Effect of SCH 497079 on Metabolic Parameters and Influence of Race/Ethnic Origin on Therapeutic Response (Study P05338)(COMPLETED)

Type 2 Diabetes Mellitus Clinical Trial

Official title:

A Randomized, Placebo-controlled, Three-Way Crossover Study to Evaluate the Effect of SCH 497079 on Metabolic Parameters and to Determine the Influence of Race/Ethnic Origin on Therapeutic Response

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00673465
• Other study ID #: P05338
• Secondary ID: MK-7079-007
• Status: Completed
• Phase: Phase 1
• Start date: April 17, 2008
• Est. completion date: December 11, 2008

Study information

• Verified date: August 2018
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: December 11, 2008
• Est. primary completion date: December 11, 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• >=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

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• SCH 497079
SCH 497079 100 mg capsule, administered orally, once daily for 4 weeks
• Placebo
Placebo capsules matching SCH 497079, administered orally, once daily for 4 weeks
• Metformin
Metformin extended release 750 mg, 2 tablets administered orally, once daily for 4 weeks (1500 mg total daily dose)

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacodynamic: Change From Baseline in Mean 24-hour Plasma Glucose (AUC/Duration) at Week 4 (Part 1 - United States)	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.	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
Primary	Pharmacodynamic: Change From Baseline in 24-hour Plasma Glucose (AUC/Duration) at Week 4 (Part 2 - India)	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.	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
Secondary	Number of Participants Who Experienced at Least One Adverse Event (Part 1 - United States)	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.	Up to 14 days after last dose of study drug (up to 98 days)
Secondary	Number of Participants Who Experienced at Least One Adverse Event (Part 2 - India)	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.	Up to 14 days after last dose of study drug (up to 98 days)
Secondary	Pharmacodynamic: Change From Baseline in 12-hour Postprandial Plasma Glucose (AUC/Duration) at Week 4 (Part 1 - United States)	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.	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
Secondary	Pharmacodynamic: Change From Baseline in 12-hour Postprandial Plasma Glucose (AUC/Duration) at Week 4 (Part 2 - India)	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.	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
Secondary	Pharmacodynamic: Change From Baseline in Plasma Glucose During the 12-hour Post Absorptive State (AUC/Duration) at Week 4 (Part 1 - United States)	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.	Baseline and Week 4
Secondary	Pharmacodynamic: Change From Baseline in Plasma Glucose During the 12-hour Post Absorptive State (AUC/Duration) at Week 4 (Part 2 - India)	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.	Baseline and Week 4
Secondary	Pharmacokinetic: Mean Plasma Glucose (Over 24 Hours) at Week 4 (Part 1 - United States)	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.	Pre-dose (0 hour), 0.5, 1, 2, 6, 12, and 24 hours after administration of study drug
Secondary	Pharmacokinetic: Mean Plasma Glucose (Over 24 Hours) at Week 4 (Part 2 - India)	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.	Pre-dose (0 hour), 0.5, 1, 2, 6, 12, and 24 hours after administration of study drug
Secondary	Pharmacokinetic: Mean Maximum Observed Plasma Concentration (Cmax) (Part 1 - United States)	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.	Pre-dose (0 hour), 0.5, 1, 2, 6, 12, and 24 hours after administration of study drug
Secondary	Pharmacokinetic: Mean Plasma Cmax (Part 2 - India)	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.	Pre-dose (0 hour), 0.5, 1, 2, 6, 12, and 24 hours after administration of study drug
Secondary	Pharmacokinetic: Mean Time to Maximum Observed Plasma Concentration (Tmax) (Part 1 - United States)	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.	Pre-dose (0 hour), 0.5, 1, 2, 6, 12, and 24 hours after administration of study drug
Secondary	Pharmacokinetic: Mean Plasma Tmax (Part 2 - India)	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.	Pre-dose (0 hour), 0.5, 1, 2, 6, 12, and 24 hours after administration of study drug