Janagliflozin Treat Type 2 Diabetes Mellitus (T2DM) Inadequately Controlled With Metformin

Efficacy and Safety of Janagliflozin in Combination With Metformin in Type 2 Diabetes Patients With Inadequate Glycemic Control With Metformin Alone

The purpose of this study is to evaluate the efficacy and safety of Janagliflozin compared to placebo, both in combination with Metformin, in Chinese patients with type 2 diabetes mellitus (T2DM) inadequately controlled with Metformin alone.

Study Overview

• Status: Unknown
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Janagliflozin plus metformin; Drug: Janagliflozin plus metformin; Device: Placebo plus metformin

Detailed Description

A multicentre, randomized, double-blind, placebo-controlled, parallel-group study (a 24-week core period followed by a 28-week extension period), to evaluate the efficacy and safety of Janagliflozin (25 mg and 50 mg) compared to placebo, all in combination with Metformin, in patients diagnosed with T2DM who are not achieving an adequate response from Metformin monotherapy. Approximately 390 patients with inadequate glycemic control with Metformin monotherapy will receive once-daily double-blind treatment with Janagliflozin 25 mg or 50 mg , both in combination with Metformin , for 52 weeks, or receive 24 weeks of double-blind treatment with placebo in combination with Metformin followed by 28 weeks of single-blind treatment with Janagliflozin 25 mg or 50 mg, both in combination with Metformin. During the treatment, if a patient's glycemic level remains high despite treatment with study drug and reinforcement with diet and exercise, the patient will receive treatment with Linagliptin (rescue therapy) consistent with local prescribing information.

• Study Type: Interventional
• Enrollment (Anticipated): 390
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Recruiting
      • Linong Ji

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:

• T2DM Patients with inadequate glycemic control (HbA1c level≥7.0% and ≤10.5% at baseline) on metformin monotherapy.
• Body Mass Index: 18.0~35.0 kg/m2 (both inclusive)

Exclusion Criteria:

• History of type 1 diabetes mellitus (T1DM), diabetes caused by pancreatic injury, or secondary diabetes (e.g., diabetes caused by Cushing's syndrome or acromegaly)
• More than 10% change in body weight within the 3 months before screening

• Any laboratory test indicators meet the following standards:

  • fasting plasma glucose ≥ 15 mmol/L
  • aspartate aminotransferase, alanine aminotransferase levels > 3 times the upper limit of normal (ULN); total bilirubin > 1.5 times ULN
  • hemoglobin < 100 g/L
  • eGFR < 60 mL/min/1.73m2
  • fasting triglycerides > 5.64 mmol/L (500 mg/dL)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Janagliflozin 25 mg plus metformin; Each patient will receive 25 mg of Janagliflozin plus metformin for 52 weeks (a 24-week core period followed by a 28-week extension period)	Drug: Janagliflozin plus metformin; Janagliflozin: Tablets, Oral, 25 mg, Once daily, 52 weeks The patient's stable dose of background therapy of metformin should be continued throughout the study.; Drug: Janagliflozin plus metformin; Janagliflozin: Tablets, Oral, 50 mg, Once daily, 52 weeks The patient's stable dose of background therapy of metformin should be continued throughout the study.
EXPERIMENTAL: Janagliflozin 50 mg plus metformin; Each patient will receive 50 mg of Janagliflozin plus metformin for 52 weeks (a 24-week core period followed by a 28-week extension period)	Drug: Janagliflozin plus metformin; Janagliflozin: Tablets, Oral, 25 mg, Once daily, 52 weeks The patient's stable dose of background therapy of metformin should be continued throughout the study.; Drug: Janagliflozin plus metformin; Janagliflozin: Tablets, Oral, 50 mg, Once daily, 52 weeks The patient's stable dose of background therapy of metformin should be continued throughout the study.
PLACEBO_COMPARATOR: Placebo/Janagliflozin plus metformin; In the core period, each patient will receive placebo plus metformin for 24 weeks and will then switch from placebo to 25 mg or 50 mg of Janagliflozin plus metformin until Week 52.	Device: Placebo plus metformin; Placebo: Tablets, Oral, 25/50 mg, Once daily, 24 weeks The patient's stable dose of background therapy of metformin should be continued throughout the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Hemoglobin A1c (HbA1c) From Baseline to Week 24 (Core period)	To examine whether the mean change in HbA1c from Baseline to Week 24 with Janagliflozin is superior to placebo	Baseline and Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients With HbA1c <6.5% at Week 24 (Core period) and Week 52 (Extension period)	To compare the percentage of patients with HbA1c <6.5% at week 24 (core period) and Week 52 (extension period) between groups	Baseline, Week 24 and Week 52
Change in Fasting Plasma Glucose (FPG) From Baseline to Week 24 (Core period) and Week 52 (Extension period)	To compare the mean change in fasting plasma glucose (FPG) from Baseline to Week 24 (core period) and Week 52 (extension period) between groups	Baseline, Week 24 and Week 52
Change in 2-hour Post-prandial Glucose From Baseline to Week 24 (Core period) and Week 52 (Extension period)	To compare the mean change in 2-hour post-prandial glucose from Baseline to Week 24 (core period) and Week 52 (extension period) between groups	Baseline, Week 24 and Week 52
Change in Blood Lipids (total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol) From Baseline to Week 24 (Core period) and Week 52 (Extension period)	To compare the mean change in blood lipids (total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol) from Baseline to Week 24 (core period) and Week 52 (extension period) between groups	Baseline, Week 24 and Week 52
Change in Blood Pressure (systolic blood pressure and diastolic blood pressure) From Baseline to Week 24 (Core period) and Week 52 (Extension period)	To compare the mean change in blood pressure (systolic blood pressure and diastolic blood pressure) from Baseline to Week 24 (core period) and Week 52 (extension period) between groups	Baseline, Week 24 and Week 52
Change in Body Weight From Baseline to Week 24 (Core period) and Week 52 (Extension period)	To compare the mean change in body weight from Baseline to Week 24 (core period) and Week 52 (extension period) between groups	Baseline, Week 24 and Week 52
Change in HbA1c From Baseline to Week 52	To compare the mean change in HbA1c from Baseline to Week 52 between groups	Baseline and Week 52
Percentage of Patients With HbA1c <7% at Week 24 (Core period) and Week 52 (Extension period)	To compare the percentage of patients with HbA1c <7% at Week 24 (core period) and Week 52 (extension period) between groups	Week 24 and week 52
Change in Fasting C-peptide From Baseline to Week 24 (Core period) and Week 52 (Extension period)	To compare the mean change in fasting C-peptide from Baseline to Week 24 (core period) and Week 52 (extension period) between groups	Baseline, Week 24 and Week 52
Change in Insulin Sensitivity From Baseline to Week 24 (Core period) and Week 52 (Extension period) by calculation Homeostasis model assessment-insulin resistance	To compare the mean change in insulin sensitivity from Baseline to Week 24 (core period) and Week 52 (extension period) between group by calculation Homeostasis model assessment-insulin resistance	Baseline, Week 24 and Week 52
Change in β-cell Function From Baseline to Week 24 (Core period) and Week 52 (Extension period)	To compare the mean change in β-cell function from Baseline to Week 24 (core period) and Week 52 (extension period) between groups	Baseline, Week 24 and Week 52
Percentage of Patients Who Have Received Rescue Therapy at Week 24 (Core period) and Week 52 (Extension period)	To compare the percentage of patients who have received rescue therapy by Week 24 (core period) and Week 52 (extension period) between groups.	Baseline, Week 24 and Week 52

Collaborators and Investigators

• Sponsor: Sihuan Pharmaceutical Holdings Group Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 30, 2019
• Primary Completion (ACTUAL): April 30, 2020
• Study Completion (ANTICIPATED): December 31, 2021

Study Registration Dates

• First Submitted: February 20, 2019
• First Submitted That Met QC Criteria: February 20, 2019
• First Posted (ACTUAL): February 22, 2019

Study Record Updates

• Last Update Posted (ACTUAL): July 16, 2020
• Last Update Submitted That Met QC Criteria: July 14, 2020
• Last Verified: July 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: 5695-DIA-3002

Drug and device information, study documents

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