Dual Add-on Therapy in Type 2 Diabetes Poorly Controlled With Metformin Monotherapy

A Multicenter, Randomized, Double-Blind, Parallel Group, Phase 3 Trial to Evaluate the Safety and Efficacy of Retagliptin Plus Henagliflozein Added to Metformin Compared to Retagliptin or Henagliflozein in Combination With Metformin in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control on Metformin Alone

2 weeks screening period, 4 weeks run-in period, 24 weeks double-blind treatment period, to evaluate the Safety and Efficacy of Retagliptin Plus Henagliflozein added to Metformin compared to Retagliptin or Henagliflozein in combination with Metformin in Subjects with Type 2 Diabetes who have Inadequate Glycemic Control on Metformin Alone

Study Overview

• Status: Unknown
• Conditions: Diabetes Mellitus, Type II
• Intervention / Treatment: Drug: Retagliptin, Henagliflozein, metformin XR

• Study Type: Interventional
• Enrollment (Anticipated): 760
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Men and women, 18-75 years old (both inclusive) at time of screening visit;
2. Subjects with T2DM with inadequate glycemic control defined as central laboratory HbA1c ≥ 7.5 and ≤ 10.5 % at the screening visit;
3. FPG ≤ 15mmol/L at the screening visit;
4. Stable metformin therapy for at least 8 weeks prior to screening at a dose ≥ 1500 mg per day;
5. 19.0<BMI ≤ 40.0 kg/m2 at the screening visit;

Exclusion Criteria:

1. Moderate or severe impairment of renal function [defined as eGFR<60mL/min/1.73 m2 (estimated by MDRD);
2. Uncontrolled hypertension defined as systolic blood pressure (SBP) ≥ 160 mmHg and/or diastolic blood pressure (DBP) ≥ 100 mmHg;
3. Cardiovascular diseases within 6 months of the screening visit;
4. ALT and/or AST > 1.5 x ULN and or Total Bilirubin > 1.2 x ULN;
5. Hemoglobin ≤ 100 g/L;
6. CK (creatine kinase) and CK-MB > 3 x ULN;
7. Malignancy within 5 years of the screening visit (with the exception of treated basal cell or treated squamous cell carcinoma);
8. Administration of any antihyperglycemic therapy, other than metformin,within 2 months prior to screening;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Retagliptin 100 mg, Henagliflozein 10 mg, plus metformin XR	Drug: Retagliptin, Henagliflozein, metformin XR; Retagliptin-DPP4 inhibitor Henagliflozein-SGLT-2 inhibitor Metformin XR
EXPERIMENTAL: Retagliptin 100 mg, Henagliflozein 5 mg, plus metformin XR	Drug: Retagliptin, Henagliflozein, metformin XR; Retagliptin-DPP4 inhibitor Henagliflozein-SGLT-2 inhibitor Metformin XR
EXPERIMENTAL: Retagliptin placebo, Henagliflozein 10 mg, plus metformin XR	Drug: Retagliptin, Henagliflozein, metformin XR; Retagliptin-DPP4 inhibitor Henagliflozein-SGLT-2 inhibitor Metformin XR
EXPERIMENTAL: Retagliptin placebo, Henagliflozein 5 mg, plus metformin XR	Drug: Retagliptin, Henagliflozein, metformin XR; Retagliptin-DPP4 inhibitor Henagliflozein-SGLT-2 inhibitor Metformin XR
EXPERIMENTAL: Retagliptin 100 mg, Henagliflozein placebo, plus metformin XR	Drug: Retagliptin, Henagliflozein, metformin XR; Retagliptin-DPP4 inhibitor Henagliflozein-SGLT-2 inhibitor Metformin XR

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change from baseline in HbA1c at Week 24	• To compare the mean change from baseline in HbA1c achieved with concurrent addition of Retagliptin Plus Henagliflozein to metformin vs the addition of Retagliptin or Henagliflozein to metformin after 24 weeks of double-blind treatment.	24 weeks

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): January 1, 2021
• Primary Completion (ANTICIPATED): September 1, 2022
• Study Completion (ANTICIPATED): October 1, 2022

Study Registration Dates

• First Submitted: December 9, 2020
• First Submitted That Met QC Criteria: December 9, 2020
• First Posted (ACTUAL): December 14, 2020

Study Record Updates

• Last Update Posted (ACTUAL): December 14, 2020
• Last Update Submitted That Met QC Criteria: December 9, 2020
• Last Verified: December 1, 2020

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; Metformin
• Other Study ID Numbers: SHR3824-SP2086-MET-301

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No