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A Drug Interaction Study of Tasisulam in Patients With Advanced Cancer or Lymphoma (JZAR)

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: NCT01185548
Recruitment Status : Terminated (Terminated based on safety results from another trial)
First Posted : August 20, 2010
Results First Posted : October 19, 2018
Last Update Posted : October 19, 2018
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Lymphoma
Advanced Cancer
Interventions Drug: Tolbutamide
Drug: Tasisulam
Enrollment 4
Recruitment Details  
Pre-assignment Details  
Arm/Group Title All Participants
Hide Arm/Group Description

Period 1: 500 milligram (mg) tolbutamide administered once on Day 1

Period 2: 500 mg of tolbutamide and individualized tasisulam dose (based on AUCalb) administered once on Day 1

Period 3: individualized tasisulam dose (based on AUCalb) administered once on Day 1 and 500 mg tolbutamide administered once on day 4

Period Title: Period 1 : Tolbutamide
Started 4
Completed 4
Not Completed 0
Period Title: Period 2: Tasisulam and Tolbutamide
Started 4
Completed 2
Not Completed 2
Reason Not Completed
Sponsor Decision             2
Period Title: Period 3: Tasisulam and Tolbutamide
Started 2
Completed 2
Not Completed 0
Arm/Group Title All Participants
Hide Arm/Group Description

Three study periods: Period 1 which was tolbutamide only and lasted 4 days and Periods 2 and 3 which had continued access to tasisulam every 28 days until disease progression:

Period 1: 500 mg tolbutamide administered once on Day 1.

Period 2: 500 mg of tolbutamide and individualized tasisulam dose administered once on Day 1.

Period 3: individualized tasisulam dose administered once on Day 1 and 500 mg tolbutamide administered once on Day 4.

Overall Number of Baseline Participants 4
Hide Baseline Analysis Population Description
All participants were included in the analysis.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants
<=18 years
0
   0.0%
Between 18 and 65 years
2
  50.0%
>=65 years
2
  50.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants
Female
1
  25.0%
Male
3
  75.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
4
 100.0%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United Kingdom Number Analyzed 4 participants
4
 100.0%
1.Primary Outcome
Title Pharmacokinetics of Tolbutamide, Concurrent Dosing, Area Under the Curve (AUC 0-∞)
Hide Description AUC0-∞ is defined as the area under the concentration time curve from time 0 to infinity.
Time Frame Period 2 Predose; and 0.5, 1, 1.5, 2, 2.5, 3, 4, 4.5, 6, 8, 24, 48, 72, 120, 168, 336 hours post tolbutamide dose
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants who started Period 2 (tasisulam and tolbutamide).
Arm/Group Title Period 2: Tasisulam and Tolbutamide
Hide Arm/Group Description:
Period 2: 500 mg of tolbutamide and individualized tasisulam dose (based on AUCalb) administered once on Day 1
Overall Number of Participants Analyzed 4
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanograms*hour per milliliter (ng*hr/mL)
2670000
(20%)
2.Secondary Outcome
Title Pharmacokinetics of Tolbutamide, Staggered Dosing in Period 3, Area Under the Curve (AUC 0-∞)
Hide Description AUC0-∞ is defined as the area under the concentration time curve from time 0 to infinity.
Time Frame Period 3 Predose; and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 24, 48, 96, and 264 hours post tolbutamide dose
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants who started period 3 (tasisulam then tolbutamide).
Arm/Group Title Tasisulam and Tolbutamide: Period 3
Hide Arm/Group Description:
Period 3: Individualized tasisulam dose (based on AUCalb) administered once on Day 1 and 500 mg tolbutamide administered once on Day 4.
Overall Number of Participants Analyzed 2
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanogram*hour per milliliter (ng*hr/mL)
2700000 [1] 
(4.03% to 6%)
[1]
There were not a sufficient number of participants to calculate the geometric coefficient of variation.
3.Secondary Outcome
Title Pharmacokinetics of Tolbutamide, Maximum Concentration (Cmax)
Hide Description [Not Specified]
Time Frame Period 1, 2, and 3 Predose; and 0.5, 1, 1.5, 2, 2.5, 3, 4, 4.5, 6, 8, 24, 48, 72, 96, 120, 168, 264, 336 hours post tolbutamide dose
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants who started Periods 1, 2, or 3.
Arm/Group Title Tolbutamide: Period 1 Tasisulam and Tolbutamide: Period 2 Tasisulam and Tolbutamide: Period 3
Hide Arm/Group Description:
Period 1: 500 mg tolbutamide administered once on Day 1
Period 2: 500 mg of tolbutamide and individualized tasisulam dose (based on AUCalb) administered once on Day 1.
Period 3: individualized tasisulam dose (based on AUCalb) administered once on Day 1 and 500 mg tolbutamide administered once on Day 4.
Overall Number of Participants Analyzed 4 4 2
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanogram per milliliter (ng/mL)
39600
(26%)
39800
(18%)
48000 [1] 
(NA%)
[1]
There were not a sufficient number of participants to calculate the geometric coefficient of variation.
4.Secondary Outcome
Title Pharmacokinetics of Tolbutamide, Observed Time at Maximal Concentration (Tmax)
Hide Description [Not Specified]
Time Frame Period 1, 2, and 3 Predose; and 0.5, 1, 1.5, 2, 2.5, 3, 4, 4.5, 6, 8, 24, 48, 72, 96, 120, 168, 264, 336 hours post tolbutamide dose
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants who started Periods 1, 2, or 3.
Arm/Group Title Period 1: Tolbutamide Period 2: Tasisulam and Tolbutamide Period 3: Tasisulam and Tolbutamide
Hide Arm/Group Description:
Period 1: 500 mg tolbutamide administered once on Day 1
Period 2: 500 mg tolbutamide and an individualized tasisulam dose (based on AUCalb) administered once on Day 1.
Period 3: Individualized tasisulam dose (based on AUCalb) administered once on Day 1 and 500 mg tolbutamide administered once on day 4 (administration day in period 3 could adjusted based on interim pharmacokinetic [PK] analyses)
Overall Number of Participants Analyzed 4 4 2
Median (Full Range)
Unit of Measure: hours
2.25
(2.00 to 3.00)
5.00
(1.50 to 8.00)
5.02
(4.03 to 6.00)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Tolbutamide Tasisulam and Tolbutamide Tasisulam
Hide Arm/Group Description Adverse events (AEs) that occurred during Period 1 and during Period 2 when 500 mg tolbutamide was administered orally prior to individualized intravenous dosing (based on AUCalb) of tasisulam. AEs that occurred during Periods 2 and 3 when both 500 mg oral tolbutamide and individualized intravenous tasisulam (based on AUCalb) were administered. AEs that occurred during Period 3 Day 1 through Day 4 until just before 500 mg oral tolbutamide was administered on Day 4, 72 hours.
All-Cause Mortality
Tolbutamide Tasisulam and Tolbutamide Tasisulam
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Hide Serious Adverse Events
Tolbutamide Tasisulam and Tolbutamide Tasisulam
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/4 (0.00%)      1/4 (25.00%)      0/2 (0.00%)    
Musculoskeletal and connective tissue disorders       
Musculoskeletal chest pain  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/2 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Tolbutamide Tasisulam and Tolbutamide Tasisulam
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/4 (75.00%)      4/4 (100.00%)      1/2 (50.00%)    
Blood and lymphatic system disorders       
Anaemia  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/2 (0.00%)  0
Thrombocytopenia  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/2 (0.00%)  0
Ear and labyrinth disorders       
Tinnitus  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/2 (0.00%)  0
Gastrointestinal disorders       
Abdominal distension  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/2 (0.00%)  0
Abdominal pain  1  0/4 (0.00%)  0 2/4 (50.00%)  2 1/2 (50.00%)  1
Constipation  1  0/4 (0.00%)  0 2/4 (50.00%)  2 0/2 (0.00%)  0
Diarrhoea  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/2 (0.00%)  0
Vomiting  1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/2 (0.00%)  0
General disorders       
Chest pain  1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/2 (50.00%)  1
Fatigue  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/2 (0.00%)  0
Mucosal inflammation  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/2 (0.00%)  0
Hepatobiliary disorders       
Hepatic pain  1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/2 (0.00%)  0
Infections and infestations       
Nasopharyngitis  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/2 (0.00%)  0
Rhinitis  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/2 (0.00%)  0
Urinary tract infection  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/2 (0.00%)  0
Metabolism and nutrition disorders       
Hypophosphataemia  1  0/4 (0.00%)  0 1/4 (25.00%)  2 0/2 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Muscle spasms  1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/2 (0.00%)  0
Musculoskeletal chest pain  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/2 (0.00%)  0
Nervous system disorders       
Dizziness  1  0/4 (0.00%)  0 2/4 (50.00%)  4 0/2 (0.00%)  0
Lethargy  1  0/4 (0.00%)  0 2/4 (50.00%)  2 0/2 (0.00%)  0
Neuropathy peripheral  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/2 (0.00%)  0
Presyncope  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/2 (0.00%)  0
Skin and subcutaneous tissue disorders       
Dermatitis acneiform  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/2 (0.00%)  0
Jessner's lymphocytic infiltration  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/2 (0.00%)  0
Night sweats  1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/2 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.0
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
Phone: 800-545-5979
Layout table for additonal information
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01185548    
Other Study ID Numbers: 13076
H8K-MC-JZAR ( Other Identifier: Eli Lilly and Company )
First Submitted: August 18, 2010
First Posted: August 20, 2010
Results First Submitted: March 17, 2018
Results First Posted: October 19, 2018
Last Update Posted: October 19, 2018