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Trial record 7 of 15 for:    PKM

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

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ClinicalTrials.gov Identifier: NCT03802487
Recruitment Status : Recruiting
First Posted : January 14, 2019
Last Update Posted : March 12, 2019
Sponsor:
Information provided by (Responsible Party):
Sanofi

Brief 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

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Mellitus Healthy Subjects Drug: Sotagliflozin (SAR439954) Drug: 14C-microtracer Drug: Charcoal Phase 1

Detailed 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 6 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : January 14, 2019
Estimated Primary Completion Date : March 2019
Estimated Study Completion Date : March 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Sotagliflozin
One treatment period includes a single oral dose of sotagliflozin + IV microdose 14C-sotagliflozin tracer plus charcoal. The other treatment period includes a single oral dose of sotagliflozin + IV microdose 14C-sotagliflozin tracer without charcoal.
Drug: Sotagliflozin (SAR439954)

Pharmaceutical form: Tablet

Route of administration: Oral


Drug: 14C-microtracer

Pharmaceutical form: Solution for injection

Route of administration: Intravenous


Drug: Charcoal

Pharmaceutical form: Granules for suspension

Route of administration: Oral





Primary Outcome Measures :
  1. Pharmacokinetic (PK) parameter: Absolute Bioavailability (F) [ Time Frame: Baseline to Day 8 of period 1 (without charcoal) ]
    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)


Secondary Outcome Measures :
  1. Assessment of PK parameter: Area under the curve (AUC) for oral investigational medicinal product (IMP) [ Time Frame: Baseline to Day 8 of each period ]
    Area under the plasma concentration versus time curve extrapolated to infinity for oral IMP

  2. Assessment of PK parameter: AUC for IMP metabolite [ Time Frame: Baseline to Day 8 of each period ]
    Area under the plasma concentration versus time curve extrapolated to infinity for IMP metabolite

  3. Assessment of PK parameter: AUC for IV 14C-IMP [ Time Frame: Baseline to Day 8 of each period ]
    Area under the plasma concentration versus time curve extrapolated to infinity for IV 14C-IMP

  4. Assessment of PK parameter: AUC for 14C-IMP metabolite [ Time Frame: Baseline to Day 8 of each period ]
    Area under the plasma concentration versus time curve extrapolated to infinity for 14C-IMP metabolite

  5. Assessment of PK parameter: Area under curve versus time (AUClast) for oral IMP [ Time Frame: Baseline to Day 8 of each period ]
    Area under the plasma concentration versus time curve calculated using the trapezoidal method from time zero to the real time tlast for oral IMP

  6. Assessment of PK parameter: AUClast for IMP metabolite [ Time Frame: Baseline to Day 8 of each period ]
    Area under the plasma concentration versus time curve calculated using the trapezoidal method from time zero to the real time tlast for IMP metabolite

  7. Assessment of PK parameter: AUClast for IV 14C-IMP [ Time Frame: Baseline to Day 8 of each period ]
    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

  8. Assessment of PK parameter: AUClast for 14C-IMP metabolite [ Time Frame: Baseline to Day 8 of each period ]
    Area under the plasma concentration versus time curve

  9. Assessment of PK parameter: Cmax for oral IMP [ Time Frame: Baseline to Day 8 of each period ]
    Maximum plasma concentration observed for oral IMP

  10. Assessment of PK parameter: Cmax for IMP metabolite [ Time Frame: Baseline to Day 8 of each period ]
    Maximum plasma concentration observed for IMP metabolite

  11. Assessment of PK parameter: Cmax for IV 14C-IMP [ Time Frame: Baseline to Day 8 of each period ]
    Maximum plasma concentration observed for IV 14C-IMP

  12. Assessment of PK parameter: Cmax for 14C-IMP metabolite [ Time Frame: Baseline to Day 8 of each period ]
    Maximum plasma concentration observed for 14C-IMP metabolite

  13. Assessment of PK parameter: tmax for oral IMP [ Time Frame: Baseline to Day 8 of each period ]
    Time to reach Cmax for oral IMP

  14. Assessment of PK parameter: tmax for IMP metabolite [ Time Frame: Baseline to Day 8 of each period ]
    Time to reach Cmax for IMP metabolite

  15. Assessment of PK parameter: tmax for IV 14C-IMP [ Time Frame: Baseline to Day 8 of each period ]
    Time to reach Cmax for IV 14C-IMP

  16. Assessment of PK parameter: tmax for 14C-IMP metabolite [ Time Frame: Baseline to Day 8 of each period ]
    Time to reach Cmax for 14C-IMP metabolite

  17. Assessment of PK parameter: t1/2z for oral IMP [ Time Frame: Baseline to Day 8 of each period ]
    Terminal half-life (t1/2z) associated with the terminal slope for oral IMP

  18. Assessment of PK parameter: t1/2z for IV 14C-IMP [ Time Frame: Baseline to Day 8 of each period ]
    Terminal half-life (t1/2z) associated with the terminal slope for IV 14C-IMP

  19. Assessment of PK parameter: Clearance (CL/F) for oral IMP [ Time Frame: Baseline to Day 8 of each period ]
    Apparent total body clearance for oral IMP

  20. Assessment of PK parameter: Clearance (CL/F) for IV 14C-IMP [ Time Frame: Baseline to Day 8 of each period ]
    Apparent total body clearance for IV 14C-IMP

  21. Assessment of PK parameter: Vz/F for oral IMP [ Time Frame: Baseline to Day 8 of each period ]
    Apparent volume of distribution for oral IMP

  22. Assessment of PK parameter: Vz/F for IV 14C-IMP [ Time Frame: Baseline to Day 8 of each period ]
    Apparent volume of distribution for IV 14C-IMP

  23. Assessment of PK parameter: Vdss/F for oral IMP [ Time Frame: Baseline to Day 8 of each period ]
    Apparent volume of distribution at the steady state for oral IMP

  24. Assessment of PK parameter: Vdss/F for IV 14C-IMP [ Time Frame: Baseline to Day 8 of each period ]
    Apparent volume of distribution at the steady state for IV 14C-IMP

  25. Safety: Adverse events [ Time Frame: Baseline to Day 8 of each period ]
    Number of subjects with adverse events including serious, non-serious, and treatment emergent adverse events



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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 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 β-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.


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): NCT03802487


Contacts
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Contact: Trial Transparency email recommended (Toll free number for US & Canada) 800-633-1610 ext 1 then # Contact-US@sanofi.com

Locations
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United Kingdom
Investigational site number 8260001 Recruiting
Nottingham, United Kingdom, NG11 6JS
Sponsors and Collaborators
Sanofi
Investigators
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Study Director: Clinical Sciences & Operations Sanofi

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Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT03802487     History of Changes
Other Study ID Numbers: PKM15402
2017-004937-94 ( EudraCT Number )
U1111-1200-2077 ( Other Identifier: UTN )
First Posted: January 14, 2019    Key Record Dates
Last Update Posted: March 12, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://www.clinicalstudydatarequest.com/

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Charcoal
(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol
Antidotes
Protective Agents
Physiological Effects of Drugs
Sodium-Glucose Transporter 2 Inhibitors
Molecular Mechanisms of Pharmacological Action
Hypoglycemic Agents