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

• ClinicalTrials.gov Identifier: NCT02577016
• Recruitment Status: Completed
• First Posted: October 15, 2015
• Results First Posted: March 7, 2018
• Last Update Posted: August 31, 2018
• Sponsor: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Merck Sharp & Dohme Corp.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Type 2 Diabetes Mellitus	Drug: Sitagliptin; Drug: Placebo; Drug: Ipragliflozin	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 141 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: November 5, 2015
• Actual Primary Completion Date: November 18, 2016
• Actual Study Completion Date: November 18, 2016

Arms and Interventions

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 Name: 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: Placebo; Placebo to sitagliptin administered orally; Drug: Ipragliflozin; 50 mg tablet administered orally as background medication

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in HbA1c at Week 24 [ Time Frame: Baseline and 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.
2. Percentage of Participants Who Experienced at Least One Adverse Event (AE) [ Time Frame: Up to 26 weeks ]
   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.
3. Percentage of Participants Who Discontinued Study Drug Due to an AE [ Time Frame: Up to 24 weeks ]
   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.

Secondary Outcome Measures :

1. Change From Baseline in 2-hr PMG at Week 24 [ Time Frame: Baseline and 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.
2. 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 [ Time Frame: Baseline and Week 24 (just before loading meal [0 min], 30 min, 60 min and 120 min) ]
   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.
3. Change From Baseline in FPG at Week 24 [ Time Frame: Baseline and 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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Sponsors and Collaborators

Merck Sharp & Dohme Corp.

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme Corp.

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Merck Sharp & Dohme Corp.
• ClinicalTrials.gov Identifier: NCT02577016
• Other Study ID Numbers: 0431J-842; 153096 ( Registry Identifier: JAPIC-CTI )
• First Posted: October 15, 2015
• Results First Posted: March 7, 2018
• Last Update Posted: August 31, 2018
• Last Verified: August 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Sitagliptin Phosphate; Ipragliflozin; Hypoglycemic Agents; Physiological Effects of Drugs; Incretins; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Dipeptidyl-Peptidase IV Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors