Back to resultsA 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)
Primary Purpose
Diabetes Mellitus
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Omarigliptin
Placebo to omarigliptin
Metformin
Sponsored by
About this trial
This is an interventional treatment trial for Diabetes Mellitus focused on measuring Diabetes Mellitus, Diabetes Mellitus, Type 2, Glucose Metabolism Disorders, Metabolic Diseases, Endocrine System Diseases, Metformin, Hypoglycemic Agents, Pharmacologic Actions, Therapeutic Uses
Eligibility 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:
- 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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Omarigliptin 25 mg
Placebo
Arm Description
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 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.
Outcomes
Primary Outcome Measures
Change From Baseline in A1C at 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)
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
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
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
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
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
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
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).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01814748
Brief Title
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
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2018
Overall Recruitment Status
Completed
Study Start Date
May 3, 2013 (Actual)
Primary Completion Date
September 14, 2015 (Actual)
Study Completion Date
September 14, 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus
Keywords
Diabetes Mellitus, Diabetes Mellitus, Type 2, Glucose Metabolism Disorders, Metabolic Diseases, Endocrine System Diseases, Metformin, Hypoglycemic Agents, Pharmacologic Actions, Therapeutic Uses
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
203 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Omarigliptin 25 mg
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Omarigliptin
Other Intervention Name(s)
MK-3102
Intervention Description
Omarigliptin 25 mg capsule administered orally once weekly
Intervention Type
Drug
Intervention Name(s)
Placebo to omarigliptin
Intervention Description
Matching placebo to omarigliptin 25 mg capsule administered orally once weekly
Intervention Type
Drug
Intervention Name(s)
Metformin
Other Intervention Name(s)
Fortamet®, Glucophage®, Glucophage® XR, Glumetza®, Riomet®, Metgluco®, Glycoran®
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change From Baseline in A1C at Week 24
Description
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.
Time Frame
Baseline and Week 24
Title
Percentage of Participants Who Experienced at Least One Adverse Event (AE)
Description
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).
Time Frame
Up to Week 27
Title
Percentage of Participants Who Discontinued Study Drug Due to an AE
Description
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).
Time Frame
Up to Week 24
Secondary Outcome Measure Information:
Title
Change From Baseline in 2-hr PMG at Week 24
Description
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.
Time Frame
Baseline and Week 24
Title
Change in Baseline in FPG at Week 24
Description
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.
Time Frame
Baseline and Week 24
Title
Percentage of Participants Attaining A1C Glycemic Goals of <7.0% at Week 24
Description
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.
Time Frame
Week 24
Title
Percentage of Participants Attaining A1C Glycemic Goals of <6.5% (48 mmol/Mol) at Week 24
Description
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.
Time Frame
Week 24
Title
Percentage of Participants Who Required Glycemic Rescue by Week 24
Description
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).
Time Frame
Up to Week 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
44 Years
Accepts Healthy Volunteers
No
Eligibility 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:
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Citations:
PubMed Identifier
28923291
Citation
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.
Results Reference
derived
Learn more about this trial
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)
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