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

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

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

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus; Healthy Subjects
• Intervention / Treatment: Drug: Sotagliflozin (SAR439954); Drug: 14C-microtracer; Drug: 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.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Nottingham, United Kingdom, NG11 6JS
    • Investigational Site Number 8260001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Sotagliflozin; 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.	Drug: Sotagliflozin (SAR439954); Pharmaceutical form: Tablet Route of administration: Oral; Drug: 14C-microtracer; Pharmaceutical form: Solution for injection Route of administration: Intravenous; Drug: Charcoal; Pharmaceutical form: Granules for suspension Route of administration: Oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	Baseline to Day 8 of period 1 (without charcoal)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Baseline to Day 8 of each period
Assessment of PK parameter: AUC for IMP metabolite	Area under the plasma concentration versus time curve extrapolated to infinity for IMP metabolite	Baseline to Day 8 of each period
Assessment of PK parameter: AUC for IV 14C-IMP	Area under the plasma concentration versus time curve extrapolated to infinity for IV 14C-IMP	Baseline to Day 8 of each period
Assessment of PK parameter: AUC for 14C-IMP metabolite	Area under the plasma concentration versus time curve extrapolated to infinity for 14C-IMP metabolite	Baseline to Day 8 of each period
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	Baseline to Day 8 of each period
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	Baseline to Day 8 of each period
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	Baseline to Day 8 of each period
Assessment of PK parameter: AUClast for 14C-IMP metabolite	Area under the plasma concentration versus time curve	Baseline to Day 8 of each period
Assessment of PK parameter: Cmax for oral IMP	Maximum plasma concentration observed for oral IMP	Baseline to Day 8 of each period
Assessment of PK parameter: Cmax for IMP metabolite	Maximum plasma concentration observed for IMP metabolite	Baseline to Day 8 of each period
Assessment of PK parameter: Cmax for IV 14C-IMP	Maximum plasma concentration observed for IV 14C-IMP	Baseline to Day 8 of each period
Assessment of PK parameter: Cmax for 14C-IMP metabolite	Maximum plasma concentration observed for 14C-IMP metabolite	Baseline to Day 8 of each period
Assessment of PK parameter: tmax for oral IMP	Time to reach Cmax for oral IMP	Baseline to Day 8 of each period
Assessment of PK parameter: tmax for IMP metabolite	Time to reach Cmax for IMP metabolite	Baseline to Day 8 of each period
Assessment of PK parameter: tmax for IV 14C-IMP	Time to reach Cmax for IV 14C-IMP	Baseline to Day 8 of each period
Assessment of PK parameter: tmax for 14C-IMP metabolite	Time to reach Cmax for 14C-IMP metabolite	Baseline to Day 8 of each period
Assessment of PK parameter: t1/2z for oral IMP	Terminal half-life (t1/2z) associated with the terminal slope for oral IMP	Baseline to Day 8 of each period
Assessment of PK parameter: t1/2z for IV 14C-IMP	Terminal half-life (t1/2z) associated with the terminal slope for IV 14C-IMP	Baseline to Day 8 of each period
Assessment of PK parameter: Clearance (CL/F) for oral IMP	Apparent total body clearance for oral IMP	Baseline to Day 8 of each period
Assessment of PK parameter: Clearance (CL/F) for IV 14C-IMP	Apparent total body clearance for IV 14C-IMP	Baseline to Day 8 of each period
Assessment of PK parameter: Vz/F for oral IMP	Apparent volume of distribution for oral IMP	Baseline to Day 8 of each period
Assessment of PK parameter: Vz/F for IV 14C-IMP	Apparent volume of distribution for IV 14C-IMP	Baseline to Day 8 of each period
Assessment of PK parameter: Vdss/F for oral IMP	Apparent volume of distribution at the steady state for oral IMP	Baseline to Day 8 of each period
Assessment of PK parameter: Vdss/F for IV 14C-IMP	Apparent volume of distribution at the steady state for IV 14C-IMP	Baseline to Day 8 of each period
Safety: Adverse events	Number of subjects with adverse events including serious, non-serious, and treatment emergent adverse events	Baseline to Day 8 of each period

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 14, 2019
• Primary Completion (ACTUAL): March 28, 2019
• Study Completion (ACTUAL): March 28, 2019

Study Registration Dates

• First Submitted: January 10, 2019
• First Submitted That Met QC Criteria: January 10, 2019
• First Posted (ACTUAL): January 14, 2019

Study Record Updates

• Last Update Posted (ACTUAL): April 25, 2022
• Last Update Submitted That Met QC Criteria: April 21, 2022
• Last Verified: April 1, 2022

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; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Sodium-Glucose Transporter 2 Inhibitors; Antidotes; (2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol; Charcoal
• Other Study ID Numbers: PKM15402; 2017-004937-94 (EUDRACT_NUMBER); U1111-1200-2077 (OTHER: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

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