A Drug to Drug Interaction Study of Sotagliflozin With Midazolam and Metoprolol

NCT02940379 | Completed Phase 1

• 2 other identifiers: INT14972U1111-1184-8677
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Primary Objective: To assess the effect of repeated once-daily oral doses of sotagliflozin on CYP2D6 and CYP3A activities using a CYP probe cocktail of metoprolol and midazolam. Secondary Objective: To assess the clinical and laboratory safety of sotagliflozin coadministered with the cocktail probes as compared to that of cocktail probes alone.

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (4)

• Assessment of midazolam pharmacokinetic (PK) parameter: Area under the curve (AUC)

  Day 1 to Day 2 of Treatment A Period

• Assessment of midazolam PK parameter: AUC

  Day 11 to Day 12 of Treatment B Period

• Assessment of metoprolol PK parameter: AUC

  Day 1 to Day 3 of Treatment A Period

• Assessment of metoprolol PK parameter: AUC

  Day 11 to Day 13 of Treatment B Period

Secondary Outcomes (12)

• Assessment of PK parameter: maximum plasma concentration (Cmax)

  Day 1 to Day 2 of Treatment A Period (midazolam)

• Assessment of PK parameter: Cmax

  Day 11 to Day 12 of Treatment B Period (midazolam)

• Assessment of PK parameter: Cmax

  Day 1 to Day 3 of Treatment A Period (metoprolol)

• Assessment of PK parameter: Cmax

  Day 11 to Day 13 of Treatment B Period (metoprolol)

• Assessment of PK parameter: time to reach Cmax (Tmax)

  Day 1 to Day 2 of Treatment A Period (midazolam)

Study Arms (2)

Cohort 1

EXPERIMENTAL

Participants will initially be given with treatment A (cocktail of metoprolol and midazolam) and then will start with treatment B (Dose 1 of Sotagliflozin plus cocktail) after 3 days

Drug: sotagliflozin (SAR439954); Drug: midazolam; Drug: metoprolol

Cohort 2

EXPERIMENTAL

Participants will initially be given with treatment A (cocktail of metoprolol and midazolam) and then will start with treatment B (Dose 2 of Sotagliflozin plus cocktail) after 3 days

Drug: sotagliflozin (SAR439954); Drug: midazolam; Drug: metoprolol

Interventions

sotagliflozin (SAR439954) DRUG

Pharmaceutical form: tablet Route of administration: oral

Cohort 1; Cohort 2

midazolam DRUG

Pharmaceutical form: HCl syrup Route of administration: oral

Cohort 1; Cohort 2

metoprolol DRUG

Pharmaceutical form: tablet Route of administration: oral

Cohort 1; Cohort 2

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female healthy 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 30.0 kg/m\^2, inclusive.
• Normal vital signs, electrocardiogram (ECG), and laboratory parameters
• Female subjects must use a double contraception method during the study, except if she has undergone sterilization at least 3 months earlier or is postmenopausal. The accepted double contraception methods include the use of one of the following contraceptive options: (1) condom; (2) diaphragm or cervical/vault cap; (3) spermicide in addition to the use of one of the following: a) Intrauterine device (IUD); b) Vasectomized partner; c) Sexual abstinence. Hormonal contraception is NOT acceptable in this study.

You may not qualify if:

• 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.
• Frequent headaches and/or migraine, recurrent nausea and/or vomiting.
• Symptomatic postural hypotension.
• Presence or history of drug hypersensitivity, allergic disease or asthma diagnosed and treated by a physician.
• History or presence of drug or alcohol abuse.
• If female, pregnancy or breast-feeding.
• Any contra-indications to metoprolol, according to the applicable labeling.
• Any contra-indications to midazolam, according to the applicable labeling.
• 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).
• The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (1)

Investigational Site Number 840001

Knoxville, Tennessee, 37920, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

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

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 19, 2016
• First Posted: October 20, 2016
• Study Start: October 1, 2016
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: April 25, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will share

Locations

US (1)