Comparison of Sotagliflozin Prototype Tablets With Reference Tablet in Healthy Subjects

Sponsor

Sanofi (Industry)

Overall Status

Completed

CT.gov ID

NCT03310944

Collaborator

(none)

Enrollment

Location

Arms

1.7

Actual Duration (Months)

7.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Type 1 Diabetes Mellitus Type 2 Diabetes Mellitus	Drug: sotagliflozin (SAR439954)	Phase 1

Detailed Description

Total duration is 37 to 75 days for each subject, with 2 to 21 days screening period; 4 dosing days, i.e. one in each of the 4 treatment periods. Observation period in each treatment period is 6 days. Washout between dosing days is 7 to 10 days. Follow-up visit is 14-21 days after last dosing.

Study Design

Study Type:

Interventional

Actual Enrollment :

12 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Primary Purpose:

Health Services Research

Official Title:

An Open-label, Randomized, Single-dose, 4-period, 4-sequence Crossover Relative Bioavailability Study Comparing Sotagliflozin Prototypes Tablets With Reference Tablet in Healthy Subjects

Actual Study Start Date :

Oct 18, 2017

Actual Primary Completion Date :

Dec 8, 2017

Actual Study Completion Date :

Dec 8, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Sotagliflozin dose 1 (reference formulation) Single oral dose on Day 1 of one of the four period in fasting condition	Drug: sotagliflozin (SAR439954) Pharmaceutical form: tablets Route of administration: oral
Experimental: Sotagliflozin dose 2 (prototype p1 formulation) Single oral dose on Day 1 of one of the four period in fasting condition	Drug: sotagliflozin (SAR439954) Pharmaceutical form: tablets Route of administration: oral
Experimental: Sotagliflozin dose 3 (prototype p2 formulation) Single oral dose on Day 1 of one of the four period in fasting condition	Drug: sotagliflozin (SAR439954) Pharmaceutical form: tablets Route of administration: oral
Experimental: Sotagliflozin dose 4 (prototype p3 formulation) Single oral dose on Day 1 of one of the four period in fasting condition	Drug: sotagliflozin (SAR439954) Pharmaceutical form: tablets Route of administration: oral

Outcome Measures

Primary Outcome Measures

Assessment of Pharmacokinetic (PK) Parameter: AUC [From 0 to 144 hours after IMP intake]
Sotagliflozin: Area under the concentration-time curve from 0 to infinity (AUC) for reference, p1, p2, and p3 formulations
Assessment of PK Parameter: Area under the concentration-time curve from 0 to last quantifiable concentration (AUClast) [From 0 to 144 hours after IMP intake]
Sotagliflozin: Area under the concentration-time curve from 0 to last quantifiable concentration for reference, p1, p2, and p3 formulations
Assessment of PK Parameter: Maximum plasma concentration (Cmax) [From 0 to 144 hours after IMP intake]
Sotagliflozin: Maximum plasma concentration (Cmax) for reference, p1, p2, and p3 formulations

Secondary Outcome Measures

Assessment of PK Parameter: Tmax [From 0 to 144 hours after investigational medicinal product (IMP) intake]
Sotagliflozin: Time to reach maximum plasma concentration (Tmax)
Assessment of PK Parameter: Time to reach AUClast (Tlast) [From 0 to 144 hours after IMP intake]
Sotagliflozin: Time to reach AUClast
Assessment of PK Parameter: Terminal elimination half-life (t1/2) [From 0 to 144 hours after IMP intake]
Sotagliflozin: Terminal elimination half-life (t1/2)
Assessment of PK Parameter: Tmax [From 0 to 144 hours after IMP intake]
Sotagliflozin 3-O-glucuronide: Tmax
Assessment of PK Parameter: Tlast [From 0 to 144 hours after IMP intake]
Sotagliflozin 3-O-glucuronide: Time to reach AUClast
Assessment of PK Parameter: t1/2 [From 0 to 144 hours after IMP intake]
Sotagliflozin 3-O-glucuronide: t1/2
Assessment of PK Parameter: Cmax [From 0 to 144 hours after IMP intake]
Sotagliflozin 3-O-glucuronide: Cmax
Assessment of PK Parameter: AUC [From 0 to 144 hours after IMP intake]
Sotagliflozin 3-O-glucuronide: AUC
Assessment of PK Parameter: AUClast [From 0 to 144 hours after IMP intake]
Sotagliflozin 3-O-glucuronide: AUClast
Adverse Events [Up to 75 days]
Number of patients with treatment emergent adverse events (serious and non-serious)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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 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:
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 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.
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 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).
Blood donation, any volume, within 2 months before inclusion.
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.
Any medication (including St John's Wort) within 14 days before inclusion; any vaccination within the last 28 days and any biologics (antibody or its derivatives) given within 4 months before inclusion.

Any oral contraceptives during the screening period or for at least 15 days prior to inclusion; any injectable contraceptives or hormonal intrauterine devices within 12 months prior to inclusion; or topical controlled delivery contraceptives (patch) for 3 months prior to inclusion.

Any subject in the exclusion period of a previous study according to applicable regulations.
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 consumption of citrus (grapefruit, orange, etc) or their juices within 5 days before inclusion.
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigational Site Number 276001	Neuss		Germany	41460

Sponsors and Collaborators

Sanofi

Investigators

Study Director: Clinical Sciences & Operations, Sanofi

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Sanofi

ClinicalTrials.gov Identifier:

NCT03310944

Other Study ID Numbers:

BDR14994
2017-002104-27
U1111-1195-6292

First Posted:

Oct 16, 2017

Last Update Posted:

Apr 13, 2022

Last Verified:

Apr 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Additional relevant MeSH terms:

Diabetes Mellitus

Diabetes Mellitus, Type 1

Diabetes Mellitus, Type 2

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

Study Results

No Results Posted as of Apr 13, 2022