A Drug-Drug Interaction Study Between Sotagliflozin and Ramipril

NCT03414723 | Completed Phase 1

• 3 other identifiers: INT149352017-002650-37U1111-1196-5355
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

Primary Objective: To evaluate the effects of multiple-dose ramipril on the steady state pharmacokinetic (PK) parameters of sotagliflozin and its main metabolite (sotagliflozin-3-O-glucuronide) in healthy male and female subjects. Secondary Objectives:

• To assess the effects of multiple-dose sotagliflozin on the PK of ramipril and its active metabolite (ramiprilat).
• To assess the safety and tolerability of multiple-dose sotagliflozin with and without multiple-dose of ramipril.

Conditions

Diabetes Mellitus; Healthy Subjects

Outcome Measures

Primary Outcomes (2)

• Assessment of PK parameter: AUCtau

  Sotagliflozin with ramipril: Area under the curve (AUC) to the end of the dosing period (AUCtau)

  On Day 10 (Period 2)

• Assessment of PK parameter: AUCtau

  Sotagliflozin without ramipril: AUCtau

  On Day 5 (Period 1)

Secondary Outcomes (5)

• Assessment of PK parameter: Cmax

  On Day 10 (Period 2)

• Assessment of PK parameter: Cmax

  On Day 5 (Period 1)

• Assessment of PK parameter: tmax

  On Day 10 (Period 2)

• Assessment of PK parameter: tmax

  On Day 5 (Period 1)

• Adverse events

  Up to Day 37

Study Arms (1)

SAR439954 with or without ramipril

EXPERIMENTAL

* On Period 1, following an overnight fast, subjects will receive once daily single morning oral intake of sotagliflozin from Day 1 to Day 5 followed by the first meal that has to be started within 10 min after dosing. * On Day 1 of the Period 2, study subjects will begin a 10-day ramipril regimen following an overnight fast. From Day 6 to Day 10, subjects will receive once daily single morning oral intake of ramipril concomitantly to the sotagliflozin dosing.

Drug: Sotagliflozin (SAR439954); Drug: Ramipril

Interventions

Sotagliflozin (SAR439954) DRUG

Pharmaceutical form: tablets Route of administration: oral

SAR439954 with or without ramipril

Ramipril DRUG

Pharmaceutical form: tablets Route of administration: oral

SAR439954 with or without ramipril

Eligibility Criteria

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

You may qualify if:

• 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, body mass index between 18.0 and 32.0 kg/m², inclusive.
• Certified as healthy by a comprehensive clinical assessment (detailed medical history and complete physical examination).
• Normal vital signs after 10 minutes resting in supine position:
• mmHg \<systolic blood pressure (SBP) \<140 mmHg,
• mmHg \<diastolic blood pressure (DBP) \<90 mmHg,
• bpm \<heart rate (HR) \<90 bpm.
• Standard 12-lead electrocardiogram (ECG) parameters after 10 minutes resting in supine position in the following ranges; 120 ms\<PR\<200 ms, QRS \<120 ms, QTc ≤430 ms if male and QTc ≤450 ms if female with normal ECG tracing unless the Investigator considers an ECG tracing abnormality to be not clinically relevant.
• Laboratory parameters within the normal range, unless the Investigator considers an abnormality to be clinically irrelevant for healthy subjects; however serum creatinine, alkaline phosphatase, hepatic enzymes (aspartate aminotransferase, alanine aminotransferase) should be strictly below the ULN. Total bilirubin out of normal range can be acceptable if total bilirubin should not exceed 1.5 the upper limit with normal conjugated bilirubin values (unless the subject has documented Gilbert syndrome).
• 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. The accepted double contraception methods include the use of 1 of the following contraceptive options: (1) intrauterine device; (2) condom or diaphragm or cervical/vault cap, in addition to spermicide. Menopause is defined as being amenorrheic for at least 2 years with plasma follicle stimulating hormone (FSH) value being within the normal range for postmenopausal women according to the local laboratory. Hormonal contraception is NOT acceptable in this study due to drug interaction.
• Having given written informed consent prior to undertaking any study-related procedure.

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.
• History of renal disease, or significant abnormal kidney function test with glomerular filtration rate (GFR) \<90 mL/min as calculated using the Cockcroft-Gault equation.
• Frequent headaches and/or migraine, recurrent nausea and/or vomiting (more than twice a month).
• 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.
• Presence or history of drug hypersensitivity, or allergic disease diagnosed and treated by a physician.
• History or presence of drug or alcohol abuse (alcohol consumption more than 40 g per day on a regular basis).
• 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 blood test if applicable), breast-feeding.
• 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 2760001

Berlin, 14050, Germany

Location

MeSH Terms

Conditions

Diabetes Mellitus

Interventions

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

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2018
• First Posted: January 30, 2018
• Study Start: January 15, 2018
• Primary Completion: March 10, 2018
• Study Completion: March 10, 2018
• Last Updated: April 25, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will share

Locations

DE (1)