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

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ClinicalTrials.gov Identifier: NCT02940379
Recruitment Status : Completed
First Posted : October 20, 2016
Last Update Posted : January 18, 2017
Sponsor:
Information provided by (Responsible Party):
Sanofi

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.


Condition or disease Intervention/treatment Phase
Type 2 Diabetes Mellitus Drug: sotagliflozin (SAR439954) Drug: midazolam Drug: metoprolol Phase 1

Detailed Description:
The total study duration per subject is up to 58 days.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Two-cohort, Open-label, Fixed-sequence, Two-period, Two-treatment Pharmacokinetic Interaction Study of Repeated Oral Doses of Sotagliflozin on a Single Dose Cocktail of Metoprolol and Midazolam Used as Probe Substrates for CYP2D6 and CYP3A Activities, Respectively, in Healthy Subjects
Study Start Date : October 2016
Actual Primary Completion Date : December 2016
Actual Study Completion Date : December 2016


Arm Intervention/treatment
Experimental: Cohort 1
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)

Pharmaceutical form: tablet

Route of administration: oral


Drug: midazolam

Pharmaceutical form: HCl syrup

Route of administration: oral


Drug: metoprolol

Pharmaceutical form: tablet

Route of administration: oral


Experimental: Cohort 2
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)

Pharmaceutical form: tablet

Route of administration: oral


Drug: midazolam

Pharmaceutical form: HCl syrup

Route of administration: oral


Drug: metoprolol

Pharmaceutical form: tablet

Route of administration: oral





Primary Outcome Measures :
  1. Assessment of midazolam pharmacokinetic (PK) parameter: Area under the curve (AUC) [ Time Frame: Day 1 to Day 2 of Treatment A Period ]
  2. Assessment of midazolam PK parameter: AUC [ Time Frame: Day 11 to Day 12 of Treatment B Period ]
  3. Assessment of metoprolol PK parameter: AUC [ Time Frame: Day 1 to Day 3 of Treatment A Period ]
  4. Assessment of metoprolol PK parameter: AUC [ Time Frame: Day 11 to Day 13 of Treatment B Period ]

Secondary Outcome Measures :
  1. Assessment of PK parameter: maximum plasma concentration (Cmax) [ Time Frame: Day 1 to Day 2 of Treatment A Period (midazolam) ]
  2. Assessment of PK parameter: Cmax [ Time Frame: Day 11 to Day 12 of Treatment B Period (midazolam) ]
  3. Assessment of PK parameter: Cmax [ Time Frame: Day 1 to Day 3 of Treatment A Period (metoprolol) ]
  4. Assessment of PK parameter: Cmax [ Time Frame: Day 11 to Day 13 of Treatment B Period (metoprolol) ]
  5. Assessment of PK parameter: time to reach Cmax (Tmax) [ Time Frame: Day 1 to Day 2 of Treatment A Period (midazolam) ]
  6. Assessment of PK parameter: Tmax [ Time Frame: Day 11 to Day 12 of Treatment B Period (midazolam) ]
  7. Assessment of PK parameter: Tmax [ Time Frame: Day 1 to Day 3 of Treatment A Period (metoprolol) ]
  8. Assessment of PK parameter: Tmax [ Time Frame: Day 11 to Day 13 of Treatment B Period (metoprolol) ]
  9. Assessment of PK parameter: terminal-half life (t1/2z) [ Time Frame: Day 1 to Day 2 of Treatment A Period (midazolam) ]
  10. Assessment of PK parameter: t1/2z [ Time Frame: Day 11 to Day 12 of Treatment B Period (midazolam) ]
  11. Assessment of PK parameter: t1/2z [ Time Frame: Day 1 to Day 3 of Treatment A Period (metoprolol) ]
  12. Assessment of PK parameter: t1/2z [ Time Frame: Day 11 to Day 13 of Treatment B Period (metoprolol) ]


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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion criteria :

  • 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.

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.

Frequent headaches and/or migraine, recurrent nausea and/or vomiting.

  • Blood donation, any volume, within 2 months before inclusion.
  • 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 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 the first dose of Period 1; any injectable contraceptives or hormonal intrauterine devices within 12 months prior to the first dose of Period 1; or topical controlled delivery contraceptives (patch) for 3 months prior to the first dose of Period 1.
  • Any contra-indications to metoprolol, according to the applicable labeling.
  • Any contra-indications to midazolam, according to the applicable labeling.
  • Any consumption of citrus (grapefruit, orange, etc.) or their juices within 5 days before inclusion.
  • 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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02940379


Locations
United States, Tennessee
Investigational Site Number 840001
Knoxville, Tennessee, United States, 37920
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT02940379     History of Changes
Other Study ID Numbers: INT14972
U1111-1184-8677 ( Other Identifier: UTN )
First Posted: October 20, 2016    Key Record Dates
Last Update Posted: January 18, 2017
Last Verified: January 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Individual participant data (IPD) and supporting clinical documents are available for request at clinicalstudydatarequest.com. While making information available we continue to protect the privacy of the participants in our clinical trials and to remove commercially confidential information (CCI). Details on Data Sharing criteria and process for requesting access can be found at this web address: clinicalstudydatarequest.com

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Midazolam
Metoprolol
Adjuvants, Anesthesia
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Anti-Arrhythmia Agents
Antihypertensive Agents
Sympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Adrenergic beta-1 Receptor Antagonists
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents