Effect of SCH 497079 on Metabolic Parameters and Influence of Race/Ethnic Origin on Therapeutic Response (Study P05338)(COMPLETED)
- Conditions
- Type 2 Diabetes Mellitus
- Interventions
- Registration Number
- NCT00673465
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
The purpose of this study is to evaluate the effect of SCH 497079 on metabolic parameters and to determine the influence of race/ethnic origin on therapeutic response.
- Detailed Description
This study includes two parts, each part includes three consecutive 28-day treatment periods. Part 1 (to be conducted in the United States): each participant will receive the following treatments for 28 days in each of three treatment periods in an order determined by a random code: SCH 497079, or matching placebo, or metformin.
Part 2 (to be conducted in India): this part of the study will be conducted after completion of Part 1 and an analysis indicates a clinically significant decrease in blood glucose in participants with type 2 diabetes mellitus (T2DM) compared to placebo. The same procedures conducted in Part 1 will be conducted in Part 2.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 17
- >=18 years of age to 65 years of age, of either sex, and having a body mass index (BMI) between 27 and 35, inclusive (USA participants)
- Clinical laboratory tests (complete blood count, blood chemistry, and urinalysis) within normal limits (excluding glucose and other changes usually associated with diabetes eg, dyslipidemia)
- Type 2 diabetes mellitus
- Female participants who are premenopausal or are not surgically sterilized. Participants who are pregnant, intend to become pregnant (within 3 months of ending the study), or are breast-feeding.
- Participants who have received insulin therapy within 6 months, prior to Day 1/Period 1 or who require thiazide diuretics, beta-blockers and cyclic hormone therapy.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Treatment sequence 1: SCH 497079 → Placebo → Metformin SCH 497079 Participants received SCH 497079 daily for 4 weeks followed by placebo daily for 4 weeks followed by metformin daily for 4 weeks. Treatment sequence 1: SCH 497079 → Placebo → Metformin Placebo Participants received SCH 497079 daily for 4 weeks followed by placebo daily for 4 weeks followed by metformin daily for 4 weeks. Treatment sequence 1: SCH 497079 → Placebo → Metformin Metformin Participants received SCH 497079 daily for 4 weeks followed by placebo daily for 4 weeks followed by metformin daily for 4 weeks. Treatment sequence 2: Placebo → Metformin → SCH 497079 Placebo Participants received placebo daily for 4 weeks followed by metformin daily for 4 weeks followed by SCH 497079 daily for 4 weeks. Treatment sequence 2: Placebo → Metformin → SCH 497079 Metformin Participants received placebo daily for 4 weeks followed by metformin daily for 4 weeks followed by SCH 497079 daily for 4 weeks. Treatment sequence 3: Metformin → SCH 497079 → Placebo SCH 497079 Participants received metformin daily for 4 weeks followed by SCH 497079 daily for 4 weeks followed by placebo daily for 4 weeks. Treatment sequence 3: Metformin → SCH 497079 → Placebo Placebo Participants received metformin daily for 4 weeks followed by SCH 497079 daily for 4 weeks followed by placebo daily for 4 weeks. Treatment sequence 3: Metformin → SCH 497079 → Placebo Metformin Participants received metformin daily for 4 weeks followed by SCH 497079 daily for 4 weeks followed by placebo daily for 4 weeks. Treatment sequence 4: SCH 497079 → Metformin → Placebo Placebo Participants received SCH 497079 daily for 4 weeks followed by metformin daily for 4 weeks followed by placebo daily for 4 weeks. Treatment sequence 5: Placebo → SCH 49709 → Metformin SCH 497079 Participants received placebo daily for 4 weeks followed by SCH 497079 daily for 4 weeks followed by metformin daily for 4 weeks. Treatment sequence 5: Placebo → SCH 49709 → Metformin Placebo Participants received placebo daily for 4 weeks followed by SCH 497079 daily for 4 weeks followed by metformin daily for 4 weeks. Treatment sequence 6: Metformin → Placebo → SCH 497079 Placebo Participants received metformin daily for 4 weeks followed by placebo daily for 4 weeks followed by SCH 497079 daily for 4 weeks. Treatment sequence 6: Metformin → Placebo → SCH 497079 Metformin Participants received metformin daily for 4 weeks followed by placebo daily for 4 weeks followed by SCH 497079 daily for 4 weeks. Treatment sequence 2: Placebo → Metformin → SCH 497079 SCH 497079 Participants received placebo daily for 4 weeks followed by metformin daily for 4 weeks followed by SCH 497079 daily for 4 weeks. Treatment sequence 4: SCH 497079 → Metformin → Placebo SCH 497079 Participants received SCH 497079 daily for 4 weeks followed by metformin daily for 4 weeks followed by placebo daily for 4 weeks. Treatment sequence 6: Metformin → Placebo → SCH 497079 SCH 497079 Participants received metformin daily for 4 weeks followed by placebo daily for 4 weeks followed by SCH 497079 daily for 4 weeks. Treatment sequence 4: SCH 497079 → Metformin → Placebo Metformin Participants received SCH 497079 daily for 4 weeks followed by metformin daily for 4 weeks followed by placebo daily for 4 weeks. Treatment sequence 5: Placebo → SCH 49709 → Metformin Metformin Participants received placebo daily for 4 weeks followed by SCH 497079 daily for 4 weeks followed by metformin daily for 4 weeks.
- Primary Outcome Measures
Name Time Method Pharmacodynamic: Change From Baseline in Mean 24-hour Plasma Glucose (AUC/Duration) at Week 4 (Part 1 - United States) Pre-dose (-30 minutes), pre-standard breakfast (0 hour), 0.5, .75, 1, 2, 3, 4, 4.5, 4.75, 5, 6, 7, 8, 9, 9.5, 9.75, 10, 11, 12, 13, 14, 15, 16, and 24 hours after the beginning of the standardized breakfast on Day -1 and Day 28 Change from baseline in 24-hour plasma glucose on the last day of treatment. On the day of the glucose collections (and the day prior to), standardized meals breakfast, lunch, dinner, and snack) were provided and consumed over 15 minutes. AUC/duration is presented as mg/dL and was calculated by dividing AUC (mg/dL\*hr) by the duration in hours. Model-based least squares mean: ANOVA extracting the effects due to treatment, sequence, period and participant.
Pharmacodynamic: Change From Baseline in 24-hour Plasma Glucose (AUC/Duration) at Week 4 (Part 2 - India) Pre-dose (-30 mnutes), pre-standard breakfast (0 hour), 0.5, .75, 1, 2, 3, 4, 4.5, 4.75, 5, 6, 7, 8, 9, 9.5, 9.75, 10, 11, 12, 13, 14, 15, 16, and 24 hours after the beginning of the standardized breakfast on Day -1 and Day 28 Change from baseline in 24-hour plasma glucose on the last day of treatment. On the day of the glucose collections (and the day prior to), standardized meals (breakfast, lunch, dinner, and snack) were provided and consumed over 15 minutes. AUC/duration is presented as mg/dL and was calculated by dividing AUC (mg/dL\*hr) by the duration in hours. Model-based least squares mean: ANOVA extracting the effects due to treatment, sequence, period and participant.
- Secondary Outcome Measures
Name Time Method Pharmacodynamic: Change From Baseline in 12-hour Postprandial Plasma Glucose (AUC/Duration) at Week 4 (Part 2 - India) Pre-dose (-30 minutes), pre-standard breakfast (0 hour), 0.5, .75, 1, 2, 3, 4, 4.5, 4.75, 5, 6, 7, 8, 9, 9.5, 9.75, 10, 11, 12, 13, 14, 15, 16, and 24 hours after the beginning of the standardized breakfast on Day -1 and Day 28 The postprandial period is defined as the sum of 4 hours after breakfast, 4 hours after lunch and 4 hours after dinner for a total of 12 hours. AUC/duration is presented as mg/dL and was calculated by dividing AUC (mg/dL\*hr) by the duration in hours. Model-based least squares mean: ANOVA extracting the effects due to treatment, sequence, period and participant.
Pharmacodynamic: Change From Baseline in Plasma Glucose During the 12-hour Post Absorptive State (AUC/Duration) at Week 4 (Part 1 - United States) Baseline and Week 4 The post absorptive state is defined as the remaining part of day and night that is not the postprandial period. The postprandial period is defined as the sum of 4 hours after breakfast, 4 hours after lunch and 4 hours after dinner for a total of 12 hours. AUC/duration is presented as mg/dL and was calculated by dividing AUC (mg/dL\*hr) by the duration in hours. Model-based least squares mean: ANOVA extracting the effects due to treatment, sequence, period and participant.
Pharmacodynamic: Change From Baseline in Plasma Glucose During the 12-hour Post Absorptive State (AUC/Duration) at Week 4 (Part 2 - India) Baseline and Week 4 The post absorptive state is defined as the remaining part of day and night that is not the postprandial period. The postprandial period is defined as the sum of 4 hours after breakfast, 4 hours after lunch and 4 hours after dinner for a total of 12 hours. AUC/duration is presented as mg/dL and was calculated by dividing AUC (mg/dL\*hr) by the duration in hours. Model-based least squares mean: ANOVA extracting the effects due to treatment, sequence, period and participant.
Number of Participants Who Experienced at Least One Adverse Event (Part 1 - United States) Up to 14 days after last dose of study drug (up to 98 days) An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product, biologic (at any dose), or medical device, which does not necessarily have a causal relationship with the treatment. AEs may include the onset of new illness and the exacerbation of pre-existing conditions.
Number of Participants Who Experienced at Least One Adverse Event (Part 2 - India) Up to 14 days after last dose of study drug (up to 98 days) An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product, biologic (at any dose), or medical device, which does not necessarily have a causal relationship with the treatment. AEs may include the onset of new illness and the exacerbation of pre-existing conditions.
Pharmacodynamic: Change From Baseline in 12-hour Postprandial Plasma Glucose (AUC/Duration) at Week 4 (Part 1 - United States) Pre-dose (-30 minutes), pre-standard breakfast (0 hour), 0.5, .75, 1, 2, 3, 4, 4.5, 4.75, 5, 6, 7, 8, 9, 9.5, 9.75, 10, 11, 12, 13, 14, 15, 16, and 24 hours after the beginning of the standardized breakfast on Day -1 and Day 28 The postprandial period is defined as the sum of 4 hours after breakfast, 4 hours after lunch and 4 hours after dinner for a total of 12 hours. AUC/duration is presented as mg/dL and was calculated by dividing AUC (mg/dL\*hr) by the duration in hours. Model-based least squares mean: ANOVA extracting the effects due to treatment, sequence, period and participant.
Pharmacokinetic: Mean Plasma Glucose (Over 24 Hours) at Week 4 (Part 1 - United States) Pre-dose (0 hour), 0.5, 1, 2, 6, 12, and 24 hours after administration of study drug Blood samples for SCH 497079 pharmacokinetics will be collected at pre-dose/0-hour on Day 1 (Period 1 only) and pre-dose Day 14 and pre-dose/0-hour and at 0.5, 1, 2, 6, 12, and 24 hours post study drug administration (not breakfast) on Day 28 of the placebo and SCH 497079 periods only. In addition to these time points, a sample for metformin level will also be collected pre-dose on Day 1, Day 14, and Day 28 of the metformin administration period only.
Pharmacokinetic: Mean Plasma Glucose (Over 24 Hours) at Week 4 (Part 2 - India) Pre-dose (0 hour), 0.5, 1, 2, 6, 12, and 24 hours after administration of study drug Blood samples for SCH 497079 pharmacokinetics will be collected at pre-dose/0-hour on Day 1 (Period 1 only) and pre-dose Day 14 and pre-dose/0-hour and at 0.5, 1, 2, 6, 12, and 24 hours post study drug administration (not breakfast) on Day 28 of the placebo and SCH 497079 periods only. In addition to these time points, a sample for metformin level will also be collected pre-dose on Day 1, Day 14, and Day 28 of the metformin administration period only.
Pharmacokinetic: Mean Maximum Observed Plasma Concentration (Cmax) (Part 1 - United States) Pre-dose (0 hour), 0.5, 1, 2, 6, 12, and 24 hours after administration of study drug Blood samples for SCH 497079 pharmacokinetics will be collected at pre-dose/0-hour on Day 1 (Period 1 only) and pre-dose Day 14 and pre-dose/0-hour and at 0.5, 1, 2, 6, 12, and 24 hours post study drug administration (not breakfast) on Day 28 of the placebo and SCH 497079 periods only. In addition to these time points, a sample for metformin level will also be collected pre-dose on Day 1, Day 14, and Day 28 of the metformin administration period only.
Pharmacokinetic: Mean Plasma Cmax (Part 2 - India) Pre-dose (0 hour), 0.5, 1, 2, 6, 12, and 24 hours after administration of study drug Blood samples for SCH 497079 pharmacokinetics will be collected at pre-dose/0-hour on Day 1 (Period 1 only) and pre-dose Day 14 and pre-dose/0-hour and at 0.5, 1, 2, 6, 12, and 24 hours post study drug administration (not breakfast) on Day 28 of the placebo and SCH 497079 periods only. In addition to these time points, a sample for metformin level will also be collected pre-dose on Day 1, Day 14, and Day 28 of the metformin administration period only.
Pharmacokinetic: Mean Time to Maximum Observed Plasma Concentration (Tmax) (Part 1 - United States) Pre-dose (0 hour), 0.5, 1, 2, 6, 12, and 24 hours after administration of study drug Blood samples for SCH 497079 pharmacokinetics will be collected at pre-dose/0-hour on Day 1 (Period 1 only) and pre-dose Day 14 and pre-dose/0-hour and at 0.5, 1, 2, 6, 12, and 24 hours post study drug administration (not breakfast) on Day 28 of the placebo and SCH 497079 periods only. In addition to these time points, a sample for metformin level will also be collected pre-dose on Day 1, Day 14, and Day 28 of the metformin administration period only.
Pharmacokinetic: Mean Plasma Tmax (Part 2 - India) Pre-dose (0 hour), 0.5, 1, 2, 6, 12, and 24 hours after administration of study drug Blood samples for SCH 497079 pharmacokinetics will be collected at pre-dose/0-hour on Day 1 (Period 1 only) and pre-dose Day 14 and pre-dose/0-hour and at 0.5, 1, 2, 6, 12, and 24 hours post study drug administration (not breakfast) on Day 28 of the placebo and SCH 497079 periods only. In addition to these time points, a sample for metformin level will also be collected pre-dose on Day 1, Day 14, and Day 28 of the metformin administration period only.