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| ID | Type | Description | Link |
|---|---|---|---|
| 41443532EDI2001 | Other Identifier | Johnson & Johnson Pharmaceutical Research & Development, L.L.C. |
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The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (what the body does to the medication) and pharmacodynamics (what the medication does to the body) of treatment with JNJ-41443532 relative to treatment with placebo in type 2 diabetes mellitus participants.
This is a randomized (the study medication is assigned by chance), double-blind (neither investigator nor participant knows the treatment that the participant receives), multicenter (study conducted at multiple sites), and placebo (an inactive substance that is compared with a medication to test whether the medication has a real effect in a clinical study) and active comparator (an established effective treatment that is compared with a medication to test whether the medication has a real effect in a clinical study) controlled study (placebo or active comparator is compared with the study medication to test whether the study medication has a real effect in clinical study). The study consists of 4 phases: screening phase (45 days before administration of study medication); pre-dosing run-in phase (a phase before a clinical study is commenced when no treatment is given. In this study, participant's glucose level will be observed during run-in-phase: days 15 to 1 before administration of study medication); treatment phase, and follow-up phase (7 to 10 days after the last dose of the study medication). Approximately 88 participants will be enrolled in this study. All participants will be randomly assigned to 4 treatment arms: JNJ-41443532 250 mg; JNJ-41443532 1000 mg; pioglitazone arm; and placebo. Safety evaluations will include assessment of adverse events including ocular assessments, clinical laboratory tests, electrocardiogram, vital signs, and physical examination which will be monitored throughout the study. The maximum study duration for each participant will be approximately 12 weeks.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| JNJ-41443532 250 mg | Experimental | Participants will receive JNJ-41443532 250 mg in morning and evening for 28 days. |
|
| JNJ-41443532 1000 mg | Experimental | Participants will receive JNJ-41443532 1000 mg (4 X 250 mg) in morning and evening for 28 days. |
|
| Pioglitazone | Active Comparator | Participants will receive pioglitazone 30 mg in morning for 28 days. |
|
| Placebo | Placebo Comparator | Participants will receive matching placebo for JNJ-41443532 and pioglitazone for 28 days. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| JNJ-41443532 | Drug | Participants will receive JNJ-41443532 tablet(s) orally in JNJ-41443532 250 mg arm (1 X 250 mg) and JNJ-41443532 1000 mg arm (4 X 250 mg) in morning and evening, for 28 days. |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline (Day -1) to Day 28 in Twenty-Four-Hour Weighted Average Glucose (24-Hour WAG) | 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. | From baseline (Day -1) to Day 28 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline to Day 28 in Fasting Plasma Glucose (FPG) | 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. | From baseline to Day 28 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial | Johnson & Johnson Pharmaceutical Research & Development, L.L.C. | Study Director |
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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.
89 participants were enrolled at 7 study sites in United States.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Participants received placebo tablets orally, twice a day for 29 days. |
| FG001 | Pioglitazone 30 mg | Participants received pioglitazone 30 mg tablet orally, once a day for 29 days. |
| FG002 | JNJ41443532 250 mg | Participants received JNJ-41443532 250 mg tablet orally, twice a day for 29 days. |
| FG003 | JNJ41443532 1000 mg | Participants received JNJ-41443532 1000 mg (4 X 250 mg tablet) orally, twice a day for 29 days. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Participants received placebo tablets orally, twice a day for 29 days. |
| BG001 | Pioglitazone 30 mg | Participants received pioglitazone 30 mg tablet orally, once a day for 29 days. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline (Day -1) to Day 28 in Twenty-Four-Hour Weighted Average Glucose (24-Hour WAG) | 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. | Analyses included all participants who received at least 1 dose of JNJ-41443532 or placebo and had at least 1 pharmacodynamic assessment posttreatment. | Posted | Least Squares Mean | Standard Error | mg/dL | From baseline (Day -1) to Day 28 |
|
12 weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Participants received placebo tablets orally, twice a day for 29 days. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cerebrovascular Accident | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Vision Blurred | Eye disorders | MedDRA 14.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Director, Translational Medicine | Janssen R&D US | 1 908 927-7881 |
| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| D003920 | Diabetes Mellitus |
| D006943 | Hyperglycemia |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| C000599181 | JNJ-41443532 |
| D000077205 | Pioglitazone |
| ID | Term |
|---|---|
| D045162 | Thiazolidinediones |
| D013844 | Thiazoles |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
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| Pioglitazone 30 mg | Drug | Participants will receive tablet pioglitazone 30 mg orally in morning for 28 days. |
|
| Placebo | Drug | Participants will receive matching placebo tablets of JNJ-41443532 and/or matching placebo tablets of pioglitazone orally as per the assigned arms. |
|
| Change From Baseline to Day 28 in Insulin Secretion | 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). | From baseline to Day 28 |
| Change From Baseline to Day 28 in Insulin Resistance | 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). | From baseline to Day 28 |
| Change From Baseline to Day 28 in Systemic Levels of Interleukin 6 (IL-6) | 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). | From baseline to Day 28 |
| Change From Baseline to Day 28 in Systemic Levels of Interleukin 18 (IL-18) | 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) | From baseline to Day 28 |
| Change From Baseline to Day 28 in Systemic Levels of C-Reactive Protein (CRP) | 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. | From baseline to Day 28 |
| Change From Baseline to Day 29 in Body Weight | 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. | From baseline to Day 29 |
| Physician Decision |
|
| Withdrawal by Subject |
|
| Fasting glucose more than 270 mg/dL |
|
| BG002 | JNJ41443532 250 mg | Participants received JNJ-41443532 250 mg tablet orally, twice a day for 29 days. |
| BG003 | JNJ41443532 1000 mg | Participants received JNJ-41443532 1000 mg (4 X 250 mg tablet) orally, twice a day for 29 days. |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG001 | JNJ41443532 250 mg | Participants received JNJ-41443532 250 mg tablet orally, twice a day for 29 days. |
| OG002 | JNJ41443532 1000 mg | Participants received JNJ-41443532 1000 mg (4 X 250 mg tablet) orally, twice a day for 29 days. |
| OG003 | Placebo | Participants received placebo orally, twice a day for 29 days |
|
|
|
| Secondary | Change From Baseline to Day 28 in Fasting Plasma Glucose (FPG) | 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. | 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. | Posted | Least Squares Mean | Standard Error | mg/dL | From baseline to Day 28 |
|
|
|
|
| Secondary | Change From Baseline to Day 28 in Insulin Secretion | 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). | 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. | Posted | Least Squares Mean | Standard Error | HOMA-B score | From baseline to Day 28 |
|
|
|
|
| Secondary | Change From Baseline to Day 28 in Insulin Resistance | 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). | 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. | Posted | Least Squares Mean | Standard Error | HOMA-IR score | From baseline to Day 28 |
|
|
|
|
| Secondary | Change From Baseline to Day 28 in Systemic Levels of Interleukin 6 (IL-6) | 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). | Analyses included all participants who received at least 1 dose of JNJ-41443532 or placebo and had at least 1 pharmacodynamic assessment posttreatment. | Posted | Geometric Mean | Standard Deviation | pg/mL | From baseline to Day 28 |
|
|
|
|
| Secondary | Change From Baseline to Day 28 in Systemic Levels of Interleukin 18 (IL-18) | 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) | Analyses included all participants who received at least 1 dose of JNJ-41443532 or placebo and had at least 1 pharmacodynamic assessment posttreatment. | Posted | Geometric Mean | Standard Deviation | pg/mL | From baseline to Day 28 |
|
|
|
|
| Secondary | Change From Baseline to Day 28 in Systemic Levels of C-Reactive Protein (CRP) | 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. | Analyses included all participants who received at least 1 dose of JNJ-41443532 or placebo and had at least 1 pharmacodynamic assessment posttreatment. | Posted | Geometric Mean | Standard Deviation | mg/dL | From baseline to Day 28 |
|
|
|
|
| Secondary | Change From Baseline to Day 29 in Body Weight | 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. | Analyses included all participants who received at least 1 dose of JNJ-41443532 or placebo and had at least 1 pharmacodynamic assessment posttreatment. | Posted | Least Squares Mean | Standard Error | Kilograms | From baseline to Day 29 |
|
|
|
|
| 0 |
| 22 |
| 6 |
| 22 |
| EG001 | Pioglitazone 30 mg | Participants received pioglitazone 30 mg tablet orally, once a day for 29 days. | 0 | 22 | 7 | 22 |
| EG002 | JNJ41443532 250 mg | Participants received JNJ-41443532 250 mg tablet orally, twice a day for 29 days. | 0 | 23 | 9 | 23 |
| EG003 | JNJ41443532 1000 mg | Participants received JNJ-41443532 1000 mg (4 X 250 mg tablet) orally, twice a day for 29 days. | 1 | 22 | 4 | 22 |
| Headache | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Dry Mouth | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
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| Upper Respiratory Tract Infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Muscle Strain | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
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| Paraesthesia | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
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| Somnolence | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
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| Oropharyngeal Pain | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
|
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| D001393 |
| Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| Difference in LSM |
| -21.97 |
| 2-Sided |
| 95 |
| -41.154 |
| -2.786 |
| No |
| Superiority or Other |
| ANCOVA | 0.069 | Difference in LSM | -17.71 | 2-Sided | 95 | -36.860 | 1.431 | No | Superiority or Other |
| Difference in LSM |
| 13.70 |
| 2-Sided |
| 95 |
| 2.392 |
| 25.008 |
| No |
| Superiority or Other |
| ANCOVA | 0.303 | Difference in LSM | 5.87 | 2-Sided | 95 | -5.417 | 17.148 | No | Superiority or Other |
| Difference in LSM |
| -0.26 |
| 2-Sided |
| 95 |
| -2.033 |
| 1.509 |
| No |
| Superiority or Other |
| ANCOVA | 0.444 | Difference in LSM | -0.69 | 2-Sided | 95 | -2.463 | 1.091 | No | Superiority or Other |
| GMR multiplied by 100 percent |
| 89.90 |
| 2-Sided |
| 90 |
| 66.567 |
| 121.403 |
| No |
| Superiority or Other |
| GMR multiplied by 100 percent |
| 101.18 |
| 2-Sided |
| 90 |
| 94.179 |
| 108.700 |
| No |
| Superiority or Other |
| GMR mulitplied by 100 percent |
| 101.82 |
| 2-Sided |
| 90 |
| 76.260 |
| 135.942 |
| No |
| Superiority or Other |
| Difference in LSM |
| 0.03 |
| 2-Sided |
| 95 |
| -0.838 |
| 0.904 |
| No |
| Superiority or Other |
| ANCOVA | 0.022 | Difference in LSM | 1.02 | 2-Sided | 95 | 0.150 | 1.892 | No | Superiority or Other |