Efficacy and Bone Safety of Sotagliflozin Dose 1 and Dose 2 Versus Placebo in Subjects With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control

ID: NCT03386344
Status: Recruiting
Phase: Phase 3
Start Date: February 19, 2018
First Submitted: December 21, 2017
Last Updated: February 22, 2018
Results: N/A
Organization: Sanofi
Sponsors & Collaborators: Sanofi
Location: United States
Conditions: Type 2 Diabetes Mellitus
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Study Description

Brief Summary

Primary Objective:

To demonstrate the superiority of sotagliflozin dose 1 versus placebo with respect to hemoglobin A1c (Hb1Ac) reduction in patients with type 2 diabetes (T2D) who have inadequate glycemic control on diet and exercise only or with a stable antidiabetes regimen.

Secondary Objectives:

- To compare the effects of sotagliflozin dose 1 and dose 2 versus placebo with respect to the percent change in bone mineral density (BMD) at lumbar spine, total hip, and femoral neck, measured by dual-energy X-ray absorptiometry (DXA).

- To demonstrate the superiority of sotagliflozin dose 1 versus placebo on change in body weight (BW), fasting plasma glucose (FPG), systolic blood pressure (SBP) for all patients; and to evaluate the proportion of patients with a HbA1C <7%.

- To demonstrate the superiority of sotagliflozin dose 2 versus placebo with respect to HbA1c reduction; change in BW, FPG, and SBP for all patients; and to evaluate the proportion of patients with HbA1c <7.0%.

- To evaluate the safety of sotagliflozin dose 1 and dose 2 compared with placebo.

Detailed Description

Study duration per participant is approximately 110 weeks (Screening period of up to 2 weeks, 2 week single-blind run-in period), a 26-week double-blind core treatment period, a 78-week double-blind extension period, and a 2- week post treatment follow up period.

DXA scans will be performed to assess Bone Mineral Density and Fat vs. Lean body mass at baseline and Weeks 26, 52, and 104.
Condition or disease Intervention/treatment Phase

Type 2 Diabetes Mellitus

Drug: Sotagliflozin (SAR439954)
Other Names
Drug: Placebo
Other Names
Phase 3

Tracking Information

First Submitted DateDecember 21, 2017
Last Update Posted DateFebruary 22, 2018
Actual Start DateFebruary 19, 2018
Anticipated Completion DateNovember 01, 2020
Actual Primary Completion DateNovember 01, 2020
Results First Submitted DateN/A
Received Results Disposit DateN/A

Current Primary Outcome Measures

  • Change in Hemoglobin A1C (HbA1c) [Time Frame: Baseline to Week 26]

    Absolute change from baseline to Week 26 HbA1c (for sotagliflozin dose 1)

Original Primary Outcome Measures

Not Available

Current Secondary Outcome Measures

  • Change in HbA1c [Time Frame: Baseline to Week 26]

    Absolute change from Baseline to Week 26 in HbA1c comparing sotagliflozin dose 2 versus placebo

  • Change in body weight (BW) [Time Frame: Baseline to Week 26]

    Absolute change from Baseline to Week 26 in BW (doses 1 and 2)

  • Change in Fasting Plasma Glucose (FPG) [Time Frame: Baseline to Week 26]

    Absolute change from Baseline to Week 26 in FPG (doses 1 and 2)

  • Change in systolic blood pressure (SBP) [Time Frame: Baseline to Week 12]

    Absolute change from Baseline to Week 12 in SBP in all patients (dose 1 and dose 2)

  • Patients with HbA1c < 7.0% [Time Frame: At Week 26]

    Percentage of patients with HbA1c < 7.0% at Week 26 (doses 1 and 2)

  • Percent change in bone mineral density (BMD) of lumbar spine [Time Frame: Baseline to Week 26]

    Percent change in BMD of lumbar spine at week 26 (doses 1 and 2)

  • Percent change in BMD of total hip [Time Frame: Baseline to Week 26]

    Percent change in BMD of total hip at week 26 (doses 1 and 2)

  • Percent change in BMD of femoral neck [Time Frame: Baseline to Week 26]

    Percent change in BMD of femoral neck at week 26 (doses 1 and 2)

  • Adverse events [Time Frame: Up to 104 weeks]

    Absolute number of patients with adverse events up to week 104 (doses 1 and 2)

Original Secondary Outcome Measures

Not Available

Study Design

Brief TitleEfficacy and Bone Safety of Sotagliflozin Dose 1 and Dose 2 Versus Placebo in Subjects With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control
Official TitleA 26-week Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter, Phase 3 Study With a 78-week Extension Period to Evaluate the Efficacy and Bone Safety of Sotagliflozin in Patients 55 Years or Older With Type 2 Diabetes Mellitus and Inadequate Glycemic Control
Brief Summary

Primary Objective:

To demonstrate the superiority of sotagliflozin dose 1 versus placebo with respect to hemoglobin A1c (Hb1Ac) reduction in patients with type 2 diabetes (T2D) who have inadequate glycemic control on diet and exercise only or with a stable antidiabetes regimen.

Secondary Objectives:

- To compare the effects of sotagliflozin dose 1 and dose 2 versus placebo with respect to the percent change in bone mineral density (BMD) at lumbar spine, total hip, and femoral neck, measured by dual-energy X-ray absorptiometry (DXA).

- To demonstrate the superiority of sotagliflozin dose 1 versus placebo on change in body weight (BW), fasting plasma glucose (FPG), systolic blood pressure (SBP) for all patients; and to evaluate the proportion of patients with a HbA1C <7%.

- To demonstrate the superiority of sotagliflozin dose 2 versus placebo with respect to HbA1c reduction; change in BW, FPG, and SBP for all patients; and to evaluate the proportion of patients with HbA1c <7.0%.

- To evaluate the safety of sotagliflozin dose 1 and dose 2 compared with placebo.

Detailed Description

Study duration per participant is approximately 110 weeks (Screening period of up to 2 weeks, 2 week single-blind run-in period), a 26-week double-blind core treatment period, a 78-week double-blind extension period, and a 2- week post treatment follow up period.

DXA scans will be performed to assess Bone Mineral Density and Fat vs. Lean body mass at baseline and Weeks 26, 52, and 104.

Study TypeInterventional
Study PhasePhase 3
Estimated Enrollment
360
Allocation
Randomized
Interventional Model
Parallel Assignment
Masking
Quadruple
Primary Purpose
Treatment
Conditions
Type 2 Diabetes Mellitus
Target Follow-Up Duration N/A
Biospecimen:
N/A
Sampling MethodN/A
Study PopulationN/A
Intervention
Drug: Sotagliflozin (SAR439954)

Pharmaceutical form: Tablet Route of administration: Oral

Other Names
Drug: Placebo

Pharmaceutical form: Tablet Route of administration: Oral

Other Names
Study Groups/Cohorts
Dose 1
Sotagliflozin dose 1 given as two (2) dose 2 sotagliflozin tablets on top of baseline antidiabetic therapy

Dose 2
Sotagliflozin dose 2 given as one (1) dose 2 sotagliflozin tablet and one (1) sotagliflozin matching placebo tablet on top of baseline antidiabetic therapy

Placebo
Placebo, given as two (2) sotagliflozin matching placebo tablets on top of baseline antidiabetic therapy

Study Arms
Experimental Dose 1
Sotagliflozin dose 1 given as two (2) dose 2 sotagliflozin tablets on top of baseline antidiabetic therapy
Drug : Sotagliflozin (SAR439954)
Pharmaceutical form: Tablet Route of administration: Oral

Experimental Dose 2
Sotagliflozin dose 2 given as one (1) dose 2 sotagliflozin tablet and one (1) sotagliflozin matching placebo tablet on top of baseline antidiabetic therapy
Drug : Sotagliflozin (SAR439954)
Pharmaceutical form: Tablet Route of administration: Oral

Experimental Dose 2
Sotagliflozin dose 2 given as one (1) dose 2 sotagliflozin tablet and one (1) sotagliflozin matching placebo tablet on top of baseline antidiabetic therapy
Drug : Placebo
Pharmaceutical form: Tablet Route of administration: Oral

Placebo Comparator Placebo
Placebo, given as two (2) sotagliflozin matching placebo tablets on top of baseline antidiabetic therapy
Drug : Placebo
Pharmaceutical form: Tablet Route of administration: Oral

Arm Intervention/Treatment
Experimental Dose 1
Sotagliflozin dose 1 given as two (2) dose 2 sotagliflozin tablets on top of baseline antidiabetic therapy
Drug : Sotagliflozin (SAR439954)
Experimental Dose 2
Sotagliflozin dose 2 given as one (1) dose 2 sotagliflozin tablet and one (1) sotagliflozin matching placebo tablet on top of baseline antidiabetic therapy
Drug : Sotagliflozin (SAR439954)
Experimental Dose 2
Sotagliflozin dose 2 given as one (1) dose 2 sotagliflozin tablet and one (1) sotagliflozin matching placebo tablet on top of baseline antidiabetic therapy
Drug : Placebo
Placebo Comparator Placebo
Placebo, given as two (2) sotagliflozin matching placebo tablets on top of baseline antidiabetic therapy
Drug : Placebo

Recruitment Information

Recruitment Status:Recruiting
Enrollment360
Completion DateNovember 01, 2020
Eligibility Criteria: Inclusion criteria :
- Patients with Type 2 Diabetes (T2D) managed with diet and exercise only or with a stable antidiabetes regimen (in monotherapy or combination therapy that can include oral antidiabetes medications, insulin, or glucagon-like peptide-1 agonists) for more than 12 weeks.
- Patient has given written informed consent to participate in the study in accordance with local regulations.
Exclusion criteria:
- Age <55 years.
- Women who have been postmenopausal (or undergone bilateral oophorectomy) for less than 5 years.
- Type 1 diabetes mellitus.
- Body mass index (BMI) ≤20 or >45 kg/m2 or body weight that exceeds the weight limits of the Dual-energy X-ray absorptiometry (DXA) scanner.
- Hemoglobin A1C (HbA1c) <7.0% or HbA1c >11.0%.
- Use of a selective sodium-glucose cotransporter type 2 (SGLT2) inhibitor or thiazolidinedione within 24 months.
- Bone mineral density (BMD) T- score <-2.0 at any site (ie, lumbar spine, total hip, or femoral neck).
- History of fracture within 12 months (except for fractures of the hand/fingers, foot/toes, facial bones, and skull).
- Treatment with medications known to affect bone mass or modify the risk of fractures within 36 months (eg, bisphosphonates, selective estrogen receptor modulators, calcitonin, teriparatide, denosumab, strontium ranelate, growth hormone, aromatase inhibitors, androgen deprivation therapy, carbamazepine, phenytoin, and phenobarbital). Use of hormonal replacement that includes systemic or transdermal estrogen or testosterone is excluded unless is stable for at least 24 months prior to Screening.
- Lower extremity complications (such as skin ulcers, infection, osteomyelitis and gangrene) identified during the Screening period, and still requiring treatment at Randomization.
- Uncontrolled high blood pressure, severe anemia, severe cardiovascular problems, such as heart failure, active cancer, or other conditions that the Investigator believes with result in a short life expectancy.
- Renal disease as defined by an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m² at the Screening Visit by the 4 variable Modification of Diet in Renal Disease equation.
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
GenderAll
Age55 Years to N/A
Accepts Healthy VolunteersNo
Contacts
Listed Location Countries
United States

Administrative Information

NCT Number:NCT03386344
Other Study ID Numbers
EFC15294
2017-002041-30
U1111-1195-6371
Has Data Monitoring CommitteeYes
U.S. FDA-regulated Product Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement
Not Available
Responsible Party,
Study Sponsor
Sanofi
Collaborators
Not Available
Investigators
Study Director
Clinical Sciences & Operations
Sanofi