Safety and Efficacy of Bexagliflozin in Type 2 Diabetes Mellitus Patients With Moderate Renal Impairment

Phase 3

Completed

Conditions: Type 2 Diabetes Mellitus

Interventions: Drug: Placebo
Drug: Bexagliflozin

Registration Number: NCT02836873

Lead Sponsor: Theracos

Brief Summary: This was a phase 3, multi-center, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of oral administration of bexagliflozin at 20 mg versus placebo in subjects with T2DM, moderate renal impairment and inadequate glycemic control.

Detailed Description: The phase 3, double-blind, placebo-controlled parallel-group study was conducted at investigative sites in the US, Japan, France and Spain. Approximately 300 subjects were to be randomly assigned to receive bexagliflozin tablets, 20 mg, or placebo in equal ratio for 24 weeks.

The study was to enrolled male and female participants who had T2DM with an HbA1c between 7.0 and 10.5% (inclusive) and stage 3 chronic kidney disease (CKD) as defined by an eGFR of ≥ 30 and\< 60 mL min-1 per 1.73 m2 at the screening visit and one additional time of measurement between 1 and 12 months prior to screening. Subjects were either treatment naïve or were treated with a stable regimen of anti-diabetic medications.

All eligible subjects were to enter a one-week single-blind, placebo run-in period. Subjects who were compliant in taking run-in medication, had screening eGFR ≥ 30 and\< 60 mL min-1 per 1.73 m2, and had stable GFR (no more than 20% change in eGFR between a historical value and the value determined at the screening visit) were eligible for randomization. Randomization was stratified by HbA1c level (7.0 to 8.5% or 8.6 to 10.5%), anti-diabetic treatment regimen and eGFR (30 - 44 mL min-1 per 1.73 m2 or 45 - 59 mL min-1 per 1.73 m2). At least 135 subjects in each of the eGFR groups were planned.

Study subjects were to schedule clinic visits at weeks 2, 6, 12, 18, and 24 for safety and efficacy evaluation. At weeks 2 and 18, the visits were to be conducted via phone interviews unless an in-person visit was considered clinically advisable. A final follow-up visit was to be conducted at week 26 or two weeks after the last dose of investigational product if the subject withdrew prior to week 24.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 312

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo tablets	Placebo	Each subject will receive a placebo (inactive) tablet once daily for the duration of the study.
Bexagliflozin tablets, 20 mg	Bexagliflozin	Each subject will receive a bexagliflozin tablet, 20 mg, once daily for the duration of the study.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in HbA1c at 24 Weeks	24 weeks	The primary efficacy objective of this trial is to evaluate the placebo-adjusted change in HbA1c from baseline after 24 weeks of treatment with 20 mg bexagliflozin tablets in type 2 diabetic subjects with moderate renal impairment.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in HbA1c in Subjects With Stage 3a CKD (eGFR 45 to 59 mL/Min/1.73 m2) at Week 24	24 weeks	A secondary objective is to evaluate the effect of bexagliflozin 20 mg on the placebo-adjusted change in HbA1c from baseline in subjects with stage 3a CKD (eGFR 45 to 59 mL/min/1.73 m2) at week 24.
Change in Body Weight From Baseline to Week 24 in Subjects With a BMI ≥ 25 kg/m2	24 weeks	A secondary objective is to evaluate the effect of bexagliflozin 20 mg on the placebo-adjusted change in BMI from baseline to week 24 in subjects with a BMI ≥ 25 kg/m2.
Change From Baseline in Systolic Blood Pressure (SBP) in Subjects With Baseline SBP ≥ 130 mm Hg at Week 24	24 weeks	A secondary objective is to evaluate the effect of bexagliflozin 20 mg on the placebo-adjusted change from baseline in SBP to in subjects with baseline SBP ≥ 130 mm Hg at Week 24.
Change From Baseline in HbA1c in Subjects With Stage 3b CKD (eGFR 30 to 44 mL/Min/1.73 m2) at Week 24	24 weeks	A secondary objective is to evaluate the effect of bexagliflozin 20 mg on the placebo-adjusted change in HbA1c from baseline in subjects with stage 3b CKD (eGFR 30 to 44 mL/min/1.73 m2) at week 24.