Trial Outcomes & Findings for A Study to Examine the Pharmacokinetics, Tolerability, Safety and Efficacy of Exenatide Once Weekly Suspension (NCT NCT00894322)
NCT ID: NCT00894322
Last Updated: 2015-09-18
Results Overview
Abbreviations: Upper Limit of Normal (ULN); milligram per deciliter (mg/dL); units per liter (U/L); micro liters (µL); creatine kinase (CK); gamma-glutamyltransferase (G-GT). Normal ranges = Hematocrit: 40.6-52.3% (male), 35.3-47.0 (female); Platelets 155-361\*10\^3/µL(male/female); Calcium: 8.6-10.4 mg/dL (male/female); CK: 43-350 U/L (male), 28-207 U/L (female); G-GT: 7-62 U/L (male/female); Glucose 73-105 mg/dL (male/female); Lipase 14-70 U/L (male/female); Uric acid: 3.5-7.8 mg/dL (male), 2.3-5.9 mg/dL (female). Blood samples for laboratories were collected at screening, Day 1, Weeks 4, 8, 12 or early termination. Value for potential clinical importance is presented in each category presented below.
COMPLETED
PHASE1/PHASE2
65 participants
Day 1 to Week 12
2015-09-18
Participant Flow
Healthy participants were enrolled in Cohort 1 while participants with type 2 diabetes mellitus were enrolled in Cohort 2.
Enrolled participants in Cohort 1 were treated on Day 1 only. Enrolled participants who were in Cohort 2 were randomized to one of 2 treatment arms (exenatide or placebo) and were treated for 12 weeks.
Participant milestones
| Measure |
Cohort 1 Exenatide 10 mg
A single 10-mg dose of exenatide once weekly suspension was given to healthy participants via 3 subcutaneous (SC) injections at Day 1. At the discretion of the investigator, participants could receive up to 2 anti-emetic medications approximately 30 minutes prior to the exenatide once weekly suspension dose.
|
Cohort 2 Exenatide 2 mg
On Day 1, participants with type 2 diabetes mellitus treated with diet and exercise alone or with a stable regimen of metformin, a thiazolidinedione (TZD), or a combination of metformin or a TZD were randomized to receive weekly injections of 2 mg exenatide suspension for 12 weeks. Study medication was administered weekly.
|
Cohort 2 Placebo
On Day 1, participants with type 2 diabetes mellitus treated with diet and exercise alone or with a stable regimen of metformin, a thiazolidinedione (TZD), or a combination of metformin or a TZD were randomized to receive weekly injections of medium-chain triglycerides (MCT)-diluent placebo for 12 weeks. Study medication was administered weekly from Visit 2 (Day 1) to Visit 15 (Week 11).
|
|---|---|---|---|
|
Overall Study
STARTED
|
30
|
23
|
12
|
|
Overall Study
COMPLETED
|
29
|
23
|
12
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
0
|
Reasons for withdrawal
| Measure |
Cohort 1 Exenatide 10 mg
A single 10-mg dose of exenatide once weekly suspension was given to healthy participants via 3 subcutaneous (SC) injections at Day 1. At the discretion of the investigator, participants could receive up to 2 anti-emetic medications approximately 30 minutes prior to the exenatide once weekly suspension dose.
|
Cohort 2 Exenatide 2 mg
On Day 1, participants with type 2 diabetes mellitus treated with diet and exercise alone or with a stable regimen of metformin, a thiazolidinedione (TZD), or a combination of metformin or a TZD were randomized to receive weekly injections of 2 mg exenatide suspension for 12 weeks. Study medication was administered weekly.
|
Cohort 2 Placebo
On Day 1, participants with type 2 diabetes mellitus treated with diet and exercise alone or with a stable regimen of metformin, a thiazolidinedione (TZD), or a combination of metformin or a TZD were randomized to receive weekly injections of medium-chain triglycerides (MCT)-diluent placebo for 12 weeks. Study medication was administered weekly from Visit 2 (Day 1) to Visit 15 (Week 11).
|
|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
0
|
Baseline Characteristics
A Study to Examine the Pharmacokinetics, Tolerability, Safety and Efficacy of Exenatide Once Weekly Suspension
Baseline characteristics by cohort
| Measure |
Cohort 1 Exenatide 10 mg
n=30 Participants
A single 10-mg dose of exenatide once weekly suspension was given to healthy participants via 3 subcutaneous (SC) injections at Day 1. At the discretion of the investigator, participants could receive up to 2 anti-emetic medications approximately 30 minutes prior to the exenatide once weekly suspension dose.
|
Cohort 2 Exenatide 2 mg
n=23 Participants
On Day 1, participants with type 2 diabetes mellitus treated with diet and exercise alone or with a stable regimen of metformin, a thiazolidinedione (TZD), or a combination of metformin or a TZD were randomized to receive weekly injections of 2 mg exenatide suspension for 12 weeks. Study medication was administered weekly.
|
Cohort 2 Placebo
n=12 Participants
On Day 1, participants with type 2 diabetes mellitus treated with diet and exercise alone or with a stable regimen of metformin, a thiazolidinedione (TZD), or a combination of metformin or a TZD were randomized to receive weekly injections of medium-chain triglycerides (MCT)-diluent placebo for 12 weeks. Study medication was administered weekly from Visit 2 (Day 1) to Visit 15 (Week 11).
|
Total
n=65 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
41.2 years
STANDARD_DEVIATION 14.4 • n=5 Participants
|
52.7 years
STANDARD_DEVIATION 11.6 • n=7 Participants
|
52.0 years
STANDARD_DEVIATION 9.3 • n=5 Participants
|
52.4 years
STANDARD_DEVIATION 10.7 • n=4 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
23 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
18 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
42 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
23 participants
n=5 Participants
|
19 participants
n=7 Participants
|
11 participants
n=5 Participants
|
53 participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Black
|
3 participants
n=5 Participants
|
1 participants
n=7 Participants
|
0 participants
n=5 Participants
|
4 participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
1 participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Native American
|
1 participants
n=5 Participants
|
1 participants
n=7 Participants
|
0 participants
n=5 Participants
|
2 participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
3 participants
n=5 Participants
|
2 participants
n=7 Participants
|
0 participants
n=5 Participants
|
5 participants
n=4 Participants
|
|
Region of Enrollment
United States
|
30 participants
n=5 Participants
|
23 participants
n=7 Participants
|
12 participants
n=5 Participants
|
65 participants
n=4 Participants
|
|
Body Weight
|
85.9 kilograms
STANDARD_DEVIATION 15.5 • n=5 Participants
|
104.9 kilograms
STANDARD_DEVIATION 23.2 • n=7 Participants
|
104.4 kilograms
STANDARD_DEVIATION 20.3 • n=5 Participants
|
104.7 kilograms
STANDARD_DEVIATION 22.0 • n=4 Participants
|
|
Body Mass Index (BMI)
|
28.5 kg/m^2
STANDARD_DEVIATION 3.5 • n=5 Participants
|
35.3 kg/m^2
STANDARD_DEVIATION 6.7 • n=7 Participants
|
34.9 kg/m^2
STANDARD_DEVIATION 4.9 • n=5 Participants
|
35.1 kg/m^2
STANDARD_DEVIATION 6.1 • n=4 Participants
|
PRIMARY outcome
Timeframe: Day 1, Week 12Population: PK evaluable population was analyzed. n in categories below = number of ITT participants with PK evaluable data.
Cohort 1: Blood samples for the assessment of plasma exenatide were collected at time = -15, 60, 90, 120, 180, 240, 360, and 480 minutes relative to study medication injection at time = 0 on Day 1 and the mean is presented below. At all visits following the single injection, a single blood sample was collected for assessment of exenatide concentrations. AUC was measured in picograms \* hours per milliliter (pg\*hr/mL). Exenatide was measured using a validated enzyme-linked immunosorbent assay (ELISA). AUC calculated using linear trapezoidal method from time x to time y; AUC (0-8h) and (0-tlast) are presented below. Pharmacokinetic (PK) evaluable population consisted of all ITT participants who had at least 4 detectable plasma exenatide measurements \[not less than (\<) lower limits of quantification (LLOQ)\] from Day 1 to Week 12 and had reliable PK data.
Outcome measures
| Measure |
Cohort 1 Exenatide 10 mg
n=30 Participants
A single 10-mg dose of exenatide once weekly suspension was given to healthy participants via 3 subcutaneous (SC) injections at Day 1. At the discretion of the investigator, participants could receive up to 2 anti-emetic medications approximately 30 minutes prior to the exenatide once weekly suspension dose.
|
Cohort 2 Exenatide 2 mg
On Day 1, participants with type 2 diabetes mellitus treated with diet and exercise alone or with a stable regimen of metformin, a thiazolidinedione (TZD), or a combination of metformin or a TZD were randomized to receive weekly injections of exenatide suspension for 12 weeks. Study medication was administered weekly from Visit 2 (Day 1) to Visit 15 (Week 11).
|
Cohort 2 Placebo
On Day 1, participants with type 2 diabetes mellitus treated with diet and exercise alone or with a stable regimen of metformin, a thiazolidinedione (TZD), or a combination of metformin or a TZD were randomized to receive weekly injections of medium-chain triglycerides (MCT)-diluent placebo for 12 weeks. Study medication was administered weekly from Visit 2 (Day 1) to Visit 15 (Week 11).
|
|---|---|---|---|
|
Area Under the Curve (AUC) for Single Dose of 10 mg Exenatide (Cohort 1) in Healthy Participants in the Pharmacokinetic Evaluable Population
AUC (0-8h), n=30
|
125.6 pg*h/mL
Standard Error 41.16
|
—
|
—
|
|
Area Under the Curve (AUC) for Single Dose of 10 mg Exenatide (Cohort 1) in Healthy Participants in the Pharmacokinetic Evaluable Population
AUC (0-Week 12), n=30
|
147220.2 pg*h/mL
Standard Error 24000.04
|
—
|
—
|
PRIMARY outcome
Timeframe: Day 1, Week 12Population: PK evaluable population.
Cohort 1: Blood samples for the assessment of plasma exenatide were collected at time = -15, 60, 90, 120, 180, 240, 360, and 480 minutes relative to study medication injection at time = 0 on Day 1 and the mean is presented below. At all visits following the single injection, a single blood sample was collected for assessment of exenatide concentrations. Cmax was measured in picograms per milliliter (pg/mL). Exenatide concentration was measured using a validated enzyme-linked immunosorbent assay (ELISA). PK evaluable population consisted of all ITT participants who had at least 4 detectable plasma exenatide measurements \[not less than (\<) lower limits of quantification (LLOQ)\] from Day 1 to Week 12 for the evaluation of the PK characteristics of plasma exenatide and had reliable PK data. Cmax (0-8h) and (0-tlast) are presented below.
Outcome measures
| Measure |
Cohort 1 Exenatide 10 mg
n=30 Participants
A single 10-mg dose of exenatide once weekly suspension was given to healthy participants via 3 subcutaneous (SC) injections at Day 1. At the discretion of the investigator, participants could receive up to 2 anti-emetic medications approximately 30 minutes prior to the exenatide once weekly suspension dose.
|
Cohort 2 Exenatide 2 mg
On Day 1, participants with type 2 diabetes mellitus treated with diet and exercise alone or with a stable regimen of metformin, a thiazolidinedione (TZD), or a combination of metformin or a TZD were randomized to receive weekly injections of exenatide suspension for 12 weeks. Study medication was administered weekly from Visit 2 (Day 1) to Visit 15 (Week 11).
|
Cohort 2 Placebo
On Day 1, participants with type 2 diabetes mellitus treated with diet and exercise alone or with a stable regimen of metformin, a thiazolidinedione (TZD), or a combination of metformin or a TZD were randomized to receive weekly injections of medium-chain triglycerides (MCT)-diluent placebo for 12 weeks. Study medication was administered weekly from Visit 2 (Day 1) to Visit 15 (Week 11).
|
|---|---|---|---|
|
Maximum Concentration (Cmax) for Single Dose of 10 mg Exenatide (Cohort 1) in Healthy Participants in the Pharmacokinetic Evaluable Population
Cmax 0 hour to 8 hours
|
34.9 pg/mL
Standard Error 8.33
|
—
|
—
|
|
Maximum Concentration (Cmax) for Single Dose of 10 mg Exenatide (Cohort 1) in Healthy Participants in the Pharmacokinetic Evaluable Population
Cmax 0 hour to Week 12
|
331.2 pg/mL
Standard Error 46.90
|
—
|
—
|
PRIMARY outcome
Timeframe: Day 1, Week 12Population: PK evaluable population. n=number of participants who had reliable PK data available to be evaluated.
Cohort 1: Blood samples for the assessment of plasma exenatide were collected at time(t) = -15, 60, 90, 120, 180, 240, 360, and 480 minutes relative to study medication injection at time = 0 on Day 1 an the mean is presented below. At all visits following the single injection, a single blood sample was collected for assessment of exenatide concentrations. Tmax was measured in hours and Tmax (0-8h) and (0-tlast) are presented below. Exenatide concentration was measured using a validated enzyme-linked immunosorbent assay (ELISA). PK evaluable population consisted of all ITT participants who had at least 4 detectable plasma exenatide measurements \[not less than (\<) lower limits of quantification (LLOQ)\] and had reliable PK data.
Outcome measures
| Measure |
Cohort 1 Exenatide 10 mg
n=27 Participants
A single 10-mg dose of exenatide once weekly suspension was given to healthy participants via 3 subcutaneous (SC) injections at Day 1. At the discretion of the investigator, participants could receive up to 2 anti-emetic medications approximately 30 minutes prior to the exenatide once weekly suspension dose.
|
Cohort 2 Exenatide 2 mg
On Day 1, participants with type 2 diabetes mellitus treated with diet and exercise alone or with a stable regimen of metformin, a thiazolidinedione (TZD), or a combination of metformin or a TZD were randomized to receive weekly injections of exenatide suspension for 12 weeks. Study medication was administered weekly from Visit 2 (Day 1) to Visit 15 (Week 11).
|
Cohort 2 Placebo
On Day 1, participants with type 2 diabetes mellitus treated with diet and exercise alone or with a stable regimen of metformin, a thiazolidinedione (TZD), or a combination of metformin or a TZD were randomized to receive weekly injections of medium-chain triglycerides (MCT)-diluent placebo for 12 weeks. Study medication was administered weekly from Visit 2 (Day 1) to Visit 15 (Week 11).
|
|---|---|---|---|
|
Time to Maximum Concentration (Tmax) for Single Dose of 10 mg Exenatide (Cohort 1) in Healthy Participants in the Pharmacokinetic Evaluable Population
Tmax (0 to 8 hours), n=27
|
7.0 hours
Standard Error 0.43
|
—
|
—
|
|
Time to Maximum Concentration (Tmax) for Single Dose of 10 mg Exenatide (Cohort 1) in Healthy Participants in the Pharmacokinetic Evaluable Population
Tmax (0 hour to Week 12), n=30
|
998.1 hours
Standard Error 67.60
|
—
|
—
|
PRIMARY outcome
Timeframe: Day 1 to Week12Population: ITT population included all participants treated with at least one dose of study drug.
Treatment emergent (TE)=occurs during or after treatment with study drug. Adverse Event (AE)=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Participants experiencing multiple episodes of a given AE are counted once. Injection site AEs: adverse events that existed prior to Day 1 and worsened after the first administration at Day 1, or occurred after the first administration at Day 1 through Week 12, or after Study Termination if considered by investigator to be clinically significant.
Outcome measures
| Measure |
Cohort 1 Exenatide 10 mg
n=30 Participants
A single 10-mg dose of exenatide once weekly suspension was given to healthy participants via 3 subcutaneous (SC) injections at Day 1. At the discretion of the investigator, participants could receive up to 2 anti-emetic medications approximately 30 minutes prior to the exenatide once weekly suspension dose.
|
Cohort 2 Exenatide 2 mg
n=23 Participants
On Day 1, participants with type 2 diabetes mellitus treated with diet and exercise alone or with a stable regimen of metformin, a thiazolidinedione (TZD), or a combination of metformin or a TZD were randomized to receive weekly injections of exenatide suspension for 12 weeks. Study medication was administered weekly from Visit 2 (Day 1) to Visit 15 (Week 11).
|
Cohort 2 Placebo
n=12 Participants
On Day 1, participants with type 2 diabetes mellitus treated with diet and exercise alone or with a stable regimen of metformin, a thiazolidinedione (TZD), or a combination of metformin or a TZD were randomized to receive weekly injections of medium-chain triglycerides (MCT)-diluent placebo for 12 weeks. Study medication was administered weekly from Visit 2 (Day 1) to Visit 15 (Week 11).
|
|---|---|---|---|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Injection Site TEAEs, Serious Adverse Events (SAEs), Deaths, and Withdrawals Due to AEs in Cohort 1 and Cohort 2 in Intent to Treat (ITT) Population
TEAE
|
26 participants
|
22 participants
|
9 participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Injection Site TEAEs, Serious Adverse Events (SAEs), Deaths, and Withdrawals Due to AEs in Cohort 1 and Cohort 2 in Intent to Treat (ITT) Population
Injection Site TEAEs
|
16 participants
|
18 participants
|
7 participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Injection Site TEAEs, Serious Adverse Events (SAEs), Deaths, and Withdrawals Due to AEs in Cohort 1 and Cohort 2 in Intent to Treat (ITT) Population
Withdrawal due to AE
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Injection Site TEAEs, Serious Adverse Events (SAEs), Deaths, and Withdrawals Due to AEs in Cohort 1 and Cohort 2 in Intent to Treat (ITT) Population
SAE
|
0 participants
|
0 participants
|
1 participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Injection Site TEAEs, Serious Adverse Events (SAEs), Deaths, and Withdrawals Due to AEs in Cohort 1 and Cohort 2 in Intent to Treat (ITT) Population
Death
|
0 participants
|
0 participants
|
0 participants
|
PRIMARY outcome
Timeframe: Day 1 to 12 weeksPopulation: ITT population included all participants treated with at least one dose of study drug.
Concomitant medications are defined as those medications received on or after the date of the first injection on Day 1, including prior medications that continued past Day 1 and new concomitant medications. Participants may be counted in more than one medication class and no more than once in each class. Categories by Anatomical Therapeutic Chemical (ATC) classification using the World Health Organization (WHO) Drug Dictionary version C1, 01 March 2009. As per protocol, all participants in Cohort 1 could receive up to 2 anti-emetic medications approximately 30 minutes prior to the exenatide.
Outcome measures
| Measure |
Cohort 1 Exenatide 10 mg
n=30 Participants
A single 10-mg dose of exenatide once weekly suspension was given to healthy participants via 3 subcutaneous (SC) injections at Day 1. At the discretion of the investigator, participants could receive up to 2 anti-emetic medications approximately 30 minutes prior to the exenatide once weekly suspension dose.
|
Cohort 2 Exenatide 2 mg
n=23 Participants
On Day 1, participants with type 2 diabetes mellitus treated with diet and exercise alone or with a stable regimen of metformin, a thiazolidinedione (TZD), or a combination of metformin or a TZD were randomized to receive weekly injections of exenatide suspension for 12 weeks. Study medication was administered weekly from Visit 2 (Day 1) to Visit 15 (Week 11).
|
Cohort 2 Placebo
n=12 Participants
On Day 1, participants with type 2 diabetes mellitus treated with diet and exercise alone or with a stable regimen of metformin, a thiazolidinedione (TZD), or a combination of metformin or a TZD were randomized to receive weekly injections of medium-chain triglycerides (MCT)-diluent placebo for 12 weeks. Study medication was administered weekly from Visit 2 (Day 1) to Visit 15 (Week 11).
|
|---|---|---|---|
|
Number of Participants With Concomitant Medications in Cohort 1 and Cohort 2 in ITT Population
|
30 participants
|
21 participants
|
11 participants
|
PRIMARY outcome
Timeframe: Day 1 to Week 12Population: ITT population included all participants treated with at least one dose of study drug.
In Cohort 1, sitting blood pressures were obtained at Screening (Visit 1), Day 1 (Visit 2), Weeks 1-11 (Visits 3-13), Week 12 (Visit 14), and at early termination. Blood pressures (diastolic and systolic) were measured in millimeters of mercury (mmHg). In Cohort 2, sitting blood pressures were obtained at Screening (Visit 1), Day 1 (Visit 2), Weeks 1-10 (Visits 3-12), Week 11 (Visit 15), Week 12 (Visit 16) and at early termination. Baseline was defined as last measurement prior to first injection of study drug.
Outcome measures
| Measure |
Cohort 1 Exenatide 10 mg
n=30 Participants
A single 10-mg dose of exenatide once weekly suspension was given to healthy participants via 3 subcutaneous (SC) injections at Day 1. At the discretion of the investigator, participants could receive up to 2 anti-emetic medications approximately 30 minutes prior to the exenatide once weekly suspension dose.
|
Cohort 2 Exenatide 2 mg
n=23 Participants
On Day 1, participants with type 2 diabetes mellitus treated with diet and exercise alone or with a stable regimen of metformin, a thiazolidinedione (TZD), or a combination of metformin or a TZD were randomized to receive weekly injections of exenatide suspension for 12 weeks. Study medication was administered weekly from Visit 2 (Day 1) to Visit 15 (Week 11).
|
Cohort 2 Placebo
n=12 Participants
On Day 1, participants with type 2 diabetes mellitus treated with diet and exercise alone or with a stable regimen of metformin, a thiazolidinedione (TZD), or a combination of metformin or a TZD were randomized to receive weekly injections of medium-chain triglycerides (MCT)-diluent placebo for 12 weeks. Study medication was administered weekly from Visit 2 (Day 1) to Visit 15 (Week 11).
|
|---|---|---|---|
|
Mean Change From Baseline to End of Study in Sitting Diastolic and Systolic Blood Pressure in Cohorts 1 and 2 in ITT Population
Diastolic Blood Pressure
|
6.2 mmHg
Standard Deviation 7.05
|
4.6 mmHg
Standard Deviation 8.81
|
6.8 mmHg
Standard Deviation 7.81
|
|
Mean Change From Baseline to End of Study in Sitting Diastolic and Systolic Blood Pressure in Cohorts 1 and 2 in ITT Population
Systolic Blood Pressure
|
-1.4 mmHg
Standard Deviation 9.59
|
-8.4 mmHg
Standard Deviation 14.15
|
-1.7 mmHg
Standard Deviation 12.47
|
PRIMARY outcome
Timeframe: Day 1 to Week 12In Cohort 1, sitting heart rates were obtained at Screening (Visit 1), Day 1 (Visit 2), Weeks 1-11 (Visits 3-13), Week 12 (Visit 14), and at early termination. Heart rate was measured in beats per minute (bpm). In Cohort 2, sitting heart rates were obtained at Screening (Visit 1), Day 1 (Visit 2), Weeks 1-10 (Visits 3-12), Week 11 (Visit 15), Week 12 (Visit 16) and at early termination. Baseline was defined as last measurement prior to first injection of study drug.
Outcome measures
| Measure |
Cohort 1 Exenatide 10 mg
n=30 Participants
A single 10-mg dose of exenatide once weekly suspension was given to healthy participants via 3 subcutaneous (SC) injections at Day 1. At the discretion of the investigator, participants could receive up to 2 anti-emetic medications approximately 30 minutes prior to the exenatide once weekly suspension dose.
|
Cohort 2 Exenatide 2 mg
n=23 Participants
On Day 1, participants with type 2 diabetes mellitus treated with diet and exercise alone or with a stable regimen of metformin, a thiazolidinedione (TZD), or a combination of metformin or a TZD were randomized to receive weekly injections of exenatide suspension for 12 weeks. Study medication was administered weekly from Visit 2 (Day 1) to Visit 15 (Week 11).
|
Cohort 2 Placebo
n=12 Participants
On Day 1, participants with type 2 diabetes mellitus treated with diet and exercise alone or with a stable regimen of metformin, a thiazolidinedione (TZD), or a combination of metformin or a TZD were randomized to receive weekly injections of medium-chain triglycerides (MCT)-diluent placebo for 12 weeks. Study medication was administered weekly from Visit 2 (Day 1) to Visit 15 (Week 11).
|
|---|---|---|---|
|
Mean Change From Baseline to End of Study in Sitting Heart Rate in Cohorts 1 and 2 in ITT Population
|
-7.5 bpm
Standard Deviation 9.38
|
-5.4 bpm
Standard Deviation 8.10
|
-9.1 bpm
Standard Deviation 7.03
|
PRIMARY outcome
Timeframe: Day 1 to Week 12Population: ITT population included all participants treated with at least one dose of study drug.
Abbreviations: Upper Limit of Normal (ULN); milligram per deciliter (mg/dL); units per liter (U/L); micro liters (µL); creatine kinase (CK); gamma-glutamyltransferase (G-GT). Normal ranges = Hematocrit: 40.6-52.3% (male), 35.3-47.0 (female); Platelets 155-361\*10\^3/µL(male/female); Calcium: 8.6-10.4 mg/dL (male/female); CK: 43-350 U/L (male), 28-207 U/L (female); G-GT: 7-62 U/L (male/female); Glucose 73-105 mg/dL (male/female); Lipase 14-70 U/L (male/female); Uric acid: 3.5-7.8 mg/dL (male), 2.3-5.9 mg/dL (female). Blood samples for laboratories were collected at screening, Day 1, Weeks 4, 8, 12 or early termination. Value for potential clinical importance is presented in each category presented below.
Outcome measures
| Measure |
Cohort 1 Exenatide 10 mg
n=30 Participants
A single 10-mg dose of exenatide once weekly suspension was given to healthy participants via 3 subcutaneous (SC) injections at Day 1. At the discretion of the investigator, participants could receive up to 2 anti-emetic medications approximately 30 minutes prior to the exenatide once weekly suspension dose.
|
Cohort 2 Exenatide 2 mg
n=23 Participants
On Day 1, participants with type 2 diabetes mellitus treated with diet and exercise alone or with a stable regimen of metformin, a thiazolidinedione (TZD), or a combination of metformin or a TZD were randomized to receive weekly injections of exenatide suspension for 12 weeks. Study medication was administered weekly from Visit 2 (Day 1) to Visit 15 (Week 11).
|
Cohort 2 Placebo
n=12 Participants
On Day 1, participants with type 2 diabetes mellitus treated with diet and exercise alone or with a stable regimen of metformin, a thiazolidinedione (TZD), or a combination of metformin or a TZD were randomized to receive weekly injections of medium-chain triglycerides (MCT)-diluent placebo for 12 weeks. Study medication was administered weekly from Visit 2 (Day 1) to Visit 15 (Week 11).
|
|---|---|---|---|
|
Number of Participants With Hematology and Serum Chemistry Laboratory Values of Potential Clinical Importance in Cohorts 1 and 2 in ITT Population
Hematocrit low <36%
|
0 participants
|
0 participants
|
1 participants
|
|
Number of Participants With Hematology and Serum Chemistry Laboratory Values of Potential Clinical Importance in Cohorts 1 and 2 in ITT Population
CK high >3*ULN
|
1 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Hematology and Serum Chemistry Laboratory Values of Potential Clinical Importance in Cohorts 1 and 2 in ITT Population
Lipase high >3*ULN in U/L
|
0 participants
|
0 participants
|
1 participants
|
|
Number of Participants With Hematology and Serum Chemistry Laboratory Values of Potential Clinical Importance in Cohorts 1 and 2 in ITT Population
Platelets high <75 to >500*10^3/µ/L
|
0 participants
|
1 participants
|
0 participants
|
|
Number of Participants With Hematology and Serum Chemistry Laboratory Values of Potential Clinical Importance in Cohorts 1 and 2 in ITT Population
Calcium high <8 to >11 mg/dL
|
0 participants
|
1 participants
|
0 participants
|
|
Number of Participants With Hematology and Serum Chemistry Laboratory Values of Potential Clinical Importance in Cohorts 1 and 2 in ITT Population
G-GT high >3*ULN in U/L
|
0 participants
|
0 participants
|
1 participants
|
|
Number of Participants With Hematology and Serum Chemistry Laboratory Values of Potential Clinical Importance in Cohorts 1 and 2 in ITT Population
Glucose low <50 to > 450 mg/dL
|
1 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Hematology and Serum Chemistry Laboratory Values of Potential Clinical Importance in Cohorts 1 and 2 in ITT Population
Uric Acid high >8.0 mg/dL
|
0 participants
|
1 participants
|
0 participants
|
PRIMARY outcome
Timeframe: Day 1 to Week 12Population: Only participants who received exenatide were analyzed (no placebo-treated participants were included). N=number of participants in each treatment at each visit and n= number of participants with reportable titers at the visit. Last visit=last visit with reportable titers.
Serum titers of antibodies to exenatide were evaluated using a validated enzyme-linked immunosorbent assay (Covance Method No. ELISA-0308). Positive antibody to exenatide titer: observed at the indicated visit following a negative or missing titer at baseline, or a positive titer that has increased by at least 3 dilutions at the indicated visit from a detectable baseline. Baseline=Day 1. Negative titers were assigned a value of 1 in order to calculate geometric mean. Geometric mean of reportable titers, by study week, are presented below.
Outcome measures
| Measure |
Cohort 1 Exenatide 10 mg
n=30 Participants
A single 10-mg dose of exenatide once weekly suspension was given to healthy participants via 3 subcutaneous (SC) injections at Day 1. At the discretion of the investigator, participants could receive up to 2 anti-emetic medications approximately 30 minutes prior to the exenatide once weekly suspension dose.
|
Cohort 2 Exenatide 2 mg
n=23 Participants
On Day 1, participants with type 2 diabetes mellitus treated with diet and exercise alone or with a stable regimen of metformin, a thiazolidinedione (TZD), or a combination of metformin or a TZD were randomized to receive weekly injections of exenatide suspension for 12 weeks. Study medication was administered weekly from Visit 2 (Day 1) to Visit 15 (Week 11).
|
Cohort 2 Placebo
On Day 1, participants with type 2 diabetes mellitus treated with diet and exercise alone or with a stable regimen of metformin, a thiazolidinedione (TZD), or a combination of metformin or a TZD were randomized to receive weekly injections of medium-chain triglycerides (MCT)-diluent placebo for 12 weeks. Study medication was administered weekly from Visit 2 (Day 1) to Visit 15 (Week 11).
|
|---|---|---|---|
|
Antibody Titers for Participants With Treatment Emergent Positive Antibodies to Exenatide in Participants Who Received Exenatide in Cohorts 1 and 2
Week 6, N=30, 23; n=0, 15
|
NA Reportable Titers
Standard Error NA
No reportable titers (n=0) available for this week in this treatment group so mean (SE) are not applicable (n/a)
|
295.9 Reportable Titers
Standard Error 129.9
|
—
|
|
Antibody Titers for Participants With Treatment Emergent Positive Antibodies to Exenatide in Participants Who Received Exenatide in Cohorts 1 and 2
Week 2, N=30, 23; n=4, 1
|
25.0 Reportable Titers
Standard Error 0.0
|
25.0 Reportable Titers
Standard Error NA
Only 1 participant with reportable titer so SE cannot be calculated.
|
—
|
|
Antibody Titers for Participants With Treatment Emergent Positive Antibodies to Exenatide in Participants Who Received Exenatide in Cohorts 1 and 2
Week 4, N=30, 23; n=14, 10
|
394.6 Reportable Titers
Standard Error 204.4
|
202.6 Reportable Titers
Standard Error 109.2
|
—
|
|
Antibody Titers for Participants With Treatment Emergent Positive Antibodies to Exenatide in Participants Who Received Exenatide in Cohorts 1 and 2
Week 8, N=29, 23; n=22,15
|
300.7 Reportable Titers
Standard Error 118.0
|
561.4 Reportable Titers
Standard Error 186.4
|
—
|
|
Antibody Titers for Participants With Treatment Emergent Positive Antibodies to Exenatide in Participants Who Received Exenatide in Cohorts 1 and 2
Week 10, N=29, 23; n=0,15
|
NA Reportable Titers
Standard Error NA
No reportable titers (n=0) available for this week in this treatment group so mean (SE) are not applicable (n/a)
|
453.0 Reportable Titers
Standard Error 190.9
|
—
|
|
Antibody Titers for Participants With Treatment Emergent Positive Antibodies to Exenatide in Participants Who Received Exenatide in Cohorts 1 and 2
Last visit, N=30, 23; n=20, 15
|
202.6 Reportable Titers
Standard Error 63.0
|
625.0 Reportable Titers
Standard Error 294.5
|
—
|
PRIMARY outcome
Timeframe: Week 10-11; Weeks 10 - 12Population: PK evaluable population was analyzed. In categories below, n = number of ITT participants with PK evaluable data. Note: Placebo-treated participants not included in this analysis.
Cohort 2: Blood samples for the assessment of plasma exenatide were collected on Day 1, Weeks 2, 4, 6, 8, and 10. At Week 10, blood samples were collected at time = -15, 60, 90, 120, 180, 240, and 360 minutes relative to study medication injection at time = 0. AUC was measured in picograms \* hours per milliliter (pg\*hr/mL). Exenatide was measured using a validated enzyme-linked immunosorbent assay (ELISA). AUC calculated using linear trapezoidal method from time x to time y; AUC (0-6h) measured at Week 10, AUC (0-168h) steady state measured between Weeks 10 and 11, and AUC (0-tlast) for time interval between Weeks 10 and 12 (approximately336 hours) are presented below. PK evaluable population consisted of all ITT participants who had at least 4 detectable plasma exenatide measurements (not \< LLOQ) from Day 1 to Week 12 and had reliable PK data.
Outcome measures
| Measure |
Cohort 1 Exenatide 10 mg
n=18 Participants
A single 10-mg dose of exenatide once weekly suspension was given to healthy participants via 3 subcutaneous (SC) injections at Day 1. At the discretion of the investigator, participants could receive up to 2 anti-emetic medications approximately 30 minutes prior to the exenatide once weekly suspension dose.
|
Cohort 2 Exenatide 2 mg
On Day 1, participants with type 2 diabetes mellitus treated with diet and exercise alone or with a stable regimen of metformin, a thiazolidinedione (TZD), or a combination of metformin or a TZD were randomized to receive weekly injections of exenatide suspension for 12 weeks. Study medication was administered weekly from Visit 2 (Day 1) to Visit 15 (Week 11).
|
Cohort 2 Placebo
On Day 1, participants with type 2 diabetes mellitus treated with diet and exercise alone or with a stable regimen of metformin, a thiazolidinedione (TZD), or a combination of metformin or a TZD were randomized to receive weekly injections of medium-chain triglycerides (MCT)-diluent placebo for 12 weeks. Study medication was administered weekly from Visit 2 (Day 1) to Visit 15 (Week 11).
|
|---|---|---|---|
|
Area Under the Curve (AUC) for 2 mg Exenatide (Cohort 2) in Participants With Diabetes in the Pharmacokinetic Evaluable Population
AUC (0-6h) at Week 10, n=18
|
1535.3 pg*hr/mL
Standard Error 232.40
|
—
|
—
|
|
Area Under the Curve (AUC) for 2 mg Exenatide (Cohort 2) in Participants With Diabetes in the Pharmacokinetic Evaluable Population
AUC (0-168h) at Weeks 10-11, n=18
|
49100.2 pg*hr/mL
Standard Error 6796.56
|
—
|
—
|
|
Area Under the Curve (AUC) for 2 mg Exenatide (Cohort 2) in Participants With Diabetes in the Pharmacokinetic Evaluable Population
AUC (0-tlast) at Weeks 10-12, n=17
|
101615.0 pg*hr/mL
Standard Error 12927.42
|
—
|
—
|
PRIMARY outcome
Timeframe: Week 10 - Week 11; Week 10 - Week 12Population: PK evaluable population was analyzed. In categories below, n = number of ITT participants with PK evaluable data. Note: Placebo-treated participants not included in this analysis.
Cohort 2: Blood samples for the assessment of plasma exenatide were collected on Day 1, Weeks 2, 4, 6, 8, and 10. At Week 10, blood samples were collected at time = -15, 60, 90, 120, 180, 240, and 360 minutes relative to study medication injection at time = 0. At all visits following the single injection, a single blood sample was collected for assessment of exenatide concentrations. Cave(0-168h) and Cave(0-tlast) was the time-weighted mean concentration over the sampling period from time x to time y corresponding to AUC (0-168h), and AUC (0-tlast), respectively. Cave was measured in picograms per milliliter (pg/mL). Exenatide concentration was measured using a validated enzyme-linked immunosorbent assay (ELISA). PK evaluable population consisted of all ITT participants who had at least 4 detectable plasma exenatide measurements (not \< LLOQ) from Day 1 to Week 12 and had reliable PK data.
Outcome measures
| Measure |
Cohort 1 Exenatide 10 mg
n=18 Participants
A single 10-mg dose of exenatide once weekly suspension was given to healthy participants via 3 subcutaneous (SC) injections at Day 1. At the discretion of the investigator, participants could receive up to 2 anti-emetic medications approximately 30 minutes prior to the exenatide once weekly suspension dose.
|
Cohort 2 Exenatide 2 mg
On Day 1, participants with type 2 diabetes mellitus treated with diet and exercise alone or with a stable regimen of metformin, a thiazolidinedione (TZD), or a combination of metformin or a TZD were randomized to receive weekly injections of exenatide suspension for 12 weeks. Study medication was administered weekly from Visit 2 (Day 1) to Visit 15 (Week 11).
|
Cohort 2 Placebo
On Day 1, participants with type 2 diabetes mellitus treated with diet and exercise alone or with a stable regimen of metformin, a thiazolidinedione (TZD), or a combination of metformin or a TZD were randomized to receive weekly injections of medium-chain triglycerides (MCT)-diluent placebo for 12 weeks. Study medication was administered weekly from Visit 2 (Day 1) to Visit 15 (Week 11).
|
|---|---|---|---|
|
Average Exenatide Concentration (Cave) of 2 mg Exenatide (Cohort 2) in Participants With Diabetes in the Pharmacokinetic Evaluable Population
Cave at Weeks 10-11; n=18
|
292.7 pg/mL
Standard Error 40.52
|
—
|
—
|
|
Average Exenatide Concentration (Cave) of 2 mg Exenatide (Cohort 2) in Participants With Diabetes in the Pharmacokinetic Evaluable Population
Cave at Weeks 10-12; n=17
|
302.4 pg/mL
Standard Error 38.47
|
—
|
—
|
PRIMARY outcome
Timeframe: Week 10, Weeks 10-11, Weeks 10-12Population: PK evaluable population was analyzed. In categories below, n = number of ITT participants with PK evaluable data. Note: Placebo-treated participants not included in this analysis.
Cohort 2: Blood samples for the assessment of plasma exenatide were collected on Day 1, Weeks 2, 4, 6, 8, and 10. At Week 10, blood samples were collected at time = -15, 60, 90, 120, 180, 240, and 360 minutes relative to study medication injection at time = 0. Cmax was measured in pg/mL. Exenatide was measured using a validated enzyme-linked immunosorbent assay (ELISA). Cmax summarized at 0-6 h at Week 10, 0-168 h at Weeks 10-11, and 0-tlast at Weeks 10-12. PK evaluable population consisted of all ITT participants who had at least 4 detectable plasma exenatide measurements (not \< LLOQ) from Day 1 to Week 12 and had reliable PK data.
Outcome measures
| Measure |
Cohort 1 Exenatide 10 mg
n=18 Participants
A single 10-mg dose of exenatide once weekly suspension was given to healthy participants via 3 subcutaneous (SC) injections at Day 1. At the discretion of the investigator, participants could receive up to 2 anti-emetic medications approximately 30 minutes prior to the exenatide once weekly suspension dose.
|
Cohort 2 Exenatide 2 mg
On Day 1, participants with type 2 diabetes mellitus treated with diet and exercise alone or with a stable regimen of metformin, a thiazolidinedione (TZD), or a combination of metformin or a TZD were randomized to receive weekly injections of exenatide suspension for 12 weeks. Study medication was administered weekly from Visit 2 (Day 1) to Visit 15 (Week 11).
|
Cohort 2 Placebo
On Day 1, participants with type 2 diabetes mellitus treated with diet and exercise alone or with a stable regimen of metformin, a thiazolidinedione (TZD), or a combination of metformin or a TZD were randomized to receive weekly injections of medium-chain triglycerides (MCT)-diluent placebo for 12 weeks. Study medication was administered weekly from Visit 2 (Day 1) to Visit 15 (Week 11).
|
|---|---|---|---|
|
Maximum Concentration (Cmax) for 2 mg Exenatide (Cohort 2) in Participants With Diabetes in the Pharmacokinetic Evaluable Population
Cmax at 0-6 h Week 10; n=18
|
304.9 pg/mL
Standard Error 47.39
|
—
|
—
|
|
Maximum Concentration (Cmax) for 2 mg Exenatide (Cohort 2) in Participants With Diabetes in the Pharmacokinetic Evaluable Population
Cmax at 0-168 h Weeks 10=11; n=18
|
362.6 pg/mL
Standard Error 50.86
|
—
|
—
|
|
Maximum Concentration (Cmax) for 2 mg Exenatide (Cohort 2) in Participants With Diabetes in the Pharmacokinetic Evaluable Population
Cmax at 0-tlast Weeks 10-12; n=17
|
410.5 pg/mL
Standard Error 53.27
|
—
|
—
|
PRIMARY outcome
Timeframe: Week 10, Weeks 10-11, Weeks 10-12Population: PK evaluable population was analyzed. In categories below, n = number of ITT participants with PK evaluable data. Note: Placebo-treated participants not included in this analysis.
Cohort 2: Blood samples for the assessment of plasma exenatide were collected on Day 1, Weeks 2, 4, 6, 8, and 10. At Week 10, blood samples were collected at time = -15, 60, 90, 120, 180, 240, and 360 minutes relative to study medication injection at time = 0. Tmax was measured in hours (h). Exenatide was measured using a validated ELISA. Tmax summarized at 0-6 h at Week 10, 0-168 h at Weeks 10-11, and 0-tlast at Weeks 10-12. PK evaluable population consisted of all ITT participants who had at least 4 detectable plasma exenatide measurements (not \< LLOQ) from Day 1 to Week 12 and had reliable PK data.
Outcome measures
| Measure |
Cohort 1 Exenatide 10 mg
n=18 Participants
A single 10-mg dose of exenatide once weekly suspension was given to healthy participants via 3 subcutaneous (SC) injections at Day 1. At the discretion of the investigator, participants could receive up to 2 anti-emetic medications approximately 30 minutes prior to the exenatide once weekly suspension dose.
|
Cohort 2 Exenatide 2 mg
On Day 1, participants with type 2 diabetes mellitus treated with diet and exercise alone or with a stable regimen of metformin, a thiazolidinedione (TZD), or a combination of metformin or a TZD were randomized to receive weekly injections of exenatide suspension for 12 weeks. Study medication was administered weekly from Visit 2 (Day 1) to Visit 15 (Week 11).
|
Cohort 2 Placebo
On Day 1, participants with type 2 diabetes mellitus treated with diet and exercise alone or with a stable regimen of metformin, a thiazolidinedione (TZD), or a combination of metformin or a TZD were randomized to receive weekly injections of medium-chain triglycerides (MCT)-diluent placebo for 12 weeks. Study medication was administered weekly from Visit 2 (Day 1) to Visit 15 (Week 11).
|
|---|---|---|---|
|
Time to Maximum Concentration (Tmax) of 2 mg Exenatide (Cohort 2) in Participants With Diabetes in Pharmacokinetic Evaluable Population
Tmax 0-6 h Week; n=18
|
1.4 hours
Standard Error 0.20
|
—
|
—
|
|
Time to Maximum Concentration (Tmax) of 2 mg Exenatide (Cohort 2) in Participants With Diabetes in Pharmacokinetic Evaluable Population
Tmax 0-168 h Weeks 10-11; n=18
|
34.3 hours
Standard Error 13.96
|
—
|
—
|
|
Time to Maximum Concentration (Tmax) of 2 mg Exenatide (Cohort 2) in Participants With Diabetes in Pharmacokinetic Evaluable Population
Tmax 0-tlast Weeks 10-12; n=17
|
60.0 hours
Standard Error 26.01
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 to Week 1Population: PK evaluable population.
Cohort 1: Blood samples for the assessment of plasma exenatide were collected at time = -15, 60, 90, 120, 180, 240, 360, and 480 minutes relative to study medication injection at time = 0 on Day 1. At all visits following the single injection, a single blood sample was collected for assessment of exenatide concentrations. AUC (0-168 h) data represents average concentration rather than maximum concentration. Exenatide concentration was measured using a validated enzyme-linked immunosorbent assay (ELISA). AUC calculated using linear trapezoidal method from time x to time y and measured in pg\*h/mL. PK evaluable population consisted of all ITT participants who had at least 4 detectable plasma exenatide measurements (not \< LLOQ) from Day 1 to Week 12 and had reliable PK data.
Outcome measures
| Measure |
Cohort 1 Exenatide 10 mg
n=30 Participants
A single 10-mg dose of exenatide once weekly suspension was given to healthy participants via 3 subcutaneous (SC) injections at Day 1. At the discretion of the investigator, participants could receive up to 2 anti-emetic medications approximately 30 minutes prior to the exenatide once weekly suspension dose.
|
Cohort 2 Exenatide 2 mg
On Day 1, participants with type 2 diabetes mellitus treated with diet and exercise alone or with a stable regimen of metformin, a thiazolidinedione (TZD), or a combination of metformin or a TZD were randomized to receive weekly injections of exenatide suspension for 12 weeks. Study medication was administered weekly from Visit 2 (Day 1) to Visit 15 (Week 11).
|
Cohort 2 Placebo
On Day 1, participants with type 2 diabetes mellitus treated with diet and exercise alone or with a stable regimen of metformin, a thiazolidinedione (TZD), or a combination of metformin or a TZD were randomized to receive weekly injections of medium-chain triglycerides (MCT)-diluent placebo for 12 weeks. Study medication was administered weekly from Visit 2 (Day 1) to Visit 15 (Week 11).
|
|---|---|---|---|
|
AUC (0 Hour to 168 Hour) for 10 mg Exenatide (Cohort 1) in Healthy Participants in the Pharmacokinetic Evaluable Population
|
3269.6 pg*h/mL
Standard Error 1661.45
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 to Week 1Population: PK evaluable population.
Cohort 1: Blood samples for the assessment of plasma exenatide were collected at time = -15, 60, 90, 120, 180, 240, 360, and 480 minutes relative to study medication injection at time = 0 on Day 1. At all visits following the single dose, a single blood sample was collected for assessment of exenatide concentrations. Cave(0-168h) was the time-weighted mean concentration over the sampling period from time x to time y corresponding to AUC (0-168h) and was measured in picograms per milliliter (pg/mL). Exenatide concentration was measured using a validated enzyme-linked immunosorbent assay (ELISA). PK evaluable population consisted of all ITT participants who had at least 4 detectable plasma exenatide measurements \[not less than (\<) lower limits of quantification (LLOQ)\] from Day 1 to Week 12 and had reliable PK data.
Outcome measures
| Measure |
Cohort 1 Exenatide 10 mg
n=30 Participants
A single 10-mg dose of exenatide once weekly suspension was given to healthy participants via 3 subcutaneous (SC) injections at Day 1. At the discretion of the investigator, participants could receive up to 2 anti-emetic medications approximately 30 minutes prior to the exenatide once weekly suspension dose.
|
Cohort 2 Exenatide 2 mg
On Day 1, participants with type 2 diabetes mellitus treated with diet and exercise alone or with a stable regimen of metformin, a thiazolidinedione (TZD), or a combination of metformin or a TZD were randomized to receive weekly injections of exenatide suspension for 12 weeks. Study medication was administered weekly from Visit 2 (Day 1) to Visit 15 (Week 11).
|
Cohort 2 Placebo
On Day 1, participants with type 2 diabetes mellitus treated with diet and exercise alone or with a stable regimen of metformin, a thiazolidinedione (TZD), or a combination of metformin or a TZD were randomized to receive weekly injections of medium-chain triglycerides (MCT)-diluent placebo for 12 weeks. Study medication was administered weekly from Visit 2 (Day 1) to Visit 15 (Week 11).
|
|---|---|---|---|
|
Average Exenatide Concentration (Cave) of 10 mg Exenatide (Cohort 1) in Healthy Participants in the Pharmacokinetic Evaluable Population
|
32.5 pg/mL
Standard Error 7.53
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 to Week 12Population: ITT population included all participants treated with at least one dose of study drug. This analysis was only done in Cohort 2 so the ITT population of Cohort 2 was available for analysis.
HbA1c was measured as a percent of hemoglobin at screening, Day 1, Weeks 4, 8, 12 or early termination. Last observation carried forward (LOCF) was applied to estimate missing values at post baseline timepoints. Baseline=Day 1, last measurement prior to first dose of study drug.
Outcome measures
| Measure |
Cohort 1 Exenatide 10 mg
n=23 Participants
A single 10-mg dose of exenatide once weekly suspension was given to healthy participants via 3 subcutaneous (SC) injections at Day 1. At the discretion of the investigator, participants could receive up to 2 anti-emetic medications approximately 30 minutes prior to the exenatide once weekly suspension dose.
|
Cohort 2 Exenatide 2 mg
n=12 Participants
On Day 1, participants with type 2 diabetes mellitus treated with diet and exercise alone or with a stable regimen of metformin, a thiazolidinedione (TZD), or a combination of metformin or a TZD were randomized to receive weekly injections of exenatide suspension for 12 weeks. Study medication was administered weekly from Visit 2 (Day 1) to Visit 15 (Week 11).
|
Cohort 2 Placebo
On Day 1, participants with type 2 diabetes mellitus treated with diet and exercise alone or with a stable regimen of metformin, a thiazolidinedione (TZD), or a combination of metformin or a TZD were randomized to receive weekly injections of medium-chain triglycerides (MCT)-diluent placebo for 12 weeks. Study medication was administered weekly from Visit 2 (Day 1) to Visit 15 (Week 11).
|
|---|---|---|---|
|
Least Square Mean Change From Baseline in Hemoglobin A1c (HbA1c) to Week 12 in Participants With Diabetes (Cohort 2) in the ITT Population
|
-0.87 Percent of hemoglobin
Standard Error 0.179
|
0.08 Percent of hemoglobin
Standard Error 0.231
|
—
|
SECONDARY outcome
Timeframe: Week 12Population: ITT population included all participants treated with at least one dose of study drug. Only those ITT participants in Cohort 2 were analyzed.
HbA1c was measured as a percent of hemoglobin at screening, Day 1, Weeks 4, 8, 12 or early termination. LOCF was applied to estimate missing values at post baseline timepoints. Baseline=Day 1, last measurement prior to first dose of study drug.
Outcome measures
| Measure |
Cohort 1 Exenatide 10 mg
n=23 Participants
A single 10-mg dose of exenatide once weekly suspension was given to healthy participants via 3 subcutaneous (SC) injections at Day 1. At the discretion of the investigator, participants could receive up to 2 anti-emetic medications approximately 30 minutes prior to the exenatide once weekly suspension dose.
|
Cohort 2 Exenatide 2 mg
n=12 Participants
On Day 1, participants with type 2 diabetes mellitus treated with diet and exercise alone or with a stable regimen of metformin, a thiazolidinedione (TZD), or a combination of metformin or a TZD were randomized to receive weekly injections of exenatide suspension for 12 weeks. Study medication was administered weekly from Visit 2 (Day 1) to Visit 15 (Week 11).
|
Cohort 2 Placebo
On Day 1, participants with type 2 diabetes mellitus treated with diet and exercise alone or with a stable regimen of metformin, a thiazolidinedione (TZD), or a combination of metformin or a TZD were randomized to receive weekly injections of medium-chain triglycerides (MCT)-diluent placebo for 12 weeks. Study medication was administered weekly from Visit 2 (Day 1) to Visit 15 (Week 11).
|
|---|---|---|---|
|
Number of Participants Achieving HbA1c Less Than Equal to (<=) 6.5% and Less Than (<) 7% at Week 12 in Participants With Diabetes (Cohort 2) in the ITT Population
Baseline HbA1c >= 7%
|
22 participants
|
12 participants
|
—
|
|
Number of Participants Achieving HbA1c Less Than Equal to (<=) 6.5% and Less Than (<) 7% at Week 12 in Participants With Diabetes (Cohort 2) in the ITT Population
Week 12 HbA1c <= 6.5%
|
9 participants
|
1 participants
|
—
|
|
Number of Participants Achieving HbA1c Less Than Equal to (<=) 6.5% and Less Than (<) 7% at Week 12 in Participants With Diabetes (Cohort 2) in the ITT Population
Week 12 HbA1c <7%
|
14 participants
|
2 participants
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: ITT population included all participants treated with at least one dose of study drug. Only Cohort 2 was analyzed for this outcome measure.
Body weight was measured in kilograms (kg). Baseline was Day 1, last measurement prior to first dose of study drug. Body weight was measured at screening, Day 1, Weeks 4, 8, 12 or early termination and the LOCF approach was applied to estimate missing value at each post baseline timepoint.
Outcome measures
| Measure |
Cohort 1 Exenatide 10 mg
n=23 Participants
A single 10-mg dose of exenatide once weekly suspension was given to healthy participants via 3 subcutaneous (SC) injections at Day 1. At the discretion of the investigator, participants could receive up to 2 anti-emetic medications approximately 30 minutes prior to the exenatide once weekly suspension dose.
|
Cohort 2 Exenatide 2 mg
n=12 Participants
On Day 1, participants with type 2 diabetes mellitus treated with diet and exercise alone or with a stable regimen of metformin, a thiazolidinedione (TZD), or a combination of metformin or a TZD were randomized to receive weekly injections of exenatide suspension for 12 weeks. Study medication was administered weekly from Visit 2 (Day 1) to Visit 15 (Week 11).
|
Cohort 2 Placebo
On Day 1, participants with type 2 diabetes mellitus treated with diet and exercise alone or with a stable regimen of metformin, a thiazolidinedione (TZD), or a combination of metformin or a TZD were randomized to receive weekly injections of medium-chain triglycerides (MCT)-diluent placebo for 12 weeks. Study medication was administered weekly from Visit 2 (Day 1) to Visit 15 (Week 11).
|
|---|---|---|---|
|
Mean Change From Baseline at Week 12 in Body Weight in Participants With Diabetes (Cohort 2) in the ITT Population
|
-1.41 kg
Standard Error 0.558
|
-0.39 kg
Standard Error 0.717
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: ITT population included all participants treated with at least one dose of study drug. Only participants in Cohort 2 were evaluated for this Outcome Measure.
Baseline was the last measurement at the screening visit. Fasting plasma glucose (FPG) was measured at screening, Day 1, Weeks 2, 4, 6, 8, 12, or early termination and reported in milligrams per deciliter (mg/dL).
Outcome measures
| Measure |
Cohort 1 Exenatide 10 mg
n=23 Participants
A single 10-mg dose of exenatide once weekly suspension was given to healthy participants via 3 subcutaneous (SC) injections at Day 1. At the discretion of the investigator, participants could receive up to 2 anti-emetic medications approximately 30 minutes prior to the exenatide once weekly suspension dose.
|
Cohort 2 Exenatide 2 mg
n=12 Participants
On Day 1, participants with type 2 diabetes mellitus treated with diet and exercise alone or with a stable regimen of metformin, a thiazolidinedione (TZD), or a combination of metformin or a TZD were randomized to receive weekly injections of exenatide suspension for 12 weeks. Study medication was administered weekly from Visit 2 (Day 1) to Visit 15 (Week 11).
|
Cohort 2 Placebo
On Day 1, participants with type 2 diabetes mellitus treated with diet and exercise alone or with a stable regimen of metformin, a thiazolidinedione (TZD), or a combination of metformin or a TZD were randomized to receive weekly injections of medium-chain triglycerides (MCT)-diluent placebo for 12 weeks. Study medication was administered weekly from Visit 2 (Day 1) to Visit 15 (Week 11).
|
|---|---|---|---|
|
Mean Change From Baseline at Week 12 in Fasting Plasma Glucose in Participants With Diabetes (Cohort 2) for the ITT Population
|
-32 mg/dL
Standard Error 9.9
|
8 mg/dL
Standard Error 11.9
|
—
|
Adverse Events
Cohort 1 Exenatide 10 mg
Cohort 2 Exenatide 2 mg
Cohort 2 Placebo
Serious adverse events
| Measure |
Cohort 1 Exenatide 10 mg
n=30 participants at risk
A single 10-mg dose of exenatide once weekly suspension was given to healthy participants via 3 subcutaneous (SC) injections at Day 1. At the discretion of the investigator, participants could receive up to 2 anti-emetic medications approximately 30 minutes prior to the exenatide once weekly suspension dose.
|
Cohort 2 Exenatide 2 mg
n=23 participants at risk
On Day 1, participants with type 2 diabetes mellitus treated with diet and exercise alone or with a stable regimen of metformin, a thiazolidinedione (TZD), or a combination of metformin or a TZD were randomized to receive weekly injections of exenatide suspension for 12 weeks. Study medication was administered weekly from Visit 2 (Day 1) to Visit 15 (Week 11).
|
Cohort 2 Placebo
n=12 participants at risk
On Day 1, participants with type 2 diabetes mellitus treated with diet and exercise alone or with a stable regimen of metformin, a thiazolidinedione (TZD), or a combination of metformin or a TZD were randomized to receive weekly injections of medium-chain triglycerides (MCT)-diluent placebo for 12 weeks. Study medication was administered weekly from Visit 2 (Day 1) to Visit 15 (Week 11).
|
|---|---|---|---|
|
Skin and subcutaneous tissue disorders
Infected Skin Ulcer
|
0.00%
0/30 • Day 1 to Week 12
|
0.00%
0/23 • Day 1 to Week 12
|
8.3%
1/12 • Day 1 to Week 12
|
Other adverse events
| Measure |
Cohort 1 Exenatide 10 mg
n=30 participants at risk
A single 10-mg dose of exenatide once weekly suspension was given to healthy participants via 3 subcutaneous (SC) injections at Day 1. At the discretion of the investigator, participants could receive up to 2 anti-emetic medications approximately 30 minutes prior to the exenatide once weekly suspension dose.
|
Cohort 2 Exenatide 2 mg
n=23 participants at risk
On Day 1, participants with type 2 diabetes mellitus treated with diet and exercise alone or with a stable regimen of metformin, a thiazolidinedione (TZD), or a combination of metformin or a TZD were randomized to receive weekly injections of exenatide suspension for 12 weeks. Study medication was administered weekly from Visit 2 (Day 1) to Visit 15 (Week 11).
|
Cohort 2 Placebo
n=12 participants at risk
On Day 1, participants with type 2 diabetes mellitus treated with diet and exercise alone or with a stable regimen of metformin, a thiazolidinedione (TZD), or a combination of metformin or a TZD were randomized to receive weekly injections of medium-chain triglycerides (MCT)-diluent placebo for 12 weeks. Study medication was administered weekly from Visit 2 (Day 1) to Visit 15 (Week 11).
|
|---|---|---|---|
|
Ear and labyrinth disorders
Vertigo
|
3.3%
1/30 • Day 1 to Week 12
|
0.00%
0/23 • Day 1 to Week 12
|
0.00%
0/12 • Day 1 to Week 12
|
|
Eye disorders
Corneal erosion
|
0.00%
0/30 • Day 1 to Week 12
|
4.3%
1/23 • Day 1 to Week 12
|
0.00%
0/12 • Day 1 to Week 12
|
|
Eye disorders
Photophobia
|
0.00%
0/30 • Day 1 to Week 12
|
4.3%
1/23 • Day 1 to Week 12
|
0.00%
0/12 • Day 1 to Week 12
|
|
Gastrointestinal disorders
Abdominal discomfort
|
3.3%
1/30 • Day 1 to Week 12
|
8.7%
2/23 • Day 1 to Week 12
|
8.3%
1/12 • Day 1 to Week 12
|
|
Gastrointestinal disorders
Abdominal distension
|
3.3%
1/30 • Day 1 to Week 12
|
4.3%
1/23 • Day 1 to Week 12
|
0.00%
0/12 • Day 1 to Week 12
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/30 • Day 1 to Week 12
|
0.00%
0/23 • Day 1 to Week 12
|
8.3%
1/12 • Day 1 to Week 12
|
|
Gastrointestinal disorders
Abdominal pain upper
|
6.7%
2/30 • Day 1 to Week 12
|
0.00%
0/23 • Day 1 to Week 12
|
0.00%
0/12 • Day 1 to Week 12
|
|
Gastrointestinal disorders
Constipation
|
3.3%
1/30 • Day 1 to Week 12
|
4.3%
1/23 • Day 1 to Week 12
|
0.00%
0/12 • Day 1 to Week 12
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/30 • Day 1 to Week 12
|
17.4%
4/23 • Day 1 to Week 12
|
16.7%
2/12 • Day 1 to Week 12
|
|
Gastrointestinal disorders
Dry Mouth
|
0.00%
0/30 • Day 1 to Week 12
|
4.3%
1/23 • Day 1 to Week 12
|
0.00%
0/12 • Day 1 to Week 12
|
|
Gastrointestinal disorders
Dyspepsia
|
6.7%
2/30 • Day 1 to Week 12
|
8.7%
2/23 • Day 1 to Week 12
|
0.00%
0/12 • Day 1 to Week 12
|
|
Gastrointestinal disorders
Eructation
|
0.00%
0/30 • Day 1 to Week 12
|
4.3%
1/23 • Day 1 to Week 12
|
0.00%
0/12 • Day 1 to Week 12
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/30 • Day 1 to Week 12
|
4.3%
1/23 • Day 1 to Week 12
|
0.00%
0/12 • Day 1 to Week 12
|
|
Gastrointestinal disorders
Hyperchlorhydria
|
0.00%
0/30 • Day 1 to Week 12
|
4.3%
1/23 • Day 1 to Week 12
|
0.00%
0/12 • Day 1 to Week 12
|
|
Gastrointestinal disorders
Nausea
|
10.0%
3/30 • Day 1 to Week 12
|
21.7%
5/23 • Day 1 to Week 12
|
8.3%
1/12 • Day 1 to Week 12
|
|
Gastrointestinal disorders
Retching
|
0.00%
0/30 • Day 1 to Week 12
|
4.3%
1/23 • Day 1 to Week 12
|
0.00%
0/12 • Day 1 to Week 12
|
|
Gastrointestinal disorders
Toothache
|
6.7%
2/30 • Day 1 to Week 12
|
4.3%
1/23 • Day 1 to Week 12
|
8.3%
1/12 • Day 1 to Week 12
|
|
Gastrointestinal disorders
Vomiting
|
3.3%
1/30 • Day 1 to Week 12
|
4.3%
1/23 • Day 1 to Week 12
|
8.3%
1/12 • Day 1 to Week 12
|
|
General disorders
Fatigue
|
0.00%
0/30 • Day 1 to Week 12
|
4.3%
1/23 • Day 1 to Week 12
|
8.3%
1/12 • Day 1 to Week 12
|
|
General disorders
Feeling hot
|
3.3%
1/30 • Day 1 to Week 12
|
0.00%
0/23 • Day 1 to Week 12
|
0.00%
0/12 • Day 1 to Week 12
|
|
General disorders
Feeling jittery
|
0.00%
0/30 • Day 1 to Week 12
|
4.3%
1/23 • Day 1 to Week 12
|
0.00%
0/12 • Day 1 to Week 12
|
|
General disorders
Infection site erythema
|
13.3%
4/30 • Day 1 to Week 12
|
52.2%
12/23 • Day 1 to Week 12
|
8.3%
1/12 • Day 1 to Week 12
|
|
General disorders
Injection site hematoma
|
16.7%
5/30 • Day 1 to Week 12
|
39.1%
9/23 • Day 1 to Week 12
|
50.0%
6/12 • Day 1 to Week 12
|
|
General disorders
Injection site pain
|
20.0%
6/30 • Day 1 to Week 12
|
21.7%
5/23 • Day 1 to Week 12
|
0.00%
0/12 • Day 1 to Week 12
|
|
General disorders
Injection site papule
|
3.3%
1/30 • Day 1 to Week 12
|
0.00%
0/23 • Day 1 to Week 12
|
0.00%
0/12 • Day 1 to Week 12
|
|
General disorders
Injection site pruritus
|
33.3%
10/30 • Day 1 to Week 12
|
47.8%
11/23 • Day 1 to Week 12
|
8.3%
1/12 • Day 1 to Week 12
|
|
General disorders
Injection site swelling
|
3.3%
1/30 • Day 1 to Week 12
|
0.00%
0/23 • Day 1 to Week 12
|
0.00%
0/12 • Day 1 to Week 12
|
|
General disorders
Injection site warmth
|
0.00%
0/30 • Day 1 to Week 12
|
8.7%
2/23 • Day 1 to Week 12
|
0.00%
0/12 • Day 1 to Week 12
|
|
General disorders
Edema peripheral
|
0.00%
0/30 • Day 1 to Week 12
|
4.3%
1/23 • Day 1 to Week 12
|
0.00%
0/12 • Day 1 to Week 12
|
|
General disorders
Pain
|
3.3%
1/30 • Day 1 to Week 12
|
0.00%
0/23 • Day 1 to Week 12
|
0.00%
0/12 • Day 1 to Week 12
|
|
General disorders
Vessel puncture site hematoma
|
0.00%
0/30 • Day 1 to Week 12
|
4.3%
1/23 • Day 1 to Week 12
|
0.00%
0/12 • Day 1 to Week 12
|
|
Infections and infestations
Bronchitis
|
3.3%
1/30 • Day 1 to Week 12
|
0.00%
0/23 • Day 1 to Week 12
|
0.00%
0/12 • Day 1 to Week 12
|
|
Infections and infestations
Candidiasis
|
0.00%
0/30 • Day 1 to Week 12
|
0.00%
0/23 • Day 1 to Week 12
|
8.3%
1/12 • Day 1 to Week 12
|
|
Infections and infestations
Folliculitis
|
0.00%
0/30 • Day 1 to Week 12
|
4.3%
1/23 • Day 1 to Week 12
|
0.00%
0/12 • Day 1 to Week 12
|
|
Infections and infestations
Fungal infection
|
0.00%
0/30 • Day 1 to Week 12
|
4.3%
1/23 • Day 1 to Week 12
|
0.00%
0/12 • Day 1 to Week 12
|
|
Infections and infestations
Sinusitis
|
3.3%
1/30 • Day 1 to Week 12
|
0.00%
0/23 • Day 1 to Week 12
|
0.00%
0/12 • Day 1 to Week 12
|
|
Infections and infestations
Tooth abscess
|
0.00%
0/30 • Day 1 to Week 12
|
4.3%
1/23 • Day 1 to Week 12
|
0.00%
0/12 • Day 1 to Week 12
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/30 • Day 1 to Week 12
|
4.3%
1/23 • Day 1 to Week 12
|
0.00%
0/12 • Day 1 to Week 12
|
|
Infections and infestations
Vaginitis bacterial
|
0.00%
0/30 • Day 1 to Week 12
|
4.3%
1/23 • Day 1 to Week 12
|
0.00%
0/12 • Day 1 to Week 12
|
|
Infections and infestations
Wound infection
|
0.00%
0/30 • Day 1 to Week 12
|
0.00%
0/23 • Day 1 to Week 12
|
8.3%
1/12 • Day 1 to Week 12
|
|
Injury, poisoning and procedural complications
Arthropod sting
|
0.00%
0/30 • Day 1 to Week 12
|
4.3%
1/23 • Day 1 to Week 12
|
0.00%
0/12 • Day 1 to Week 12
|
|
Injury, poisoning and procedural complications
Blister
|
0.00%
0/30 • Day 1 to Week 12
|
4.3%
1/23 • Day 1 to Week 12
|
0.00%
0/12 • Day 1 to Week 12
|
|
Injury, poisoning and procedural complications
Foot fracture
|
0.00%
0/30 • Day 1 to Week 12
|
4.3%
1/23 • Day 1 to Week 12
|
0.00%
0/12 • Day 1 to Week 12
|
|
Injury, poisoning and procedural complications
Joint sprain
|
3.3%
1/30 • Day 1 to Week 12
|
0.00%
0/23 • Day 1 to Week 12
|
0.00%
0/12 • Day 1 to Week 12
|
|
Injury, poisoning and procedural complications
Rib fracture
|
0.00%
0/30 • Day 1 to Week 12
|
4.3%
1/23 • Day 1 to Week 12
|
0.00%
0/12 • Day 1 to Week 12
|
|
Injury, poisoning and procedural complications
Wound
|
0.00%
0/30 • Day 1 to Week 12
|
0.00%
0/23 • Day 1 to Week 12
|
8.3%
1/12 • Day 1 to Week 12
|
|
Metabolism and nutrition disorders
Decreased appetite
|
10.0%
3/30 • Day 1 to Week 12
|
21.7%
5/23 • Day 1 to Week 12
|
0.00%
0/12 • Day 1 to Week 12
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/30 • Day 1 to Week 12
|
4.3%
1/23 • Day 1 to Week 12
|
0.00%
0/12 • Day 1 to Week 12
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/30 • Day 1 to Week 12
|
8.7%
2/23 • Day 1 to Week 12
|
0.00%
0/12 • Day 1 to Week 12
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
0.00%
0/30 • Day 1 to Week 12
|
0.00%
0/23 • Day 1 to Week 12
|
8.3%
1/12 • Day 1 to Week 12
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
3.3%
1/30 • Day 1 to Week 12
|
0.00%
0/23 • Day 1 to Week 12
|
0.00%
0/12 • Day 1 to Week 12
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/30 • Day 1 to Week 12
|
4.3%
1/23 • Day 1 to Week 12
|
0.00%
0/12 • Day 1 to Week 12
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/30 • Day 1 to Week 12
|
4.3%
1/23 • Day 1 to Week 12
|
8.3%
1/12 • Day 1 to Week 12
|
|
Nervous system disorders
Dizziness
|
0.00%
0/30 • Day 1 to Week 12
|
8.7%
2/23 • Day 1 to Week 12
|
0.00%
0/12 • Day 1 to Week 12
|
|
Nervous system disorders
Headache
|
20.0%
6/30 • Day 1 to Week 12
|
13.0%
3/23 • Day 1 to Week 12
|
0.00%
0/12 • Day 1 to Week 12
|
|
Nervous system disorders
Paraesthesia
|
3.3%
1/30 • Day 1 to Week 12
|
0.00%
0/23 • Day 1 to Week 12
|
0.00%
0/12 • Day 1 to Week 12
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/30 • Day 1 to Week 12
|
0.00%
0/23 • Day 1 to Week 12
|
8.3%
1/12 • Day 1 to Week 12
|
|
Renal and urinary disorders
Dysuria
|
0.00%
0/30 • Day 1 to Week 12
|
0.00%
0/23 • Day 1 to Week 12
|
8.3%
1/12 • Day 1 to Week 12
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
3.3%
1/30 • Day 1 to Week 12
|
4.3%
1/23 • Day 1 to Week 12
|
8.3%
1/12 • Day 1 to Week 12
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
10.0%
3/30 • Day 1 to Week 12
|
4.3%
1/23 • Day 1 to Week 12
|
0.00%
0/12 • Day 1 to Week 12
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory tract congestion
|
3.3%
1/30 • Day 1 to Week 12
|
0.00%
0/23 • Day 1 to Week 12
|
0.00%
0/12 • Day 1 to Week 12
|
|
Skin and subcutaneous tissue disorders
Acne
|
0.00%
0/30 • Day 1 to Week 12
|
0.00%
0/23 • Day 1 to Week 12
|
8.3%
1/12 • Day 1 to Week 12
|
|
Skin and subcutaneous tissue disorders
Petechiae
|
0.00%
0/30 • Day 1 to Week 12
|
4.3%
1/23 • Day 1 to Week 12
|
0.00%
0/12 • Day 1 to Week 12
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/30 • Day 1 to Week 12
|
13.0%
3/23 • Day 1 to Week 12
|
0.00%
0/12 • Day 1 to Week 12
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
- Publication restrictions are in place
Restriction type: OTHER