Trial Outcomes & Findings for A Study of Multiple Oral Doses of JNJ-41443532 in Patients With Type 2 Diabetes Mellitus (NCT NCT01230749)
NCT ID: NCT01230749
Last Updated: 2013-12-11
Results Overview
Difference is calculated as the change in 24-hour WAG in Least Square Mean (LSM) from baseline to Day 28 of each treatment group (pioglitazone, JNJ-41443532 250 mg, JNJ-41443532 1000 mg, and placebo). The statistical analyses shows the treatment differences (ie, each study medication group minus placebo) in the LSM change. 24-hour WAG is defined as the area under the plasma glucose concentration time curve over 0 to 24 hours, divided by 24.
COMPLETED
PHASE2
89 participants
From baseline (Day -1) to Day 28
2013-12-11
Participant Flow
89 participants were enrolled at 7 study sites in United States.
89 participants were randomly assigned to 4 treatment groups (Placebo: 22; Pioglitazone 30 mg: 22; JNJ41443532 250 mg: 23, and JNJ41443532 1000 mg: 22) and all participants received at least one dose of the study medication.
Participant milestones
| Measure |
Placebo
Participants received placebo tablets orally, twice a day for 29 days.
|
Pioglitazone 30 mg
Participants received pioglitazone 30 mg tablet orally, once a day for 29 days.
|
JNJ41443532 250 mg
Participants received JNJ-41443532 250 mg tablet orally, twice a day for 29 days.
|
JNJ41443532 1000 mg
Participants received JNJ-41443532 1000 mg (4 X 250 mg tablet) orally, twice a day for 29 days.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
22
|
22
|
23
|
22
|
|
Overall Study
COMPLETED
|
22
|
20
|
21
|
20
|
|
Overall Study
NOT COMPLETED
|
0
|
2
|
2
|
2
|
Reasons for withdrawal
| Measure |
Placebo
Participants received placebo tablets orally, twice a day for 29 days.
|
Pioglitazone 30 mg
Participants received pioglitazone 30 mg tablet orally, once a day for 29 days.
|
JNJ41443532 250 mg
Participants received JNJ-41443532 250 mg tablet orally, twice a day for 29 days.
|
JNJ41443532 1000 mg
Participants received JNJ-41443532 1000 mg (4 X 250 mg tablet) orally, twice a day for 29 days.
|
|---|---|---|---|---|
|
Overall Study
Adverse Event
|
0
|
0
|
0
|
1
|
|
Overall Study
Physician Decision
|
0
|
0
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
0
|
0
|
|
Overall Study
Fasting glucose more than 270 mg/dL
|
0
|
1
|
1
|
1
|
Baseline Characteristics
A Study of Multiple Oral Doses of JNJ-41443532 in Patients With Type 2 Diabetes Mellitus
Baseline characteristics by cohort
| Measure |
Placebo
n=22 Participants
Participants received placebo tablets orally, twice a day for 29 days.
|
Pioglitazone 30 mg
n=22 Participants
Participants received pioglitazone 30 mg tablet orally, once a day for 29 days.
|
JNJ41443532 250 mg
n=23 Participants
Participants received JNJ-41443532 250 mg tablet orally, twice a day for 29 days.
|
JNJ41443532 1000 mg
n=22 Participants
Participants received JNJ-41443532 1000 mg (4 X 250 mg tablet) orally, twice a day for 29 days.
|
Total
n=89 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age Continuous
|
52.7 years
STANDARD_DEVIATION 8.93 • n=5 Participants
|
54.5 years
STANDARD_DEVIATION 8.93 • n=7 Participants
|
51.7 years
STANDARD_DEVIATION 7.06 • n=5 Participants
|
57.1 years
STANDARD_DEVIATION 6.03 • n=4 Participants
|
54 years
STANDARD_DEVIATION 7.96 • n=21 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
11 Participants
n=4 Participants
|
34 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
11 Participants
n=4 Participants
|
55 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: From baseline (Day -1) to Day 28Population: Analyses included all participants who received at least 1 dose of JNJ-41443532 or placebo and had at least 1 pharmacodynamic assessment posttreatment.
Difference is calculated as the change in 24-hour WAG in Least Square Mean (LSM) from baseline to Day 28 of each treatment group (pioglitazone, JNJ-41443532 250 mg, JNJ-41443532 1000 mg, and placebo). The statistical analyses shows the treatment differences (ie, each study medication group minus placebo) in the LSM change. 24-hour WAG is defined as the area under the plasma glucose concentration time curve over 0 to 24 hours, divided by 24.
Outcome measures
| Measure |
Pioglitazone 30 mg
n=20 Participants
Participants received pioglitazone 30 mg tablet orally, once a day for 29 days.
|
JNJ41443532 250 mg
n=21 Participants
Participants received JNJ-41443532 250 mg tablet orally, twice a day for 29 days.
|
JNJ41443532 1000 mg
n=20 Participants
Participants received JNJ-41443532 1000 mg (4 X 250 mg tablet) orally, twice a day for 29 days.
|
Placebo
n=22 Participants
Participants received placebo orally, twice a day for 29 days
|
|---|---|---|---|---|
|
Change From Baseline (Day -1) to Day 28 in Twenty-Four-Hour Weighted Average Glucose (24-Hour WAG)
|
-18.88 mg/dL
Standard Error 7.74 • Interval -46.792 to -8.008
|
-11.95 mg/dL
Standard Error 7.33 • Interval -39.801 to -1.142
|
-4.72 mg/dL
Standard Error 7.56 • Interval -32.635 to 6.151
|
8.52 mg/dL
Standard Error 7.23
|
SECONDARY outcome
Timeframe: From baseline to Day 28Population: Analyses included all participants who received at least 1 dose of JNJ-41443532 or placebo and had at least 1 pharmacodynamic assessment posttreatment. Two participants (1 in JNJ-41443532 250-mg group and 1 in Pioglitazone group) were excluded from the analysis because a blood sample for FPG was not collected on Day 28.
Difference is calculated as the change in FPG in Least Square Mean (LSM) from baseline to Day 28 of each treatment group (pioglitazone, JNJ-41443532 250 mg, JNJ-41443532 1000 mg, and placebo). The statistical analyses shows the treatment differences (ie, each study medication group minus placebo) in the LSM change.
Outcome measures
| Measure |
Pioglitazone 30 mg
n=19 Participants
Participants received pioglitazone 30 mg tablet orally, once a day for 29 days.
|
JNJ41443532 250 mg
n=20 Participants
Participants received JNJ-41443532 250 mg tablet orally, twice a day for 29 days.
|
JNJ41443532 1000 mg
n=20 Participants
Participants received JNJ-41443532 1000 mg (4 X 250 mg tablet) orally, twice a day for 29 days.
|
Placebo
n=21 Participants
Participants received placebo orally, twice a day for 29 days
|
|---|---|---|---|---|
|
Change From Baseline to Day 28 in Fasting Plasma Glucose (FPG)
|
-14.57 mg/dL
Standard Error 7.93 • Interval -47.606 to -8.957
|
-8.26 mg/dL
Standard Error 7.47 • Interval -41.154 to -2.786
|
-4.00 mg/dL
Standard Error 7.29 • Interval -36.86 to 1.431
|
13.71 mg/dL
Standard Error 7.23
|
SECONDARY outcome
Timeframe: From baseline to Day 28Population: Analyses included all participants who received at least 1 dose of JNJ-41443532 or placebo and had at least 1 pharmacodynamic assessment posttreatment. Two participants (1 in JNJ-41443532 250-mg group and 1 in Pioglitazone group) were excluded from the analysis because a blood sample for HOMA-%B was not collected on Day 28.
Difference is calculated as the change in insulin secretion in Least Square Mean (LSM) from baseline to Day 28 of each treatment group (pioglitazone, JNJ-41443532 250 mg, JNJ-41443532 1000 mg, and placebo). The statistical analyses shows the treatment differences (ie, each study medication group minus placebo) in the LSM change. Insulin secretion is measured by the absolute change in Homeostasis Model Assessment of steady state islet beta cell (HOMA-%B). HOMA-%B calculated as: (360 multiplied by Insulin \[pmol/L\]) divided by (\[Glucose {mg/dL} minus 63\] multiplied by 6.945). Higher value is better (signifies improvement relative to baseline).
Outcome measures
| Measure |
Pioglitazone 30 mg
n=19 Participants
Participants received pioglitazone 30 mg tablet orally, once a day for 29 days.
|
JNJ41443532 250 mg
n=20 Participants
Participants received JNJ-41443532 250 mg tablet orally, twice a day for 29 days.
|
JNJ41443532 1000 mg
n=20 Participants
Participants received JNJ-41443532 1000 mg (4 X 250 mg tablet) orally, twice a day for 29 days.
|
Placebo
n=21 Participants
Participants received placebo orally, twice a day for 29 days
|
|---|---|---|---|---|
|
Change From Baseline to Day 28 in Insulin Secretion
|
-4.00 HOMA-B score
Standard Error 4.644 • Interval -15.852 to 26.334
|
6.94 HOMA-B score
Standard Error 4.415 • Interval 3.146 to 45.37
|
-0.89 HOMA-B score
Standard Error 4.301 • Interval -8.022 to 34.107
|
-6.76 HOMA-B score
Standard Error 4.255
|
SECONDARY outcome
Timeframe: From baseline to Day 28Population: Analyses included all participants who received at least 1 dose of JNJ-41443532 or placebo and had at least 1 pharmacodynamic assessment posttreatment. Two participants (1 in JNJ-41443532 250-mg group and 1 in Pioglitazone group) were excluded from the analysis because a blood sample for HOMA-IR was not collected on Day 28.
Difference is calculated as the change in insulin resistance in Least Square Mean (LSM) from baseline to Day 28 of each treatment group (pioglitazone, JNJ-41443532 250 mg, JNJ-41443532 1000 mg, and placebo). The statistical analyses shows the treatment differences (ie, each study medication group minus placebo) in the LSM change. Insuline sensitivity is measured by absolute change in Homeostasis Model Assessment of insulin resistance (HOMA-IR). Insulin sensitivity is HOMA-%S and HOMA-IR is the reciprocal of HOMA-%S. HOMA-IR calculated as: (Glucose \[mg/dL\]) multiplied by Insulin \[pmol/L\]) divided by (405 multiplied by 6.945). Lower value is better (signifies improvement relative to baseline).
Outcome measures
| Measure |
Pioglitazone 30 mg
n=19 Participants
Participants received pioglitazone 30 mg tablet orally, once a day for 29 days.
|
JNJ41443532 250 mg
n=20 Participants
Participants received JNJ-41443532 250 mg tablet orally, twice a day for 29 days.
|
JNJ41443532 1000 mg
n=20 Participants
Participants received JNJ-41443532 1000 mg (4 X 250 mg tablet) orally, twice a day for 29 days.
|
Placebo
n=21 Participants
Participants received placebo orally, twice a day for 29 days
|
|---|---|---|---|---|
|
Change From Baseline to Day 28 in Insulin Resistance
|
-1.52 HOMA-IR score
Standard Error 0.739 • Interval -48.37 to -7.18
|
0.07 HOMA-IR score
Standard Error 0.689 • Interval -24.534 to 16.542
|
-0.35 HOMA-IR score
Standard Error 0.675 • Interval -30.592 to 10.615
|
0.33 HOMA-IR score
Standard Error 0.666
|
SECONDARY outcome
Timeframe: From baseline to Day 28Population: Analyses included all participants who received at least 1 dose of JNJ-41443532 or placebo and had at least 1 pharmacodynamic assessment posttreatment.
Difference is calculated as the geometric mean change in IL-6 from baseline to Day 28 of each treatment group (JNJ-41443532 250 mg, JNJ-41443532 1000 mg, and placebo). The statistical analyses shows the treatment differences (ie, each study medication group minus placebo) in the geometric mean change. IL-6 is a systemic inflammatory markers and is an independent predictors of insulin resistance and progression to type 2 diabetes mellitus. IL-6 was not measured for pioglitazone guoup. The unit of IL-6 is picograms per milliliter (pg/mL).
Outcome measures
| Measure |
Pioglitazone 30 mg
n=21 Participants
Participants received pioglitazone 30 mg tablet orally, once a day for 29 days.
|
JNJ41443532 250 mg
n=20 Participants
Participants received JNJ-41443532 250 mg tablet orally, twice a day for 29 days.
|
JNJ41443532 1000 mg
n=22 Participants
Participants received JNJ-41443532 1000 mg (4 X 250 mg tablet) orally, twice a day for 29 days.
|
Placebo
Participants received placebo orally, twice a day for 29 days
|
|---|---|---|---|---|
|
Change From Baseline to Day 28 in Systemic Levels of Interleukin 6 (IL-6)
|
0.86 pg/mL
Standard Deviation 0.85 • Interval 71.031 to 127.324
|
0.81 pg/mL
Standard Deviation 0.34 • Interval 66.567 to 121.403
|
0.91 pg/mL
Standard Deviation 0.71
|
—
|
SECONDARY outcome
Timeframe: From baseline to Day 28Population: Analyses included all participants who received at least 1 dose of JNJ-41443532 or placebo and had at least 1 pharmacodynamic assessment posttreatment.
Difference is calculated as the geometric mean change in IL-18 from baseline to Day 28 of each treatment group (JNJ-41443532 250 mg, JNJ-41443532 1000 mg, and placebo). The statistical analyses shows the treatment differences (ie, each study medication group minus placebo) in the geometric mean change. IL-18 was not measured for pioglitazone group. The unit of IL-18 is picograms per milliliter (pg/mL)
Outcome measures
| Measure |
Pioglitazone 30 mg
n=21 Participants
Participants received pioglitazone 30 mg tablet orally, once a day for 29 days.
|
JNJ41443532 250 mg
n=20 Participants
Participants received JNJ-41443532 250 mg tablet orally, twice a day for 29 days.
|
JNJ41443532 1000 mg
n=22 Participants
Participants received JNJ-41443532 1000 mg (4 X 250 mg tablet) orally, twice a day for 29 days.
|
Placebo
Participants received placebo orally, twice a day for 29 days
|
|---|---|---|---|---|
|
Change From Baseline to Day 28 in Systemic Levels of Interleukin 18 (IL-18)
|
1.02 pg/mL
Standard Deviation 0.16 • Interval 93.217 to 107.647
|
1.03 pg/mL
Standard Deviation 0.12 • Interval 94.179 to 108.7
|
1.02 pg/mL
Standard Deviation 0.15
|
—
|
SECONDARY outcome
Timeframe: From baseline to Day 28Population: Analyses included all participants who received at least 1 dose of JNJ-41443532 or placebo and had at least 1 pharmacodynamic assessment posttreatment.
Difference is calculated as the geometric mean change in CRP from baseline to Day 28 of each treatment group (JNJ-41443532 250 mg, JNJ-41443532 1000 mg, and placebo). The statistical analyses shows the treatment differences (ie, each study medication group minus placebo) in the geometric mean change. CRP was not measured for pioglitazone group.
Outcome measures
| Measure |
Pioglitazone 30 mg
n=21 Participants
Participants received pioglitazone 30 mg tablet orally, once a day for 29 days.
|
JNJ41443532 250 mg
n=20 Participants
Participants received JNJ-41443532 250 mg tablet orally, twice a day for 29 days.
|
JNJ41443532 1000 mg
n=22 Participants
Participants received JNJ-41443532 1000 mg (4 X 250 mg tablet) orally, twice a day for 29 days.
|
Placebo
Participants received placebo orally, twice a day for 29 days
|
|---|---|---|---|---|
|
Change From Baseline to Day 28 in Systemic Levels of C-Reactive Protein (CRP)
|
1.12 mg/dL
Standard Deviation 0.56 • Interval 100.275 to 177.115
|
0.86 mg/dL
Standard Deviation 0.30 • Interval 76.26 to 135.942
|
0.84 mg/dL
Standard Deviation 0.63
|
—
|
SECONDARY outcome
Timeframe: From baseline to Day 29Population: Analyses included all participants who received at least 1 dose of JNJ-41443532 or placebo and had at least 1 pharmacodynamic assessment posttreatment.
Difference is calculated as the change in body weight in Least Square Mean (LSM) from baseline to Day 29 of each treatment group (pioglitazone, JNJ-41443532 250 mg, JNJ-41443532 1000 mg, and placebo). The statistical analyses shows the treatment differences (ie, each study medication group minus placebo) in the LSM change.
Outcome measures
| Measure |
Pioglitazone 30 mg
n=20 Participants
Participants received pioglitazone 30 mg tablet orally, once a day for 29 days.
|
JNJ41443532 250 mg
n=21 Participants
Participants received JNJ-41443532 250 mg tablet orally, twice a day for 29 days.
|
JNJ41443532 1000 mg
n=20 Participants
Participants received JNJ-41443532 1000 mg (4 X 250 mg tablet) orally, twice a day for 29 days.
|
Placebo
n=22 Participants
Participants received placebo orally, twice a day for 29 days
|
|---|---|---|---|---|
|
Change From Baseline to Day 29 in Body Weight
|
-0.75 Kilograms
Standard Error 0.35 • Interval -0.408 to 1.323
|
-1.18 Kilograms
Standard Error 0.34 • Interval -0.838 to 0.904
|
-0.19 Kilograms
Standard Error 0.34 • Interval 0.15 to 1.892
|
-1.21 Kilograms
Standard Error 0.32
|
Adverse Events
Placebo
Pioglitazone 30 mg
JNJ41443532 250 mg
JNJ41443532 1000 mg
Serious adverse events
| Measure |
Placebo
n=22 participants at risk
Participants received placebo tablets orally, twice a day for 29 days.
|
Pioglitazone 30 mg
n=22 participants at risk
Participants received pioglitazone 30 mg tablet orally, once a day for 29 days.
|
JNJ41443532 250 mg
n=23 participants at risk
Participants received JNJ-41443532 250 mg tablet orally, twice a day for 29 days.
|
JNJ41443532 1000 mg
n=22 participants at risk
Participants received JNJ-41443532 1000 mg (4 X 250 mg tablet) orally, twice a day for 29 days.
|
|---|---|---|---|---|
|
Nervous system disorders
Cerebrovascular Accident
|
0.00%
0/22 • 12 weeks
|
0.00%
0/22 • 12 weeks
|
0.00%
0/23 • 12 weeks
|
4.5%
1/22 • 12 weeks
|
|
Nervous system disorders
Headache
|
0.00%
0/22 • 12 weeks
|
0.00%
0/22 • 12 weeks
|
0.00%
0/23 • 12 weeks
|
4.5%
1/22 • 12 weeks
|
Other adverse events
| Measure |
Placebo
n=22 participants at risk
Participants received placebo tablets orally, twice a day for 29 days.
|
Pioglitazone 30 mg
n=22 participants at risk
Participants received pioglitazone 30 mg tablet orally, once a day for 29 days.
|
JNJ41443532 250 mg
n=23 participants at risk
Participants received JNJ-41443532 250 mg tablet orally, twice a day for 29 days.
|
JNJ41443532 1000 mg
n=22 participants at risk
Participants received JNJ-41443532 1000 mg (4 X 250 mg tablet) orally, twice a day for 29 days.
|
|---|---|---|---|---|
|
Eye disorders
Vision Blurred
|
9.1%
2/22 • 12 weeks
|
4.5%
1/22 • 12 weeks
|
4.3%
1/23 • 12 weeks
|
0.00%
0/22 • 12 weeks
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/22 • 12 weeks
|
13.6%
3/22 • 12 weeks
|
4.3%
1/23 • 12 weeks
|
4.5%
1/22 • 12 weeks
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/22 • 12 weeks
|
0.00%
0/22 • 12 weeks
|
8.7%
2/23 • 12 weeks
|
9.1%
2/22 • 12 weeks
|
|
Gastrointestinal disorders
Dry Mouth
|
0.00%
0/22 • 12 weeks
|
9.1%
2/22 • 12 weeks
|
0.00%
0/23 • 12 weeks
|
0.00%
0/22 • 12 weeks
|
|
Gastrointestinal disorders
Nausea
|
18.2%
4/22 • 12 weeks
|
0.00%
0/22 • 12 weeks
|
0.00%
0/23 • 12 weeks
|
0.00%
0/22 • 12 weeks
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
0.00%
0/22 • 12 weeks
|
0.00%
0/22 • 12 weeks
|
8.7%
2/23 • 12 weeks
|
0.00%
0/22 • 12 weeks
|
|
Injury, poisoning and procedural complications
Muscle Strain
|
0.00%
0/22 • 12 weeks
|
9.1%
2/22 • 12 weeks
|
0.00%
0/23 • 12 weeks
|
0.00%
0/22 • 12 weeks
|
|
Nervous system disorders
Headache
|
18.2%
4/22 • 12 weeks
|
9.1%
2/22 • 12 weeks
|
17.4%
4/23 • 12 weeks
|
4.5%
1/22 • 12 weeks
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/22 • 12 weeks
|
9.1%
2/22 • 12 weeks
|
0.00%
0/23 • 12 weeks
|
0.00%
0/22 • 12 weeks
|
|
Nervous system disorders
Somnolence
|
0.00%
0/22 • 12 weeks
|
9.1%
2/22 • 12 weeks
|
0.00%
0/23 • 12 weeks
|
0.00%
0/22 • 12 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal Pain
|
0.00%
0/22 • 12 weeks
|
0.00%
0/22 • 12 weeks
|
8.7%
2/23 • 12 weeks
|
4.5%
1/22 • 12 weeks
|
Additional Information
Director, Translational Medicine
Janssen R&D US
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60