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

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04940026
• Other study ID #: BEX15859
• Status: Completed
• Phase: Phase 1
• Start date: June 15, 2021
• Est. completion date: August 19, 2021

Study information

• Verified date: April 2022
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: August 19, 2021
• Est. primary completion date: August 19, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 40 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Healthy Volunteers

Intervention

Drug:
• amcenestrant
Tablet Oral
• [14C]-SAR439859 microtracer
Solution for infusion Intravenous
• [14C]-SAR439859
Powder for oral solution Oral

Locations

Country	Name	City	State
United Kingdom	Investigational Site Number 8260001	Nottingham

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of radioactive dose, SAR439859 and M7 excreted in urine and feces after IV administration		Day 1 to Day 6
Primary	Percentage of radioactive dose excreted in urine and feces after oral administration		Day 7 up to max Day 44
Primary	Assessment of Pharmacokinetic (PK) parameter: AUC for radioactivity and SAR439859 after IV administration	Area under the plasma concentration versus time curve extrapolated to infinity	Day 1 to Day 3
Primary	Assessment of PK parameter: t1/2z for radioactivity and SAR439859 after IV administration	Terminal half-life associated with the terminal slope (?z)	Day 1 to Day 3
Primary	Assessment of PK parameter: CL for SAR439859 after IV administration	Total body clearance	Day 1 to Day 3
Primary	Assessment of PK parameter: AUC ratios after IV administration	SAR439859 to radioactivity ratio for plasma AUC	Day 1 to Day 3
Primary	Assessment of PK parameter: Cmax for radioactivity and SAR439859 after oral administration	Maximum plasm concentration observed	Day 1 to Day 5, Day 7 to Day 11
Primary	Assessment of PK parameter: tmax for radioactivity and SAR439859 after oral administration	Time to reach Cmax	Day 1 to Day 5, Day 7 to Day 11
Primary	Assessment of PK parameter: AUC for radioactivity and SAR439859 after oral administration		Day 1 to Day 5, Day 7 to Day 11
Primary	Assessment of PK parameter: t1/2z for radioactivity and SAR439859 after oral administration		Day 1 to Day 5, Day 7 to Day 11
Primary	Assessment of PK parameter: AUC ratios after oral administration	SAR439859 to radioactivity ratio for plasma AUC	Day 7 to Day 11
Primary	Assessment of PK parameter: Cmax for M7 after IV and oral administration		Day 1 to Day 5, Day 7 to Day 11
Primary	Assessment of PK parameter: AUC for M7 after IV and oral administration		Day 1 to Day 5, Day 7 to Day 11
Primary	Assessment of PK parameter: t1/2z for M7 after IV and oral administration		Day 1 to Day 5, Day 7 to Day 11
Primary	Assessment of PK parameter: Rmet Cmax after IV and oral administration	M7 to SAR439859 ratio for plasma Cmax	Day 1 to Day 5, Day 7 to Day 11
Primary	Assessment of PK parameter: Rmet AUC after IV and oral administration	M7 to SAR439859 ratio for plasma AUC	Day 1 to Day 5, Day 7 to Day 11
Primary	Absolute oral bioavailability of SAR439859	Absolute oral bioavailability, expressed as a percentage, estimated from AUCs obtained after oral and IV administration	Day 1 to Day 5, Day 7 to Day 11
Primary	Relative bioavailability of SAR439859 after oral administration		Day 1 to Day 5, Day 7 to Day 11
Secondary	Number of participants with adverse events		Day 1 to Day 44