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)

Phase 3

Completed

• Conditions: Diabetes Mellitus
• Interventions: Drug: Omarigliptin; Drug: Placebo to omarigliptin; Drug: Metformin

• Registration Number: NCT01814748
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-03-18
• Study First Submitted QC: 2013-03-18
• Study First Posted: 2013-03-20
• Study Start: 2013-05-03
• Primary Completion: 2015-09-14
• Study Completion: 2015-09-14
• Results First Submitted: 2016-06-07
• Results First Submitted QC: 2016-06-07
• Results First Posted: 2016-07-18
• Status Verified: 2018-08
• Last Update Submitted: 2018-08-09
• Last Update Posted: 2018-09-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 203

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Omarigliptin 25 mg	Metformin	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.
Omarigliptin 25 mg	Omarigliptin	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.
Placebo	Placebo to omarigliptin	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.
Placebo	Metformin	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.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Who Discontinued Study Drug Due to an AE	Up to Week 24	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).
Change From Baseline in A1C at Week 24	Baseline and Week 24	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)	Up to Week 27	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).

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Attaining A1C Glycemic Goals of <6.5% (48 mmol/Mol) at Week 24	Week 24	Percentage of participants was estimated using standard multiple imputation techniques (cLDA). Within-group CIs were calculated via the Wilson score method.; 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	Up to Week 24	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).
Change From Baseline in 2-hr PMG at Week 24	Baseline and Week 24	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	Baseline and Week 24	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	Week 24	Percentage of participants was estimated using standard multiple imputation techniques (constrained longitudinal data analysis \[cLDA\] model). Within-group confidence intervals (CIs) were calculated via the Wilson score method.; 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.