Clinical trial NCT03802487: Study To Determine Bioavailability of Sotagliflozin in Healthy Male and Female Subjects
Official title: A Phase 1, Single-Center, Open-Label, Two-Period, One-Sequence, Single Dose Study to Determine the Absolute Bioavailability of Sotagliflozin in Healthy Male and Female Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Type 2 Diabetes Mellitus
Healthy Subjects
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2019-01-14
Enrollment: 6
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: TREATMENT

Brief summary: Primary Objective:

To assess the absolute bioavailability of sotagliflozin via administration of an intravenous (IV) microdose of a 14C-sotagliflozin tracer on top of a single oral dose of unlabeled sotagliflozin without charcoal administration

Secondary Objectives:

* To assess the PK of sotagliflozin and its main metabolite sotagliflozin-3-O-glucuronide (M19) after a single oral dose of sotagliflozin and an IV microdose of a 14C-sotagliflozin tracer without charcoal administration
* To assess the safety and tolerability of single doses of sotagliflozin when administered with and without charcoal

Detailed description: Study duration per participant is up to 54 days including a screening period of up to 28 days, period 1 of 8 days, period 2 of 8 days, a washout period of at least 10 days, and a follow up period of 12-16 days.

The oral drug Sotagliflozin is metabolized by the liver and released in the bile juice into the intestine. Ingestion of charcoal a few hours after the drug administration circumvents the re-uptake of the drug from the intestine back into the blood circulation; instead, Sotagliflozin is eliminated with the feces. By comparison of Sotagliflozin drug administration with and without charcoal, the extent of this so-called enterohepatic circulation can be assessed.

Eligibility criteria: Inclusion criteria :

* Male or female subjects, between 18 and 55 years of age, inclusive.
* Body weight between 50.0 and 120.0 kg, inclusive, if male, and between 40.0 and 100.0 kg, inclusive, if female, body mass index (BMI) between 18.0 and 30.0 kg/m2, inclusive. BMI between 30.0 and 32.0 is acceptable if investigator judges the subject to have a high muscle mass.
* Certified as healthy by a comprehensive clinical assessment (detailed medical history and complete physical examination).
* Normal vital signs, ECG and laboratory parameters.

Exclusion criteria:

* Any history or presence of clinically relevant abnormalities at screening which could interfere with the objectives of the study or the safety of the subject's participation.
* Blood donation (400 mL) within 3 months before inclusion.
* History or presence of drug or alcohol abuse.
* Smoking regularly more than 5 cigarettes or equivalent per week, unable to stop smoking during the study.

Excessive consumption of beverages containing xanthine bases.

* If female, pregnancy (defined as positive β-Human Chorionic Gonadotropin blood test), breast-feeding.
* Any medication (including St John's Wort) within 14 days before inclusion with the exception of menopausal hormone replacement therapy; any vaccination within last 28 days; any biologics given within last 4 months.
* Any subject in the exclusion period of a previous study.
* Any subject who cannot be contacted in case of emergency.
* 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.
* Positive result on urine drug screen.
* Positive alcohol test.
* Participation in a study in which radioisotopes were administered or in which subject was exposed to any radiation other than normal background radiation within the 12 months before the screening visit.

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

Primary outcomes:
measure: Pharmacokinetic (PK) parameter: Absolute Bioavailability (F)
timeFrame: Baseline to Day 8 of period 1 (without charcoal)
Secondary outcomes:
measure: Assessment of PK parameter: Area under the curve (AUC) for oral investigational medicinal product (IMP)
timeFrame: Baseline to Day 8 of each period
measure: Assessment of PK parameter: AUC for IMP metabolite
timeFrame: Baseline to Day 8 of each period
measure: Assessment of PK parameter: AUC for IV 14C-IMP
timeFrame: Baseline to Day 8 of each period
measure: Assessment of PK parameter: AUC for 14C-IMP metabolite
timeFrame: Baseline to Day 8 of each period
measure: Assessment of PK parameter: Area under curve versus time (AUClast) for oral IMP
timeFrame: Baseline to Day 8 of each period
measure: Assessment of PK parameter: AUClast for IMP metabolite
timeFrame: Baseline to Day 8 of each period
measure: Assessment of PK parameter: AUClast for IV 14C-IMP
timeFrame: Baseline to Day 8 of each period
measure: Assessment of PK parameter: AUClast for 14C-IMP metabolite
timeFrame: Baseline to Day 8 of each period
measure: Assessment of PK parameter: Cmax for oral IMP
timeFrame: Baseline to Day 8 of each period
measure: Assessment of PK parameter: Cmax for IMP metabolite
timeFrame: Baseline to Day 8 of each period
measure: Assessment of PK parameter: Cmax for IV 14C-IMP
timeFrame: Baseline to Day 8 of each period
measure: Assessment of PK parameter: Cmax for 14C-IMP metabolite
timeFrame: Baseline to Day 8 of each period
measure: Assessment of PK parameter: tmax for oral IMP
timeFrame: Baseline to Day 8 of each period
measure: Assessment of PK parameter: tmax for IMP metabolite
timeFrame: Baseline to Day 8 of each period
measure: Assessment of PK parameter: tmax for IV 14C-IMP
timeFrame: Baseline to Day 8 of each period
measure: Assessment of PK parameter: tmax for 14C-IMP metabolite
timeFrame: Baseline to Day 8 of each period
measure: Assessment of PK parameter: t1/2z for oral IMP
timeFrame: Baseline to Day 8 of each period
measure: Assessment of PK parameter: t1/2z for IV 14C-IMP
timeFrame: Baseline to Day 8 of each period
measure: Assessment of PK parameter: Clearance (CL/F) for oral IMP
timeFrame: Baseline to Day 8 of each period
measure: Assessment of PK parameter: Clearance (CL/F) for IV 14C-IMP
timeFrame: Baseline to Day 8 of each period
measure: Assessment of PK parameter: Vz/F for oral IMP
timeFrame: Baseline to Day 8 of each period
measure: Assessment of PK parameter: Vz/F for IV 14C-IMP
timeFrame: Baseline to Day 8 of each period
measure: Assessment of PK parameter: Vdss/F for oral IMP
timeFrame: Baseline to Day 8 of each period
measure: Assessment of PK parameter: Vdss/F for IV 14C-IMP
timeFrame: Baseline to Day 8 of each period
measure: Safety: Adverse events
timeFrame: Baseline to Day 8 of each period
Other outcomes:
Locations:
city: Nottingham
country: United Kingdom
facility: Investigational site number 8260001
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: