Clinical trial NCT03811548: Janagliflozin Treat T2DM Monotherapy
Official title: A Multicentre, Randomized, Double-blind, Parallel Group, Placebo-controlled Study, to Evaluate the Efficacy and Safety of Janagliflozin (25 mg and 50 mg) as Monotherapy in Chinese Patients Diagnosed With T2DM
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Diabetes Type 2
Lead sponsor: Sihuan Pharmaceutical Holdings Group Ltd.
Sponsor class: INDUSTRY
First posted: 2019-01-22
Enrollment: 442
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 assess the effect of Janagliflozin relative to placebo on glycated hemoglobin (HbA1c) after 24 weeks of treatment, and to assess the efficacy after 52 weeks of treatment, overall safety and Population pharmacokinetics.

Detailed description: A multicentre, randomized, double-blind, parallel group, placebo-controlled study(24 weeks core period followed by 28 Weeks Extension period), to evaluate the efficacy and safety of Janagliflozin (25 mg and 50 mg) compared to placebo in patients diagnosed with T2DM who are not achieving an adequate response from diet and exercise to control their diabetes. Approximately 390 patients with inadequate glycemic control with diet and exercise will receive once-daily double-blind treatment with Janagliflozin 25 mg or 50 mg once daily for 52 weeks, or 24 weeks of double-blind treatment with placebo followed by 28 weeks of single-blind treatment with Janagliflozin 25 mg or 50 mg. 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 metformin (rescue therapy) consistent with local prescribing information. Study drug will be taken orally once daily.

Eligibility criteria: Inclusion Criteria:

* All patients must have a diagnosis of T2DM (meet the diagnostic criteria for diabetes issued by the World Health Organization in 1999)
* Patients must have a hemoglobin A1c (HbA1c) level ≥7.5% and ≤11% at screening, and ≥7.0% and ≤10.5% at baseline.
* Drug -naïve (never received anti-diabetic medication or did not receive anti-diabetic medication within 8 weeks before screening).
* 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 HbA1c From Baseline to Week 24
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
timeFrame: Baseline, 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)
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: Week 24 and Week 52
Other outcomes:
measure: Urinary albumin/creatinine ratio (UACR)
timeFrame: From Baseline to Week 52
measure: Occurrence of adverse events
timeFrame: From Baseline to Week 52
measure: Occurrence of hypoglycaemic episodes
timeFrame: From Baseline to Week 52
measure: Population pharmacokinetics assessment
timeFrame: Baseline, Week 2, Week4, Week8, Week24
Locations:
city: Beijing
country: China
facility: Linong Ji
state: Beijing
Study officials:
References: