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Sitagliptin Dose Comparison Study in Patients With Type 2 Diabetes (MK-0431-077)(COMPLETED)

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: NCT00541229
Recruitment Status : Completed
First Posted : October 10, 2007
Results First Posted : July 28, 2009
Last Update Posted : May 12, 2017
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Type 2 Diabetes
Interventions Drug: sitagliptin phosphate
Drug: Comparator: Placebo
Enrollment 103
Recruitment Details First Patient In: 17-Oct-2007; Last Patient Last Visit: 01-Jul-2008; Seventeen medical clinics worldwide (8 in the United States, 8 in Europe and 1 in Mexico).
Pre-assignment Details Following a 4-week (wk) diet/exercise (and wash-off period for patients on antihyperglycemic agent [AHA]), patients with fasting plasma glucose (FPG) 130-250 mg/dL were eligible to enter a 2-wk placebo run-in period prior to randomization.
Arm/Group Title Placebo / 100 mg / 200 mg 100 mg / 200 mg / Placebo 200 mg / Placebo / 100 mg Placebo / 200 mg / 100 mg 100 mg / Placebo / 200 mg 200 mg / 100 mg / Placebo
Hide Arm/Group Description Placebo / 100 mg / 200 mg Group includes patients receiving once daily administration of the following treatments: sitagliptin-matching placebo in Treatment Period I, sitagliptin 100 mg in Treatment Period II (after Washout Period I), and sitagliptin 200 mg in Treatment Period III (after Washout Period II) 100 mg / 200 mg / Placebo Group includes patients receiving once daily administration of the following treatments: sitagliptin 100 mg in Treatment Period I, sitagliptin 200 mg in Treatment Period II (after Washout Period I), and sitagliptin-matching placebo in Treatment Period III (after Washout Period II) 200 mg / Placebo / 100 mg Group includes patients receiving once daily administration of the following treatments: sitagliptin 200 mg in Treatment Period I, sitagliptin-matching placebo in Treatment Period II (after Washout Period I), and sitagliptin 100 mg in Treatment Period III (after Washout Period II) Placebo / 200 mg / 100 mg Group includes patients receiving once daily administration of the following treatments: sitagliptin-matching placebo in Treatment Period I, sitagliptin 200 mg in Treatment Period II (after Washout Period I), and sitagliptin 100 mg in Treatment Period III (after Washout Period II) 100 mg / Placebo / 200 mg Group includes patients receiving once daily administration of the following treatments: sitagliptin 100 mg in Treatment Period I, sitagliptin-matching placebo in Treatment Period II (after Washout Period I), and sitagliptin 200 mg in Treatment Period III (after Washout Period II) 200 mg / 100 mg / Placebo includes patients receiving once daily administration of the following treatments: sitagliptin 200 mg in Treatment Period I, sitagliptin 100 mg in Treatment Period II (after Washout Period I), and sitagliptin-matching placebo in Treatment Period III (after Washout Period II)
Period Title: Treatment Period I (Week 1)
Started 17 16 20 18 14 18
Completed 17 15 17 17 14 16
Not Completed 0 1 3 1 0 2
Reason Not Completed
Physician Decision             0             0             1             0             0             0
Withdrawal by Subject             0             0             0             0             0             1
Protocol Specified Criteria             0             0             0             0             0             1
Study Terminated by Sponsor             0             1             2             1             0             0
Period Title: Washout Period I (Week 2-5)
Started 17 15 17 17 14 16
Completed 13 13 13 13 13 11
Not Completed 4 2 4 4 1 5
Reason Not Completed
Adverse Event             1             0             1             0             0             0
Physician Decision             0             0             0             1             0             0
Protocol Violation             0             0             0             0             0             1
Study Terminated by Sponsor             3             2             3             3             1             4
Period Title: Treatment Period II (Week 6)
Started 13 13 13 13 13 11
Completed 11 12 12 12 11 8
Not Completed 2 1 1 1 2 3
Reason Not Completed
Protocol Violation             0             0             0             0             1             1
Study Terminated by Sponsor             2             1             1             1             1             2
Period Title: Washout Period II (Week 7-10)
Started 11 12 12 12 11 8
Completed 7 8 10 8 7 5
Not Completed 4 4 2 4 4 3
Reason Not Completed
Protocol Violation             1             0             0             0             0             0
Withdrawal by Subject             0             0             0             0             1             0
Study Terminated by Sponsor             3             4             2             4             3             3
Period Title: Treatment Period III (Week 11)
Started 7 8 10 8 7 5
Completed 7 8 9 8 6 4
Not Completed 0 0 1 0 1 1
Reason Not Completed
Adverse Event             0             0             0             0             1             0
Protocol Specified Criteria             0             0             0             0             0             1
Study Terminated by Sponsor             0             0             1             0             0             0
Arm/Group Title Placebo / 100 mg / 200 mg 100 mg / 200 mg / Placebo 200 mg / Placebo / 100 mg Placebo / 200 mg / 100 mg 100 mg / Placebo / 200 mg 200 mg / 100 mg / Placebo Total
Hide Arm/Group Description Placebo / 100 mg / 200 mg Group includes patients receiving once daily administration of the following treatments: sitagliptin-matching placebo in Treatment Period I, sitagliptin 100 mg in Treatment Period II (after Washout Period I), and sitagliptin 200 mg in Treatment Period III (after Washout Period II) 100 mg / 200 mg / Placebo Group includes patients receiving once daily administration of the following treatments: sitagliptin 100 mg in Treatment Period I, sitagliptin 200 mg in Treatment Period II (after Washout Period I), and sitagliptin-matching placebo in Treatment Period III (after Washout Period II) 200 mg / Placebo / 100 mg Group includes patients receiving once daily administration of the following treatments: sitagliptin 200 mg in Treatment Period I, sitagliptin-matching placebo in Treatment Period II (after Washout Period I), and sitagliptin 100 mg in Treatment Period III (after Washout Period II) Placebo / 200 mg / 100 mg Group includes patients receiving once daily administration of the following treatments: sitagliptin-matching placebo in Treatment Period I, sitagliptin 200 mg in Treatment Period II (after Washout Period I), and sitagliptin 100 mg in Treatment Period III (after Washout Period II) 100 mg / Placebo / 200 mg Group includes patients receiving once daily administration of the following treatments: sitagliptin 100 mg in Treatment Period I, sitagliptin-matching placebo in Treatment Period II (after Washout Period I), and sitagliptin 200 mg in Treatment Period III (after Washout Period II) 200 mg / 100 mg / Placebo includes patients receiving once daily administration of the following treatments: sitagliptin 200 mg in Treatment Period I, sitagliptin 100 mg in Treatment Period II (after Washout Period I), and sitagliptin-matching placebo in Treatment Period III (after Washout Period II) Total of all reporting groups
Overall Number of Baseline Participants 17 16 20 18 14 18 103
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 17 participants 16 participants 20 participants 18 participants 14 participants 18 participants 103 participants
54.5  (8.4) 56.6  (5.8) 55.7  (7.2) 55.3  (8.3) 50.0  (10.0) 48.6  (9.6) 53.5  (8.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 17 participants 16 participants 20 participants 18 participants 14 participants 18 participants 103 participants
Female
5
  29.4%
5
  31.3%
7
  35.0%
4
  22.2%
4
  28.6%
3
  16.7%
28
  27.2%
Male
12
  70.6%
11
  68.8%
13
  65.0%
14
  77.8%
10
  71.4%
15
  83.3%
75
  72.8%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 17 participants 16 participants 20 participants 18 participants 14 participants 18 participants 103 participants
White 12 14 15 15 11 12 79
Asian 0 0 0 0 0 1 1
Other 5 2 5 3 3 5 23
Fasting Plasma Glucose  
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 17 participants 16 participants 20 participants 18 participants 14 participants 18 participants 103 participants
179.3  (32.1) 167.0  (41.1) 184.0  (42.1) 173.2  (43.2) 158.5  (17.3) 166.0  (36.5) 172.0  (36.9)
1.Primary Outcome
Title 24-hour Weighted Mean Glucose (WMG)
Hide Description The 24-hour WMG was calculated as the area under the 24-hour glucose curve (AUC(0-24 hr)) divided by 24 using linear trapezoidal method.
Time Frame Day 7 of Treatment Period I. Due to a carry-over effect that was observed between treatment periods, efficacy results are presented from Treatment Period I only.
Hide Outcome Measure Data
Hide Analysis Population Description
The per-protocol (PP) population consisted of all patients randomized who had a measurement at Day 7 in Treatment Period I and did not have any major protocol violations. Missing data were not imputed.
Arm/Group Title Sitagliptin 200mg Sitagliptin 100mg Placebo
Hide Arm/Group Description:
Sitagliptin 200 mg group included the Treatment Period I data from patients randomized to treatment sequence Sitagliptin 200 mg/Sitagliptin 100 mg/placebo and treatment sequence Sitagliptin 200 mg/ placebo/ Sitagliptin 100 mg.
Sitagliptin 100 mg group included the Treatment Period I data from patients randomized to treatment sequence Sitagliptin 100 mg/Sitagliptin 200 mg/placebo and treatment sequence Sitagliptin 100 mg/ placebo/ Sitagliptin 200 mg.
Placebo group included the Treatment Period I data from patients randomized to treatment sequence placebo/Sitagliptin 100 mg/Sitagliptin 200 mg and treatment sequence placebo/Sitagliptin 200 mg/Sitagliptin 100 mg.
Overall Number of Participants Analyzed 28 26 30
Least Squares Mean (95% Confidence Interval)
Unit of Measure: mg/dL
169.1
(153.8 to 184.4)
159.0
(143.1 to 174.9)
200.9
(186.1 to 215.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sitagliptin 200mg, Placebo
Comments For this comparison, the mean in the placebo group was subtracted from the mean in the sitagliptin 200 mg group.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments [Not Specified]
Method ANOVA
Comments Model term: treatment
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -31.8
Confidence Interval 95%
-53.1 to -10.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Sitagliptin 100mg, Placebo
Comments For this comparison, the mean in the placebo group was subtracted from the mean in the sitagliptin 100 mg group.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANOVA
Comments Model term: treatment
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -41.9
Confidence Interval 95%
-63.6 to -20.2
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Sitagliptin 200mg, Sitagliptin 100mg
Comments This was pre-defined as a non-superiority test, i.e., to show that sitagliptin 200 mg is not superior to sitagliptin 100 mg. For this comparison, the mean in the sitagliptin 100 mg group was subtracted from the mean in the sitagliptin 200 mg group.
Type of Statistical Test Non-Inferiority or Equivalence
Comments The hypothesis stated that the lower bound of 80% one-sided confidence interval for the comparison in 24-hour WMG reduction between sitagliptin 200 mg and sitagliptin 100 mg is above -5 mg/dL.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 10.1
Confidence Interval 80%
0.61 to 9999999
Estimation Comments This is a 1-sided 80% confidence interval and the upper bound 9999999 was used here to indicate positive infinity.
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Sitagliptin 200 mg Sitagliptin 100 mg Placebo
Hide Arm/Group Description Sitagliptin 200 mg Group included data from all randomized patients in treatment periods with once-daily administration of sitagliptin 200 mg. Due to the crossover design, patients are counted in the denominator for each treatment that they received. Patients are counted in the numerator for the treatment that they were receiving at the time when the AE occurred. Sitagliptin 100 mg Group included data from all randomized patients in treatment periods with once-daily administration of sitagliptin 100 mg. Due to the crossover design, patients are counted in the denominator for each treatment that they received. Patients are counted in the numerator for the treatment that they were receiving at the time when the AE occurred. Placebo Group included data from all randomized patients in treatment periods with once-daily administration of sitagliptin-matching placebo tablets. Due to the crossover design, patients are counted in the denominator for each treatment that they received. Patients are counted in the numerator for the treatment that they were receiving at the time when the AE occurred.
All-Cause Mortality
Sitagliptin 200 mg Sitagliptin 100 mg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Hide Serious Adverse Events
Sitagliptin 200 mg Sitagliptin 100 mg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/78 (0.00%)   0/72 (0.00%)   0/74 (0.00%) 
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Sitagliptin 200 mg Sitagliptin 100 mg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   4/78 (5.13%)   2/72 (2.78%)   4/74 (5.41%) 
Nervous system disorders       
Headache * 1  4/78 (5.13%)  2/72 (2.78%)  4/74 (5.41%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 11.0
The pre-specified rule for non-superiority of sitagliptin 200 mg compared with 100 mg was met at the planned interim analysis. As such, the trial was terminated as pre-specified.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp
Phone: 1-800-672-6372
Layout table for additonal information
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00541229    
Other Study ID Numbers: 0431-077
2007_533
First Submitted: October 5, 2007
First Posted: October 10, 2007
Results First Submitted: June 5, 2009
Results First Posted: July 28, 2009
Last Update Posted: May 12, 2017