Study to Determine Absorption, Metabolism, and Excretion of [14C]-SAR439859, and to Assess Absolute Oral Bioavailability of Amcenestrant (SAR439859), in Healthy Post-menopausal Women

Sanofi6 enrolled

Overview

Primary Objectives: * To assess the excretion balance after oral and IV administration of \[14C\]-SAR439859 * To assess PK of total radioactivity, \[14C\] -SAR439859 and its metabolite (M7) after IV administration of \[14C\]-SAR439859 and, PK of radioactivity, SAR439859 and M7 after oral administration of SAR439859 alone or with \[14C\]-SAR439859 * To assess IV clearance and absolute bioavailability of SAR439859 using microdose of \[14C\]-SAR439859 tracer on top of a single tablet oral dose. * To assess relative bioavailability of SAR439859 given as tablet or solution Secondary objectives: * To collect samples in order to assess metabolic profile in plasma and excreta of SAR439859 after oral administration of \[14C\]-SAR439859 as solution, contribution in plasma of SAR439859 and metabolite relative to total radioactivity and identify metabolites (samples will be analyzed according to metabolic analysis plan and results will be documented in a separate report). * To assess safety and tolerance of SAR439859

Total study duration is 3 to 10 weeks, including a screening period of up to 27 days, treatment period of up to 16 days and a follow-up and end of study of up to 4 weeks.

Study Type

INTERVENTIONAL

Allocation

Purpose

OTHER

Masking

NONE

Enrollment

Conditions

Breast Cancer Healthy Volunteers

Eligibility

Sex: FEMALEMin age: 40 YearsMax age: 75 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: Female participants (age between 40 and 75 years old) who are postmenopausal or had post-bilateral surgical oophorectomy not linked to a history of cancer. Participants who are overtly healthy. Body weight within 40.0 and 95.0 kg and body mass index (BMI) within the range 18.0 and 30 kg/m2 (inclusive). Capable of giving signed informed consent. Exclusion Criteria: Subject has clinical signs and symptoms consistent with COVID-19, e.g., fever, dry cough, dyspnea, loss of taste and smell, sore throat, fatigue or confirmed infection by appropriate laboratory test within the last 4 weeks prior to Screening. Subject who had severe course of COVID-19 (i.e., hospitalization, extracorporeal membrane oxygenation, mechanically ventilated). Frequent headaches and/or migraine, recurrent nausea and/or vomiting (for vomiting only: more than twice a month). Blood donation, any volume (usually approximately 500 mL), within 2 months before inclusion. 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). Smoking regularly more than 5 cigarettes or equivalent per week, unable to stop smoking during the study (occasional smoker can be enrolled). Excessive consumption of beverages containing xanthine bases (more than 5 cups or glasses per day). Subjects who are occupationally exposed to radiation as defined in the Ionizing Radiation Regulations 2017. Participation in a trial with \[13C\] or \[14C\] radiolabeled medication in the 12 months preceding the study. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Outcomes

Primary Outcomes

Percentage of radioactive dose, SAR439859 and M7 excreted in urine and feces after IV administration

Time frame: Day 1 to Day 6

Percentage of radioactive dose excreted in urine and feces after oral administration

Time frame: Day 7 up to max Day 44

Assessment of Pharmacokinetic (PK) parameter: AUC for radioactivity and SAR439859 after IV administration

Area under the plasma concentration versus time curve extrapolated to infinity

Time frame: Day 1 to Day 3

Assessment of PK parameter: t1/2z for radioactivity and SAR439859 after IV administration

Terminal half-life associated with the terminal slope (λz)

Time frame: Day 1 to Day 3

Assessment of PK parameter: CL for SAR439859 after IV administration

Total body clearance

Time frame: Day 1 to Day 3

Assessment of PK parameter: AUC ratios after IV administration

SAR439859 to radioactivity ratio for plasma AUC

Time frame: Day 1 to Day 3

Assessment of PK parameter: Cmax for radioactivity and SAR439859 after oral administration

Maximum plasm concentration observed