Clinical Trials/NCT05126329

NCT05126329

Terminated

Phase 1

An Open-label Pharmacokinetic and Tolerability Study of Amcenestrant Given as a Single Dose in Female Participants With Mild and Moderate Hepatic Impairment, and in Matched Participants With Normal Hepatic Function

Sanofi3 sites in 2 countries13 target enrollmentNovember 15, 2021

ConditionsHepatic Function Abnormal

Interventionsamcenestrant

Overview

Phase: Phase 1
Intervention: amcenestrant
Conditions: Hepatic Function Abnormal
Sponsor: Sanofi
Enrollment: 13
Locations: 3
Primary Endpoint: PK assessment: Area under the plasma concentration (AUC)
Status: Terminated
Last Updated: 7 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a Phase 1, parallel, open-label, 3-arm study to investigate the pharmacokinetic (PK) parameters of amcenestrant in female participants aged 40 to 75 years with mild and moderate hepatic impairment, and in matched participants with normal hepatic function.

Detailed Description

The total study duration from screening period is approximately 41 days.

Registry

clinicaltrials.gov

Start Date

November 15, 2021

End Date

May 16, 2022

Last Updated

7 months ago

Study Type

Interventional

Study Design

Parallel

Sex

Female

Investigators

Sponsor

Sanofi

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•For participants with hepatic impairment:
•Participant must be 40 to 75 years of age, inclusive.
•Female participants who are postmenopausal or are post-bilateral surgical oophorectomy not linked to a history of cancer. Menopause is defined as being amenorrheic for at least 12 months without an alternative medical cause, with plasma FSH level \>30 IU/L or age ≥60 years.
•Stable chronic liver disease assessed by medical history, physical examination, laboratory values
•Body weight within the range 50 kg (40 kg for site in South Korea) to 110 kg and body mass index (BMI) within the range 18 to 36 kg/m2, inclusive.
•For moderate hepatic impairment cohort: Child-Pugh total score ranging from 7 to 9, inclusive.
•For mild hepatic impairment cohort: Child-Pugh total score ranging from 5 to 6, inclusive
•For matched subjects:
•Participant must be 40 to 75 years of age, inclusive.
•Female participants who are postmenopausal or are post-bilateral surgical oophorectomy not linked to a history of cancer. Menopause is defined as being amenorrheic for at least 12 months without an alternative medical cause, with plasma FSH level \>30 IU/L or age ≥60 years.

Exclusion Criteria

•For participants with hepatic impairment:
•History or presence of drug or alcohol abuse (alcohol consumption more than 40 g per day on a regular basis) within 1 year before inclusion.
•Smoking regularly more than 15 cigarettes or equivalent per day, unable to refrain from smoking over 8 cigarettes per day during the institutionalization (Smoking is not allowed within 8 hours after amcenestrant administration).
•Excessive consumption of beverages containing xanthine bases (more than 5 cups or glasses per day).
•Non-live vaccines including Covid-19: last administration of a vaccine within 1 week (symptoms-free) to 2 weeks before inclusion.
•Any consumption of citrus fruits (grapefruit, orange, etc) or their juices within 72 hours before inclusion.
•Use of any herbal medicines 1 week before IMP administration and up to the end of PK sampling following the IMP administration
•Live-vaccines: last administration of a vaccine within 4 weeks before inclusion
•Treatment with a strong CYP3A, CYP2C8 or any UGTs inhibitor within 14 days before first study treatment administration or 5 half-lives whichever is longer.
•Treatment with a strong or moderate CYP3A, CYP2C8 or any UGTs inducer within 14 days before first study treatment administration or 5 half-lives whichever is longer.

Arms & Interventions

Participants with mild hepatic impairment

Amcenestrant 200 mg single dose on Day 1 in fed condition

Intervention: amcenestrant

Participants with moderate hepatic impairment

Amcenestrant 200 mg single dose on Day 1 in fed condition

Intervention: amcenestrant

Participants with normal hepatic function

Amcenestrant 200 mg single dose on Day 1 in fed condition

Intervention: amcenestrant

Outcomes

Primary Outcomes

PK assessment: Area under the plasma concentration (AUC)

Time Frame: From Day 1 to Day 5

Area under the plasma concentration versus time curve of amcenestrant

Pharmacokinetic (PK) assessment: Maximum plasma concentration observed (Cmax)

Time Frame: From Day 1 to Day 5

Maximum plasma concentration observed (Cmax) of amcenestrant

Secondary Outcomes

PK assessment: AUCu of amcenestrant(From Day 1 to Day 5)
Number of participants with adverse events (AEs) / treatment-emergent adverse events (TEAEs)(From the date when the ICF is signed to the end of study (approximately Day 10))
PK assessment: AUC of M7(From Day 1 to Day 5)
PK assessment: Tmax of amcenestrant(From Day 1 to Day 5)
PK assessment: Area under the plasma concentration versus time curve (AUClast) of amcenestrant(From Day 1 to Day 5)
PK assessment: AUClast of M7(From Day 1 to Day 5)
PK assessment: Maximum unbound plasma concentration (Cmax u) of amcenestrant(From Day 1 to Day 5)
PK assessment: Cmax of M7(From Day 1 to Day 5)