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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00673465
First received: May 5, 2008
Last updated: March 21, 2017
Last verified: March 2017
  Purpose
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.

Condition Intervention Phase
Type 2 Diabetes Mellitus Drug: SCH 497079 Drug: Placebo Drug: Metformin Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Participant, Investigator
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Pharmacodynamic: Change From Baseline in Mean 24-hour Plasma Glucose (AUC/Duration) at Week 4 (Part 1 - United States) [ Time Frame: 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) [ Time Frame: 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:
  • Number of Participants Who Experienced at Least One Adverse Event (Part 1 - United States) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 12-hour Postprandial Plasma Glucose (AUC/Duration) at Week 4 (Part 2 - India) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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.

  • Pharmacokinetic: Mean Plasma Glucose (Over 24 Hours) at Week 4 (Part 1 - United States) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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.


Enrollment: 17
Study Start Date: April 2008
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment sequence 1: SCH 497079 → Placebo → Metformin
Participants received SCH 497079 daily for 4 weeks followed by placebo daily for 4 weeks followed by metformin daily for 4 weeks.
Drug: SCH 497079
SCH 497079 100 mg capsule, administered orally, once daily for 4 weeks
Drug: Placebo
Placebo capsules matching SCH 497079, administered orally, once daily for 4 weeks
Drug: Metformin
Metformin extended release 750 mg, 2 tablets administered orally, once daily for 4 weeks (1500 mg total daily dose)
Experimental: Treatment sequence 2: Placebo → Metformin → SCH 497079
Participants received placebo daily for 4 weeks followed by metformin daily for 4 weeks followed by SCH 497079 daily for 4 weeks.
Drug: SCH 497079
SCH 497079 100 mg capsule, administered orally, once daily for 4 weeks
Drug: Placebo
Placebo capsules matching SCH 497079, administered orally, once daily for 4 weeks
Drug: Metformin
Metformin extended release 750 mg, 2 tablets administered orally, once daily for 4 weeks (1500 mg total daily dose)
Experimental: Treatment sequence 3: Metformin → SCH 497079 → Placebo
Participants received metformin daily for 4 weeks followed by SCH 497079 daily for 4 weeks followed by placebo daily for 4 weeks.
Drug: SCH 497079
SCH 497079 100 mg capsule, administered orally, once daily for 4 weeks
Drug: Placebo
Placebo capsules matching SCH 497079, administered orally, once daily for 4 weeks
Drug: Metformin
Metformin extended release 750 mg, 2 tablets administered orally, once daily for 4 weeks (1500 mg total daily dose)
Experimental: Treatment sequence 4: SCH 497079 → Metformin → Placebo
Participants received SCH 497079 daily for 4 weeks followed by metformin daily for 4 weeks followed by placebo daily for 4 weeks.
Drug: SCH 497079
SCH 497079 100 mg capsule, administered orally, once daily for 4 weeks
Drug: Placebo
Placebo capsules matching SCH 497079, administered orally, once daily for 4 weeks
Drug: Metformin
Metformin extended release 750 mg, 2 tablets administered orally, once daily for 4 weeks (1500 mg total daily dose)
Experimental: Treatment sequence 5: Placebo → SCH 49709 → Metformin
Participants received placebo daily for 4 weeks followed by SCH 497079 daily for 4 weeks followed by metformin daily for 4 weeks.
Drug: SCH 497079
SCH 497079 100 mg capsule, administered orally, once daily for 4 weeks
Drug: Placebo
Placebo capsules matching SCH 497079, administered orally, once daily for 4 weeks
Drug: Metformin
Metformin extended release 750 mg, 2 tablets administered orally, once daily for 4 weeks (1500 mg total daily dose)
Experimental: Treatment sequence 6: Metformin → Placebo → SCH 497079
Participants received metformin daily for 4 weeks followed by placebo daily for 4 weeks followed by SCH 497079 daily for 4 weeks.
Drug: SCH 497079
SCH 497079 100 mg capsule, administered orally, once daily for 4 weeks
Drug: Placebo
Placebo capsules matching SCH 497079, administered orally, once daily for 4 weeks
Drug: Metformin
Metformin extended release 750 mg, 2 tablets administered orally, once daily for 4 weeks (1500 mg total daily dose)

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00673465

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00673465     History of Changes
Other Study ID Numbers: P05338
MK-7079-007 ( Other Identifier: Merck protocol number )
Study First Received: May 5, 2008
Results First Received: October 13, 2016
Last Updated: March 21, 2017

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on June 26, 2017