Clinical trial NCT03851432: Janagliflozin Treat Type 2 Diabetes Mellitus (T2DM) Inadequately Controlled With Metformin
Official title: Efficacy and Safety of Janagliflozin in Combination With Metformin in Type 2 Diabetes Patients With Inadequate Glycemic Control With Metformin Alone
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Sihuan Pharmaceutical Holdings Group Ltd.
Sponsor class: INDUSTRY
First posted: 2019-02-22
Enrollment: 390
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Change in Hemoglobin A1c (HbA1c) From Baseline to Week 24 (Core period)
timeFrame: Baseline and Week 24
Secondary outcomes:
measure: Change in HbA1c From Baseline to Week 52
timeFrame: Baseline and Week 52
measure: Percentage of Patients With HbA1c <7% at Week 24 (Core period) and Week 52 (Extension period)
timeFrame: Week 24 and week 52
measure: Percentage of Patients With HbA1c <6.5% at Week 24 (Core period) and Week 52 (Extension period)
timeFrame: Baseline, Week 24 and Week 52
measure: Change in Fasting Plasma Glucose (FPG) From Baseline to Week 24 (Core period) and Week 52 (Extension period)
timeFrame: Baseline, Week 24 and Week 52
measure: Change in 2-hour Post-prandial Glucose From Baseline to Week 24 (Core period) and Week 52 (Extension period)
timeFrame: Baseline, Week 24 and Week 52
measure: 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)
timeFrame: Baseline, Week 24 and Week 52
measure: Change in Blood Pressure (systolic blood pressure and diastolic blood pressure) From Baseline to Week 24 (Core period) and Week 52 (Extension period)
timeFrame: Baseline, Week 24 and Week 52
measure: Change in Body Weight From Baseline to Week 24 (Core period) and Week 52 (Extension period)
timeFrame: Baseline, Week 24 and Week 52
measure: Change in Fasting C-peptide From Baseline to Week 24 (Core period) and Week 52 (Extension period)
timeFrame: Baseline, Week 24 and Week 52
measure: Change in Insulin Sensitivity From Baseline to Week 24 (Core period) and Week 52 (Extension period) by calculation Homeostasis model assessment-insulin resistance
timeFrame: Baseline, Week 24 and Week 52
measure: Change in β-cell Function From Baseline to Week 24 (Core period) and Week 52 (Extension period)
timeFrame: Baseline, Week 24 and Week 52
measure: Percentage of Patients Who Have Received Rescue Therapy at Week 24 (Core period) and Week 52 (Extension period)
timeFrame: Baseline, Week 24 and Week 52
Other outcomes:
Locations:
city: Beijing
country: China
facility: Linong Ji
state: Beijing
Study officials:
References: