Clinical trial NCT03070678: Interaction Study to Evaluate the Effects of Mefenamic Acid on the Pharmacokinetics and Pharmacodynamics of Sotagliflozin in Healthy Male and Female Subjects
Official title: Open-label, Cross Over, Single-sequence, Two Periods Phase 1 Drug-drug Interaction Study to Evaluate the Effects of Multiple-dose Mefenamic Acid, a Known UGT1A9 Inhibitor, on the Pharmacokinetics and Pharmacodynamics of Single-dose Sotagliflozin in Healthy Male and Female Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes Mellitus
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2017-03-03
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: Primary Objective:

To assess the effect of multiple dose mefenamic acid on the pharmacokinetics (PK) of sotagliflozin and its metabolite in healthy male and female subjects.

Secondary Objectives:

* To assess total 24 hour urinary glucose excretion (UGE) after 400 mg sotagliflozin alone and in combination with mefenamic acid in healthy male and female subjects.
* To assess the safety and tolerability of sotagliflozin alone and in combination with mefenamic acid in healthy male and female subjects.

Detailed description: The expected duration of the study is approximately 59 days per subject, including 2-28 days of screening, treatment period 1 of 7 days, treatment period 2 of 8 days, at least 7 days of wash-out period, and an end of study visit, which is between 14-21 days after the last dose of sotagliflozin.

Eligibility criteria: 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.
* Certified as healthy by a comprehensive clinical assessment (detailed medical history and complete physical examination).
* Normal vital signs, ECG, and laboratory parameters, aPTT (activated partial thromboplastin time) should not exceed normal control more than 10 seconds.
* 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.
* 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.

Exclusion criteria:

* Any history or presence of clinically relevant disease 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, 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.
* History or presence of drug or alcohol abuse.
* 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 (human chorionic gonadotropin) blood test if applicable), 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. 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.
* 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.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Primary outcomes:
measure: Maximum plasma concentration (Cmax)
timeFrame: Up to 144 hours after each SAR439954 intake
measure: Area under the concentration-time curve from 0 to the last quantifiable concentration (AUClast)
timeFrame: Up to 144 hours after each SAR439954 intake
measure: Area under the concentration-time curve from 0 to infinity (AUC0 ∞)
timeFrame: Up to 144 hours after each SAR439954 intake
Secondary outcomes:
measure: Total 24-hour UGE (urinary glucose excretion) after each dose with sotagliflozin
timeFrame: Up to 24 hours after each SAR439954 intake
Other outcomes:
Locations:
city: Gières
country: France
facility: Investigational site 250001
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: