Study to Investigate Hepatic Impairment on PK, Safety, Tolerability of Camizestrant in Post-Menopausal Female Subjects

Study identifier:D8532C00002

ClinicalTrials.gov identifier:NCT05790304

EudraCT identifier:N/A

CTIS identifier:2022-502277-41-00

Study Complete

Official Title

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

Medical condition

Hepatic Impairment

Phase

Phase 1

Healthy volunteers

Yes

Study drug

Camizestrant

Sex

Female

Actual Enrollment

Study type

Interventional

Age

50 Years - 75 Years

Date

Study Start Date: 20 Feb 2023

Primary Completion Date: 22 Feb 2024

Study Completion Date: 22 Feb 2024

Study design

Allocation: Non-randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: -
Primary Purpose: Other

Verification:

Verified 01 Mar 2025 by AstraZeneca

Collaborators

Inclusion and exclusion 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:
(a) 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 -1.
(b) 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 -1.
- 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.
-Must agree to not use warfarin or phenytoin (and other coumarin-derived vitamin K antagonist anticoagulants) from screening, throughout the study, and for 2 weeks after the dose of study drug

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:
(a) 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.
(b) Use of any prescribed or non-prescribed medication
(c) Any drug known to be moderate or strong inhibitors or inducers of CYP3A and/or P-gp, including St. John’s Wort, within 14 and 28 days, respectively, prior to the dose of study drug and throughout the study unless they are deemed acceptable following consultation with the sponsor medical monitor and the investigator.
(d) Human immunodeficiency virus protease inhibitor, anticoagulant within 14 days prior to the dose of study drug and throughout the study.
(e) Acetaminophen and ethacrynic acid within 24 hours prior to the dose of study drug and throughout the study.
- Dosed in another clinical trial within 28 days or 5 half-lives (if known), whichever is longer, prior to the dose of study drug
-Previous enrolment in the present study.
-Any clinically significant abnormalities at screening or Day -1 on 12-lead ECG as judged by the investigator
-Known history of hypersensitivity to active or inactive excipients of camizestrant or drugs with a similar chemical structure or class to camizestrant noted at screening or Day -1
-Donation of blood > 500 mL or significant blood loss within 56 days prior to the dose of study drug
- Plasma donation within 28 days prior to the dose of study drug.
- Is working at or has an immediate family member (spouse or children) who works at the investigational site or is a sponsor staff directly involved with this study."
- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)."
- Judgment by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements.
-Participants with hepatic impairment are excluded from the study if any of the following criteria apply:
• History or presence of drug abuse within the past 2 years prior to screening.
• Positive results for the alcohol test and/or urine drug screen at screening or Day -1
• Positive results at screening for hepatitis B surface antigen or HCV
• Known history of HIV
• Participant has evidence of hepatorenal syndrome or creatinine clearance < 60 mL/minute
• History of unstable diabetes mellitus
• Presence of transjugular intrahepatic portosystemic shunt."
- Participants with normal hepatic function are excluded from the study if any of the following criteria apply:
• History or presence of clinically significant thyroid disease
• History or presence of alcoholism and/or drug abuse within the past 2 years prior to screening.
• Positive results for the alcohol test and/or urine drug screen at screening or Day -1
• Known history of HIV, positive results at screening for hepatitis B surface antigen or HCV.
• Participant has creatinine clearance <80 mL/minute
• Supine blood pressure < 90/40 mmHg or > 150/95 mmHg at screening or Day -1.
• Supine pulse rate < 50 bpm or > 99 bpm at screening or Day -1.
• Haemoglobin level below the lower limit of normal at screening or Day -1

Location

Research Site

San Antonio, TX, United States, 78215

Location

Research Site

Sofia, Bulgaria, 1612

Location

Research Site

Bratislava, Slovakia, 831 01

Location

Research Site

San Antonio, TX, United States, 78229

Arms	Assigned Interventions
Other: Group 1 Matched-control healthy participants with normal hepatic function.	Drug: Camizestrant Camizestrant 75 mg tablets. Experimental drug. Other Name: AZD9833
Other: Group 2 Participants with moderate hepatic impairment (CP Class B, score of 7 to 9).	Drug: Camizestrant Camizestrant 75 mg tablets. Experimental drug. Other Name: AZD9833
Other: Group 3 Participants with severe hepatic impairment (CP Class C, score of 10 to 15).	Drug: Camizestrant Camizestrant 75 mg tablets. Experimental drug. Other Name: AZD9833

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
For participant with hepatic impairment: Participant was required to be 50 to 75 years of age, inclusive, at the time of informed consent. For participant with normal hepatic function: Participant was required to be matched to participant with hepatic impairment by age (±10 years).

Reporting Groups

	Description
Normal Hepatic Function	Matched-control healthy participants with normal hepatic function
Moderate Hepatic Impairment	Participants with moderate hepatic impairment (CP Class B, score of 7 to 9)
Severe Hepatic Impairment	Participants with severe hepatic impairment (CP Class C, score of 10 to 15)

Participant Flow: Overall Study

	Normal Hepatic Function	Moderate Hepatic Impairment	Severe Hepatic Impairment
STARTED	8	8	6
COMPLETED	8	8	6
NOT COMPLETED	0	0	0

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Reporting Groups

	Description
Normal Hepatic Function	Matched-control healthy participants with normal hepatic function
Moderate Hepatic Impairment	Participants with moderate hepatic impairment (CP Class B, score of 7 to 9)
Severe Hepatic Impairment	Participants with severe hepatic impairment (CP Class C, score of 10 to 15)

Baseline Measures

	Normal Hepatic Function	Moderate Hepatic Impairment	Severe Hepatic Impairment	Total
Number of Participants [units: Participants]	8	8	6	22
Age, Customized ^[1] [units: Participants]
>= 50 - < 65 years	4	5	4	13
>= 65 - < 75 years	4	3	2	9
>= 75 years	0	0	0	0
>=65 years	4	3	2	9
<65 years	4	5	4	13
Ethnicity (NIH/OMB) [units: Participants]
Hispanic or Latino	6	3	3	12
Not Hispanic or Latino	2	5	3	10
Sex: Female, Male [units: Participants] Female	8	8	6	22
Race (NIH/OMB) [units: Participants]
American Indian or Alaska Native	0	0	0	0
Asian	0	0	0	0
Black or African American	0	0	0	0
Native Hawaiian or other Pacific Islander	0	0	0	0
Other	0	0	0	0
White	8	8	6	22
Age Continuous ^[2] [units: Years] Mean ( Full Range )	63.4 (53 to 73)	61 (52 to 68)	62.8 (54 to 74)	62.4 (52 to 74)

Outcome Measures

1. Primary Outcome Measure: Pharmacokinetic Parameters: Cmax [ Time Frame: Pharmacokinetic samples were taken predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 48, 60, 72, and 96 hours (h) postdose. ]

Measure Type	Primary
Measure Name	Pharmacokinetic Parameters: Cmax
Measure Description	Maximum observed concentration (Cmax) was analysed using an analysis of variance model, with hepatic impairment category as a fixed effect, following a natural logarithmic transformation.
Time Frame	Pharmacokinetic samples were taken predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 48, 60, 72, and 96 hours (h) postdose.
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Pharmacokinetic Analysis Set

Reporting Groups

	Description
Normal Hepatic Function	Matched-control healthy participants with normal hepatic function
Moderate Hepatic Impairment	Participants with moderate hepatic impairment (CP Class B, score of 7 to 9)
Severe Hepatic Impairment	Participants with severe hepatic impairment (CP Class C, score of 10 to 15)

Measured Values

	Normal Hepatic Function	Moderate Hepatic Impairment	Severe Hepatic Impairment
Number of Participants Analyzed [units:participants]	8	8	6
Pharmacokinetic Parameters: Cmax [units: ng/mL] Geometric Mean (Geometric Coefficient of Variation)	34.40 (19.38%)	93.41 (59.51%)	106.6 (57.97%)

No statistical analysis provided for Pharmacokinetic Parameters: Cmax

2. Primary Outcome Measure: Pharmacokinetic Parameters: tmax [ Time Frame: Pharmacokinetic samples were taken predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 48, 60, 72, and 96 h postdose. ]

Measure Type	Primary
Measure Name	Pharmacokinetic Parameters: tmax
Measure Description	For tmax, number of observations, median, minimum, and maximum were used. tmax = time to reach maximum observed concentration
Time Frame	Pharmacokinetic samples were taken predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 48, 60, 72, and 96 h postdose.
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Pharmacokinetic Analysis Set

Reporting Groups

	Description
Normal Hepatic Function	Matched-control healthy participants with normal hepatic function
Moderate Hepatic Impairment	Participants with moderate hepatic impairment (CP Class B, score of 7 to 9)
Severe Hepatic Impairment	Participants with severe hepatic impairment (CP Class C, score of 10 to 15)

Measured Values

	Normal Hepatic Function	Moderate Hepatic Impairment	Severe Hepatic Impairment
Number of Participants Analyzed [units:participants]	8	8	6
Pharmacokinetic Parameters: tmax [units: hours] Median (Full Range)	5 (1.9333 to 8)	1.5 (0.5 to 5.9333)	1 (0.5 to 3)

No statistical analysis provided for Pharmacokinetic Parameters: tmax

3. Primary Outcome Measure: Pharmacokinetic Parameters: AUCinf and AUClast [ Time Frame: Pharmacokinetic samples were taken predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 48, 60, 72, and 96 h postdose. ]

Measure Type	Primary
Measure Name	Pharmacokinetic Parameters: AUCinf and AUClast
Measure Description	AUCinf and AUClast were analysed using an analysis of variance model, with hepatic imapirment category as a fixed effect, following a natural logarithmic transformation. AUCinf = area under the concentration-time curve from zero to infinity AUClast = area under the concentration-time curve from zero to the last measurable concentration
Time Frame	Pharmacokinetic samples were taken predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 48, 60, 72, and 96 h postdose.
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Pharmacokinetic Analysis Set

Reporting Groups

	Description
Normal Hepatic Function	Matched-control healthy participants with normal hepatic function
Moderate Hepatic Impairment	Participants with moderate hepatic impairment (CP Class B, score of 7 to 9)
Severe Hepatic Impairment	Participants with severe hepatic impairment (CP Class C, score of 10 to 15)

Measured Values

	Normal Hepatic Function	Moderate Hepatic Impairment	Severe Hepatic Impairment
Number of Participants Analyzed [units:participants]	8	8	6
Pharmacokinetic Parameters: AUCinf and AUClast [units: h*ng/mL] Geometric Mean (Geometric Coefficient of Variation)
AUCinf	709.0 (31.53%)	1715 (87.55%)	2680 (46.32%)
AUClast	667.4 (30.10%)	1539 (81.34%)	2262 (37.97%)

No statistical analysis provided for Pharmacokinetic Parameters: AUCinf and AUClast

4. Primary Outcome Measure: Other Pharmacokinetic Parameters: tlast [ Time Frame: Pharmacokinetic samples were taken predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 48, 60, 72, and 96 h postdose. ]

Measure Type	Primary
Measure Name	Other Pharmacokinetic Parameters: tlast
Measure Description	For tlast, number of observations, median, minimum, and maximum were used. tlast = time of the last measurable concentration
Time Frame	Pharmacokinetic samples were taken predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 48, 60, 72, and 96 h postdose.
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Normal Hepatic Function	Matched-control healthy participants with normal hepatic function
Moderate Hepatic Impairment	Participants with moderate hepatic impairment (CP Class B, score of 7 to 9)
Severe Hepatic Impairment	Participants with severe hepatic impairment (CP Class C, score of 10 to 15)

Measured Values

	Normal Hepatic Function	Moderate Hepatic Impairment	Severe Hepatic Impairment
Number of Participants Analyzed [units:participants]	8	8	6
Other Pharmacokinetic Parameters: tlast [units: hours] Median (Full Range)	96 (59.9167 to 96)	96 (72.1 to 96.0833)	96 (95.7667 to 96.0833)

No statistical analysis provided for Other Pharmacokinetic Parameters: tlast

5. Primary Outcome Measure: Other Pharmacokinetic Parameters: t1/2λz [ Time Frame: Pharmacokinetic samples were taken predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 48, 60, 72, and 96 h postdose. ]

Measure Type	Primary
Measure Name	Other Pharmacokinetic Parameters: t1/2λz
Measure Description	t1/2λz = apparent terminal elimination half-life
Time Frame	Pharmacokinetic samples were taken predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 48, 60, 72, and 96 h postdose.
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Pharmacokinetic Analysis Set

Reporting Groups

	Description
Normal Hepatic Function	Matched-control healthy participants with normal hepatic function
Moderate Hepatic Impairment	Participants with moderate hepatic impairment (CP Class B, score of 7 to 9)
Severe Hepatic Impairment	Participants with severe hepatic impairment (CP Class C, score of 10 to 15)

Measured Values

	Normal Hepatic Function	Moderate Hepatic Impairment	Severe Hepatic Impairment
Number of Participants Analyzed [units:participants]	8	8	8
Other Pharmacokinetic Parameters: t1/2λz [units: hours] Geometric Mean (Geometric Coefficient of Variation)	22.43 (29.79%)	28.61 (25.98%)	36.14 (29.06%)

No statistical analysis provided for Other Pharmacokinetic Parameters: t1/2λz

6. Primary Outcome Measure: Other Pharmacokinetic Parameters: CL/F [ Time Frame: Pharmacokinetic samples were taken predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 48, 60, 72, and 96 h postdose. ]

Measure Type	Primary
Measure Name	Other Pharmacokinetic Parameters: CL/F
Measure Description	CL/F = apparent total body clearance; summarised using descriptive statistics.
Time Frame	Pharmacokinetic samples were taken predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 48, 60, 72, and 96 h postdose.
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Pharmacokinetic Analysis Set

Reporting Groups

	Description
Normal Hepatic Function	Matched-control healthy participants with normal hepatic function
Moderate Hepatic Impairment	Participants with moderate hepatic impairment (CP Class B, score of 7 to 9)
Severe Hepatic Impairment	Participants with severe hepatic impairment (CP Class C, score of 10 to 15)

Measured Values

	Normal Hepatic Function	Moderate Hepatic Impairment	Severe Hepatic Impairment
Number of Participants Analyzed [units:participants]	8	8	6
Other Pharmacokinetic Parameters: CL/F [units: L/h] Geometric Mean (Geometric Coefficient of Variation)	105.8 (31.53%)	43.72 (87.55%)	27.98 (46.32%)

No statistical analysis provided for Other Pharmacokinetic Parameters: CL/F

7. Primary Outcome Measure: Other Pharmacokinetic Parameters: Vz/F [ Time Frame: Pharmacokinetic samples were taken predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 48, 60, 72, and 96 h postdose. ]

Measure Type	Primary
Measure Name	Other Pharmacokinetic Parameters: Vz/F
Measure Description	Vz/F = apparent volume of distribution following extravascular administration (based on terminal phase)
Time Frame	Pharmacokinetic samples were taken predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 48, 60, 72, and 96 h postdose.
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Pharmacokinetic Analysis Set

Reporting Groups

	Description
Normal Hepatic Function	Matched-control healthy participants with normal hepatic function
Moderate Hepatic Impairment	Participants with moderate hepatic impairment (CP Class B, score of 7 to 9)
Severe Hepatic Impairment	Participants with severe hepatic impairment (CP Class C, score of 10 to 15)

Measured Values

	Normal Hepatic Function	Moderate Hepatic Impairment	Severe Hepatic Impairment
Number of Participants Analyzed [units:participants]	8	8	8
Other Pharmacokinetic Parameters: Vz/F [units: liter (L)] Geometric Mean (Geometric Coefficient of Variation)	3423 (21.31%)	1805 (61.76%)	1459 (25.83%)

No statistical analysis provided for Other Pharmacokinetic Parameters: Vz/F

8. Secondary Outcome Measure: Clinically significant changes from baseline in vital signs [ Time Frame: Vital signs were taken during screening, Day -1, Day 1 predose (within <2 h prior to dose) and 4 h postdose (±1 h), 24 h postdose (±1 h) on Day 2; 48 h postdose (±2 h) on Day 3; 72 h postdose (±2 h) on Day 4; and 96 h postdose (±2 h) on Day 5. ]

Measure Type	Secondary
Measure Name	Clinically significant changes from baseline in vital signs
Measure Description	Vital signs were summarised for the following parameters: supine blood pressure, pulse rate, and temperature. Clinical significance was assessed by the investigator.
Time Frame	Vital signs were taken during screening, Day -1, Day 1 predose (within <2 h prior to dose) and 4 h postdose (±1 h), 24 h postdose (±1 h) on Day 2; 48 h postdose (±2 h) on Day 3; 72 h postdose (±2 h) on Day 4; and 96 h postdose (±2 h) on Day 5.
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety Analysis Set

Reporting Groups

	Description
Normal Hepatic Function	Matched-control healthy participants with normal hepatic function
Moderate Hepatic Impairment	Participants with moderate hepatic impairment (CP Class B, score of 7 to 9)
Severe Hepatic Impairment	Participants with severe hepatic impairment (CP Class C, score of 10 to 15)

Measured Values

	Normal Hepatic Function	Moderate Hepatic Impairment	Severe Hepatic Impairment
Number of Participants Analyzed [units:participants]	8	8	8
Clinically significant changes from baseline in vital signs [units: participants]	0	0	0

No statistical analysis provided for Clinically significant changes from baseline in vital signs

9. Secondary Outcome Measure: Clinically significant changes from baseline in clinical chemistry parameters [ Time Frame: Clinical chemistry evaluations were done at screening, Day -1, and 72 h postdose (±2 h) on Day 4. ]

Measure Type	Secondary
Measure Name	Clinically significant changes from baseline in clinical chemistry parameters
Measure Description	For clinical chemistry variables, the change from baseline for each laboratory parameter as well as the change from baseline based on reference range classification (low [below range], normal [within range or on limits of range], and high [above range]) were analysed. Clinical significance was assessed by the investigator.
Time Frame	Clinical chemistry evaluations were done at screening, Day -1, and 72 h postdose (±2 h) on Day 4.
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety Analysis Set

Reporting Groups

	Description
Normal Hepatic Function	Matched-control healthy participants with normal hepatic function
Moderate Hepatic Impairment	Participants with moderate hepatic impairment (CP Class B, score of 7 to 9)
Severe Hepatic Impairment	Participants with severe hepatic impairment (CP Class C, score of 10 to 15)

Measured Values

	Normal Hepatic Function	Moderate Hepatic Impairment	Severe Hepatic Impairment
Number of Participants Analyzed [units:participants]	8	8	6
Clinically significant changes from baseline in clinical chemistry parameters [units: participants]	0	0	0

No statistical analysis provided for Clinically significant changes from baseline in clinical chemistry parameters

10. Secondary Outcome Measure: Clinically significant changes from baseline in haematology parameters [ Time Frame: Haematology evaluations were done at screening, Day -1, and 72 h postdose (±2 h) on Day 4. ]

Measure Type	Secondary
Measure Name	Clinically significant changes from baseline in haematology parameters
Measure Description	For haematology variables, the change from baseline for each laboratory parameter as well as the change from baseline based on reference range classification (low [below range], normal [within range or on limits of range], and high [above range]) were analysed. Clinical significance was assessed by the investigator.
Time Frame	Haematology evaluations were done at screening, Day -1, and 72 h postdose (±2 h) on Day 4.
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety Analysis Set

Reporting Groups

	Description
Normal Hepatic Function	Matched-control healthy participants with normal hepatic function
Moderate Hepatic Impairment	Participants with moderate hepatic impairment (CP Class B, score of 7 to 9)
Severe Hepatic Impairment	Participants with severe hepatic impairment (CP Class C, score of 10 to 15)

Measured Values

	Normal Hepatic Function	Moderate Hepatic Impairment	Severe Hepatic Impairment
Number of Participants Analyzed [units:participants]	8	8	6
Clinically significant changes from baseline in haematology parameters [units: participants]	0	0	0

No statistical analysis provided for Clinically significant changes from baseline in haematology parameters

11. Secondary Outcome Measure: Clinically significant changes from baseline in ECGs (12-lead paper and digital recordings), including rhythm, heart rate, conduction, PR, QRS, RR, QT, and QTcF intervals, and overall evaluation [ Time Frame: Triplicate at screening, single ECG on Day -1, Day 1 predose (within < 2 h prior to dose) and 4 h postdose (±1 h), 24 h postdose (±1 h) on Day 2; 48 h postdose (±2 h) on Day 3; 72 h postdose (±2 h) on Day 4; and 96 h postdose (±2 h) on Day 5. ]

Measure Type	Secondary
Measure Name	Clinically significant changes from baseline in ECGs (12-lead paper and digital recordings), including rhythm, heart rate, conduction, PR, QRS, RR, QT, and QTcF intervals, and overall evaluation
Measure Description	The 12-lead electrocardiogram (ECG) parameters were summarised by hepatic impairment group using descriptive statistics by timepoint. Change from baseline in ECG endpoints was calculated for each postdose timepoint. Summary tables considered the average of triplicate measurements, where applicable, as the single reported value. Clinical significance was assessed by the investigator.
Time Frame	Triplicate at screening, single ECG on Day -1, Day 1 predose (within < 2 h prior to dose) and 4 h postdose (±1 h), 24 h postdose (±1 h) on Day 2; 48 h postdose (±2 h) on Day 3; 72 h postdose (±2 h) on Day 4; and 96 h postdose (±2 h) on Day 5.
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Normal Hepatic Function	Matched-control healthy participants with normal hepatic function
Moderate Hepatic Impairment	Participants with moderate hepatic impairment (CP Class B, score of 7 to 9)
Severe Hepatic Impairment	Participants with severe hepatic impairment (CP Class C, score of 10 to 15)

Measured Values

	Normal Hepatic Function	Moderate Hepatic Impairment	Severe Hepatic Impairment
Number of Participants Analyzed [units:participants]	8	8	6
Clinically significant changes from baseline in ECGs (12-lead paper and digital recordings), including rhythm, heart rate, conduction, PR, QRS, RR, QT, and QTcF intervals, and overall evaluation [units: participants]	0	0	0

No statistical analysis provided for Clinically significant changes from baseline in ECGs (12-lead paper and digital recordings), including rhythm, heart rate, conduction, PR, QRS, RR, QT, and QTcF intervals, and overall evaluation

12. Secondary Outcome Measure: Clinically significant findings in physical examinations [ Time Frame: Complete physical examination was performed at screening. Brief examination on Day -1 and Day 5. ]

Measure Type	Secondary
Measure Name	Clinically significant findings in physical examinations
Measure Description	A complete physical examination will include assessments of the following: general appearance, respiratory, cardiovascular, abdomen, skin, head and neck (including ears, eyes, nose, and throat), lymph nodes, thyroid, muscular-skeletal (including spine and extremities), and neurological systems. A brief physical examination will include, at a minimum, assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). Clinical significance was assessed by the investigator.
Time Frame	Complete physical examination was performed at screening. Brief examination on Day -1 and Day 5.
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety Analysis Set

Reporting Groups

	Description
Normal Hepatic Function	Matched-control healthy participants with normal hepatic function
Moderate Hepatic Impairment	Participants with moderate hepatic impairment (CP Class B, score of 7 to 9)
Severe Hepatic Impairment	Participants with severe hepatic impairment (CP Class C, score of 10 to 15)

Measured Values

	Normal Hepatic Function	Moderate Hepatic Impairment	Severe Hepatic Impairment
Number of Participants Analyzed [units:participants]	8	8	6
Clinically significant findings in physical examinations [units: participants]	0	0	0

No statistical analysis provided for Clinically significant findings in physical examinations

13. Secondary Outcome Measure: Identification of AEs assessed as causally related to IMP which led to study discontinuation by the participant [ Time Frame: Adverse events with onset date on or after Day 1 up to and including the follow-up telephone call (about 12 days) were included. ]

Measure Type	Secondary
Measure Name	Identification of AEs assessed as causally related to IMP which led to study discontinuation by the participant
Measure Description	As this was a single-dose study, discontinuation from study intervention was not applicable. Causality of adverse events was assessed by the investigator.
Time Frame	Adverse events with onset date on or after Day 1 up to and including the follow-up telephone call (about 12 days) were included.
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety Analysis Set

Reporting Groups

	Description
Normal Hepatic Function	Matched-control healthy participants with normal hepatic function
Moderate Hepatic Impairment	Participants with moderate hepatic impairment (CP Class B, score of 7 to 9)
Severe Hepatic Impairment	Participants with severe hepatic impairment (CP Class C, score of 10 to 15)

Measured Values

	Normal Hepatic Function	Moderate Hepatic Impairment	Severe Hepatic Impairment
Number of Participants Analyzed [units:participants]	8	8	8
Identification of AEs assessed as causally related to IMP which led to study discontinuation by the participant [units: participants]	0	0	0

No statistical analysis provided for Identification of AEs assessed as causally related to IMP which led to study discontinuation by the participant

Serious Adverse Events

Time Frame	Adverse events were collected from the time of signing of the informed consent form throughout the treatment period and including the follow-up telephone call (up to 5 weeks).
Additional Description	Adverse events with an onset date on or after the date of administration of camizestrant up to and including the follow-up telephone call were presented. Participants with multiple occurrences are counted once per system organ class and preferred term regardless of the number of occurrences.

Reporting Groups

	Description
Normal Hepatic Function	Matched-control healthy participants with normal hepatic function
Moderate Hepatic Impairment	Participants with moderate hepatic impairment (CP Class B, score of 7 to 9)
Severe Hepatic Impairment	Participants with severe hepatic impairment (CP Class C, score of 10 to 15)

Serious Adverse Events

	Normal Hepatic Function	Moderate Hepatic Impairment	Severe Hepatic Impairment
Total, serious adverse events
# participants affected / at risk	0/8 (0.00%)	0/8 (0.00%)	0/6 (0.00%)

Other Adverse Events

Time Frame	Adverse events were collected from the time of signing of the informed consent form throughout the treatment period and including the follow-up telephone call (up to 5 weeks).
Additional Description	Adverse events with an onset date on or after the date of administration of camizestrant up to and including the follow-up telephone call were presented. Participants with multiple occurrences are counted once per system organ class and preferred term regardless of the number of occurrences.

Frequency Threshold

Threshold above which other adverse events are reported	0%

Reporting Groups

	Description
Normal Hepatic Function	Matched-control healthy participants with normal hepatic function
Moderate Hepatic Impairment	Participants with moderate hepatic impairment (CP Class B, score of 7 to 9)
Severe Hepatic Impairment	Participants with severe hepatic impairment (CP Class C, score of 10 to 15)

Other Adverse Events

Normal Hepatic Function

Moderate Hepatic Impairment

Severe Hepatic Impairment

Total, other (not including serious) adverse events

# participants affected / at risk

1/8 (12.50%)

2/8 (25.00%)

0/6 (0.00%)

Musculoskeletal and connective tissue disorders

Muscle spasms¹,^†

# participants affected / at risk

0/8 (0.00%)

1/8 (12.50%)

0/6 (0.00%)

# events

Nervous system disorders

Headache¹,^†

# participants affected / at risk

1/8 (12.50%)

0/6 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 26.1

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: The investigator shall be entitled to publish the results of, or make presentations related to, the Study, provided that any publications or presentations to be made within 2 years after completion of the Study shall require the Sponsor's prior written consent.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact

Name/Title:	Global Clinical Lead
Organization:	AstraZeneca
Phone	1-877-240-9479
E-mail:	[email protected]

Documents available

Download
D8532C00002_CSR Synopsis_redacted
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

D8532C00002_CSR Synopsis_redacted

Trial Results Summaries