Clinical trial NCT05126329: Pharmacokinetics of Amcenestrant in Female Hepatic Impaired Participants as Compared to Participants With Normal Hepatic Function
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Hepatic Function Abnormal
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2021-11-19
Enrollment: 13
Sex: FEMALE
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.
* 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

Primary outcomes:
measure: Pharmacokinetic (PK) assessment: Maximum plasma concentration observed (Cmax)
timeFrame: From Day 1 to Day 5
measure: PK assessment: Area under the plasma concentration (AUC)
timeFrame: From Day 1 to Day 5
Secondary outcomes:
measure: PK assessment: Tmax of amcenestrant
timeFrame: From Day 1 to Day 5
measure: PK assessment: Area under the plasma concentration versus time curve (AUClast) of amcenestrant
timeFrame: From Day 1 to Day 5
measure: PK assessment: Maximum unbound plasma concentration (Cmax u) of amcenestrant
timeFrame: From Day 1 to Day 5
measure: PK assessment: AUCu of amcenestrant
timeFrame: From Day 1 to Day 5
measure: PK assessment: Cmax of M7
timeFrame: From Day 1 to Day 5
measure: PK assessment: AUClast of M7
timeFrame: From Day 1 to Day 5
measure: PK assessment: AUC of M7
timeFrame: From Day 1 to Day 5
measure: Number of participants with adverse events (AEs) / treatment-emergent adverse events (TEAEs)
timeFrame: From the date when the ICF is signed to the end of study (approximately Day 10)
Other outcomes:
Locations:
city: Kiel
country: Germany
facility: Investigational Site Number :2760001
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number :4100001
state: Seoul-teukbyeolsi
city: Cheongju-si
country: Korea, Republic of
facility: Investigational site number :4100002
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: