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)

Tracking Information
First Submitted Date ICMJE	March 18, 2013
First Posted Date ICMJE	March 20, 2013
Results First Submitted Date	June 7, 2016
Results First Posted Date	July 18, 2016
Last Update Posted Date	November 20, 2017
Actual Study Start Date ICMJE	May 3, 2013
Actual Primary Completion Date	September 14, 2015 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: June 7, 2016)	Change From Baseline in A1C at Week 24 [ Time Frame: 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) [ Time Frame: 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).; Percentage of Participants Who Discontinued Study Drug Due to an AE [ Time Frame: 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).
Original Primary Outcome Measures ICMJE; (submitted: March 18, 2013)	Change From Baseline in A1C at Week 24 [ Time Frame: Baseline and Week 24 ]; Percentage of Participants Who Experienced at Least One Adverse Event [ Time Frame: Up to Week 27 ]; Percentage of Participants Who Discontinued from the Study Due to an Adverse Event [ Time Frame: Up to Week 24 ]
Change History	Complete list of historical versions of study NCT01814748 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: July 25, 2016)	Change From Baseline in 2-hr PMG at Week 24 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.; Percentage of Participants Attaining A1C Glycemic Goals of <6.5% (48 mmol/Mol) at Week 24 [ Time Frame: 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 [ Time Frame: 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).
Original Secondary Outcome Measures ICMJE; (submitted: March 18, 2013)	Change from Baseline in 2-hour Post-Meal Glucose (PMG) at Week 24 [ Time Frame: Baseline and Week 24 ]; Change in Baseline in Fasting Plasma Glucose (FPG) at Week 24 [ Time Frame: Baseline and Week 24 ]; Number of Participants Attaining A1C Glycemic Goals of <7.0% and <6.5% at Week 24 [ Time Frame: Week 24 ]; Time to Participant Rescue with Open-label Metformin for Participants Exceeding Pre-specified Glycemic Thresholds [ Time Frame: Up to Week 24 ]
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	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)
Official Title ICMJE	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
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 Provided
Study Type ICMJE	Interventional
Study Phase	Phase 3
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
Condition ICMJE	Diabetes Mellitus
Intervention ICMJE	Drug: Omarigliptin Omarigliptin 25 mg capsule administered orally once weekly Other Name: MK-3102; 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®
Study Arms	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. Interventions: Drug: Omarigliptin Drug: Metformin; 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. Interventions: Drug: Placebo to omarigliptin Drug: Metformin
Publications *	Gantz I, Sokolova L, Jain L, Iredale C, O'Neill EA, Wei Z, Lam R, Suryawanshi S, Kaufman KD, Engel SS, Lai E. Use of Prohibited Medication, a Potentially Overlooked Confounder in Clinical Trials: Omarigliptin (Once-weekly DPP-4 Inhibitor) Monotherapy Trial in 18- to 45-year-olds. Clin Ther. 2017 Oct;39(10):2024-2037. doi: 10.1016/j.clinthera.2017.08.009. Epub 2017 Sep 18.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: September 24, 2015)	203
Original Estimated Enrollment ICMJE; (submitted: March 18, 2013)	200
Actual Study Completion Date	September 14, 2015
Actual Primary Completion Date	September 14, 2015 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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: Male Female who is not of reproductive potential 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: Acute coronary syndrome Coronary artery intervention 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
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years to 44 Years (Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Not Provided
Removed Location Countries	Mexico, Romania, Russian Federation, Serbia, South Africa, Ukraine, United States
Administrative Information
NCT Number ICMJE	NCT01814748
Other Study ID Numbers ICMJE	3102-028; 2012-004303-12 ( EudraCT Number )
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Merck Sharp & Dohme Corp.
Study Sponsor ICMJE	Merck Sharp & Dohme Corp.
Collaborators ICMJE	Not Provided
Investigators ICMJE	Study Director: Medical Director Merck Sharp & Dohme Corp.
PRS Account	Merck Sharp & Dohme Corp.
Verification Date	October 2017
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP