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

Study Overview
=================
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.

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

Conditions
-----------------
Type 2 Diabetes Mellitus

Intervention / Treatment
-----------------
* Drug: Sitagliptin
* Drug: Placebo
* Drug: Ipragliflozin


Participation Criteria
=================
Eligibility 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

Ages Eligible for Study
-----------------
Minimum Age: 20 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

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 |