A Drug to Drug Interaction Study of Sotagliflozin With Hydrochlorothiazide

A Phase 1, Single-Center, Open-Label, Two-Period, Single-Sequence, Multiple Dosing Drug-Drug Interaction Study of Sotagliflozin and Hydrochlorothiazide in Healthy Male and Female Subjects

Primary Objective:

To assess the effects of multiple-dose hydrochlorothiazide (HCTZ) on the steady-state pharmacokinetics (PK) of sotagliflozin.

Secondary Objectives:

• To assess the safety and tolerability of multiple-dose sotagliflozin with and without co-administration of multiple-dose HCTZ
• To assess the effects of multiple-dose sotagliflozin on the steady-state PK of HCTZ
• To assess the effects of multiple-dose HCTZ on the steady-state PK of sotagliflozin-3-O-glucuronide

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Sotagliflozin (SAR439954); Drug: Hydrochlorothiazide

Detailed Description

Duration of the study for each subject will be between 33 to 77 days, including screening up to 28 days, 5 days of treatment Period 1, washout period of 7-21 days, 9 days of treatment Period 2, and follow-up period of 10-14 days after last dose of the Investigational Medicinal Product (IMP) in Period 2.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75247
      • Investigational Site Number 8400001

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 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).
• Normal vital signs, electrocardiogram, and laboratory parameters.
• Female subject must use a double contraception method including a highly effective method of birth control, except if she has undergone sterilization at least 3 months earlier or is postmenopausal. The accepted double contraception methods include the use of 1 of the following contraceptive options: (1) intrauterine device; (2) condom or diaphragm or cervical/vault cap, in addition to spermicide. Menopause is defined as being amenorrheic for at least 2 years with plasma follicle stimulating hormone level >30 IU. Hormonal contraception is NOT acceptable in this study.
• Male subject, whose partners are of childbearing potential (including lactating women), must accept to use, during sexual intercourse, a double contraception method according to the following algorithm: (condom) plus (spermicide or intra-uterine device or hormonal contraceptive) from the inclusion up to 4 months after the last dosing.
• Male subject, whose partners are pregnant, must use, during sexual intercourse, a condom from the inclusion up to 4 months after the last dosing.
• Male subject has agreed not to donate sperm from the inclusion up to 4 months after the last dosing.

Exclusion criteria:

• 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, with the exception of hormonal contraception or menopausal hormone replacement therapy; any vaccination within the last 28 days and any biologics (antibody or its derivatives) given within 4 months before inclusion.
• 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 (anti-HIV1 and anti HIV2 Ab).
• Positive result on urine drug screen or alcohol test.
• Any contra-indications to hydrochlorothiazide, according to the applicable labeling.
• Any history or presence of deep leg vein thrombosis or embolism or a recurrent or frequent appearance of deep leg vein thrombosis in first degree relatives (parents, siblings or children).

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: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sotagliflozin + Hydrochlorothiazide (HCTZ); Sotagliflozin to be administered alone in Period 1. HCTZ to be given in Period 2 for 4 days followed immediately by HCTZ and sotagliflozin for 5 days.	Drug: Sotagliflozin (SAR439954); Pharmaceutical form: Tablet Route of administration: Oral; Drug: Hydrochlorothiazide; Pharmaceutical form: Tablet Route of administration: Oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of PK parameter: AUCtau	Sotagliflozin without HCTZ: AUC to the end of the dosing period (AUCtau)	Period 1, days 2 to 6
Assessment of PK parameter: AUCtau	Sotagliflozin with HCTZ: AUCtau	Period 2, days 6 to 10

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of PK parameter: AUCtau	HCTZ without sotagliflozin: AUCtau	Period 2, days 4 to 5
Assessment of PK parameter: AUCtau	HCTZ with sotagliflozin: AUCtau	Period 2, days 9 to 10
Assessment of PK parameter: AUCtau	Sotagliflozin-3-O-glucuronide without HCTZ: AUCtau	Period 1, days 2 to 6
Assessment of PK parameter: AUCtau	Sotagliflozin-3-O-glucuronide with HCTZ: AUCtau	Period 2, days 6 to 10
Assessment of PK parameter: Cmax	HCTZ without sotagliflozin: Maximum plasma concentration (Cmax)	Period 2, days 4 to 5
Assessment of PK parameter: Cmax	HCTZ with sotagliflozin: Cmax	Period 2, days 9 to 10
Assessment of PK parameter: Cmax	Sotagliflozin-3-O-glucuronide without HCTZ: Cmax	Period 1, days 2 to 6
Assessment of PK parameter: Cmax	Sotagliflozin-3-O-glucuronide with HCTZ: Cmax	Period 2, days 6 to 10
Assessment of PK parameter: tmax	HCTZ without sotagliflozin: Time to reach Cmax (tmax)	Period 2, days 4 to 5
Assessment of PK parameter: tmax	HCTZ with sotagliflozin: tmax	Period 2, days 9 to 10
Assessment of PK parameter: tmax	Sotagliflozin-3-O-glucuronide without HCTZ: tmax	Period 1, days 2 to 6
Assessment of PK parameter: tmax	Sotagliflozin-3-O-glucuronide with HCTZ: tmax	Period 2, days 6 to 10
Assessment of PK parameter: Cmax	Sotagliflozin without HCTZ: Cmax	Period 1, days 2 to 6
Assessment of PK parameter: Cmax	Sotagliflozin with HCTZ: Cmax	Period 2, days 6 to 10
Assessment of PK parameter: tmax	Sotagliflozin without HCTZ: tmax	Period 1, days 2 to 6
Assessment of PK parameter: tmax	Sotagliflozin with HCTZ: tmax	Period 2, days 6 to 10

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2018
• Primary Completion (Actual): March 2, 2018
• Study Completion (Actual): March 2, 2018

Study Registration Dates

• First Submitted: December 20, 2017
• First Submitted That Met QC Criteria: December 22, 2017
• First Posted (Actual): January 2, 2018

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; Antihypertensive Agents; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Sodium-Glucose Transporter 2 Inhibitors; Sodium Chloride Symporter Inhibitors; (2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol; Hydrochlorothiazide
• Other Study ID Numbers: INT14905; U1111-1186-2718 (Other Identifier: 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