A Study of the Safety and Efficacy of Omarigliptin (MK-3102) in ≥18 and <45 Year-Old Participants With Type 2 Diabetes Mellitus and Inadequate Glycemic Control (MK-3102-028)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01814748
First received: March 18, 2013
Last updated: June 7, 2016
Last verified: June 2016
  Purpose
This study will examine the safety and efficacy of once-weekly omarigliptin in participants 18 to <45 years of age with Type 2 diabetes mellitus and inadequate glycemic control. The study hypothesis is that treatment with omarigliptin compared with placebo provides greater reduction in hemoglobin A1c (A1C) in participants after 24 weeks.

Condition Intervention Phase
Diabetes Mellitus
Drug: Omarigliptin
Drug: Placebo to omarigliptin
Drug: Metformin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Safety and Efficacy of MK-3102 in ≥18 and <45 Year-Old Subjects With Type 2 Diabetes Mellitus and Inadequate Glycemic Control

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Change From Baseline in A1C at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]

    A1C (%) is used to report average blood glucose levels over prolonged periods of time.

    The unexpected absence of a treatment effect in this study led to investigations that included measurement of metformin levels in available samples collected for future research during the study. Of the 92 participants with samples who had not been rescued with metformin, 57% (25/44) in the placebo group and 29% (14/48) in the omarigliptin group had detectable metformin, indicating the use of metformin that was prohibited by the protocol. The use of metformin prohibited by the protocol was without investigator knowledge and is a confounding factor impacting the ability to draw any conclusions regarding the efficacy results from this study.


  • Percentage of Participants Who Experienced at Least One Adverse Event (AE) [ Time Frame: Up to Week 27 ] [ Designated as safety issue: Yes ]

    An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. Data presented exclude data following the initiation of glycemic rescue.

    The safety database was analyzed in a standard fashion in the all participants as treated (APaT) population for all participants who took at least one dose of study medication. This analysis may have been confounded by the use of metformin prohibited by the protocol (see efficacy results description above).


  • Percentage of Participants Who Discontinued Study Drug Due to an AE [ Time Frame: Up to Week 24 ] [ Designated as safety issue: Yes ]

    An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. Data presented exclude data following the initiation of glycemic rescue.

    The safety database was analyzed in a standard fashion in the APaT population for all participants who took at least one dose of study medication. This analysis may have been confounded by the use of metformin prohibited by the protocol (see efficacy results description above).



Secondary Outcome Measures:
  • Change From Baseline in 2-hr PMG at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]

    Blood glucose was measured 120 minutes from start of meal.

    The unexpected absence of a treatment effect in this study led to investigations that included measurement of metformin levels in available samples collected for future research during the study. Of the 92 participants with samples who had not been rescued with metformin, 57% (25/44) in the placebo group and 29% (14/48) in the omarigliptin group had detectable metformin, indicating the use of metformin that was prohibited by the protocol. The use of metformin prohibited by the protocol was without investigator knowledge and is a confounding factor impacting the ability to draw any conclusions regarding the efficacy results from this study.


  • Change in Baseline in FPG at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]

    Blood glucose was measured on a fasting basis.

    The unexpected absence of a treatment effect in this study led to investigations that included measurement of metformin levels in available samples collected for future research during the study. Of the 92 participants with samples who had not been rescued with metformin, 57% (25/44) in the placebo group and 29% (14/48) in the omarigliptin group had detectable metformin, indicating the use of metformin that was prohibited by the protocol. The use of metformin prohibited by the protocol was without investigator knowledge and is a confounding factor impacting the ability to draw any conclusions regarding the efficacy results from this study.


  • Percentage of Participants Attaining A1C Glycemic Goals of <7.0% at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]

    The percentage of participants who achieved A1C values <7% (53 mmol/mol) in the full analysis set population at Week 24.

    The unexpected absence of a treatment effect in this study led to investigations that included measurement of metformin levels in available samples collected for future research during the study. Of the 92 participants with samples who had not been rescued with metformin, 57% (25/44) in the placebo group and 29% (14/48) in the omarigliptin group had detectable metformin, indicating the use of metformin that was prohibited by the protocol. The use of metformin prohibited by the protocol was without investigator knowledge and is a confounding factor impacting the ability to draw any conclusions regarding the efficacy results from this study.


  • Percentage of Participants Attaining A1C Glycemic Goals of <6.5% at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]

    The percentage of participants who achieved A1C values <6.5% (48 mmol/mol) in the full analysis set population at Week 24.

    The unexpected absence of a treatment effect in this study led to investigations that included measurement of metformin levels in available samples collected for future research during the study. Of the 92 participants with samples who had not been rescued with metformin, 57% (25/44) in the placebo group and 29% (14/48) in the omarigliptin group had detectable metformin, indicating the use of metformin that was prohibited by the protocol. The use of metformin prohibited by the protocol was without investigator knowledge and is a confounding factor impacting the ability to draw any conclusions regarding the efficacy results from this study.


  • Percentage of Participants Who Required Glycemic Rescue by Week 24 [ Time Frame: Up to Week 24 ] [ Designated as safety issue: No ]

    Participants exceeding pre-specified glycemic thresholds after starting the double-blind treatment period may have received rescue therapy (per protocol) with open-label metformin initiated by the investigator.

    This analysis may have been confounded by the use of metformin prohibited by the protocol (see efficacy results description above).



Enrollment: 203
Study Start Date: May 2013
Study Completion Date: September 2015
Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Omarigliptin 25 mg
Omarigliptin 25 mg, once weekly, for 24 weeks. Open-label metformin daily was to be initiated for participants meeting protocol-specified glycemic criteria, but was otherwise prohibited.
Drug: Omarigliptin
Omarigliptin 25 mg capsule administered orally once weekly
Other Name: MK-3102
Drug: Metformin
Open-label metformin (dosed daily according to the country-specific product label) was to be initiated for participants meeting protocol-specified glycemic criteria, but was otherwise prohibited.
Other Names:
  • Fortamet®
  • Glucophage®
  • Glucophage® XR
  • Glumetza®
  • Riomet®
  • Metgluco®
  • Glycoran®
Placebo Comparator: Placebo
Placebo to omarigliptin, once weekly, for 24 weeks. Open-label metformin daily was to be initiated for participants meeting protocol-specified glycemic criteria, but was otherwise prohibited.
Drug: Placebo to omarigliptin
Matching placebo to omarigliptin 25 mg capsule administered orally once weekly
Drug: Metformin
Open-label metformin (dosed daily according to the country-specific product label) was to be initiated for participants meeting protocol-specified glycemic criteria, but was otherwise prohibited.
Other Names:
  • Fortamet®
  • Glucophage®
  • Glucophage® XR
  • Glumetza®
  • Riomet®
  • Metgluco®
  • Glycoran®

  Eligibility

Ages Eligible for Study:   18 Years to 44 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Has type 2 diabetes mellitus
  • Currently not on an antihyperglycemic agent (AHA) for at least the past 12 weeks and has not been treated with omarigliptin at any time prior to study participation
  • Participant is one of the following:

    1. Male
    2. Female who is not of reproductive potential
    3. Female of reproductive potential who agrees to remain abstinent from heterosexual activity or use (or have her partner use) 2 acceptable methods of contraception to prevent pregnancy during the study and for 21 days after the last dose of study drug

Exclusion Criteria:

  • History of type 1 diabetes mellitus or a history of ketoacidosis
  • History of hypersensitivity to dipeptidyl-peptidase-4 (DPP-4) inhibitor
  • Currently participating in or has participated in a clinical trial in the past 12 weeks
  • Is on a weight loss program and not in the maintenance phase; has been on a weight loss medication in the past 6 months; or has undergone bariatric surgery within 12 months prior to study participation
  • Has undergone a surgical procedure within 4 weeks of study participation or has planned major surgery during the study
  • Is on or likely to require treatment for ≥14 consecutive days or repeated courses of pharmacologic doses of corticosteroids
  • Is currently being treated for hyperthyroidism or is on thyroid replacement therapy and has not been on a stable dose for at least 6 weeks
  • Is expecting to undergo hormonal therapy in preparation to donate eggs during the study, including 21 days following the last dose of study drug
  • History of active liver disease (other than non-alcoholic hepatic steatosis) including chronic active hepatitis B or C, primary biliary cirrhosis, or symptomatic gallbladder disease
  • Has human immunodeficiency virus (HIV)
  • Has had new or worsening coronary heart disease or congestive heart failure within the past 3 months, or has any of the following disorders within the past 3 months:

    1. Acute coronary syndrome
    2. Coronary artery intervention
    3. Stroke or transient ischemic neurological disorder
  • Has poorly controlled hypertension
  • History of malignancy ≤5 years prior to study participation, except for basal cell or squamous cell skin cancer or in situ cervical cancer
  • Has a hematological disorder (such as aplastic anemia, myeloproliferative or myelodysplastic syndromes, thrombocytopenia)
  • Has a positive urine pregnancy test
  • Pregnant or breastfeeding, or is expecting to conceive during the study, including 21 days following the last dose of study drug
  • User of recreational or illicit drugs or has had a recent history of drug abuse. Routinely consumes >2 alcoholic drinks per day or >14 alcoholic drinks per week, or engages in binge drinking.
  • Has donated blood products or has had a phlebotomy (>300 mL) within 8 weeks of study participation, or intends to donate blood products during the study or has received, or is anticipated to receive, blood products within 12 weeks of study participation or during the study
  • Has a clinically significant electrocardiogram abnormality
  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: NCT01814748

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: NCT01814748     History of Changes
Other Study ID Numbers: 3102-028  2012-004303-12 
Study First Received: March 18, 2013
Results First Received: June 7, 2016
Last Updated: June 7, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Merck Sharp & Dohme Corp.:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Metformin
Hypoglycemic Agents
Pharmacologic Actions
Therapeutic Uses

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 July 28, 2016