-THF in tumor after the different treatments.
Time Frame Sample taken Day 1 (Day of surgery) at 0 min (before anesthetics) and 5, 10, 20, 40, 60, 90, 120, 180, 240, 360 min after study drug administration, and 24 h after study drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure.
Arm/Group Title Levoleucovorin 200 mg/m2 Levoleucovorin 60 mg/m2 Modufolin 200 mg/m2 Modufolin 60 mg/m2
Hide Arm/Group Description:
Levoleucovorin: i.v. bolus injection
Levoleucovorin: i.v. bolus injection
[6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection
[6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection
Overall Number of Participants Analyzed 8 6 8 7
Mean (Standard Deviation)
Unit of Measure: pmol/g
1329  (720) 933  (598) 4175  (3127) 2219  (1995)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Modufolin 200 mg/m2, Modufolin 60 mg/m2
Comments The exploratory evaluation of [6S]-5-THF concentration in tumor was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1182
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Levoleucovorin 60 mg/m2, Modufolin 60 mg/m2
Comments The exploratory evaluation of [6S]-5-THF concentration in tumor was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0538
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Levoleucovorin 200 mg/m2, Modufolin 60 mg/m2
Comments The exploratory evaluation of [6S]-5-THF concentration in tumor was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5244
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Levoleucovorin 60 mg/m2, Modufolin 200 mg/m2
Comments The exploratory evaluation of [6S]-5-THF concentration in tumor was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0081
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Levoleucovorin 200 mg/m2, Modufolin 200 mg/m2
Comments The exploratory evaluation of [6S]-5-THF concentration in tumor was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0313
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Levoleucovorin 200 mg/m2, Levoleucovorin 60 mg/m2
Comments The exploratory evaluation of [6S]-5-THF concentration in tumor was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4777
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
4.Primary Outcome
Title Concentration of [6S]-5-THF in Adjacent Mucosa Tissue
Hide Description Comparison of concentration of the metabolite [6S]-5-THF in mucosa adjacent to the tumor after the different treatments.
Time Frame Sample taken Day 1 (Day of surgery) at 0 min (before anesthetics) and 5, 10, 20, 40, 60, 90, 120, 180, 240, 360 min after study drug administration, and 24 h after study drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure.
Arm/Group Title Levoleucovorin 200 mg/m2 Levoleucovorin 60 mg/m2 Modufolin 200 mg/m2 Modufolin 60 mg/m2
Hide Arm/Group Description:
Levoleucovorin: i.v. bolus injection
Levoleucovorin: i.v. bolus injection
[6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection
[6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection
Overall Number of Participants Analyzed 8 6 8 7
Mean (Standard Deviation)
Unit of Measure: pmol/g
1333  (852) 626  (439) 5099  (3927) 3481  (3926)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Modufolin 200 mg/m2, Modufolin 60 mg/m2
Comments The exploratory evaluation of [6S]-5-THF concentration in mucosa adjacent to the tumor was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2716
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Levoleucovorin 60 mg/m2, Modufolin 60 mg/m2
Comments The exploratory evaluation of [6S]-5-THF concentration in mucosa adjacent to the tumor was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0124
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Levoleucovorin 200 mg/m2, Modufolin 60 mg/m2
Comments The exploratory evaluation of [6S]-5-THF concentration in mucosa adjacent to the tumor was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0728
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Levoleucovorin 60 mg/m2, Modufolin 200 mg/m2
Comments The exploratory evaluation of [6S]-5-THF concentration in mucosa adjacent to the tumor was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Levoleucovorin 200 mg/m2, Modufolin 200 mg/m2
Comments The exploratory evaluation of [6S]-5-THF concentration in mucosa adjacent to the tumor was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0039
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Levoleucovorin 200 mg/m2, Levoleucovorin 60 mg/m2
Comments The exploratory evaluation of [6S]-5-THF concentration in mucosa adjacent to the tumor was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0454
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
5.Primary Outcome
Title Concentration of [6S]-5-methyl-THF in Tumor Tissue
Hide Description Comparison of concentration of the metabolite [6S]-5-methyl-THF in tumor after the different treatments.
Time Frame Sample taken Day 1 (Day of surgery) at 0 min (before anesthetics) and 5, 10, 20, 40, 60, 90, 120, 180, 240, 360 min after study drug administration, and 24 h after study drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure.
Arm/Group Title Levoleucovorin 200 mg/m2 Levoleucovorin 60 mg/m2 Modufolin 200 mg/m2 Modufolin 60 mg/m2
Hide Arm/Group Description:
Levoleucovorin: i.v. bolus injection
Levoleucovorin: i.v. bolus injection
[6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection
[6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection
Overall Number of Participants Analyzed 8 6 8 7
Mean (Standard Deviation)
Unit of Measure: pmol/g
3574  (2415) 1904  (918) 4396  (1858) 1882  (1204)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Modufolin 200 mg/m2, Modufolin 60 mg/m2
Comments The exploratory evaluation of [6S]-5-methyl-THF concentration in tumor was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0092
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Levoleucovorin 60 mg/m2, Modufolin 60 mg/m2
Comments The exploratory evaluation of [6S]-5-methyl-THF concentration in tumor was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8303
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Levoleucovorin 200 mg/m2, Modufolin 60 mg/m2
Comments The exploratory evaluation of [6S]-5-methyl-THF concentration in tumor was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1182
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Levoleucovorin 60 mg/m2, Modufolin 200 mg/m2
Comments The exploratory evaluation of [6S]-5-methyl-THF concentration in tumor was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0081
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Levoleucovorin 200 mg/m2, Modufolin 200 mg/m2
Comments The exploratory evaluation of [6S]-5-methyl-THF concentration in tumor was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3184
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Levoleucovorin 200 mg/m2, Levoleucovorin 60 mg/m2
Comments The exploratory evaluation of [6S]-5-methyl-THF concentration in tumor was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1752
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
6.Primary Outcome
Title Concentration of [6S]-5-methyl-THF in Adjacent Mucosa Tissue
Hide Description Comparison of concentration of the metabolite [6S]-5-methyl-THF in mucosa adjacent to the tumor after the different treatments.
Time Frame Sample taken Day 1 (Day of surgery) at 0 min (before anesthetics) and 5, 10, 20, 40, 60, 90, 120, 180, 240, 360 min after study drug administration, and 24 h after study drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure.
Arm/Group Title Levoleucovorin 200 mg/m2 Levoleucovorin 60 mg/m2 Modufolin 200 mg/m2 Modufolin 60 mg/m2
Hide Arm/Group Description:
Levoleucovorin: i.v. bolus injection
Levoleucovorin: i.v. bolus injection
[6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection
[6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection
Overall Number of Participants Analyzed 8 6 8 7
Mean (Standard Deviation)
Unit of Measure: pmol/g
3667  (2043) 1216  (455) 2494  (765) 2066  (1517)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Modufolin 200 mg/m2, Modufolin 60 mg/m2
Comments The exploratory evaluation of [6S]-5-methyl-THF concentration in mucosa adjacent to the tumor was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0728
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Levoleucovorin 60 mg/m2, Modufolin 60 mg/m2
Comments The exploratory evaluation of [6S]-5-methyl-THF concentration in mucosa adjacent to the tumor was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2246
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Levoleucovorin 200 mg/m2, Modufolin 60 mg/m2
Comments The exploratory evaluation of [6S]-5-methyl-THF concentration in mucosa adjacent to the tumor was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0428
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Levoleucovorin 60 mg/m2, Modufolin 200 mg/m2
Comments The exploratory evaluation of [6S]-5-methyl-THF concentration in mucosa adjacent to the tumor was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Levoleucovorin 200 mg/m2, Modufolin 200 mg/m2
Comments The exploratory evaluation of [6S]-5-methyl-THF concentration in mucosa adjacent to the tumor was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4309
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Levoleucovorin 200 mg/m2, Levoleucovorin 60 mg/m2
Comments The exploratory evaluation of [6S]-5-methyl-THF concentration in mucosa adjacent to the tumor was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0055
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
7.Primary Outcome
Title Concentration of [6S]-5-formyl-THF in Tumor Tissue
Hide Description Comparison of concentration of the metabolite [6S]-5-formyl-THF in tumor after the different treatments.
Time Frame Sample taken Day 1 (Day of surgery) at 0 min (before anesthetics) and 5, 10, 20, 40, 60, 90, 120, 180, 240, 360 min after study drug administration, and 24 h after study drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure.
Arm/Group Title Levoleucovorin 200 mg/m2 Levoleucovorin 60 mg/m2 Modufolin 200 mg/m2 Modufolin 60 mg/m2
Hide Arm/Group Description:
Levoleucovorin: i.v. bolus injection
Levoleucovorin: i.v. bolus injection
[6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection
[6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection
Overall Number of Participants Analyzed 8 6 8 7
Mean (Standard Deviation)
Unit of Measure: pmol/g
3611  (3899) 512  (259) 100  (47) 57  (48)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Modufolin 200 mg/m2, Modufolin 60 mg/m2
Comments The exploratory evaluation of [6S]-5-formyl-THF concentration in tumor was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0728
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Levoleucovorin 60 mg/m2, Modufolin 60 mg/m2
Comments The exploratory evaluation of [6S]-5-formyl-THF concentration in tumor was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0034
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Levoleucovorin 200 mg/m2, Modufolin 60 mg/m2
Comments The exploratory evaluation of [6S]-5-formyl-THF concentration in tumor was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0015
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Levoleucovorin 60 mg/m2, Modufolin 200 mg/m2
Comments The exploratory evaluation of [6S]-5-formyl-THF concentration in tumor was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0024
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Levoleucovorin 200 mg/m2, Modufolin 200 mg/m2
Comments The exploratory evaluation of [6S]-5-formyl-THF concentration in tumor was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0009
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Levoleucovorin 200 mg/m2, Levoleucovorin 60 mg/m2
Comments The exploratory evaluation of [6S]-5-formyl-THF concentration in tumor was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0055
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
8.Primary Outcome
Title Concentration of [6S]-5-formyl-THF in Adjacent Mucosa Tissue
Hide Description Comparison of concentration of the metabolite [6S]-5-formyl-THF in mucosa adjacent to the tumor after the different treatments.
Time Frame Sample taken Day 1 (Day of surgery) at 0 min (before anesthetics) and 5, 10, 20, 40, 60, 90, 120, 180, 240, 360 min after study drug administration, and 24 h after study drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure.
Arm/Group Title Levoleucovorin 200 mg/m2 Levoleucovorin 60 mg/m2 Modufolin 200 mg/m2 Modufolin 60 mg/m2
Hide Arm/Group Description:
Levoleucovorin: i.v. bolus injection
Levoleucovorin: i.v. bolus injection
[6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection
[6R] 5,10-methylenetetrahydrofolate: i.v. bolus injection
Overall Number of Participants Analyzed 8 6 8 7
Mean (Standard Deviation)
Unit of Measure: pmol/g
5456  (3963) 1403  (640) 82  (77) 42  (18)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Modufolin 200 mg/m2, Modufolin 60 mg/m2
Comments The exploratory evaluation of [6S]-5-formyl-THF concentration in mucosa adjacent to the tumor was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0240
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Levoleucovorin 60 mg/m2, Modufolin 60 mg/m2
Comments The exploratory evaluation of [6S]-5-formyl-THF concentration in mucosa adjacent to the tumor was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0058
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Levoleucovorin 200 mg/m2, Modufolin 60 mg/m2
Comments The exploratory evaluation of [6S]-5-formyl-THF concentration in mucosa adjacent to the tumor was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0015
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Levoleucovorin 60 mg/m2, Modufolin 200 mg/m2
Comments The exploratory evaluation of [6S]-5-formyl-THF concentration in mucosa adjacent to the tumor was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Levoleucovorin 200 mg/m2, Modufolin 200 mg/m2
Comments The exploratory evaluation of [6S]-5-formyl-THF concentration in mucosa adjacent to the tumor was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0014
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Levoleucovorin 200 mg/m2, Levoleucovorin 60 mg/m2
Comments The exploratory evaluation of [6S]-5-formyl-THF concentration in mucosa adjacent to the tumor was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0338
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
9.Secondary Outcome
Title AUC(0-2h) of [6R]-5,10-methylene-THF
Hide Description Area under the plasma concentration versus time curve from time 0 to 2 hours, for the active substance in Modufolin: [6R]-5,10-methylene-THF
Time Frame Samples taken Day 1 (Day of surgery)
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure.
Arm/Group Title L-LV(200) L-LV(60) Mod(200) Mod(60)
Hide Arm/Group Description:
Levoleucovorin 200 mg/m2
Levoleucovorin 60 mg/m2
Modufolin 200 mg/m2
Modufolin 60 mg/m2
Overall Number of Participants Analyzed 8 6 8 7
Mean (Standard Deviation)
Unit of Measure: mcg*h/L
326.40261  (61.98416) 239.90076  (0) 7734.09113  (1557.76552) 0  (0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mod(200), Mod(60)
Comments The exploratory evaluation of AUC(0-2h) was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection L-LV(60), Mod(60)
Comments The exploratory evaluation of AUC(0-2h) was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection L-LV(200), Mod(60)
Comments The exploratory evaluation of AUC(0-2h) was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection L-LV(60), Mod(200)
Comments The exploratory evaluation of AUC(0-2h) was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection L-LV(200), Mod(200)
Comments The exploratory evaluation of AUC(0-2h) was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0015
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection L-LV(200), L-LV(60)
Comments The exploratory evaluation of AUC(0-2h) was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
10.Secondary Outcome
Title AUC(0-2h) of [6S]-5-THF
Hide Description Area under the plasma concentration versus time curve from time 0 to 2 hours, for the metabolite [6S]-5-THF
Time Frame Samples taken Day 1 (Day of surgery)
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure.
Arm/Group Title L-LV(200) L-LV(60) Mod(200) Mod(60)
Hide Arm/Group Description:
Levoleucovorin 200 mg/m2
Levoleucovorin 60 mg/m2
Modufolin 200 mg/m2
Modufolin 60 mg/m2
Overall Number of Participants Analyzed 8 6 8 7
Mean (Standard Deviation)
Unit of Measure: mcg*h/L
827.1083  (178.23243) 640.0489  (0) 19408.1712  (3000.64794) 5639.2700  (885.82223)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mod(200), Mod(60)
Comments The exploratory evaluation of AUC(0-2h) was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0015
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection L-LV(60), Mod(60)
Comments The exploratory evaluation of AUC(0-2h) was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection L-LV(200), Mod(60)
Comments The exploratory evaluation of AUC(0-2h) was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0015
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection L-LV(60), Mod(200)
Comments The exploratory evaluation of AUC(0-2h) was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection L-LV(200), Mod(200)
Comments The exploratory evaluation of AUC(0-2h) was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0009
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection L-LV(200), L-LV(60)
Comments The exploratory evaluation of AUC(0-2h) was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
11.Secondary Outcome
Title AUC(0-2h) of [6S]-5-methyl-THF
Hide Description Area under the plasma concentration versus time curve from time 0 to 2 hours, for the metabolite: [6S]-5-methyl-THF
Time Frame Samples taken Day 1 (Day of surgery)
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure.
Arm/Group Title L-LV(200) L-LV(60) Mod(200) Mod(60)
Hide Arm/Group Description:
Levoleucovorin 200 mg/m2
Levoleucovorin 60 mg/m2
Modufolin 200 mg/m2
Modufolin 60 mg/m2
Overall Number of Participants Analyzed 8 6 8 7
Mean (Standard Deviation)
Unit of Measure: mcg*h/L
2336.24432  (829.18634) 1258.60184  (247.51353) 2277.89290  (1132.95603) 997.74091  (413.68052)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mod(200), Mod(60)
Comments The exploratory evaluation of AUC(0-2h) was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0728
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection L-LV(60), Mod(60)
Comments The exploratory evaluation of AUC(0-2h) was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2246
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection L-LV(200), Mod(60)
Comments The exploratory evaluation of AUC(0-2h) was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0166
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection L-LV(60), Mod(200)
Comments The exploratory evaluation of AUC(0-2h) was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1752
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection L-LV(200), Mod(200)
Comments The exploratory evaluation of AUC(0-2h) was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9581
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection L-LV(200), L-LV(60)
Comments The exploratory evaluation of AUC(0-2h) was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0118
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
12.Secondary Outcome
Title AUC(0-2h) of [6SR]-5-formyl-THF
Hide Description Area under the plasma concentration versus time curve from time 0 to 2 hours, for the metabolite [6S]-5-formyl-THF
Time Frame Samples taken Day 1 (Day of surgery)
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure.
Arm/Group Title L-LV(200) L-LV(60) Mod(200) Mod(60)
Hide Arm/Group Description:
Levoleucovorin 200 mg/m2
Levoleucovorin 60 mg/m2
Modufolin 200 mg/m2
Modufolin 60 mg/m2
Overall Number of Participants Analyzed 8 6 8 7
Mean (Standard Deviation)
Unit of Measure: mcg*h/L
29911.9184  (6924.78031) 7595.4599  (764.27650) 0  (0) 0  (0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mod(200), Mod(60)
Comments The exploratory evaluation of AUC(0-2h) was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection L-LV(60), Mod(60)
Comments The exploratory evaluation of AUC(0-2h) was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection L-LV(200), Mod(60)
Comments The exploratory evaluation of AUC(0-2h) was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection L-LV(60), Mod(200)
Comments The exploratory evaluation of AUC(0-2h) was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection L-LV(200), Mod(200)
Comments The exploratory evaluation of AUC(0-2h) was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection L-LV(200), L-LV(60)
Comments The exploratory evaluation of AUC(0-2h) was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0024
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
13.Secondary Outcome
Title AUC(Last) of [6R]-5,10-methylene-THF
Hide Description Area under the plasma concentration versus time curve, from time 0 to the last time point, for the active substance in Modufolin: [6R]-5,10-methylene-THF
Time Frame Samples taken Day 1 (Day of surgery) and Day 2
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure.
Arm/Group Title L-LV(200) L-LV(60) Mod(200) Mod(60)
Hide Arm/Group Description:
Levoleucovorin 200 mg/m2
Levoleucovorin 60 mg/m2
Modufolin 200 mg/m2
Modufolin 60 mg/m2
Overall Number of Participants Analyzed 8 6 8 7
Mean (Standard Deviation)
Unit of Measure: mcg*h/L
462.10746  (221.85761) 239.90076  (0) 7910.61038  (1623.24300) 2272.78010  (448.01407)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mod(200), Mod(60)
Comments The exploratory evaluation of AUC(last) was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0015
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection L-LV(60), Mod(60)
Comments The exploratory evaluation of AUC(last) was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection L-LV(200), Mod(60)
Comments The exploratory evaluation of AUC(last) was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0022
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection L-LV(60), Mod(200)
Comments The exploratory evaluation of AUC(last) was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection L-LV(200), Mod(200)
Comments The exploratory evaluation of AUC(last) was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0015
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection L-LV(200), L-LV(60)
Comments The exploratory evaluation of AUC(last) was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
14.Secondary Outcome
Title AUC(Last) of [6S]-5-THF
Hide Description Area under the plasma concentration versus time curve, from time 0 to the last time point, for the metabolite [6S]-5-THF
Time Frame Samples taken Day 1 (Day of surgery) and Day 2
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure.
Arm/Group Title L-LV(200) L-LV(60) Mod(200) Mod(60)
Hide Arm/Group Description:
Levoleucovorin 200 mg/m2
Levoleucovorin 60 mg/m2
Modufolin 200 mg/m2
Modufolin 60 mg/m2
Overall Number of Participants Analyzed 8 6 8 7
Mean (Standard Deviation)
Unit of Measure: mcg*h/L
2231.1443  (1051.06650) 640.0489  (0) 28466.5389  (5303.28705) 6766.9104  (1484.91243)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mod(200), Mod(60)
Comments The exploratory evaluation of AUC(last) was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0015
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection L-LV(60), Mod(60)
Comments The exploratory evaluation of AUC(last) was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection L-LV(200), Mod(60)
Comments The exploratory evaluation of AUC(last) was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0015
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection L-LV(60), Mod(200)
Comments The exploratory evaluation of AUC(last) was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection L-LV(200), Mod(200)
Comments The exploratory evaluation of AUC(last) was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0009
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection L-LV(200), L-LV(60)
Comments The exploratory evaluation of AUC(last) was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
15.Secondary Outcome
Title AUC(Last) of [6S]-5-methyl-THF
Hide Description Area under the plasma concentration versus time curve, from time 0 to the last time point, for the metabolite [6S]-5-methyl-THF
Time Frame Samples taken Day 1 (Day of surgery) and Day 2
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure.
Arm/Group Title L-LV(200) L-LV(60) Mod(200) Mod(60)
Hide Arm/Group Description:
Levoleucovorin 200 mg/m2
Levoleucovorin 60 mg/m2
Modufolin 200 mg/m2
Modufolin 60 mg/m2
Overall Number of Participants Analyzed 8 6 8 7
Mean (Standard Deviation)
Unit of Measure: mcg*h/L
32206.2771  (9121.1818) 7689.0921  (5164.6098) 21737.2428  (21757.1545) 5495.1924  (6110.0065)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mod(200), Mod(60)
Comments The exploratory evaluation of AUC(last) was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0240
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection L-LV(60), Mod(60)
Comments The exploratory evaluation of AUC(last) was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1336
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection L-LV(200), Mod(60)
Comments The exploratory evaluation of AUC(last) was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0015
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection L-LV(60), Mod(200)
Comments The exploratory evaluation of AUC(last) was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2725
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection L-LV(200), Mod(200)
Comments The exploratory evaluation of AUC(last) was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1893
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection L-LV(200), L-LV(60)
Comments The exploratory evaluation of AUC(last) was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0024
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
16.Secondary Outcome
Title AUC(Last) of [6S]-5-formyl-THF
Hide Description Area under the plasma concentration versus time curve, from time 0 to the last time point, for the metabolite [6S]-5-formyl-THF
Time Frame Samples taken Day 1 (Day of surgery) and Day 2
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure.
Arm/Group Title L-LV(200) L-LV(60) Mod(200) Mod(60)
Hide Arm/Group Description:
Levoleucovorin 200 mg/m2
Levoleucovorin 60 mg/m2
Modufolin 200 mg/m2
Modufolin 60 mg/m2
Overall Number of Participants Analyzed 8 6 8 7
Mean (Standard Deviation)
Unit of Measure: mcg*h/L
43429.1885  (12411.2844) 9637.0308  (1637.2118) 75.6174  (69.2176) 50.1858  (0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mod(200), Mod(60)
Comments The exploratory evaluation of AUC(last) was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection L-LV(60), Mod(60)
Comments The exploratory evaluation of AUC(last) was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection L-LV(200), Mod(60)
Comments The exploratory evaluation of AUC(last) was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection L-LV(60), Mod(200)
Comments The exploratory evaluation of AUC(last) was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0142
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection L-LV(200), Mod(200)
Comments The exploratory evaluation of AUC(last) was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0085
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection L-LV(200), L-LV(60)
Comments The exploratory evaluation of AUC(last) was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0024
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
17.Secondary Outcome
Title Cmax of [6R]-5,10-methylene-THF
Hide Description Maximum concentration (Cmax) in plasma of the active substance in Modufolin: [6R]-5,10-methylene-THF
Time Frame Samples taken Day 1 (Day of surgery) and Day 2
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure.
Arm/Group Title L-LV(200) L-LV(60) Mod(200) Mod(60)
Hide Arm/Group Description:
Levoleucovorin 200 mg/m2
Levoleucovorin 60 mg/m2
Modufolin 200 mg/m2
Modufolin 60 mg/m2
Overall Number of Participants Analyzed 8 6 8 7
Mean (Standard Deviation)
Unit of Measure: µg/L
195.0000  (40.76763) 123.0000  (0) 22087.5000  (5635.45853) 6452.8571  (559.18477)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mod(200), Mod(60)
Comments The exploratory evaluation of Cmax was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0014
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection L-LV(60), Mod(60)
Comments The exploratory evaluation of Cmax was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection L-LV(200), Mod(60)
Comments The exploratory evaluation of Cmax was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0021
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection L-LV(60), Mod(200)
Comments The exploratory evaluation of Cmax was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection L-LV(200), Mod(200)
Comments The exploratory evaluation of Cmax was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0014
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection L-LV(200), L-LV(60)
Comments The exploratory evaluation of Cmax was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
18.Secondary Outcome
Title Cmax of [6S]-5-THF in Plasma
Hide Description Maximum concentration (Cmax) in plasma of the metabolite [6S]-5-THF
Time Frame Samples taken Day 1 (Day of surgery) and Day 2
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure.
Arm/Group Title L-LV(200) L-LV(60) Mod(200) Mod(60)
Hide Arm/Group Description:
Levoleucovorin 200 mg/m2
Levoleucovorin 60 mg/m2
Modufolin 200 mg/m2
Modufolin 60 mg/m2
Overall Number of Participants Analyzed 8 6 8 7
Mean (Standard Deviation)
Unit of Measure: µg/L
577.6250  (190.74436) 335.0000  (0) 13372.5000  (2108.15932) 5015.7143  (427.35064)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mod(200), Mod(60)
Comments The exploratory evaluation of Cmax was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0015
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection L-LV(60), Mod(60)
Comments The exploratory evaluation of Cmax was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection L-LV(200), Mod(60)
Comments The exploratory evaluation of Cmax was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0015
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection L-LV(60), Mod(200)
Comments The exploratory evaluation of Cmax was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection L-LV(200), Mod(200)
Comments The exploratory evaluation of Cmax was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0009
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection L-LV(200), L-LV(60)
Comments The exploratory evaluation of Cmax was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
19.Secondary Outcome
Title Cmax of [6S]-5-methyl-THF in Plasma
Hide Description Maximum concentration (Cmax) in plasma of the metabolite [6S]-5-methyl-THF
Time Frame Samples taken Day 1 (Day of surgery) and Day 2
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure.
Arm/Group Title L-LV(200) L-LV(60) Mod(200) Mod(60)
Hide Arm/Group Description:
Levoleucovorin 200 mg/m2
Levoleucovorin 60 mg/m2
Modufolin 200 mg/m2
Modufolin 60 mg/m2
Overall Number of Participants Analyzed 8 6 8 7
Mean (Standard Deviation)
Unit of Measure: µg/L
2786.25000  (822.6253) 1078.00000  (275.26206) 2020.50000  (1142.25116) 800.42857  (396.41849)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mod(200), Mod(60)
Comments The exploratory evaluation of Cmax was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0240
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection L-LV(60), Mod(60)
Comments The exploratory evaluation of Cmax was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1336
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection L-LV(200), Mod(60)
Comments The exploratory evaluation of Cmax was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0015
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection L-LV(60), Mod(200)
Comments The exploratory evaluation of Cmax was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1551
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection L-LV(200), Mod(200)
Comments The exploratory evaluation of Cmax was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1563
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection L-LV(200), L-LV(60)
Comments The exploratory evaluation of Cmax was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0024
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
20.Secondary Outcome
Title Cmax of [6S]-5-formyl-THF in Plasma
Hide Description Maximum concentration (Cmax) in plasma of the active substance in Modufolin: [6R] 5,10- methylene-THF and the metabolites: [6S]-5-THF, [6S]-5-methyl-THF, and [6S]-5-formyl-THF
Time Frame Samples taken Day 1 (Day of surgery) and Day 2
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure.
Arm/Group Title L-LV(200) L-LV(60) Mod(200) Mod(60)
Hide Arm/Group Description:
Levoleucovorin 200 mg/m2
Levoleucovorin 60 mg/m2
Modufolin 200 mg/m2
Modufolin 60 mg/m2
Overall Number of Participants Analyzed 8 6 8 7
Mean (Standard Deviation)
Unit of Measure: µg/L
32962.5000  (8594.17369) 10168.3333  (2271.47896) 252.7500  (141.51178) 261.0000  (0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mod(200), Mod(60)
Comments The exploratory evaluation of Cmax was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection L-LV(60), Mod(60)
Comments The exploratory evaluation of Cmax was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection L-LV(200), Mod(60)
Comments The exploratory evaluation of Cmax was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection L-LV(60), Mod(200)
Comments The exploratory evaluation of Cmax was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0142
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection L-LV(200), Mod(200)
Comments The exploratory evaluation of Cmax was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0085
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection L-LV(200), L-LV(60)
Comments The exploratory evaluation of Cmax was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0024
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
21.Secondary Outcome
Title Tmax of [6R]-5,10-methylene-THF
Hide Description Timepoint (tmax) when Cmax in plasma occurs of the active substance in Modufolin: [6R]-5,10-methylene-THF
Time Frame Samples taken Day 1 (Day of surgery) and Day 2
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure.
Arm/Group Title L-LV(200) L-LV(60) Mod(200) Mod(60)
Hide Arm/Group Description:
Levoleucovorin 200 mg/m2
Levoleucovorin 60 mg/m2
Modufolin 200 mg/m2
Modufolin 60 mg/m2
Overall Number of Participants Analyzed 8 6 8 7
Mean (Standard Deviation)
Unit of Measure: h
1.14285857  (0.53079605) 1.00000000  (0) 0.08333000  (0.00000000) 0.08333000  (0.00000000)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mod(200), Mod(60)
Comments The exploratory evaluation of tmax was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0000
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection L-LV(60), Mod(60)
Comments The exploratory evaluation of tmax was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection L-LV(200), Mod(60)
Comments The exploratory evaluation of tmax was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0010
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection L-LV(60), Mod(200)
Comments The exploratory evaluation of tmax was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection L-LV(200), Mod(200)
Comments The exploratory evaluation of tmax was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0005
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection L-LV(200), L-LV(60)
Comments The exploratory evaluation of tmax was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
22.Secondary Outcome
Title Tmax of [6S]-5-THF
Hide Description Timepoint (tmax) when Cmax in plasma occurs for the metabolite [6S]-5-THF
Time Frame Samples taken Day 1 (Day of surgery) and Day 2
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure.
Arm/Group Title L-LV(200) L-LV(60) Mod(200) Mod(60)
Hide Arm/Group Description:
Levoleucovorin 200 mg/m2
Levoleucovorin 60 mg/m2
Modufolin 200 mg/m2
Modufolin 60 mg/m2
Overall Number of Participants Analyzed 8 6 8 7
Mean (Standard Deviation)
Unit of Measure: h
2.02083375  (1.03677360) 1.50000000  (0) 0.38541750  (0.24775936) 0.09523571  (0.03149956)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mod(200), Mod(60)
Comments The exploratory evaluation of tmax was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0056
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection L-LV(60), Mod(60)
Comments The exploratory evaluation of tmax was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection L-LV(200), Mod(60)
Comments The exploratory evaluation of tmax was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0010
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection L-LV(60), Mod(200)
Comments The exploratory evaluation of tmax was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection L-LV(200), Mod(200)
Comments The exploratory evaluation of tmax was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0014
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection L-LV(200), L-LV(60)
Comments The exploratory evaluation of tmax was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
23.Secondary Outcome
Title Tmax of [6S]-5-methyl-THF
Hide Description Timepoint (tmax) when Cmax in plasma occurs for the metabolite [6S]-5-methyl-THF
Time Frame Samples taken Day 1 (Day of surgery) and Day 2
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure.
Arm/Group Title L-LV(200) L-LV(60) Mod(200) Mod(60)
Hide Arm/Group Description:
Levoleucovorin 200 mg/m2
Levoleucovorin 60 mg/m2
Modufolin 200 mg/m2
Modufolin 60 mg/m2
Overall Number of Participants Analyzed 8 6 8 7
Mean (Standard Deviation)
Unit of Measure: h
4.75000000  (1.38873015) 2.41666667  (0.66458007) 3.75000000  (1.16496475) 2.92857143  (0.93222724)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mod(200), Mod(60)
Comments The exploratory evaluation of tmax was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1796
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection L-LV(60), Mod(60)
Comments The exploratory evaluation of tmax was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3243
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection L-LV(200), Mod(60)
Comments The exploratory evaluation of tmax was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0263
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection L-LV(60), Mod(200)
Comments The exploratory evaluation of tmax was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0268
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection L-LV(200), Mod(200)
Comments The exploratory evaluation of tmax was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2041
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection L-LV(200), L-LV(60)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0061
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
24.Secondary Outcome
Title Tmax of [6S]-5-formyl-THF
Hide Description Timepoint (tmax) when Cmax in plasma occurs for the metabolite [6S]-5-formyl-THF
Time Frame Samples taken Day 1 (Day of surgery) and Day 2
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure.
Arm/Group Title L-LV(200) L-LV(60) Mod(200) Mod(60)
Hide Arm/Group Description:
Levoleucovorin 200 mg/m2
Levoleucovorin 60 mg/m2
Modufolin 200 mg/m2
Modufolin 60 mg/m2
Overall Number of Participants Analyzed 8 6 8 7
Mean (Standard Deviation)
Unit of Measure: h
0.12499750  (0.08908753) 0.08333000  (0.00000000) 0.10416500  (0.04167000) 0.08333000  (0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mod(200), Mod(60)
Comments The exploratory evaluation of tmax was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection L-LV(60), Mod(60)
Comments The exploratory evaluation of tmax was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection L-LV(200), Mod(60)
Comments The exploratory evaluation of tmax was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection L-LV(60), Mod(200)
Comments The exploratory evaluation of tmax was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection L-LV(200), Mod(200)
Comments The exploratory evaluation of tmax was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection L-LV(200), L-LV(60)
Comments The exploratory evaluation of tmax was done respectively for differences between treatments using Wilcoxon test. Differences in variability between the treatment groups were assessed using Proc GLM and Levene’s test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
25.Secondary Outcome
Title T(1/2) of [6R]-5,10-methylene-THF
Hide Description Terminal plasma elimination half-life time for the active substance in Modufolin: [6R]-5,10-methylene-THF
Time Frame Samples taken Day 1 (Day of surgery) and Day 2
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol population, all patients who complete the trial without any major deviations from the protocol procedure.
Arm/Group Title L-LV(200) L-LV(60) Mod(200) Mod(60)