Trial Outcomes & Findings for A Study to Evaluate BMS-986036 in Obese Adults With Type-2 Diabetes (NCT NCT02097277)
NCT ID: NCT02097277
Last Updated: 2019-07-31
Results Overview
HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Percent Change in Glycosylated Hemoglobin A1c (HbA1c) from Baseline to Week 12 was reported.
COMPLETED
PHASE2
219 participants
Baseline (Day 1) and Week 12
2019-07-31
Participant Flow
219 participants were enrolled; 138 entered the lead-in period. Reasons for not entering lead-in period included "not meeting study eligibility criteria". 120 were randomized to treatment. Reasons not randomized: 6 withdrew consent, 2 lost to follow-up, 4 no longer met study criteria, 1 due to admin.reason by Sponsor and 4 due to other reasons.
Participant milestones
| Measure |
Treatment A: Placebo
Placebo (Matching with BMS-986036) 0 mg subcutaneous injection once daily for 12 weeks.
|
Treatment B: BMS-986036 (1 mg Daily)
BMS-986036 1 mg subcutaneous injection once daily for 12 weeks.
|
Treatment C: BMS-986036 (5 mg Daily)
BMS-986036 5 mg subcutaneous injection once daily for 12 weeks.
|
Treatment D: BMS-986036 (20 mg Daily)
BMS-986036 20 mg subcutaneous injection once daily for 12 weeks.
|
Treatment E: BMS-986036 (20 mg Weekly)
BMS-986036 20 mg subcutaneous injection once weekly (on Day 1 of each week) for 12 weeks followed by Placebo (Matching with BMS-986036) 0 mg subcutaneous injection on Days 2-7 of each week for 12 weeks
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
24
|
24
|
24
|
24
|
24
|
|
Overall Study
COMPLETED
|
22
|
21
|
22
|
20
|
23
|
|
Overall Study
NOT COMPLETED
|
2
|
3
|
2
|
4
|
1
|
Reasons for withdrawal
| Measure |
Treatment A: Placebo
Placebo (Matching with BMS-986036) 0 mg subcutaneous injection once daily for 12 weeks.
|
Treatment B: BMS-986036 (1 mg Daily)
BMS-986036 1 mg subcutaneous injection once daily for 12 weeks.
|
Treatment C: BMS-986036 (5 mg Daily)
BMS-986036 5 mg subcutaneous injection once daily for 12 weeks.
|
Treatment D: BMS-986036 (20 mg Daily)
BMS-986036 20 mg subcutaneous injection once daily for 12 weeks.
|
Treatment E: BMS-986036 (20 mg Weekly)
BMS-986036 20 mg subcutaneous injection once weekly (on Day 1 of each week) for 12 weeks followed by Placebo (Matching with BMS-986036) 0 mg subcutaneous injection on Days 2-7 of each week for 12 weeks
|
|---|---|---|---|---|---|
|
Overall Study
Subject no longer meets study criteria
|
0
|
1
|
0
|
1
|
0
|
|
Overall Study
Subject request to discontinue treatment
|
0
|
0
|
0
|
0
|
1
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
1
|
0
|
0
|
|
Overall Study
Withdrawal by Subject
|
2
|
1
|
0
|
1
|
0
|
|
Overall Study
Adverse Event
|
0
|
0
|
1
|
2
|
0
|
Baseline Characteristics
A Study to Evaluate BMS-986036 in Obese Adults With Type-2 Diabetes
Baseline characteristics by cohort
| Measure |
Treatment A: Placebo
n=24 Participants
Placebo (Matching with BMS-986036) 0 mg subcutaneous injection once daily for 12 weeks.
|
Treatment B: BMS-986036 (1 mg Daily)
n=24 Participants
BMS-986036 1 mg subcutaneous injection once daily for 12 weeks
|
Treatment C: BMS-986036 (5 mg Daily)
n=24 Participants
BMS-986036 5 mg subcutaneous injection once daily for 12 weeks.
|
Treatment D: BMS-986036 (20 mg Daily)
n=24 Participants
BMS-986036 20 mg subcutaneous injection once daily for 12 weeks.
|
Treatment E: BMS-986036 (20 mg Weekly)
n=24 Participants
BMS-986036 20 mg subcutaneous injection once weekly (on Day 1 of each week) for 12 weeks followed by Placebo (Matching with BMS-986036) 0 mg subcutaneous injection on Days 2-7 of each week for 12 weeks.
|
Total
n=120 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Continuous
|
57.9 years
STANDARD_DEVIATION 7.58 • n=99 Participants
|
55.4 years
STANDARD_DEVIATION 9.44 • n=107 Participants
|
55.3 years
STANDARD_DEVIATION 9.92 • n=206 Participants
|
56.2 years
STANDARD_DEVIATION 8.17 • n=7 Participants
|
55.2 years
STANDARD_DEVIATION 12.62 • n=31 Participants
|
56.0 years
STANDARD_DEVIATION 9.60 • n=30 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=99 Participants
|
11 Participants
n=107 Participants
|
11 Participants
n=206 Participants
|
9 Participants
n=7 Participants
|
12 Participants
n=31 Participants
|
53 Participants
n=30 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=99 Participants
|
13 Participants
n=107 Participants
|
13 Participants
n=206 Participants
|
15 Participants
n=7 Participants
|
12 Participants
n=31 Participants
|
67 Participants
n=30 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
0 Participants
n=30 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=31 Participants
|
10 Participants
n=30 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
0 Participants
n=30 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=31 Participants
|
15 Participants
n=30 Participants
|
|
Race (NIH/OMB)
White
|
22 Participants
n=99 Participants
|
20 Participants
n=107 Participants
|
18 Participants
n=206 Participants
|
20 Participants
n=7 Participants
|
15 Participants
n=31 Participants
|
95 Participants
n=30 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
0 Participants
n=30 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
0 Participants
n=30 Participants
|
PRIMARY outcome
Timeframe: Baseline (Day 1) and Week 12Population: The Pharmacodynamic Population included all subjects who received at least one dose of study medication and had PD biomarker data available, although only participants with both baseline and post-baseline data were included in the statistical analysis. Here, 'N' signifies number of participants analyzed for this outcome measure.
HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Percent Change in Glycosylated Hemoglobin A1c (HbA1c) from Baseline to Week 12 was reported.
Outcome measures
| Measure |
Treatment A: Placebo
n=24 Participants
Placebo (Matching with BMS-986036) 0 mg subcutaneous injection once daily for 12 weeks.
|
Treatment B: BMS-986036 (1 mg Daily)
n=24 Participants
BMS-986036 1 mg subcutaneous injection once daily for 12 weeks.
|
Treatment C: BMS-986036 (5 mg Daily)
n=24 Participants
BMS-986036 5 mg subcutaneous injection once daily for 12 weeks.
|
Treatment D: BMS-986036 (20 mg Daily)
n=24 Participants
BMS-986036 20 mg subcutaneous injection once daily for 12 weeks.
|
Treatment E: BMS-986036 (20 mg Weekly)
n=24 Participants
BMS-986036 20 mg subcutaneous injection once weekly (on Day 1 of each week) for 12 weeks followed by Placebo (Matching with BMS-986036) 0 mg subcutaneous injection on Days 2-7 of each week for 12 weeks.
|
|---|---|---|---|---|---|
|
Percent Change in Glycosylated Hemoglobin A1c (HbA1c) From Baseline to Week 12
|
0.0005 Percent Change
Standard Deviation 0.00622
|
0.0029 Percent Change
Standard Deviation 0.00882
|
0.0007 Percent Change
Standard Deviation 0.00692
|
0.0004 Percent Change
Standard Deviation 0.00814
|
-0.0004 Percent Change
Standard Deviation 0.00418
|
SECONDARY outcome
Timeframe: Baseline (Day 1) and Week 12Population: The Pharmacodynamic Population included all subjects who received at least one dose of study medication and had PD biomarker data available, although only subjects with both baseline and post-baseline data were included in the statistical analysis. Here, 'N' signifies number of participants analyzed for this outcome measure.
Change in Body Weight from Baseline to Week 12 as a part of Physical measurement was reported.
Outcome measures
| Measure |
Treatment A: Placebo
n=24 Participants
Placebo (Matching with BMS-986036) 0 mg subcutaneous injection once daily for 12 weeks.
|
Treatment B: BMS-986036 (1 mg Daily)
n=24 Participants
BMS-986036 1 mg subcutaneous injection once daily for 12 weeks.
|
Treatment C: BMS-986036 (5 mg Daily)
n=24 Participants
BMS-986036 5 mg subcutaneous injection once daily for 12 weeks.
|
Treatment D: BMS-986036 (20 mg Daily)
n=24 Participants
BMS-986036 20 mg subcutaneous injection once daily for 12 weeks.
|
Treatment E: BMS-986036 (20 mg Weekly)
n=24 Participants
BMS-986036 20 mg subcutaneous injection once weekly (on Day 1 of each week) for 12 weeks followed by Placebo (Matching with BMS-986036) 0 mg subcutaneous injection on Days 2-7 of each week for 12 weeks.
|
|---|---|---|---|---|---|
|
Change in Body Weight From Baseline to Week 12
|
-0.22 Kilogram
Standard Deviation 2.615
|
-0.26 Kilogram
Standard Deviation 1.718
|
-0.10 Kilogram
Standard Deviation 2.883
|
-1.09 Kilogram
Standard Deviation 2.583
|
-0.50 Kilogram
Standard Deviation 2.297
|
SECONDARY outcome
Timeframe: Baseline (Day 1) and Week 12Population: The Pharmacodynamic Population included all participants who received at least one dose of study medication and had PD biomarker data available, although only participants with both baseline and post-baseline data were included in the statistical analysis. Here, 'N' signifies number of participants analyzed for this outcome measure.
Whole body insulin sensitivity as quantified by Matsuda Index at the end of the treatment period, calculated by the following equation: 10,000/square root of(FPG\*FI)\*(FPG+PG30\*2+PG60\*3+PG120\*2)/8\*(FPI+PI30\*2+PI60\*3+PI120\*2)/8). FPG=fasting plasma glucose level; FPI=fasting plasma insulin level; PG30,60,90, and 120=plasma glucose levels sampled at 30,60, and 120 minutes after oral glucose load; PI30,60,and 120=plasma insulin levels sampled at 30,60 and 120 minutes after the oral glucose load.
Outcome measures
| Measure |
Treatment A: Placebo
n=24 Participants
Placebo (Matching with BMS-986036) 0 mg subcutaneous injection once daily for 12 weeks.
|
Treatment B: BMS-986036 (1 mg Daily)
n=24 Participants
BMS-986036 1 mg subcutaneous injection once daily for 12 weeks.
|
Treatment C: BMS-986036 (5 mg Daily)
n=24 Participants
BMS-986036 5 mg subcutaneous injection once daily for 12 weeks.
|
Treatment D: BMS-986036 (20 mg Daily)
n=24 Participants
BMS-986036 20 mg subcutaneous injection once daily for 12 weeks.
|
Treatment E: BMS-986036 (20 mg Weekly)
n=24 Participants
BMS-986036 20 mg subcutaneous injection once weekly (on Day 1 of each week) for 12 weeks followed by Placebo (Matching with BMS-986036) 0 mg subcutaneous injection on Days 2-7 of each week for 12 weeks.
|
|---|---|---|---|---|---|
|
Change From Baseline to Week 12 in Insulin Sensitivity Quantified by Composite Index of Insulin Sensitivity (CISI) (Matsuda Index)
|
-0.18 Unit on a scale
Standard Deviation 0.967
|
-0.19 Unit on a scale
Standard Deviation 1.348
|
-0.18 Unit on a scale
Standard Deviation 2.102
|
0.77 Unit on a scale
Standard Deviation 2.455
|
0.54 Unit on a scale
Standard Deviation 1.772
|
SECONDARY outcome
Timeframe: Baseline (Day 1) and Week 12Population: The Pharmacodynamic Population included all participants who received at least one dose of study medication and had PD biomarker data available, although only participants with both baseline and post-baseline data were included in the statistical analysis. Here, 'N' signifies number of participants analyzed for this outcome measure.
Homeostasis model assessment of insulin resistance (HOMA-IR) was used as a validated measure of insulin resistance. HOMA-IR is calculated using the following formula's fasting glucose(mg/dL) x fasting insulin(mU/L) / 405.
Outcome measures
| Measure |
Treatment A: Placebo
n=24 Participants
Placebo (Matching with BMS-986036) 0 mg subcutaneous injection once daily for 12 weeks.
|
Treatment B: BMS-986036 (1 mg Daily)
n=24 Participants
BMS-986036 1 mg subcutaneous injection once daily for 12 weeks.
|
Treatment C: BMS-986036 (5 mg Daily)
n=24 Participants
BMS-986036 5 mg subcutaneous injection once daily for 12 weeks.
|
Treatment D: BMS-986036 (20 mg Daily)
n=24 Participants
BMS-986036 20 mg subcutaneous injection once daily for 12 weeks.
|
Treatment E: BMS-986036 (20 mg Weekly)
n=24 Participants
BMS-986036 20 mg subcutaneous injection once weekly (on Day 1 of each week) for 12 weeks followed by Placebo (Matching with BMS-986036) 0 mg subcutaneous injection on Days 2-7 of each week for 12 weeks.
|
|---|---|---|---|---|---|
|
Change From Baseline to Week 12 in Insulin Sensitivity Quantified by Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)
|
-0.19 Unit on a Scale
Standard Deviation 4.136
|
0.00 Unit on a Scale
Standard Deviation 5.633
|
-1.88 Unit on a Scale
Standard Deviation 8.940
|
-1.73 Unit on a Scale
Standard Deviation 4.589
|
-0.34 Unit on a Scale
Standard Deviation 3.707
|
SECONDARY outcome
Timeframe: Baseline (Day 1) and Week 12Population: The Pharmacodynamic Population included all subjects who received at least one dose of study medication and had PD biomarker data available, although only participants with both baseline and post-baseline data were included in the statistical analysis. Here, 'N' signifies number of participants analyzed for this outcome measure.
The Quantitative Insulin Sensitivity Check Index (QUICKI) score, measures insulin sensitivity which is the inverse of insulin resistance. QUICKI is derived using the inverse of the sum of the logarithms of the fasting insulin and fasting glucose: 1 / (log(fasting insulin mU/L) + log(fasting glucose mg/dL)).
Outcome measures
| Measure |
Treatment A: Placebo
n=24 Participants
Placebo (Matching with BMS-986036) 0 mg subcutaneous injection once daily for 12 weeks.
|
Treatment B: BMS-986036 (1 mg Daily)
n=24 Participants
BMS-986036 1 mg subcutaneous injection once daily for 12 weeks.
|
Treatment C: BMS-986036 (5 mg Daily)
n=24 Participants
BMS-986036 5 mg subcutaneous injection once daily for 12 weeks.
|
Treatment D: BMS-986036 (20 mg Daily)
n=24 Participants
BMS-986036 20 mg subcutaneous injection once daily for 12 weeks.
|
Treatment E: BMS-986036 (20 mg Weekly)
n=24 Participants
BMS-986036 20 mg subcutaneous injection once weekly (on Day 1 of each week) for 12 weeks followed by Placebo (Matching with BMS-986036) 0 mg subcutaneous injection on Days 2-7 of each week for 12 weeks.
|
|---|---|---|---|---|---|
|
Change From Baseline to Week 12 in Insulin Sensitivity Quantified by Quantitative Insulin Sensitivity Check Index (QUICKI)
|
0.00 Unit on a scale
Standard Deviation 0.011
|
0.00 Unit on a scale
Standard Deviation 0.010
|
0.00 Unit on a scale
Standard Deviation 0.015
|
0.00 Unit on a scale
Standard Deviation 0.016
|
0.00 Unit on a scale
Standard Deviation 0.011
|
SECONDARY outcome
Timeframe: Baseline (Day 1) and Week 12Population: The Pharmacodynamic Population included all participants who received at least one dose of study medication and had PD biomarker data available, although only participants with both baseline and post-baseline data were included in the statistical analysis. Here, 'N' signifies number of participants analyzed for this outcome measure.
Blood samples were drawn after an overnight fast and standard OGTT from 0 to 120 minutes. Plasma Glucose levels over 2 hours were shown as Area Under the Curve, (AUC).
Outcome measures
| Measure |
Treatment A: Placebo
n=24 Participants
Placebo (Matching with BMS-986036) 0 mg subcutaneous injection once daily for 12 weeks.
|
Treatment B: BMS-986036 (1 mg Daily)
n=24 Participants
BMS-986036 1 mg subcutaneous injection once daily for 12 weeks.
|
Treatment C: BMS-986036 (5 mg Daily)
n=24 Participants
BMS-986036 5 mg subcutaneous injection once daily for 12 weeks.
|
Treatment D: BMS-986036 (20 mg Daily)
n=24 Participants
BMS-986036 20 mg subcutaneous injection once daily for 12 weeks.
|
Treatment E: BMS-986036 (20 mg Weekly)
n=24 Participants
BMS-986036 20 mg subcutaneous injection once weekly (on Day 1 of each week) for 12 weeks followed by Placebo (Matching with BMS-986036) 0 mg subcutaneous injection on Days 2-7 of each week for 12 weeks.
|
|---|---|---|---|---|---|
|
Change in Oral Glucose Tolerance Test (OGTT) Area Under the Curve From 0 to 2 Hours for Postprandial Glucose From Baseline to Week 12
|
1.538 Millimole*hour per Liter (mmol*hr/L)
Standard Deviation 4.2940
|
2.594 Millimole*hour per Liter (mmol*hr/L)
Standard Deviation 5.8193
|
-0.646 Millimole*hour per Liter (mmol*hr/L)
Standard Deviation 7.0591
|
-0.215 Millimole*hour per Liter (mmol*hr/L)
Standard Deviation 4.7397
|
-2.293 Millimole*hour per Liter (mmol*hr/L)
Standard Deviation 4.9322
|
SECONDARY outcome
Timeframe: Bseline (Day 1) and Week 12Population: The Pharmacodynamic Population included all participants who received at least one dose of study medication and had PD biomarker data available, although only participants with both baseline and post-baseline data were included in the statistical analysis. Here, 'N' signifies number of participants analyzed for this outcome measure.
Blood samples were drawn after an overnight fast and standard OGTT from 0 to 120 minutes. Insulin levels over 2 hours were shown as Area Under the Curve, (AUC).
Outcome measures
| Measure |
Treatment A: Placebo
n=24 Participants
Placebo (Matching with BMS-986036) 0 mg subcutaneous injection once daily for 12 weeks.
|
Treatment B: BMS-986036 (1 mg Daily)
n=24 Participants
BMS-986036 1 mg subcutaneous injection once daily for 12 weeks.
|
Treatment C: BMS-986036 (5 mg Daily)
n=24 Participants
BMS-986036 5 mg subcutaneous injection once daily for 12 weeks.
|
Treatment D: BMS-986036 (20 mg Daily)
n=24 Participants
BMS-986036 20 mg subcutaneous injection once daily for 12 weeks.
|
Treatment E: BMS-986036 (20 mg Weekly)
n=24 Participants
BMS-986036 20 mg subcutaneous injection once weekly (on Day 1 of each week) for 12 weeks followed by Placebo (Matching with BMS-986036) 0 mg subcutaneous injection on Days 2-7 of each week for 12 weeks.
|
|---|---|---|---|---|---|
|
Change in OGTT Insulin AUC (0-2 Hours) From Baseline to Week 12
|
-64.648 mmol*hr/L
Standard Deviation 231.6043
|
-72.155 mmol*hr/L
Standard Deviation 277.4819
|
-83.850 mmol*hr/L
Standard Deviation 215.3974
|
-58.313 mmol*hr/L
Standard Deviation 205.1879
|
-150.679 mmol*hr/L
Standard Deviation 257.5965
|
SECONDARY outcome
Timeframe: Baseline (Day 1) and Week 12Population: The Pharmacodynamic Population included all participants who received at least one dose of study medication and had PD biomarker data available, although only participants with both baseline and post-baseline data were included in the statistical analysis. Here, 'N' signifies number of participants analyzed for this outcome measure.
Blood samples were drawn after an overnight fast and standard OGTT from 0 to 120 minutes. C-peptide levels over 2 hours were shown as Area Under the Curve, (AUC).
Outcome measures
| Measure |
Treatment A: Placebo
n=24 Participants
Placebo (Matching with BMS-986036) 0 mg subcutaneous injection once daily for 12 weeks.
|
Treatment B: BMS-986036 (1 mg Daily)
n=24 Participants
BMS-986036 1 mg subcutaneous injection once daily for 12 weeks.
|
Treatment C: BMS-986036 (5 mg Daily)
n=24 Participants
BMS-986036 5 mg subcutaneous injection once daily for 12 weeks.
|
Treatment D: BMS-986036 (20 mg Daily)
n=24 Participants
BMS-986036 20 mg subcutaneous injection once daily for 12 weeks.
|
Treatment E: BMS-986036 (20 mg Weekly)
n=24 Participants
BMS-986036 20 mg subcutaneous injection once weekly (on Day 1 of each week) for 12 weeks followed by Placebo (Matching with BMS-986036) 0 mg subcutaneous injection on Days 2-7 of each week for 12 weeks.
|
|---|---|---|---|---|---|
|
Change in OGTT C-peptide AUC (0-2 Hours) From Baseline to Week 12
|
-0.287 mmol*hr/L
Standard Deviation 1.2463
|
0.031 mmol*hr/L
Standard Deviation 1.3926
|
-0.181 mmol*hr/L
Standard Deviation 0.8927
|
-0.169 mmol*hr/L
Standard Deviation 1.0176
|
-0.750 mmol*hr/L
Standard Deviation 1.2224
|
SECONDARY outcome
Timeframe: Pre-dose, 6, 24 hours postdose on Week 8; pre-dose on Weeks 1, 2, 4, 6, 8, and 12; post treatment period on Week 13, 15 and 18 (Day 126)Population: Serum concentration-time data will be used to develop a population PK model, and estimates of individual PK parameters will be derived from this model using a validated PK analysis program. Here, 'N' signifies number of participants evaluable for this outcome measure.
Cavg of C-terminal Intact BMS-986036 was reported.
Outcome measures
| Measure |
Treatment A: Placebo
n=21 Participants
Placebo (Matching with BMS-986036) 0 mg subcutaneous injection once daily for 12 weeks.
|
Treatment B: BMS-986036 (1 mg Daily)
n=22 Participants
BMS-986036 1 mg subcutaneous injection once daily for 12 weeks.
|
Treatment C: BMS-986036 (5 mg Daily)
n=20 Participants
BMS-986036 5 mg subcutaneous injection once daily for 12 weeks.
|
Treatment D: BMS-986036 (20 mg Daily)
n=23 Participants
BMS-986036 20 mg subcutaneous injection once daily for 12 weeks.
|
Treatment E: BMS-986036 (20 mg Weekly)
BMS-986036 20 mg subcutaneous injection once weekly (on Day 1 of each week) for 12 weeks followed by Placebo (Matching with BMS-986036) 0 mg subcutaneous injection on Days 2-7 of each week for 12 weeks.
|
|---|---|---|---|---|---|
|
Average Concentration (Cavg) of C-terminal Intact BMS-986036
|
50.6 Microgram per Liter (ug/L)
Geometric Coefficient of Variation 60.6
|
204 Microgram per Liter (ug/L)
Geometric Coefficient of Variation 50.4
|
762 Microgram per Liter (ug/L)
Geometric Coefficient of Variation 49.2
|
197 Microgram per Liter (ug/L)
Geometric Coefficient of Variation 60.5
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 6, 24 hours postdose on Week 8; pre-dose on Weeks 1, 2, 4, 6, 8, and 12; post treatment period on Week 13, 15 and 18 (Day 126)Population: Serum concentration-time data will be used to develop a population PK model, and estimates of individual PK parameters will be derived from this model using a validated PK analysis program. Here, 'N' signifies number of participants evaluable for this outcome measure.
Maximum observed concentration (Cmax) of C-terminal Intact BMS-986036 was reported.
Outcome measures
| Measure |
Treatment A: Placebo
n=21 Participants
Placebo (Matching with BMS-986036) 0 mg subcutaneous injection once daily for 12 weeks.
|
Treatment B: BMS-986036 (1 mg Daily)
n=22 Participants
BMS-986036 1 mg subcutaneous injection once daily for 12 weeks.
|
Treatment C: BMS-986036 (5 mg Daily)
n=20 Participants
BMS-986036 5 mg subcutaneous injection once daily for 12 weeks.
|
Treatment D: BMS-986036 (20 mg Daily)
n=23 Participants
BMS-986036 20 mg subcutaneous injection once daily for 12 weeks.
|
Treatment E: BMS-986036 (20 mg Weekly)
BMS-986036 20 mg subcutaneous injection once weekly (on Day 1 of each week) for 12 weeks followed by Placebo (Matching with BMS-986036) 0 mg subcutaneous injection on Days 2-7 of each week for 12 weeks.
|
|---|---|---|---|---|---|
|
Maximum Observed Concentration (Cmax) of C-terminal Intact BMS-986036
|
53.3 microgram/liter
Geometric Coefficient of Variation 61.2
|
213 microgram/liter
Geometric Coefficient of Variation 50.4
|
807 microgram/liter
Geometric Coefficient of Variation 48.8
|
459 microgram/liter
Geometric Coefficient of Variation 41.4
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 6, 24 hours postdose on Week 8Population: Serum concentration-time data will be used to develop a population PK model, and estimates of individual PK parameters will be derived from this model using a validated PK analysis program. Here, 'N' signifies number of participants evaluable for this outcome measure.
AUC \[0-24 hours, ss\] of C-terminal Intact BMS-986036 was reported.
Outcome measures
| Measure |
Treatment A: Placebo
n=21 Participants
Placebo (Matching with BMS-986036) 0 mg subcutaneous injection once daily for 12 weeks.
|
Treatment B: BMS-986036 (1 mg Daily)
n=22 Participants
BMS-986036 1 mg subcutaneous injection once daily for 12 weeks.
|
Treatment C: BMS-986036 (5 mg Daily)
n=20 Participants
BMS-986036 5 mg subcutaneous injection once daily for 12 weeks.
|
Treatment D: BMS-986036 (20 mg Daily)
BMS-986036 20 mg subcutaneous injection once daily for 12 weeks.
|
Treatment E: BMS-986036 (20 mg Weekly)
BMS-986036 20 mg subcutaneous injection once weekly (on Day 1 of each week) for 12 weeks followed by Placebo (Matching with BMS-986036) 0 mg subcutaneous injection on Days 2-7 of each week for 12 weeks.
|
|---|---|---|---|---|---|
|
Area Under the Concentration-time Curve From Time Zero to 24 Hours at Steady State (AUC [0-24 Hours, ss]) of C-terminal Intact BMS-986036
|
1210 hour*microgram/liter
Geometric Coefficient of Variation 60.6
|
4900 hour*microgram/liter
Geometric Coefficient of Variation 50.4
|
18300 hour*microgram/liter
Geometric Coefficient of Variation 49.2
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 6, 24 hours postdose on Week 8; pre-dose on Weeks 1, 2, 4, 6, 8, and 12; post treatment period on Week 13, 15 and 18 (Day 126)Population: Serum concentration-time data will be used to develop a population PK model, and estimates of individual PK parameters will be derived from this model using a validated PK analysis program. Here, 'N' signifies number of participants evaluable for this outcome measure.
AUC \[0-168 hours, ss\] of C-terminal Intact BMS-986036 was reported.
Outcome measures
| Measure |
Treatment A: Placebo
Placebo (Matching with BMS-986036) 0 mg subcutaneous injection once daily for 12 weeks.
|
Treatment B: BMS-986036 (1 mg Daily)
BMS-986036 1 mg subcutaneous injection once daily for 12 weeks.
|
Treatment C: BMS-986036 (5 mg Daily)
BMS-986036 5 mg subcutaneous injection once daily for 12 weeks.
|
Treatment D: BMS-986036 (20 mg Daily)
n=23 Participants
BMS-986036 20 mg subcutaneous injection once daily for 12 weeks.
|
Treatment E: BMS-986036 (20 mg Weekly)
BMS-986036 20 mg subcutaneous injection once weekly (on Day 1 of each week) for 12 weeks followed by Placebo (Matching with BMS-986036) 0 mg subcutaneous injection on Days 2-7 of each week for 12 weeks.
|
|---|---|---|---|---|---|
|
Area Under the Concentration-time Curve From Time Zero to 168 Hours at Steady State (AUC [0-168 Hours, ss]) of C-terminal Intact BMS-986036
|
—
|
—
|
—
|
31800 hour*microgram/liter
Geometric Coefficient of Variation 57.6
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 6, 24 hours postdose on Week 8; pre-dose on Weeks 1, 2, 4, 6, 8, and 12; post treatment period on Week 13, 15 and 18 (Day 126)Population: Serum concentration-time data will be used to develop a population PK model, and estimates of individual PK parameters will be derived from this model using a validated PK analysis program. Here, 'N' signifies number of participants evaluable for this outcome measure.
Cavg of Total BMS-986036 was reported.
Outcome measures
| Measure |
Treatment A: Placebo
n=21 Participants
Placebo (Matching with BMS-986036) 0 mg subcutaneous injection once daily for 12 weeks.
|
Treatment B: BMS-986036 (1 mg Daily)
n=22 Participants
BMS-986036 1 mg subcutaneous injection once daily for 12 weeks.
|
Treatment C: BMS-986036 (5 mg Daily)
n=20 Participants
BMS-986036 5 mg subcutaneous injection once daily for 12 weeks.
|
Treatment D: BMS-986036 (20 mg Daily)
n=23 Participants
BMS-986036 20 mg subcutaneous injection once daily for 12 weeks.
|
Treatment E: BMS-986036 (20 mg Weekly)
BMS-986036 20 mg subcutaneous injection once weekly (on Day 1 of each week) for 12 weeks followed by Placebo (Matching with BMS-986036) 0 mg subcutaneous injection on Days 2-7 of each week for 12 weeks.
|
|---|---|---|---|---|---|
|
Average Concentration (Cavg) of Total BMS-986036
|
342 Microgram per Liter (ug/L)
Geometric Coefficient of Variation 42.3
|
1560 Microgram per Liter (ug/L)
Geometric Coefficient of Variation 44.6
|
6390 Microgram per Liter (ug/L)
Geometric Coefficient of Variation 43.2
|
1130 Microgram per Liter (ug/L)
Geometric Coefficient of Variation 38.9
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 6, 24 hours postdose on Week 8; pre-dose on Weeks 1, 2, 4, 6, 8, and 12; post treatment period on Week 13, 15 and 18 (Day 126)Population: Serum concentration-time data will be used to develop a population PK model, and estimates of individual PK parameters will be derived from this model using a validated PK analysis program. Here, 'N' signifies number of participants evaluable for this outcome measure.
Maximum observed concentration (Cmax) of Total BMS-986036 was reported.
Outcome measures
| Measure |
Treatment A: Placebo
n=21 Participants
Placebo (Matching with BMS-986036) 0 mg subcutaneous injection once daily for 12 weeks.
|
Treatment B: BMS-986036 (1 mg Daily)
n=22 Participants
BMS-986036 1 mg subcutaneous injection once daily for 12 weeks.
|
Treatment C: BMS-986036 (5 mg Daily)
n=20 Participants
BMS-986036 5 mg subcutaneous injection once daily for 12 weeks.
|
Treatment D: BMS-986036 (20 mg Daily)
n=23 Participants
BMS-986036 20 mg subcutaneous injection once daily for 12 weeks.
|
Treatment E: BMS-986036 (20 mg Weekly)
BMS-986036 20 mg subcutaneous injection once weekly (on Day 1 of each week) for 12 weeks followed by Placebo (Matching with BMS-986036) 0 mg subcutaneous injection on Days 2-7 of each week for 12 weeks.
|
|---|---|---|---|---|---|
|
Maximum Observed Concentration (Cmax) of Total BMS-986036
|
344 microgram/liter
Geometric Coefficient of Variation 42.5
|
1570 microgram/liter
Geometric Coefficient of Variation 44.5
|
6440 microgram/liter
Geometric Coefficient of Variation 43.1
|
1420 microgram/liter
Geometric Coefficient of Variation 36.1
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 6, 24 hours postdose on Week 8Population: Serum concentration-time data will be used to develop a population PK model, and estimates of individual PK parameters will be derived from this model using a validated PK analysis program. Here, 'N' signifies number of participants evaluable for this outcome measure.
AUC \[0-24 hours, ss\] of Total BMS-986036 was reported.
Outcome measures
| Measure |
Treatment A: Placebo
n=21 Participants
Placebo (Matching with BMS-986036) 0 mg subcutaneous injection once daily for 12 weeks.
|
Treatment B: BMS-986036 (1 mg Daily)
n=22 Participants
BMS-986036 1 mg subcutaneous injection once daily for 12 weeks.
|
Treatment C: BMS-986036 (5 mg Daily)
n=20 Participants
BMS-986036 5 mg subcutaneous injection once daily for 12 weeks.
|
Treatment D: BMS-986036 (20 mg Daily)
BMS-986036 20 mg subcutaneous injection once daily for 12 weeks.
|
Treatment E: BMS-986036 (20 mg Weekly)
BMS-986036 20 mg subcutaneous injection once weekly (on Day 1 of each week) for 12 weeks followed by Placebo (Matching with BMS-986036) 0 mg subcutaneous injection on Days 2-7 of each week for 12 weeks.
|
|---|---|---|---|---|---|
|
Area Under the Concentration-time Curve From Time Zero to 24 Hours at Steady State (AUC [0-24 Hours, ss]) Total BMS-986036
|
8200 hour*microgram/liter
Geometric Coefficient of Variation 42.3
|
37400 hour*microgram/liter
Geometric Coefficient of Variation 44.6
|
153000 hour*microgram/liter
Geometric Coefficient of Variation 43.2
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 6, 24 hours postdose on Week 8; pre-dose on Weeks 1, 2, 4, 6, 8, and 12; post treatment period on Week 13, 15 and 18 (Day 126)Population: Serum concentration-time data will be used to develop a population PK model, and estimates of individual PK parameters will be derived from this model using a validated PK analysis program. Here, 'N' signifies number of participants evaluable for this outcome measure.
AUC \[0-168 hours, ss\] of Total BMS- 986036 was reported.
Outcome measures
| Measure |
Treatment A: Placebo
Placebo (Matching with BMS-986036) 0 mg subcutaneous injection once daily for 12 weeks.
|
Treatment B: BMS-986036 (1 mg Daily)
BMS-986036 1 mg subcutaneous injection once daily for 12 weeks.
|
Treatment C: BMS-986036 (5 mg Daily)
BMS-986036 5 mg subcutaneous injection once daily for 12 weeks.
|
Treatment D: BMS-986036 (20 mg Daily)
n=23 Participants
BMS-986036 20 mg subcutaneous injection once daily for 12 weeks.
|
Treatment E: BMS-986036 (20 mg Weekly)
BMS-986036 20 mg subcutaneous injection once weekly (on Day 1 of each week) for 12 weeks followed by Placebo (Matching with BMS-986036) 0 mg subcutaneous injection on Days 2-7 of each week for 12 weeks.
|
|---|---|---|---|---|---|
|
Area Under the Concentration-time Curve From Time Zero to 168 Hours at Steady State (AUC [0-168 Hours, ss]) of Total BMS-986036
|
—
|
—
|
—
|
172000 hour*microgram/liter
Geometric Coefficient of Variation 39.1
|
—
|
SECONDARY outcome
Timeframe: Baseline and Day 126Population: It included all treated participants who were randomized to treatment and subsequently received at least one dose of study medication.
Percentage of Participants with ANTI-BMS-986036 Antibody Response (ADA positive and ADA Negative) was reported. Participants were monitored for antibodies to BMS-986036 with an anti-BMS-986036 antibody assay. Titers were reported for samples testing positive in an assay.
Outcome measures
| Measure |
Treatment A: Placebo
n=24 Participants
Placebo (Matching with BMS-986036) 0 mg subcutaneous injection once daily for 12 weeks.
|
Treatment B: BMS-986036 (1 mg Daily)
n=24 Participants
BMS-986036 1 mg subcutaneous injection once daily for 12 weeks.
|
Treatment C: BMS-986036 (5 mg Daily)
n=24 Participants
BMS-986036 5 mg subcutaneous injection once daily for 12 weeks.
|
Treatment D: BMS-986036 (20 mg Daily)
n=24 Participants
BMS-986036 20 mg subcutaneous injection once daily for 12 weeks.
|
Treatment E: BMS-986036 (20 mg Weekly)
BMS-986036 20 mg subcutaneous injection once weekly (on Day 1 of each week) for 12 weeks followed by Placebo (Matching with BMS-986036) 0 mg subcutaneous injection on Days 2-7 of each week for 12 weeks.
|
|---|---|---|---|---|---|
|
Percentage of Participants With ANTI-BMS-986036 Antibody Response
ADA Positive
|
37.5 Percentage of participants
|
79.2 Percentage of participants
|
83.3 Percentage of participants
|
58.3 Percentage of participants
|
—
|
|
Percentage of Participants With ANTI-BMS-986036 Antibody Response
ADA Negative
|
62.5 Percentage of participants
|
16.7 Percentage of participants
|
12.5 Percentage of participants
|
37.5 Percentage of participants
|
—
|
Adverse Events
Treatment A: Placebo
Treatment B: BMS-986036 (1 mg Daily)
Treatment C: BMS-986036 (5 mg Daily)
Treatment D: BMS-986036 (20 mg Daily)
Treatment E: BMS-986036 (20 mg Weekly)
Serious adverse events
| Measure |
Treatment A: Placebo
n=24 participants at risk
Placebo (Matching with BMS-986036) 0 mg subcutaneous injection once daily for 12 weeks.
|
Treatment B: BMS-986036 (1 mg Daily)
n=24 participants at risk
BMS-986036 1 mg subcutaneous injection once daily for 12 weeks.
|
Treatment C: BMS-986036 (5 mg Daily)
n=24 participants at risk
BMS-986036 5 mg subcutaneous injection once daily for 12 weeks.
|
Treatment D: BMS-986036 (20 mg Daily)
n=24 participants at risk
BMS-986036 20 mg subcutaneous injection once daily for 12 weeks.
|
Treatment E: BMS-986036 (20 mg Weekly)
n=24 participants at risk
BMS-986036 20 mg subcutaneous injection once weekly (on Day 1 of each week) for 12 weeks followed by Placebo (Matching with BMS-986036) 0 mg subcutaneous injection on Days 2-7 of each week for 12 weeks.
|
|---|---|---|---|---|---|
|
Cardiac disorders
Mitral Valve Disease
|
0.00%
0/24 • Approximately 2 years
|
0.00%
0/24 • Approximately 2 years
|
0.00%
0/24 • Approximately 2 years
|
4.2%
1/24 • Approximately 2 years
|
0.00%
0/24 • Approximately 2 years
|
|
Cardiac disorders
Tricuspid Valve Disease
|
0.00%
0/24 • Approximately 2 years
|
0.00%
0/24 • Approximately 2 years
|
0.00%
0/24 • Approximately 2 years
|
4.2%
1/24 • Approximately 2 years
|
0.00%
0/24 • Approximately 2 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal Cell Carcinoma
|
4.2%
1/24 • Approximately 2 years
|
0.00%
0/24 • Approximately 2 years
|
0.00%
0/24 • Approximately 2 years
|
0.00%
0/24 • Approximately 2 years
|
0.00%
0/24 • Approximately 2 years
|
Other adverse events
| Measure |
Treatment A: Placebo
n=24 participants at risk
Placebo (Matching with BMS-986036) 0 mg subcutaneous injection once daily for 12 weeks.
|
Treatment B: BMS-986036 (1 mg Daily)
n=24 participants at risk
BMS-986036 1 mg subcutaneous injection once daily for 12 weeks.
|
Treatment C: BMS-986036 (5 mg Daily)
n=24 participants at risk
BMS-986036 5 mg subcutaneous injection once daily for 12 weeks.
|
Treatment D: BMS-986036 (20 mg Daily)
n=24 participants at risk
BMS-986036 20 mg subcutaneous injection once daily for 12 weeks.
|
Treatment E: BMS-986036 (20 mg Weekly)
n=24 participants at risk
BMS-986036 20 mg subcutaneous injection once weekly (on Day 1 of each week) for 12 weeks followed by Placebo (Matching with BMS-986036) 0 mg subcutaneous injection on Days 2-7 of each week for 12 weeks.
|
|---|---|---|---|---|---|
|
General disorders
Injection Site Bruising
|
20.8%
5/24 • Approximately 2 years
|
25.0%
6/24 • Approximately 2 years
|
16.7%
4/24 • Approximately 2 years
|
4.2%
1/24 • Approximately 2 years
|
12.5%
3/24 • Approximately 2 years
|
|
General disorders
Injection Site Erythema
|
4.2%
1/24 • Approximately 2 years
|
4.2%
1/24 • Approximately 2 years
|
0.00%
0/24 • Approximately 2 years
|
8.3%
2/24 • Approximately 2 years
|
4.2%
1/24 • Approximately 2 years
|
|
General disorders
Fatigue
|
0.00%
0/24 • Approximately 2 years
|
4.2%
1/24 • Approximately 2 years
|
4.2%
1/24 • Approximately 2 years
|
0.00%
0/24 • Approximately 2 years
|
8.3%
2/24 • Approximately 2 years
|
|
General disorders
Hunger
|
0.00%
0/24 • Approximately 2 years
|
0.00%
0/24 • Approximately 2 years
|
8.3%
2/24 • Approximately 2 years
|
8.3%
2/24 • Approximately 2 years
|
0.00%
0/24 • Approximately 2 years
|
|
Infections and infestations
Nasopharyngitis
|
4.2%
1/24 • Approximately 2 years
|
12.5%
3/24 • Approximately 2 years
|
4.2%
1/24 • Approximately 2 years
|
4.2%
1/24 • Approximately 2 years
|
8.3%
2/24 • Approximately 2 years
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
0.00%
0/24 • Approximately 2 years
|
0.00%
0/24 • Approximately 2 years
|
8.3%
2/24 • Approximately 2 years
|
0.00%
0/24 • Approximately 2 years
|
4.2%
1/24 • Approximately 2 years
|
|
Gastrointestinal disorders
Diarrhea
|
4.2%
1/24 • Approximately 2 years
|
12.5%
3/24 • Approximately 2 years
|
8.3%
2/24 • Approximately 2 years
|
16.7%
4/24 • Approximately 2 years
|
20.8%
5/24 • Approximately 2 years
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/24 • Approximately 2 years
|
8.3%
2/24 • Approximately 2 years
|
0.00%
0/24 • Approximately 2 years
|
4.2%
1/24 • Approximately 2 years
|
12.5%
3/24 • Approximately 2 years
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/24 • Approximately 2 years
|
12.5%
3/24 • Approximately 2 years
|
0.00%
0/24 • Approximately 2 years
|
4.2%
1/24 • Approximately 2 years
|
4.2%
1/24 • Approximately 2 years
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/24 • Approximately 2 years
|
8.3%
2/24 • Approximately 2 years
|
0.00%
0/24 • Approximately 2 years
|
0.00%
0/24 • Approximately 2 years
|
0.00%
0/24 • Approximately 2 years
|
|
Metabolism and nutrition disorders
Increased Appetite
|
8.3%
2/24 • Approximately 2 years
|
4.2%
1/24 • Approximately 2 years
|
12.5%
3/24 • Approximately 2 years
|
4.2%
1/24 • Approximately 2 years
|
4.2%
1/24 • Approximately 2 years
|
|
Nervous system disorders
Headache
|
8.3%
2/24 • Approximately 2 years
|
4.2%
1/24 • Approximately 2 years
|
4.2%
1/24 • Approximately 2 years
|
0.00%
0/24 • Approximately 2 years
|
4.2%
1/24 • Approximately 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
8.3%
2/24 • Approximately 2 years
|
0.00%
0/24 • Approximately 2 years
|
4.2%
1/24 • Approximately 2 years
|
0.00%
0/24 • Approximately 2 years
|
4.2%
1/24 • Approximately 2 years
|
|
Investigations
Blood Creatine Phosphokinase Increased
|
0.00%
0/24 • Approximately 2 years
|
8.3%
2/24 • Approximately 2 years
|
0.00%
0/24 • Approximately 2 years
|
0.00%
0/24 • Approximately 2 years
|
0.00%
0/24 • Approximately 2 years
|
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