Study To Determine Bioavailability of Sotagliflozin in Healthy Male and Female Subjects

Phase 1

Completed

• Conditions: Type 2 Diabetes Mellitus; Healthy Subjects
• Interventions: Drug: Sotagliflozin (SAR439954); Drug: 14C-microtracer; Drug: Charcoal

• Registration Number: NCT03802487
• Lead Sponsor: Sanofi

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.

Study Timeline

• Study First Submitted: 2019-01-10
• Study First Submitted QC: 2019-01-10
• Study Start: 2019-01-14
• Study First Posted: 2019-01-14
• Primary Completion: 2019-03-28
• Study Completion: 2019-03-28
• Status Verified: 2022-04
• Last Update Submitted: 2022-04-21
• Last Update Posted: 2022-04-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 6

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Sotagliflozin	Sotagliflozin (SAR439954)	One treatment period includes a single oral dose of sotagliflozin + IV microdose 14C-sotagliflozin tracer plus charcoal. The other treatment period includes a single oral dose of sotagliflozin + IV microdose 14C-sotagliflozin tracer without charcoal.
Sotagliflozin	14C-microtracer	One treatment period includes a single oral dose of sotagliflozin + IV microdose 14C-sotagliflozin tracer plus charcoal. The other treatment period includes a single oral dose of sotagliflozin + IV microdose 14C-sotagliflozin tracer without charcoal.
Sotagliflozin	Charcoal	One treatment period includes a single oral dose of sotagliflozin + IV microdose 14C-sotagliflozin tracer plus charcoal. The other treatment period includes a single oral dose of sotagliflozin + IV microdose 14C-sotagliflozin tracer without charcoal.

Primary Outcome Measures

Name	Time	Method
Pharmacokinetic (PK) parameter: Absolute Bioavailability (F)	Baseline to Day 8 of period 1 (without charcoal)	Absolute Bioavailability (F) will be a composite endpoint and include Area under plasma concentration (AUC) dose normalized for intravenous (IV) 14C-IMP AUClast dose normalized for oral Investigational Medicinal Product (IMP)

Secondary Outcome Measures

Name	Time	Method
Assessment of PK parameter: Area under the curve (AUC) for oral investigational medicinal product (IMP)	Baseline to Day 8 of each period	Area under the plasma concentration versus time curve extrapolated to infinity for oral IMP
Assessment of PK parameter: Cmax for oral IMP	Baseline to Day 8 of each period	Maximum plasma concentration observed for oral IMP
Assessment of PK parameter: Cmax for IMP metabolite	Baseline to Day 8 of each period	Maximum plasma concentration observed for IMP metabolite
Assessment of PK parameter: AUC for IMP metabolite	Baseline to Day 8 of each period	Area under the plasma concentration versus time curve extrapolated to infinity for IMP metabolite
Assessment of PK parameter: AUC for IV 14C-IMP	Baseline to Day 8 of each period	Area under the plasma concentration versus time curve extrapolated to infinity for IV 14C-IMP
Assessment of PK parameter: AUC for 14C-IMP metabolite	Baseline to Day 8 of each period	Area under the plasma concentration versus time curve extrapolated to infinity for 14C-IMP metabolite
Assessment of PK parameter: Area under curve versus time (AUClast) for oral IMP	Baseline to Day 8 of each period	Area under the plasma concentration versus time curve calculated using the trapezoidal method from time zero to the real time tlast for oral IMP
Assessment of PK parameter: AUClast for IMP metabolite	Baseline to Day 8 of each period	Area under the plasma concentration versus time curve calculated using the trapezoidal method from time zero to the real time tlast for IMP metabolite
Assessment of PK parameter: AUClast for IV 14C-IMP	Baseline to Day 8 of each period	Area under the plasma concentration versus time curve calculated using the trapezoidal method from time zero to the real time tlast for IV 14C-IMP
Assessment of PK parameter: AUClast for 14C-IMP metabolite	Baseline to Day 8 of each period	Area under the plasma concentration versus time curve
Assessment of PK parameter: tmax for IMP metabolite	Baseline to Day 8 of each period	Time to reach Cmax for IMP metabolite
Assessment of PK parameter: Cmax for IV 14C-IMP	Baseline to Day 8 of each period	Maximum plasma concentration observed for IV 14C-IMP
Assessment of PK parameter: Cmax for 14C-IMP metabolite	Baseline to Day 8 of each period	Maximum plasma concentration observed for 14C-IMP metabolite
Assessment of PK parameter: tmax for oral IMP	Baseline to Day 8 of each period	Time to reach Cmax for oral IMP
Assessment of PK parameter: tmax for IV 14C-IMP	Baseline to Day 8 of each period	Time to reach Cmax for IV 14C-IMP
Assessment of PK parameter: tmax for 14C-IMP metabolite	Baseline to Day 8 of each period	Time to reach Cmax for 14C-IMP metabolite
Assessment of PK parameter: t1/2z for oral IMP	Baseline to Day 8 of each period	Terminal half-life (t1/2z) associated with the terminal slope for oral IMP
Assessment of PK parameter: t1/2z for IV 14C-IMP	Baseline to Day 8 of each period	Terminal half-life (t1/2z) associated with the terminal slope for IV 14C-IMP
Assessment of PK parameter: Clearance (CL/F) for oral IMP	Baseline to Day 8 of each period	Apparent total body clearance for oral IMP
Assessment of PK parameter: Clearance (CL/F) for IV 14C-IMP	Baseline to Day 8 of each period	Apparent total body clearance for IV 14C-IMP
Assessment of PK parameter: Vz/F for oral IMP	Baseline to Day 8 of each period	Apparent volume of distribution for oral IMP
Assessment of PK parameter: Vz/F for IV 14C-IMP	Baseline to Day 8 of each period	Apparent volume of distribution for IV 14C-IMP
Assessment of PK parameter: Vdss/F for oral IMP	Baseline to Day 8 of each period	Apparent volume of distribution at the steady state for oral IMP
Assessment of PK parameter: Vdss/F for IV 14C-IMP	Baseline to Day 8 of each period	Apparent volume of distribution at the steady state for IV 14C-IMP
Safety: Adverse events	Baseline to Day 8 of each period	Number of subjects with adverse events including serious, non-serious, and treatment emergent adverse events

Trial Locations

Locations (1)

Investigational site number 8260001; 🇬🇧 Nottingham, United Kingdom