Double-blind Sitagliptin Add-on Study in Japanese Participants With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Ipragliflozin (MK-0431J-842)

A Phase III, Multicenter, Randomized, Placebo-Controlled, Parallel-Group, Double-Blind Trial to Assess the Safety and Efficacy of Addition of Sitagliptin in Japanese Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Ipragliflozin Monotherapy in Addition to Diet and Exercise Therapy

This is a study to assess the safety and efficacy of the addition of sitagliptin in Japanese participants with Type 2 diabetes mellitus (T2DM) who have inadequate glycemic control on ipragliflozin, diet, and exercise therapy. The primary hypothesis of the study is that the addition of sitagliptin once daily compared with placebo provides greater reduction in hemoglobin A1C (HbA1c) as assessed by change from baseline (Week 0) to Week 24.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Sitagliptin; Drug: Ipragliflozin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 141
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Type 2 diabetes mellitus
• Inadequate glycemic control on diet/exercise therapy and ipragliflozin monotherapy
• HbA1c ≥7.0% and ≤10.0% before study start

Exclusion Criteria:

• History of type 1 diabetes mellitus or a history of ketoacidosis
• History of any of the following medications: thiazolidinediones (TZD) and/or insulin within 12 weeks prior to study participation, sitagliptin within 8 weeks prior to study participation.
• Currently has a urinary tract infection or genital infection with subjective symptom

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sitagliptin + Ipragliflozin; Sitagliptin, oral, once daily for 24 weeks plus ipragliflozin (base therapy), in addition to diet and exercise.	Drug: Sitagliptin; 50 mg tablet administered orally; Other Names: Januvia®, Tesavel®, Xelevia®, Ristaben®, Glactiv®; Drug: Ipragliflozin; 50 mg tablet administered orally as background medication
Active Comparator: Placebo + Ipragliflozin; Placebo to sitagliptin, oral, once daily for 24 weeks plus ipragliflozin (base therapy), in addition to diet and exercise.	Drug: Ipragliflozin; 50 mg tablet administered orally as background medication; Drug: Placebo; Placebo to sitagliptin administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in HbA1c at Week 24	HbA1c is measured as percent. Thus, this change from baseline reflects the Week 24 HbA1c percent minus the Week 0 HbA1c percent. Statistical analysis based on a constrained longitudinal data analysis (cLDA) model with terms for treatment, time, prior use of AHAs, the interactions of treatment by time, time by prior use of AHAs, and treatment by time by prior use of AHAs with the constraint that the mean baseline is the same for both treatment groups.	Baseline and Week 24
Percentage of Participants Who Experienced at Least One Adverse Event (AE)	An adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.	Up to 26 weeks
Percentage of Participants Who Discontinued Study Drug Due to an AE	An adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.	Up to 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in 2-hr PMG at Week 24	Change from baseline in 2-hr PMG at Week 24 is defined as Week 24 2-hr PMG minus Week 0 2-hr PMG. Statistical analysis based on a cLDA model with terms for treatment, time, prior use of AHAs, the interactions of treatment by time, time by prior use of AHAs, and treatment by time by prior use of AHAs with the constraint that the mean baseline 2-hr PMG is the same for both treatment groups.	Baseline and Week 24
Change From Baseline in Glucose Total Area Under the Plasma Concentration Curve From Hour 0 to Hour 2 (AUC0-2hr) After Meal at Week 24	Change from Baseline in Glucose Total AUC0-2hr after Meal at Week 24 is defined as Week 24 Glucose Total AUC0-2hr after a meal minus Week 0 Glucose Total AUC0-2hr after a meal. Statistical analysis based on a cLDA model with terms for treatment, time, prior use of AHAs, the interactions of treatment by time, time by prior use of AHAs, and treatment by time by prior use of AHAs with the constraint that the mean baseline glucose total AUC0-2hr after meal is the same for both treatment groups.	Baseline and Week 24 (just before loading meal [0 min], 30 min, 60 min and 120 min)
Change From Baseline in FPG at Week 24	Change from baseline in FPG at Week 24 is defined as Week 24 FPG minus Week 0 FPG. Statistical analysis based on a cLDA model with terms for treatment, time, prior use of AHAs, the interactions of treatment by time, time by prior use of AHAs, and treatment by time by prior use of AHAs with the constraint that the mean baseline FPG is the same for both treatment groups.	Baseline and Week 24

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Seino Y, Kaku K, Kadowaki T, Okamoto T, Sato A, Shirakawa M, O'Neill EA, Engel SS, Kaufman KD. A randomized, placebo-controlled trial to assess the efficacy and safety of sitagliptin in Japanese patients with type 2 diabetes and inadequate glycaemic control on ipragliflozin. Diabetes Obes Metab. 2021 Jun;23(6):1342-1350. doi: 10.1111/dom.14346. Epub 2021 Feb 28.

Study record dates

Study Major Dates

• Study Start (Actual): November 5, 2015
• Primary Completion (Actual): November 18, 2016
• Study Completion (Actual): November 18, 2016

Study Registration Dates

• First Submitted: October 14, 2015
• First Submitted That Met QC Criteria: October 14, 2015
• First Posted (Estimate): October 15, 2015

Study Record Updates

• Last Update Posted (Actual): August 31, 2018
• Last Update Submitted That Met QC Criteria: August 3, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Sodium-Glucose Transporter 2 Inhibitors; Dipeptidyl-Peptidase IV Inhibitors; Sitagliptin Phosphate; Ipragliflozin
• Other Study ID Numbers: 0431J-842; 153096 (Registry Identifier: JAPIC-CTI)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf