Clinical trial NCT04940026: Study to Determine Absorption, Metabolism, and Excretion of [14C]-SAR439859, and to Assess Absolute Oral Bioavailability of Amcenestrant (SAR439859), in Healthy Post-menopausal Women
Official title: A Phase 1, Open-label, Single Center, One Period, One Sequence Study to Determine Absorption, Metabolism, and Excretion of a Single Oral Dose of Radiolabeled [14C]- SAR439859 and an Assessment of the Absolute Oral Bioavailability Using the Microdosing Technique in Healthy Post-menopausal Women
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Breast Cancer
Healthy Volunteers
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2021-06-25
Enrollment: 6
Sex: FEMALE
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: 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

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of radioactive dose, SAR439859 and M7 excreted in urine and feces after IV administration
timeFrame: Day 1 to Day 6
measure: Percentage of radioactive dose excreted in urine and feces after oral administration
timeFrame: Day 7 up to max Day 44
measure: Assessment of Pharmacokinetic (PK) parameter: AUC for radioactivity and SAR439859 after IV administration
timeFrame: Day 1 to Day 3
measure: Assessment of PK parameter: t1/2z for radioactivity and SAR439859 after IV administration
timeFrame: Day 1 to Day 3
measure: Assessment of PK parameter: CL for SAR439859 after IV administration
timeFrame: Day 1 to Day 3
measure: Assessment of PK parameter: AUC ratios after IV administration
timeFrame: Day 1 to Day 3
measure: Assessment of PK parameter: Cmax for radioactivity and SAR439859 after oral administration
timeFrame: Day 1 to Day 5, Day 7 to Day 11
measure: Assessment of PK parameter: tmax for radioactivity and SAR439859 after oral administration
timeFrame: Day 1 to Day 5, Day 7 to Day 11
measure: Assessment of PK parameter: AUC for radioactivity and SAR439859 after oral administration
timeFrame: Day 1 to Day 5, Day 7 to Day 11
measure: Assessment of PK parameter: t1/2z for radioactivity and SAR439859 after oral administration
timeFrame: Day 1 to Day 5, Day 7 to Day 11
measure: Assessment of PK parameter: AUC ratios after oral administration
timeFrame: Day 7 to Day 11
measure: Assessment of PK parameter: Cmax for M7 after IV and oral administration
timeFrame: Day 1 to Day 5, Day 7 to Day 11
measure: Assessment of PK parameter: AUC for M7 after IV and oral administration
timeFrame: Day 1 to Day 5, Day 7 to Day 11
measure: Assessment of PK parameter: t1/2z for M7 after IV and oral administration
timeFrame: Day 1 to Day 5, Day 7 to Day 11
measure: Assessment of PK parameter: Rmet Cmax after IV and oral administration
timeFrame: Day 1 to Day 5, Day 7 to Day 11
measure: Assessment of PK parameter: Rmet AUC after IV and oral administration
timeFrame: Day 1 to Day 5, Day 7 to Day 11
measure: Absolute oral bioavailability of SAR439859
timeFrame: Day 1 to Day 5, Day 7 to Day 11
measure: Relative bioavailability of SAR439859 after oral administration
timeFrame: Day 1 to Day 5, Day 7 to Day 11
Secondary outcomes:
measure: Number of participants with adverse events
timeFrame: Day 1 to Day 44
Other outcomes:
Locations:
city: Nottingham
country: United Kingdom
facility: Investigational Site Number 8260001
Study officials:
References: