Comparison of Sotagliflozin Prototype Tablets With Reference Tablet in Healthy Subjects

NCT03310944 | Completed Phase 1

• 3 other identifiers: BDR149942017-002104-27U1111-1195-6292
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Primary Objective: To assess the relative bioavailability of sotagliflozin following single doses of 3 sotagliflozin prototype tablet formulations p1, p2 and p3 versus the reference tablet formulation in fasted conditions in healthy subjects. Secondary Objectives:

• To assess the pharmacokinetic characteristics of sotagliflozin and its 3-O-glucuronide following single doses of 3 sotagliflozin prototype tablet formulations p1, p2 and p3 and of the reference formulation in fasted conditions in healthy subjects.
• To assess the clinical and laboratory safety of single oral doses of 3 sotagliflozin prototype tablet formulations p1, p2 and p3 and the reference tablet formulation in fasted conditions in healthy subjects.

Conditions

Type 1 Diabetes Mellitus; Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (3)

• Assessment of Pharmacokinetic (PK) Parameter: AUC

  Sotagliflozin: Area under the concentration-time curve from 0 to infinity (AUC) for reference, p1, p2, and p3 formulations

  From 0 to 144 hours after IMP intake

• Assessment of PK Parameter: Area under the concentration-time curve from 0 to last quantifiable concentration (AUClast)

  Sotagliflozin: Area under the concentration-time curve from 0 to last quantifiable concentration for reference, p1, p2, and p3 formulations

  From 0 to 144 hours after IMP intake

• Assessment of PK Parameter: Maximum plasma concentration (Cmax)

  Sotagliflozin: Maximum plasma concentration (Cmax) for reference, p1, p2, and p3 formulations

  From 0 to 144 hours after IMP intake

Secondary Outcomes (10)

• Assessment of PK Parameter: Tmax

  From 0 to 144 hours after investigational medicinal product (IMP) intake

• Assessment of PK Parameter: Time to reach AUClast (Tlast)

  From 0 to 144 hours after IMP intake

• Assessment of PK Parameter: Terminal elimination half-life (t1/2)

  From 0 to 144 hours after IMP intake

• Assessment of PK Parameter: Tmax

  From 0 to 144 hours after IMP intake

• Assessment of PK Parameter: Tlast

  From 0 to 144 hours after IMP intake

Study Arms (4)

Sotagliflozin dose 1 (reference formulation)

ACTIVE COMPARATOR

Single oral dose on Day 1 of one of the four period in fasting condition

Drug: sotagliflozin (SAR439954)

Sotagliflozin dose 2 (prototype p1 formulation)

EXPERIMENTAL

Single oral dose on Day 1 of one of the four period in fasting condition

Drug: sotagliflozin (SAR439954)

Sotagliflozin dose 3 (prototype p2 formulation)

EXPERIMENTAL

Single oral dose on Day 1 of one of the four period in fasting condition

Drug: sotagliflozin (SAR439954)

Sotagliflozin dose 4 (prototype p3 formulation)

EXPERIMENTAL

Single oral dose on Day 1 of one of the four period in fasting condition

Drug: sotagliflozin (SAR439954)

Interventions

sotagliflozin (SAR439954) DRUG

Pharmaceutical form: tablets Route of administration: oral

Sotagliflozin dose 1 (reference formulation); Sotagliflozin dose 2 (prototype p1 formulation); Sotagliflozin dose 3 (prototype p2 formulation); Sotagliflozin dose 4 (prototype p3 formulation)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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 32.0 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:
• mmHg \<systolic blood pressure (SBP) \<140 mmHg,
• mmHg \<diastolic blood pressure (DBP) \<90 mmHg,
• bpm \<heart rate (HR) \<100 bpm.
• Standard 12-lead electrocardiogram 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 and QTc≤450 ms if female with normal electrocardiogram (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 international normalized ratio (INR) should not exceed the upper laboratory norm. Activated partial thromboplastin time (aPTT) should not exceed normal control more than 10 seconds. Total bilirubin out of normal range can be acceptable if total bilirubin should not exceed 1.5 the upper limit with normal conjugated bilirubin values (unless the subject has documented Gilbert syndrome).
• 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 (FSH) level \>30 IU/L. Hormonal contraception is NOT acceptable in this study due to drug interaction.
• Having given written informed consent prior to undertaking any study-related procedure.
• Covered by a health insurance system where applicable, and/or in compliance with the recommendations of the national laws in force relating to biomedical research.
• Not under any administrative or legal supervision.

You may not qualify if:

• Any history or presence of clinically relevant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, metabolic, hematological, neurological, osteomuscular, articular, psychiatric, systemic, ocular, or infectious disease, or signs of acute illness.
• History of renal disease, or significant abnormal kidney function test with glomerular filtration rate (GFR) \<90 mL/min as calculated using the Cockcroft-Gault equation.
• Frequent headaches and/or migraine, recurrent nausea and/or vomiting (more than twice a month).
• 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, 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 β-HCG blood test if applicable), breast-feeding.
• 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 (amphetamines/methamphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, opiates).
• Positive alcohol test.
• 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).
• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (1)

Investigational Site Number 276001

Neuss, 41460, Germany

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2

Interventions

(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 11, 2017
• First Posted: October 16, 2017
• Study Start: October 18, 2017
• Primary Completion: December 8, 2017
• Study Completion: December 8, 2017
• Last Updated: April 13, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will share

Locations

DE (1)