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

Type 2 Diabetes Mellitus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03802487
• Other study ID #: PKM15402
• Secondary ID: 2017-004937-94U1
• Status: Completed
• Phase: Phase 1
• Start date: January 14, 2019
• Est. completion date: March 28, 2019

Study information

• Verified date: April 2022
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: March 28, 2019
• Est. primary completion date: March 28, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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 ß-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.

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Healthy Subjects
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Sotagliflozin (SAR439954)
Pharmaceutical form: Tablet Route of administration: Oral
• 14C-microtracer
Pharmaceutical form: Solution for injection Route of administration: Intravenous
• Charcoal
Pharmaceutical form: Granules for suspension Route of administration: Oral

Locations

Country	Name	City	State
United Kingdom	Investigational site number 8260001	Nottingham

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetic (PK) parameter: Absolute Bioavailability (F)	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)	Baseline to Day 8 of period 1 (without charcoal)
Secondary	Assessment of PK parameter: Area under the curve (AUC) for oral investigational medicinal product (IMP)	Area under the plasma concentration versus time curve extrapolated to infinity for oral IMP	Baseline to Day 8 of each period
Secondary	Assessment of PK parameter: AUC for IMP metabolite	Area under the plasma concentration versus time curve extrapolated to infinity for IMP metabolite	Baseline to Day 8 of each period
Secondary	Assessment of PK parameter: AUC for IV 14C-IMP	Area under the plasma concentration versus time curve extrapolated to infinity for IV 14C-IMP	Baseline to Day 8 of each period
Secondary	Assessment of PK parameter: AUC for 14C-IMP metabolite	Area under the plasma concentration versus time curve extrapolated to infinity for 14C-IMP metabolite	Baseline to Day 8 of each period
Secondary	Assessment of PK parameter: Area under curve versus time (AUClast) for oral IMP	Area under the plasma concentration versus time curve calculated using the trapezoidal method from time zero to the real time tlast for oral IMP	Baseline to Day 8 of each period
Secondary	Assessment of PK parameter: AUClast for IMP metabolite	Area under the plasma concentration versus time curve calculated using the trapezoidal method from time zero to the real time tlast for IMP metabolite	Baseline to Day 8 of each period
Secondary	Assessment of PK parameter: AUClast for IV 14C-IMP	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	Baseline to Day 8 of each period
Secondary	Assessment of PK parameter: AUClast for 14C-IMP metabolite	Area under the plasma concentration versus time curve	Baseline to Day 8 of each period
Secondary	Assessment of PK parameter: Cmax for oral IMP	Maximum plasma concentration observed for oral IMP	Baseline to Day 8 of each period
Secondary	Assessment of PK parameter: Cmax for IMP metabolite	Maximum plasma concentration observed for IMP metabolite	Baseline to Day 8 of each period
Secondary	Assessment of PK parameter: Cmax for IV 14C-IMP	Maximum plasma concentration observed for IV 14C-IMP	Baseline to Day 8 of each period
Secondary	Assessment of PK parameter: Cmax for 14C-IMP metabolite	Maximum plasma concentration observed for 14C-IMP metabolite	Baseline to Day 8 of each period
Secondary	Assessment of PK parameter: tmax for oral IMP	Time to reach Cmax for oral IMP	Baseline to Day 8 of each period
Secondary	Assessment of PK parameter: tmax for IMP metabolite	Time to reach Cmax for IMP metabolite	Baseline to Day 8 of each period
Secondary	Assessment of PK parameter: tmax for IV 14C-IMP	Time to reach Cmax for IV 14C-IMP	Baseline to Day 8 of each period
Secondary	Assessment of PK parameter: tmax for 14C-IMP metabolite	Time to reach Cmax for 14C-IMP metabolite	Baseline to Day 8 of each period
Secondary	Assessment of PK parameter: t1/2z for oral IMP	Terminal half-life (t1/2z) associated with the terminal slope for oral IMP	Baseline to Day 8 of each period
Secondary	Assessment of PK parameter: t1/2z for IV 14C-IMP	Terminal half-life (t1/2z) associated with the terminal slope for IV 14C-IMP	Baseline to Day 8 of each period
Secondary	Assessment of PK parameter: Clearance (CL/F) for oral IMP	Apparent total body clearance for oral IMP	Baseline to Day 8 of each period
Secondary	Assessment of PK parameter: Clearance (CL/F) for IV 14C-IMP	Apparent total body clearance for IV 14C-IMP	Baseline to Day 8 of each period
Secondary	Assessment of PK parameter: Vz/F for oral IMP	Apparent volume of distribution for oral IMP	Baseline to Day 8 of each period
Secondary	Assessment of PK parameter: Vz/F for IV 14C-IMP	Apparent volume of distribution for IV 14C-IMP	Baseline to Day 8 of each period
Secondary	Assessment of PK parameter: Vdss/F for oral IMP	Apparent volume of distribution at the steady state for oral IMP	Baseline to Day 8 of each period
Secondary	Assessment of PK parameter: Vdss/F for IV 14C-IMP	Apparent volume of distribution at the steady state for IV 14C-IMP	Baseline to Day 8 of each period
Secondary	Safety: Adverse events	Number of subjects with adverse events including serious, non-serious, and treatment emergent adverse events	Baseline to Day 8 of each period