Janagliflozin Treat T2DM Monotherapy

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

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.

Study Overview

• Status: Unknown
• Conditions: Diabetes Type 2
• Intervention / Treatment: Drug: Janagliflozin 25mg; Drug: Janagliflozin 50mg; Drug: Placebo/Janagliflozin

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.

• Study Type: Interventional
• Enrollment (Anticipated): 442
• Phase: Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Janagliflozin 25mg; Each patient will receive 25 mg of Janagliflozin once daily for 52 weeks (24 weeks core period followed by 28 Weeks Extension period)	Drug: Janagliflozin 25mg; Tablets, Oral, 25 mg, Tablets, Oral, 50 mg; Other Names: Placebo 50mg
Experimental: Janagliflozin 50mg; Each patient will receive 50 mg of Janagliflozin once daily for 52 weeks (24 weeks core period followed by 28 Weeks Extension period)	Drug: Janagliflozin 50mg; Tablets, Oral, 25 mg, Once daily, 52 weeks; Other Names: Placebo 25mg
Experimental: Placebo/Janagliflozin; In the core period, each patient will receive placebo once daily for 24 weeks and will then switch from placebo to 25 mg or 50 mg of Janagliflozin once daily until Week 52.	Drug: Placebo/Janagliflozin; Tablets, Oral, 25 mg, Once daily, 52 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in HbA1c From Baseline to Week 24	To examine whether the mean change in HbA1c from baseline to week 24 with Janagliflozin is superiority (superiority margin of 0.5%) to placebo	Baseline and Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	To compare the percentage of patients with HbA1c <7% at week 24 (core period) and week 52 (extension period) between groups	Baseline, Week 24 and week 52
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 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)	To compare the mean change in insulin sensitivity from Baseline to Week 24 (core period) and Week 52 (extension period) between groups	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	Week 24 and Week 52

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urinary albumin/creatinine ratio (UACR)	To evaluate Urinary albumin/creatinine ratio in different group	From Baseline to Week 52
Occurrence of adverse events	To evaluate adverse events in different group	From Baseline to Week 52
Occurrence of hypoglycaemic episodes	To evaluate adverse events in different group	From Baseline to Week 52
Population pharmacokinetics assessment	By compare patients' Minimum Plasma Concentration (on week 2, 4, 8, 24)to eveluate Janagliflozin population pharmacokinetics characteristics	Baseline, Week 2, Week4, Week8, Week24

Collaborators and Investigators

• Sponsor: Sihuan Pharmaceutical Holdings Group Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): May 23, 2019
• Primary Completion (Actual): June 24, 2020
• Study Completion (Anticipated): December 31, 2020

Study Registration Dates

• First Submitted: January 17, 2019
• First Submitted That Met QC Criteria: January 17, 2019
• First Posted (Actual): January 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
• Other Study ID Numbers: 5695-DIA-3001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No