Pharmacokinetics of Amcenestrant in Female Hepatic Impaired Participants as Compared to Participants With Normal Hepatic Function

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

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.

Study Overview

• Status: Terminated
• Conditions: Hepatic Function Abnormal
• Intervention / Treatment: Drug: amcenestrant

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Kiel, Germany, 24105
    • Investigational Site Number :2760001
• Korea, Republic of
  • Cheongju-si, Korea, Republic of, 28644
    • Investigational Site Number :4100002
  • Seoul-teukbyeolsi
    • Seoul, Seoul-teukbyeolsi, Korea, Republic of, 03080
      • Investigational Site Number :4100001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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.
• Certified as healthy by a comprehensive clinical assessment (detailed medical history and complete physical examination).
• Body weight within the range 50 kg (40 kg for site in South Korea) to 100 kg and body mass index (BMI) within the range 18 to 36 kg/m2, inclusive.

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.
• Uncontrolled clinically relevant cardiovascular, pulmonary, gastrointestinal, metabolic, hematological, neurological, psychiatric, systemic, ocular, gynecologic, renal, infectious disease, severe hepatic impairment (Child-Pugh total score greater than or equal to 10), or signs of acute illness, hepatocarcinoma, acute hepatitis, Hepatic encephalopathy Grade 2, 3, and 4
• Esophageal bleeding, which is caused by esophageal varices, within 3 months before inclusion

For matched subjects:

• 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).
• Any history or presence of clinically relevant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, metabolic, hematological, neurological, osteomuscular, articular, psychiatric, systemic, ocular, gynecologic, or infectious disease, or signs of acute illness, unless the Investigator considers an abnormality to be not clinically significant.
• Frequent headaches and/or migraine, recurrent nausea and/or vomiting (for vomiting only: more than twice a month.
• Non-live vaccines including Covid-19: last administration of a vaccine within 1 week (symptoms-free) to 2 weeks before inclusion
• 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.
• 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 The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Participants with mild hepatic impairment; Amcenestrant 200 mg single dose on Day 1 in fed condition	Drug: amcenestrant; tablet for oral use
Experimental: Participants with moderate hepatic impairment; Amcenestrant 200 mg single dose on Day 1 in fed condition	Drug: amcenestrant; tablet for oral use
Experimental: Participants with normal hepatic function; Amcenestrant 200 mg single dose on Day 1 in fed condition	Drug: amcenestrant; tablet for oral use

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic (PK) assessment: Maximum plasma concentration observed (Cmax)	Maximum plasma concentration observed (Cmax) of amcenestrant	From Day 1 to Day 5
PK assessment: Area under the plasma concentration (AUC)	Area under the plasma concentration versus time curve of amcenestrant	From Day 1 to Day 5

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK assessment: Tmax of amcenestrant	Time to reach Cmax of amcenestrant	From Day 1 to Day 5
PK assessment: Area under the plasma concentration versus time curve (AUClast) of amcenestrant	Area under the plasma concentration versus time curve calculated using the trapezoidal method from time zero to the real time tlast of amcenestrant	From Day 1 to Day 5
PK assessment: Maximum unbound plasma concentration (Cmax u) of amcenestrant	Maximum unbound plasma concentration of amcenestrant	From Day 1 to Day 5
PK assessment: AUCu of amcenestrant	Unbound area under the plasma concentration versus time curve extrapolated to infinity of amcenestrant	From Day 1 to Day 5
PK assessment: Cmax of M7	Maximum observed plasma concentration of M7	From Day 1 to Day 5
PK assessment: AUClast of M7	Area under the plasma concentration versus time curve calculated using the trapezoidal method from time zero to the real time tlast of M7	From Day 1 to Day 5
PK assessment: AUC of M7	Area under the plasma concentration versus time curve extrapolated to infinity of M7	From Day 1 to Day 5
Number of participants with adverse events (AEs) / treatment-emergent adverse events (TEAEs)	Incidence of adverse events (AEs) and treatment-emergent adverse events (TEAEs)	From the date when the ICF is signed to the end of study (approximately Day 10)

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2021
• Primary Completion (Actual): May 16, 2022
• Study Completion (Actual): May 16, 2022

Study Registration Dates

• First Submitted: November 3, 2021
• First Submitted That Met QC Criteria: November 15, 2021
• First Posted (Actual): November 19, 2021

Study Record Updates

• Last Update Posted (Actual): September 14, 2022
• Last Update Submitted That Met QC Criteria: September 9, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: POP16301; U1111-1244-1929 (Registry Identifier: ICTRP); 2021-001784-24 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No