The purpose of this study is to evaluate the efficacy and safety of omarigliptin in participants with type 2 diabetes mellitus and moderate or severe chronic renal insufficiency or end stage renal disease on dialysis with inadequate glycemic control. The primary hypothesis of the study is that omarigliptin compared to placebo produces greater reduction in glycosylated hemoglobin (A1C) after 24 weeks.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
213
Participants with moderate renal insufficiency will receive one omarigliptin 25 mg capsule orally once a week; participants with severe renal insufficiency or end stage renal disease will receive one omarigliptin 12.5 mg capsule orally once a week
Matching placebo to omarigliptin capsule administered orally once a week
Phase A: Participants may receive open-label glipizide as rescue therapy up to Week 24 of the study. Phase B: Participants who received placebo to omarigliptin during Phase A and are not on background insulin therapy or who did not receive open-label glipizide or insulin as rescue therapy during Phase A of the study Week 1 through Week 24) will receive glipizide capsule(s) 2.5 daily up to a maximum of 20 mg daily (based on glycemic control) in a blinded manner during Phase B of the study (Week 24 through Week 54).
Change From Baseline in Glycosylated Hemoglobin (A1C) at Week 24
A1C is measured as a percent. Change from baseline in A1C at Week 24 was analyzed using constrained longitudinal data analysis (cLDA) method with a restriction of the same baseline mean across treatment groups. The cLDA model included terms for treatment, renal insufficiency stratum, baseline treatment with insulin stratum, time, the interaction of time by treatment, the interaction of time by renal insufficiency stratum, and the interaction of time by baseline treatment with insulin stratum.
Time frame: Baseline and Week 24
Percentage of Participants Who Experienced at Least One Adverse Event (Phase A: 24-week Placebo Controlled Period)
An adverse event is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. Presented data exclude data after glycemic rescue.
Time frame: Up to 28 weeks (including 28 days following the last dose of study therapy for participants who discontinued study drug)
Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (Phase A: 24-week Placebo Controlled Period)
An adverse event is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. Presented data exclude data after glycemic rescue.
Time frame: Up to 24 weeks
Percentage of Participants Who Experienced at Least One Adverse Event (Phase A: 24-week Placebo Controlled Period + Phase B: 30-week Active Controlled Period)
An adverse event is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. Presented data exclude data after glycemic rescue.
Time frame: Up to 58 weeks (including 28 days following the last dose of study therapy)
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Matching placebo to glipizide daily
Participants on insulin therapy at screening will continue insulin therapy during the study. Insulin glargine therapy may be administered as rescue therapy as determined by the investigator.
Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (Phase A: 24-week Placebo Controlled Period + Phase B: 30-week Active Controlled Period)
An adverse event is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. Presented data exclude data after glycemic rescue.
Time frame: Up to 54 weeks
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24
Change from baseline in FPG at Week 24 was analyzed using cLDA method with a restriction of the same baseline mean across treatment groups. The cLDA model included terms for treatment, renal insufficiency stratum, baseline treatment with insulin stratum, time, the interaction of time by treatment, the interaction of time by renal insufficiency stratum, and the interaction of time by baseline treatment with insulin stratum.
Time frame: Baseline and Week 24
Change From Baseline in A1C at Week 54
A1C is measured as a percent. Change from baseline in A1C at Week 54 was analyzed using cLDA method with a restriction of the same baseline mean across treatment groups. The cLDA model included terms for treatment, renal insufficiency stratum, baseline treatment with insulin stratum, time, the interaction of time by treatment, the interaction of time by renal insufficiency stratum, and the interaction of time by baseline treatment with insulin stratum.
Time frame: Baseline and Week 54
Change From Baseline in FPG at Week 54
Change from baseline in FPG at Week 54 was analyzed using cLDA method with a restriction of the same baseline mean across treatment groups. The cLDA model included terms for treatment, renal insufficiency stratum, baseline treatment with insulin stratum, time, the interaction of time by treatment, the interaction of time by renal insufficiency stratum, and the interaction of time by baseline treatment with insulin stratum.
Time frame: Baseline and Week 54
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 24
Based on an cLDA model including terms for treatment, renal status stratum, treatment on insulin at screening stratum, time, the interaction of time by treatment, the interaction of time by renal status stratum, and the interaction of time by treatment on insulin at screening stratum, with the constraint that the mean baseline is the same for all treatment groups. Excluding data after glycemic rescue or initiation of dialysis as well as participants classified with end stage renal disease (ESRD) on dialysis.
Time frame: Baseline and Week 24
Change From Baseline in eGFR at Week 54
Based on an cLDA model including terms for treatment, renal status stratum, treatment on insulin at screening stratum, time, the interaction of time by treatment, the interaction of time by renal status stratum, and the interaction of time by treatment on insulin at screening stratum, with the constraint that the mean baseline is the same for all treatment groups. Excluding data after glycemic rescue or initiation of dialysis as well as participants classified with ESRD on dialysis.
Time frame: Baseline and Week 54