Healthy Adults, Healthy, Hepatic Insufficiency, Hepatic Impairment
Conditions
Brief summary
The purpose of this study to understand how the study medicine atirmociclib behaves in the body and how safe it is for people with different levels of liver health. The study is seeking participants who are: * Aged 18 years or older * Have a BMI of 17.5 to 40 kg/m2, and body weight more than 50 kg. * Have normal liver function or have stable mild, moderate, or severe liver disease Participants will receive study medicine by mouth. Blood samples will be collected to see how much of the medicine is in the body over time. This will help understand whether liver disease changes how the medicine is handled. Participants will be in the study for about 9 weeks. Those with normal liver function will stay in the clinic for about 7 days. People with liver disease will stay for about 9 days. After leaving the clinic, people may be contacted for follow-up. This may be done by phone or through a clinic visit.
Interventions
DRUGAtirmociclib
atirmociclib administered as a single oral dose
Sponsors
Pfizer
Study design
Allocation
NA
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
including but not limited to: * BMI of 17.5-40 kg/m2; and a total body weight \>50 kg (110 lb). * Willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures. * Capable of giving signed informed consent. Normal hepatic function group only: \- Overtly healthy as determined by medical evaluations including medical history, physical examination, laboratory tests, vital signs and standard 12-lead ECGs. Hepatic impairment groups only: \- Stable hepatic impairment meeting the criteria for Child-Pugh Class A, B, or C . Stable hepatic impairment is defined as no clinically significant change in disease status within the last 28 days prior to the screening visit, as documented by the participant's recent medical history.
Exclusion criteria
including but not limited to: * Any condition or history of surgery possibly affecting drug absorption. * Use of prohibited prior or concomitant medications. Normal hepatic function group only: \- Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing). Hepatic impairment groups only: \- A diagnosis of hepatic dysfunction secondary to any acute ongoing hepatocellular process that is documented by medical history, PE, liver biopsy, hepatic ultrasound, CT scan, or MRI.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) for atirmociclib in participants with normal hepatic function | Pre-dose and at, 1, 2, 4, 6, 8, 12, and 24, 36, 48, 60, 72, 96, 120, 144 hours after a single oral dose | Maximum observed plasma concentration (Cmax) for atirmociclib following a single oral dose in participants with normal hepatic function |
| Maximum Observed Plasma Concentration (Cmax) for atirmociclib in participants with hepatic impairment | Pre-dose and at, 1, 2, 4, 6, 8, 12, and 24, 36, 48, 60, 72, 96, 120, 144, 168, 192 hours after a single oral dose | Maximum observed plasma concentration (Cmax) for atirmociclib following a single oral dose in participants with hepatic impairment |
| Area under the curve from time zero to extrapolated infinite time [AUC (0 - ∞)] for atirmociclib in participants with normal hepatic function | Pre-dose and at, 1, 2, 4, 6, 8, 12, and 24, 36, 48, 60, 72, 96, 120, 144 hours after a single oral dose | AUC (0 - ∞)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞). |
| Area under the curve from time zero to extrapolated infinite time [AUC (0 - ∞)] for atirmociclib in participants with impaired hepatic function | Pre-dose and at, 1, 2, 4, 6, 8, 12, and 24, 36, 48, 60, 72, 96, 120, 144, 168, 192 hours after a single oral dose | AUC (0 - ∞)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞). |
Secondary
| Measure | Time frame |
|---|---|
| Number of Participants With Treatment-Emergent Adverse Events | Time from baseline through and including follow-up contact occurring 28 to 35 calendar days after the last administration of atirmociclib |
| Number of Participants With Normal Hepatic Function having Clinically Significant Clinical Laboratory Abnormalities | Baseline and Day 2, Day 7 after a single oral dose of atirmociclib |
| Number of Participants With Impaired Hepatic Function having Clinically Significant Clinical Laboratory Abnormalities | Baseline and Day 2, Day 9 after a single oral dose of atirmociclib |
| Number of Participants With Normal Hepatic Function having Clinically Significant Change From Baseline in Vital Signs | Predose and at 4, 144 hours after a single oral dose of atirmociclib |
| Number of Participants With Impaired Hepatic function having Clinically Significant Change From Baseline in Vital Signs | Predose and at 4, 192 hours after a single oral dose of atirmociclib |
| Number of Participants With Normal Hepatic Function having Clinically Significant Electrocardiogram (ECG) Abnormalities | Predose and at 4, 144 hours after a single oral dose of atirmociclib |
| Number of Participants With Impaired Hepatic Function having Clinically Significant Electrocardiogram (ECG) Abnormalities | Predose and at 4, 192 hours after a single oral dose of atirmociclib |
Countries
United States
Contacts
CONTACTPfizer CT.gov Call Center
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Outcome results
None listed