A Drug to Drug Interaction Study of Sotagliflozin With Hydrochlorothiazide

Study Overview
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Brief Summary
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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

Detailed Description
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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.

Official Title
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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

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Sotagliflozin (SAR439954)
* Drug: Hydrochlorothiazide


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sotagliflozin + Hydrochlorothiazide (HCTZ)<br>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)<br>* Pharmaceutical form: Tablet Route of administration: Oral<br>Drug: Hydrochlorothiazide<br>* Pharmaceutical form: Tablet Route of administration: Oral<br>|

What is the study measuring?
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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 |