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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Diabetes Mellitus

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


Participation Criteria
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Eligibility Criteria
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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.

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
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 |