A Bioequivalence Study Testing Two Formulations of Sotagliflozin in Healthy Male and Female Subjects Under Fasted Conditions

Primary Objective:

To determine the bioequivalence of a single dose of one tablet of sotagliflozin (test) compared to two tablets of sotagliflozin (reference) under fasting conditions in healthy male and female subjects

Secondary Objectives:

• To evaluate the single-dose pharmacokinetics of sotagliflozin following administration of one tablet sotagliflozin (test) compared to two tablets of sotagliflozin (reference) in healthy male and female subjects under fasting conditions
• To evaluate safety and tolerability of one tablet sotagliflozin (test) compared to two tablets of sotagliflozin (reference) administered under fasted conditions in healthy male and female subjects

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus; Healthy Subjects
• Intervention / Treatment: Drug: sotagliflozin (SAR439954)

Detailed Description

Study duration per participant is approximately 103 days including a screening period up to 21 days before first dose, 4 periods of dosing and pharmacokinetic (PK) sampling each lasting 7 days, a washout period of 8-21 days between dosing, and an end of study visit 10-15 days after the last dose.

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33014
      • Investigational Site Number 8400001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria :

• Healthy 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 after 10 minutes resting in supine position and after 3 minutes in standing position:

  • 95 mmHg < systolic blood pressure (SBP) <140 mmHg
  • 45 mmHg < diastolic blood pressure (DBP) <90 mmHg
  • 40 bpm < heart rate (HR) <100 bpm
• Standard 12-lead electrocardiogram (ECG) parameters after 10 minutes resting in supine position in the following ranges; 120 ms<PR<220 ms, QRS<120 ms, QTc≤430 ms if male, ≤450 ms if female and normal ECG tracing unless the Investigator considers an ECG tracing abnormality to be not clinically relevant.
• Laboratory parameters within the normal range, unless the Investigator considers an abnormality to be clinically irrelevant for healthy subjects; however serum creatinine, alkaline phosphatase, hepatic enzymes (aspartate aminotransferase, alanine aminotransferase), and total bilirubin (unless the subject has documented Gilbert syndrome) should not exceed the upper laboratory norm.
• 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 2 of the following 3 contraceptive options: (1) intrauterine device; (2) hormonal contraception; (3) condom or diaphragm or cervical/vault cap, in addition to spermicide. Menopause is defined as being amenorrheic for at least 2 years with plasma follicule-stimulating hormone (FSH) level >30 UI/L. Hormonal contraception is acceptable in this study (contraceptive guidance will be described in the study protocol).
• Having given written informed consent prior to undertaking any study-related procedure.
• Not under any administrative or legal supervision.
• 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 (intra-uterine device or hormonal contraceptive) from the inclusion up to 3 months after the last dosing. Male subject, whose partners are pregnant, must use, during sexual intercourse, a condom from the inclusion up to 3 months after the last dosing.
• Male subject has agreed not to donate sperm from the inclusion up to 3 months after the last dosing.

Exclusion criteria:

• Any history or presence of clinically relevant cardiovascular, pulmonary, gastrointestinal (especially pancreatitis), hepatic (especially biliary disease, including cholecystectomy), renal, metabolic, hematological, neurological, musculoskeletal, articular, psychiatric, systemic, ocular, gynecologic (if female), or infectious disease, or signs of acute illness.
• History of renal disease, or significantly abnormal kidney function test (glomerular filtration rate (GFR) <90 mL/min as calculated using the Cockcroft-Gault equation (7) at screening.
• Frequent headaches and/or migraine, recurrent nausea and/or vomiting (more than twice a month).
• Blood donation of a pint or more within 2 months before inclusion.
• Symptomatic postural hypotension, irrespective of the decrease in blood pressure, or asymptomatic postural hypotension defined as a decrease in systolic blood pressure ≥20 mmHg within 3 minutes when changing from supine to standing position.
• Presence or history of drug hypersensitivity, or allergic disease diagnosed and treated by a physician.
• History or presence of drug or alcohol abuse (alcohol consumption more than 40 g per day on a regular basis).
• Smoking more than 5 cigarettes or equivalent per day and/or unable to stop smoking during the study.
• Excessive consumption of beverages containing xanthine bases (more than 4 cups or glasses per day).
• If female, pregnancy (defined as positive human chorionic gonadotropin (β-HCG blood test), breast-feeding.
• Any medication (over-the counter or prescription medications, including St John's Wort), or any herbal supplements or supra-therapeutic vitamins within 14 days before inclusion or within 5 times the elimination half-life or pharmacodynamic half-life of the substance; any vaccination within the last 28 days, and any biologics (antibody or its derivatives) given within 4 months before inclusion.
• Any subject who, in the judgment of the Investigator, is likely to be noncompliant during the study, or unable to cooperate because of a language problem or poor mental development.
• Any subject in the exclusion period of a previous study according to applicable regulations.
• Any subject who cannot be contacted in case of emergency.
• Any subject who is the Investigator or any sub-investigator, research assistant, pharmacist, study coordinator, or other staff thereof, directly involved in conducting the study.
• Positive result on any of the following tests: hepatitis B surface (HBs Ag) antigen, anti hepatitis C virus antibodies, anti-human immunodeficiency virus 1 and 2 antibodies (anti HIV1 and anti HIV2 Ab).
• Positive result on urine drug screen (amphetamines/methamphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, opiates).
• Positive alcohol test.
• Any consumption of citrus (grapefruit, orange, etc) or their juices within 5 days before inclusion.
• Any history or presence of deep leg vein thrombosis or pulmonary embolism or a recurrent or frequent history of deep vein thrombosis in first degree relatives (parents, siblings or children).
• Any presence or history of urinary tract infection or genital mycotic infection in the last 4 weeks before screening.

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 Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sotagliflozin Test; One tablet of sotagliflozin administered orally under fasting conditions	Drug: sotagliflozin (SAR439954); Pharmaceutical form: tablet Route of administration: oral
Active Comparator: Sotagliflozin Reference; Two tablets of sotagliflozin administered orally under fasting conditions	Drug: sotagliflozin (SAR439954); Pharmaceutical form: tablet Route of administration: oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	Maximum plasma concentration observed	Day 1 of each period
AUC 0-72h (area under the curve)	Truncated AUC 0-72h	Day 1 to Day 3 of each period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to reach Cmax (tmax)	Time to reach Cmax	Day 1 of each period
Terminal half-life (t1/2z)	Terminal half-life associated with the terminal slope (λz)	Day 1 to Day 7 of each period
Area under the plasma concentration versus time curve (AUClast)	Area under the plasma concentration versus time curve calculated using the trapezoidal method from time zero to the real time tlast	Day 1 to Day 7 of each period
Adverse events	Number of participants with adverse events	Day 1 to Day 7 of each period
Electrocardiograms (ECGs)	Number of patients with clinically significant changes in electrocardiograms (ECGs)	Day 1 to Day 7 of each period
Vital signs	Number of patients with clinically significant changes in vital signs	Day 1 to Day 7 of each period
Clinical laboratory tests	Number of patients with clinically significant changes in clinical laboratory tests	Day 1 to Day 7 of each period
Area under the curve (AUC)	Area under the plasma concentration versus time curve extrapolated to infinity	Day 1 to Day 7 of each period

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): January 25, 2019
• Primary Completion (Actual): April 22, 2019
• Study Completion (Actual): April 22, 2019

Study Registration Dates

• First Submitted: December 12, 2018
• First Submitted That Met QC Criteria: December 12, 2018
• First Posted (Actual): December 14, 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; 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: BEQ14993; U1111-1205-3319 (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