A Study to Evaluate the Effect of Food on the Pharmacokinetics of Sotagliflozin and to Explore the Relative Bioavailability in Healthy Subjects

A Phase 1, Randomized, Single-center, Open-label, Three-sequence, Three-period, Three-treatment Crossover Study to Evaluate the Effect of Food on the Single-dose Pharmacokinetics of Sotagliflozin and to Explore the Relative Bioavailability of Sotagliflozin Oral Tablet to Oral Solution in Healthy Male and Female Subjects

Primary Objective:

To evaluate the effect of food on the single-dose pharmacokinetics of sotagliflozin relative to a fasted state in healthy adult male and female subjects.

Secondary Objectives:

• To evaluate the effect of food on the single-dose pharmacokinetics of the main metabolite (sotagliflozin 3-O-glucuronide) relative to a fasted state in healthy adult male and female subjects.
• To investigate the relative bioavailability of sotagliflozin tablet to oral solution under fasting conditions
• To evaluate safety and tolerability of single-dose sotagliflozin under fed and fasted conditions in healthy adult male and female subjects.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus
• Intervention / Treatment: Drug: Sotagliflozin (SAR439954); Drug: Sotagliflozin (SAR439954)

Detailed Description

The study duration per subject will be 26 to 83 days and will consist of a screening period of 2-28 days, a treatment period of 6 days each for Periods 1, 2 and 3, a washout between treatment periods of 1-14 days, and follow up visit 10-15 days after the last Investigational Medicinal Product administration in period 3.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Leeds, United Kingdom, LS2 9LH
    • Investigational Site Number 826001

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 :

• Healthy male and female subjects, between 18 and 55 years of age, inclusive, at the time of screening.
• Body weight between 50.0 and 100.0 kg, inclusive, if male, and between 40.0 and 90.0 kg, inclusive, if female; body mass index between 18.0 and 30.0 kg/m2, inclusive.
• Certified as healthy by a comprehensive clinical assessment (detailed medical history and complete physical examination), vital signs, ECG, and clinical laboratory parameters.

Exclusion criteria:

• Any history or presence of clinically relevant illness at screening, which could interfere with the objectives of the study or the safety of the subject's participation.
• Frequent headaches and/or migraine, recurrent nausea and/or vomiting (more than twice a month).
• Blood donation any volume, within 2 months before inclusion.
• Symptomatic postural hypotension.
• Presence or history of drug hypersensitivity, or allergic disease diagnosed and treated by a physician.
• History or presence of drug or alcohol abuse.
• Smoking more than 5 cigarettes or equivalent per day, unable to stop smoking during the study.
• If female, pregnancy, breast-feeding.
• Any medication (including St John's Wort) within 14 days before inclusion or within 5 times the elimination half-life or pharmacodynamic half-life of the medication; any vaccination within the last 28 days and any biologics (antibody or its derivatives) given within 4 months before inclusion.

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: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Fed Tablet period (Test, T); Sotagliflozin oral in fed conditions	Drug: Sotagliflozin (SAR439954); Pharmaceutical form: tablet Route of administration: oral; Drug: Sotagliflozin (SAR439954); Pharmaceutical form: solution Route of administration: oral
EXPERIMENTAL: Fasted Tablet period (Reference, R); Sotagliflozin oral in fasting conditions	Drug: Sotagliflozin (SAR439954); Pharmaceutical form: tablet Route of administration: oral; Drug: Sotagliflozin (SAR439954); Pharmaceutical form: solution Route of administration: oral
EXPERIMENTAL: Oral Solution period (S); Sotagliflozin oral solution in fasting conditions	Drug: Sotagliflozin (SAR439954); Pharmaceutical form: tablet Route of administration: oral; Drug: Sotagliflozin (SAR439954); Pharmaceutical form: solution Route of administration: oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum plasma drug concentration (Cmax) of sotagliflozin	From 0 to 120 hours after sotagliflozin intake
Area under curve (AUC) of sotagliflozin	From 0 to 120 hours after sotagliflozin intake

Secondary Outcome Measures

Outcome Measure	Time Frame
Sotagliflozin (tablet and oral solution):Apparent volume of distribution during terminal phase after non-intravenous administration (Vz/F)	From 0 to 120 hours after sotagliflozin intake
Sotagliflozin (tablet and oral solution): Time to reach maximum plasma concentration (tmax)	From 0 to 120 hours after sotagliflozin intake
Sotagliflozin (tablet and oral solution): Elimination half-life (t1/2z)	From 0 to 120 hours after sotagliflozin intake
Sotagliflozin-O-glucuronide (tablet and oral solution): Cmax	From 0 to 120 hours after sotagliflozin intake
Sotagliflozin-O-glucuronide (tablet and oral solution): tmax	From 0 to 120 hours after sotagliflozin intake
Sotagliflozin-O-glucuronide (tablet and oral solution): t1/2z	From 0 to 120 hours after sotagliflozin intake
Sotagliflozin-O-glucuronide (tablet and oral solution): Area under the plasma concentration-time curve from time zero to time of last measurable concentration (AUClast)	From 0 to 120 hours after sotagliflozin intake
Sotagliflozin-O-glucuronide (tablet and oral solution): AUC	From 0 to 120 hours after sotagliflozin intake
Relative bioavailability (Frel)	From 0 to 120 hours after sotagliflozin intake
Number (%) of subjects with treatment emergent adverse events	Over 9 weeks

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 12, 2017
• Primary Completion (ACTUAL): September 15, 2017
• Study Completion (ACTUAL): September 15, 2017

Study Registration Dates

• First Submitted: May 31, 2017
• First Submitted That Met QC Criteria: June 1, 2017
• First Posted (ACTUAL): June 2, 2017

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: Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; (2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol
• Other Study ID Numbers: PKM15047; 2016-004650-15 (EUDRACT_NUMBER); U1111-1189-5094 (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: Yes
• Studies a U.S. FDA-regulated device product: No