A Phase I, Single Dose, Non-Randomised, Multicentre, Open-Label, Parallel Group Study to Investigate the Effect of Hepatic Impairment on the Pharmacokinetics, Safety and Tolerability of Camizestrant in Post Menopausal Female Subjects
Overview
- Phase
- Phase 1
- Intervention
- Camizestrant
- Conditions
- Hepatic Impairment
- Sponsor
- AstraZeneca
- Enrollment
- 22
- Locations
- 1
- Primary Endpoint
- PK parameters AUClast,
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This will be a Phase I, multicentre, single-dose, non-randomized, open-label, parallel-group study to examine the PK, safety, and tolerability of camizestrant 75 mg in post-menopausal female participants with moderate or severe hepatic impairment compared with post-menopausal female participants with normal hepatic function.
Participants will be enrolled within the following groups based on their CP classification score as determined at screening:
- Group 1: Matched-control healthy participants with normal hepatic function.
- Group 2: Participants with moderate hepatic impairment (CP Class B, score of 7 to 9).
- Group 3: Participants with severe hepatic impairment (CP Class C, score of 10 to 15).
Detailed Description
This will be an open-label, non-randomized, multicentre, parallel-group, single-dose study to investigate the PK, safety, and tolerability of camizestrant 75 mg administered orally to post-menopausal female participants with moderate or severe hepatic impairment compared to control post-menopausal female participants with normal hepatic function. A total of approximately 14 participants with hepatic impairment (8 participants with moderate impairment and 6 participants with severe impairment per CP classification) and 8 to 14 matched-control healthy participants with normal hepatic function are planned to be enrolled, with the goal of having approximately 8 participants with moderate impairment and approximately 6 participants with severe impairment and sufficient matching participants with normal hepatic function complete the study. All participants will receive a single oral dose of 75 mg camizestrant on Day 1 following an overnight fast. Study intervention will be administered orally with approximately 240 mL of water. Child-Pugh scoring, detailed in Table 3, will be used to determine the level of hepatic impairment. Participants will be enrolled into the following groups based on their CP classification score as determined at screening: * Group 1: Matched-control healthy participants with normal hepatic function. * Group 2: Participants with moderate hepatic impairment (CP Class B, score of 7 to 9). * Group 3: Participants with severe hepatic impairment (CP Class C, score of 10 to 15).
Investigators
Eligibility Criteria
Inclusion Criteria
- •For participant with hepatic impairment: Participant must be 50 to 75 years of age, inclusive, at the time of signing the informed consent.
- •. For participant with normal hepatic function: Participant must be matched to participant with hepatic impairment by age (±10 years; determined at the time of signing the informed consent).
- •For participant with hepatic impairment:
- •Participant must have medical history, physical examination, vital signs, ECGs, and laboratory safety tests consistent with a diagnosis of hepatic impairment, but is otherwise judged to be in good health as determined by the investigator at screening and Day -
- •Participant must have a diagnosis of chronic (\>6 months), stable (no acute episodes of illness within the previous 2 months due to deterioration in hepatic function) hepatic insufficiency with features of cirrhosis due to any aetiology at screening and Day -
- •For participant with normal hepatic function: Participants must be medically healthy with no clinically significant medical history, physical examination, laboratory profiles (including serum amylase and lipase, haematology, and thyroid function), vital signs, or 12-lead ECGs, as deemed by the investigator at screening and Day -1
- •For participant with hepatic impairment: Body weight within 50 to 100 kg and BMI within the range 19.0 to 35.0 kg/m2 (inclusive) as measured at screening.
- •For participant with normal hepatic function: Participant must be matched to participant with hepatic impairment by weight in kg (±20%; data obtained at screening).
- •Female, post-menopausal. (a) Women will be considered post-menopausal if they have been amenorrhoeic for 12 months prior to the planned date of study intervention without an alternative medical or surgical cause, confirmed by an FSH result of ≥ 30 IU/L obtained at screening.
- •Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
Exclusion Criteria
- •History of or ongoing, clinically significant, in the opinion of the investigator, visual disturbances including, but not limited to, visual hallucinations, migraine with visual symptoms, blurred vision, and frequent floaters/flashes associated with other symptoms such as dizziness at screening or Day -1
- •History or presence of clinically significant or unstable medical or psychiatric condition or disease in the opinion of the investigator at screening or Day -1
- •Participant is mentally or legally incapacitated or has significant emotional problems at the time of the screening or Day -1 visit or expected during the conduct of the study
- •History of any illness that, in the opinion of the investigator, might confound the results of the study or poses an additional risk to the participant by their participation in the study noted at screening or Day -1
- •Presence of any clinically significant, ongoing systemic bacterial, fungal, or viral infections (including upper respiratory tract infections, but excluding localized cutaneous fungal infections), in the opinion of the investigator at screening or Day -1
- •History of any major surgical procedure within 30 days prior to the dose of study drug
- •Any clinically significant condition that may affect camizestrant absorption in the opinion of the investigator, including gastric restrictions and bariatric surgery (eg, gastric bypass), noted at screening or Day -1
- •Signs or confirmation of COVID-19 infection at screening or Day -1
- •Unable to refrain from or anticipates the use of:
- •Any drugs known to prolong QT interval or drugs associated with a known risk of Torsades de pointes within 4 weeks or 5 PK half-lives (whichever is longer) prior to the dose of study drug and throughout the study.
Arms & Interventions
Group 1
Matched-control healthy participants with normal hepatic function.
Intervention: Camizestrant
Group 2
Participants with moderate hepatic impairment (CP Class B, score of 7 to 9).
Intervention: Camizestrant
Group 3
Participants with severe hepatic impairment (CP Class C, score of 10 to 15).
Intervention: Camizestrant
Outcomes
Primary Outcomes
PK parameters AUClast,
Time Frame: 5 days
area under the concentration-time curve (AUC) from zero to the last measurable concentration (AUClast)
PK parameters AUCinf.;
Time Frame: 5 days
area under the concentration-time curve (AUC) from zero to infinity (AUCinf)
PK parameters CL/F
Time Frame: 5 days
CL/F: apparent clearance;
PK parameters Cmax
Time Frame: 5 days
Cmax: maximum concentration
PK parameters tmax
Time Frame: 5 days
tmax : time to maximum concentration
PK parameters tlast
Time Frame: 5 days
tlast: time of the last measurable concentration
PK parameters t1/2λz
Time Frame: 5 days
t1/2λz: apparent terminal elimination half-life
PK parameters Vz/F.
Time Frame: 5 days
Vz/F: apparent volume of distribution.
Secondary Outcomes
- Number of participants with an AE causally related to IMP leading to study discontinuation(4.5 weeks)
- Number of subjects with adverse events (AEs) and serious adverse events (SAEs)(4.5 weeks)