Clinical trial NCT03414723: A Drug-Drug Interaction Study Between Sotagliflozin and Ramipril
Official title: An Open Label, 2-treatment, 2-period, Single Sequence Study to Evaluate Pharmacokinetic Drug-drug Interaction Between Ramipril and Sotagliflozin at Steady State in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes Mellitus
Healthy Subjects
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2018-01-30
Enrollment: 16
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: BASIC_SCIENCE

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.

Detailed description: The expected duration of subject participation, including Screening of up to 29 days, Treatment Periods of 6 days and 11 days each with a Washout period of minimum of 7 days in between periods, Follow-up period of 6 days, and end-of-study-period of 10-14 days after last sotagliflozin dose, is approximately 66 days.

Eligibility criteria: Inclusion criteria :

* 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:
* 100 mmHg \<systolic blood pressure (SBP) \<140 mmHg,
* 60 mmHg \<diastolic blood pressure (DBP) \<90 mmHg,
* 50 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.

Exclusion criteria:

* 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).
* Blood donation, any volume, within 2 months before inclusion.
* 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.
* Any medication (including St John's Wort) within 14 days before inclusion or within 5 times the elimination half-life or pharmacodynamic half-life of the medication; any vaccination within the last 28 days and any biologics (antibody or its derivatives) given within 4 months before inclusion. Any oral contraceptives during the screening period or for at least 15 days prior to inclusion; any injectable contraceptives or hormonal intrauterine devices within 12 months prior to inclusion; or topical controlled delivery contraceptives (patch) for 3 months prior to inclusion.

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

Primary outcomes:
measure: Assessment of PK parameter: AUCtau
timeFrame: On Day 10 (Period 2)
measure: Assessment of PK parameter: AUCtau
timeFrame: On Day 5 (Period 1)
Secondary outcomes:
measure: Assessment of PK parameter: Cmax
timeFrame: On Day 10 (Period 2)
measure: Assessment of PK parameter: Cmax
timeFrame: On Day 5 (Period 1)
measure: Assessment of PK parameter: tmax
timeFrame: On Day 10 (Period 2)
measure: Assessment of PK parameter: tmax
timeFrame: On Day 5 (Period 1)
measure: Adverse events
timeFrame: Up to Day 37
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Investigational Site Number 2760001
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: