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Study To Determine Bioavailability of Sotagliflozin in Healthy Male and Female Subjects

Primary Purpose

Type 2 Diabetes Mellitus, Healthy Subjects

Status

Completed

Phase

Phase 1

Locations

United Kingdom

Study Type

Interventional

Intervention

Sotagliflozin (SAR439954)

14C-microtracer

Charcoal

About this trial

This is an interventional treatment trial for Type 2 Diabetes Mellitus

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion criteria :

Male or female subjects, between 18 and 55 years of age, inclusive.
Body weight between 50.0 and 120.0 kg, inclusive, if male, and between 40.0 and 100.0 kg, inclusive, if female, body mass index (BMI) between 18.0 and 30.0 kg/m2, inclusive. BMI between 30.0 and 32.0 is acceptable if investigator judges the subject to have a high muscle mass.
Certified as healthy by a comprehensive clinical assessment (detailed medical history and complete physical examination).
Normal vital signs, ECG and laboratory parameters.

Exclusion criteria:

Any history or presence of clinically relevant abnormalities at screening which could interfere with the objectives of the study or the safety of the subject's participation.
Blood donation (400 mL) within 3 months before inclusion.
History or presence of drug or alcohol abuse.
Smoking regularly more than 5 cigarettes or equivalent per week, unable to stop smoking during the study.

Excessive consumption of beverages containing xanthine bases.

If female, pregnancy (defined as positive β-Human Chorionic Gonadotropin blood test), breast-feeding.
Any medication (including St John's Wort) within 14 days before inclusion with the exception of menopausal hormone replacement therapy; any vaccination within last 28 days; any biologics given within last 4 months.
Any subject in the exclusion period of a previous study.
Any subject who cannot be contacted in case of emergency.
Positive result on any of the following tests: hepatitis B surface (HBs Ag) antigen, anti-hepatitis C virus (anti-HCV) antibodies, anti-human immunodeficiency virus 1 and 2 antibodies.
Positive result on urine drug screen.
Positive alcohol test.
Participation in a study in which radioisotopes were administered or in which subject was exposed to any radiation other than normal background radiation within the 12 months before the screening visit.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Sites / Locations

Investigational site number 8260001

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Sotagliflozin

Arm Description

One treatment period includes a single oral dose of sotagliflozin + IV microdose 14C-sotagliflozin tracer plus charcoal. The other treatment period includes a single oral dose of sotagliflozin + IV microdose 14C-sotagliflozin tracer without charcoal.

Outcomes

Primary Outcome Measures

Pharmacokinetic (PK) parameter: Absolute Bioavailability (F)

Absolute Bioavailability (F) will be a composite endpoint and include Area under plasma concentration (AUC) dose normalized for intravenous (IV) 14C-IMP AUClast dose normalized for oral Investigational Medicinal Product (IMP)

Secondary Outcome Measures

Assessment of PK parameter: Area under the curve (AUC) for oral investigational medicinal product (IMP)

Area under the plasma concentration versus time curve extrapolated to infinity for oral IMP

Assessment of PK parameter: AUC for IMP metabolite

Area under the plasma concentration versus time curve extrapolated to infinity for IMP metabolite

Assessment of PK parameter: AUC for IV 14C-IMP

Area under the plasma concentration versus time curve extrapolated to infinity for IV 14C-IMP

Assessment of PK parameter: AUC for 14C-IMP metabolite

Area under the plasma concentration versus time curve extrapolated to infinity for 14C-IMP metabolite

Assessment of PK parameter: Area under curve versus time (AUClast) for oral IMP

Area under the plasma concentration versus time curve calculated using the trapezoidal method from time zero to the real time tlast for oral IMP

Assessment of PK parameter: AUClast for IMP metabolite

Area under the plasma concentration versus time curve calculated using the trapezoidal method from time zero to the real time tlast for IMP metabolite

Assessment of PK parameter: AUClast for IV 14C-IMP

Area under the plasma concentration versus time curve calculated using the trapezoidal method from time zero to the real time tlast for IV 14C-IMP

Assessment of PK parameter: AUClast for 14C-IMP metabolite

Area under the plasma concentration versus time curve

Assessment of PK parameter: Cmax for oral IMP

Maximum plasma concentration observed for oral IMP

Assessment of PK parameter: Cmax for IMP metabolite

Maximum plasma concentration observed for IMP metabolite

Assessment of PK parameter: Cmax for IV 14C-IMP

Maximum plasma concentration observed for IV 14C-IMP

Assessment of PK parameter: Cmax for 14C-IMP metabolite

Maximum plasma concentration observed for 14C-IMP metabolite

Assessment of PK parameter: tmax for oral IMP

Time to reach Cmax for oral IMP

Assessment of PK parameter: tmax for IMP metabolite

Time to reach Cmax for IMP metabolite

Assessment of PK parameter: tmax for IV 14C-IMP

Time to reach Cmax for IV 14C-IMP

Assessment of PK parameter: tmax for 14C-IMP metabolite

Time to reach Cmax for 14C-IMP metabolite

Assessment of PK parameter: t1/2z for oral IMP

Terminal half-life (t1/2z) associated with the terminal slope for oral IMP

Assessment of PK parameter: t1/2z for IV 14C-IMP

Terminal half-life (t1/2z) associated with the terminal slope for IV 14C-IMP

Assessment of PK parameter: Clearance (CL/F) for oral IMP

Apparent total body clearance for oral IMP

Assessment of PK parameter: Clearance (CL/F) for IV 14C-IMP

Apparent total body clearance for IV 14C-IMP

Assessment of PK parameter: Vz/F for oral IMP

Apparent volume of distribution for oral IMP

Assessment of PK parameter: Vz/F for IV 14C-IMP

Apparent volume of distribution for IV 14C-IMP

Assessment of PK parameter: Vdss/F for oral IMP

Apparent volume of distribution at the steady state for oral IMP

Assessment of PK parameter: Vdss/F for IV 14C-IMP

Apparent volume of distribution at the steady state for IV 14C-IMP

Safety: Adverse events

Number of subjects with adverse events including serious, non-serious, and treatment emergent adverse events

Full Information

NCT ID

NCT03802487

First Posted

January 10, 2019

Last Updated

April 21, 2022

Sponsor

Sanofi

1. Study Identification

Unique Protocol Identification Number

NCT03802487

Brief Title

Study To Determine Bioavailability of Sotagliflozin in Healthy Male and Female Subjects

Official Title

A Phase 1, Single-Center, Open-Label, Two-Period, One-Sequence, Single Dose Study to Determine the Absolute Bioavailability of Sotagliflozin in Healthy Male and Female Subjects

Study Type

Interventional

2. Study Status

Record Verification Date

April 2022

Overall Recruitment Status

Completed

Study Start Date

January 14, 2019 (Actual)

Primary Completion Date

March 28, 2019 (Actual)

Study Completion Date

March 28, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Sanofi

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

Brief Summary

Primary Objective: To assess the absolute bioavailability of sotagliflozin via administration of an intravenous (IV) microdose of a 14C-sotagliflozin tracer on top of a single oral dose of unlabeled sotagliflozin without charcoal administration Secondary Objectives: To assess the PK of sotagliflozin and its main metabolite sotagliflozin-3-O-glucuronide (M19) after a single oral dose of sotagliflozin and an IV microdose of a 14C-sotagliflozin tracer without charcoal administration To assess the safety and tolerability of single doses of sotagliflozin when administered with and without charcoal

Detailed Description

Study duration per participant is up to 54 days including a screening period of up to 28 days, period 1 of 8 days, period 2 of 8 days, a washout period of at least 10 days, and a follow up period of 12-16 days. The oral drug Sotagliflozin is metabolized by the liver and released in the bile juice into the intestine. Ingestion of charcoal a few hours after the drug administration circumvents the re-uptake of the drug from the intestine back into the blood circulation; instead, Sotagliflozin is eliminated with the feces. By comparison of Sotagliflozin drug administration with and without charcoal, the extent of this so-called enterohepatic circulation can be assessed.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Type 2 Diabetes Mellitus, Healthy Subjects

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

6 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Sotagliflozin

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Sotagliflozin (SAR439954)

Intervention Description

Pharmaceutical form: Tablet Route of administration: Oral

Intervention Type

Drug

Intervention Name(s)

14C-microtracer

Intervention Description

Pharmaceutical form: Solution for injection Route of administration: Intravenous

Intervention Type

Drug

Intervention Name(s)

Charcoal

Intervention Description

Pharmaceutical form: Granules for suspension Route of administration: Oral

Primary Outcome Measure Information:

Title

Pharmacokinetic (PK) parameter: Absolute Bioavailability (F)

Description

Time Frame

Baseline to Day 8 of period 1 (without charcoal)

Secondary Outcome Measure Information:

Title

Assessment of PK parameter: Area under the curve (AUC) for oral investigational medicinal product (IMP)

Description

Area under the plasma concentration versus time curve extrapolated to infinity for oral IMP

Time Frame