Diabetes Type 2
Conditions
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.
Interventions
DRUGJanagliflozin 25mg
Tablets, Oral, 25 mg, Tablets, Oral, 50 mg
DRUGJanagliflozin 50mg
Tablets, Oral, 25 mg, Once daily, 52 weeks
DRUGPlacebo/Janagliflozin
Tablets, Oral, 25 mg, Once daily, 52 weeks
Sponsors
Sihuan Pharmaceutical Holdings Group Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double Blind
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in HbA1c From Baseline to Week 24 | Baseline and 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in 2-hour Post-prandial Glucose From Baseline to Week 24 (Core period) and Week 52 (Extension period) | Baseline, Week 24 and Week 52 | 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 |
| Change in Fasting C-peptide From Baseline to Week 24 (Core period) and Week 52 (Extension period) | Baseline, Week 24 and Week 52 | To compare the mean change in fasting C-peptide from Baseline to Week 24 (core period) and Week 52 (extension period) between groups. |
| Change in Insulin Sensitivity From Baseline to Week 24 (Core period) and Week 52 (Extension period) | Baseline, Week 24 and Week 52 | To compare the mean change in insulin sensitivity from Baseline to Week 24 (core period) and Week 52 (extension period) between groups |
| Change in β-cell Function From Baseline to Week 24 (Core period) and Week 52 (Extension period) | Baseline, Week 24 and Week 52 | To compare the mean change in β-cell function from Baseline to Week 24 (core period) and Week 52 (extension period) between groups. |
| Percentage of Patients Who Have Received Rescue Therapy at Week 24 (Core period) and Week 52 (Extension period) | Week 24 and Week 52 | To compare the percentage of patients who have received rescue therapy by Week 24 (core period) and Week 52 (extension period) between groups |
| Change in HbA1c From Baseline to Week 52 | Baseline and Week 52 | To compare the mean change in HbA1c from baseline to week 52 between groups |
| Percentage of Patients With HbA1c <7% at Week 24 (Core period) and week 52 | Baseline, Week 24 and week 52 | To compare the percentage of patients with HbA1c \<7% at week 24 (core period) and week 52 (extension period) between groups |
| Percentage of Patients With HbA1c <6.5% at Week 24 (Core period) and Week 52 (Extension period) | Baseline, Week 24 and Week 52 | To compare the percentage of patients with HbA1c \<6.5% at week 24 (core period) and Week 52 (extension period) between groups |
| Change in Fasting Plasma Glucose (FPG) From Baseline to Week 24 (Core period) and Week 52 (Extension period) | Baseline, Week 24 and Week 52 | To compare the mean change in fasting plasma glucose (FPG) from Baseline to Week 24 (core period) and Week 52 (extension period) between groups |
| 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) | Baseline, Week 24 and Week 52 | 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 |
| Change in Blood Pressure (systolic blood pressure and diastolic blood pressure) From Baseline to Week 24 (Core period) and Week 52 (Extension period) | Baseline, Week 24 and Week 52 | 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 |
| Change in Body Weight From Baseline to Week 24 (Core period) and Week 52 (Extension period) | Baseline, Week 24 and Week 52 | To compare the mean change in body weight from Baseline to Week 24 (core period) and Week 52 (extension period) between groups |
Other
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of hypoglycaemic episodes | From Baseline to Week 52 | To evaluate adverse events in different group |
| Population pharmacokinetics assessment | Baseline, Week 2, Week4, Week8, Week24 | By compare patients' Minimum Plasma Concentration (on week 2, 4, 8, 24)to eveluate Janagliflozin population pharmacokinetics characteristics |
| Urinary albumin/creatinine ratio (UACR) | From Baseline to Week 52 | To evaluate Urinary albumin/creatinine ratio in different group |
| Occurrence of adverse events | From Baseline to Week 52 | To evaluate adverse events in different group |
Countries
China
Contacts
Primary ContactLeili Gao, Doctor
Backup ContactLinong Ji, Doctor
Outcome results
None listed