Clinical trial NCT04604496: STUDY OF PF-06882961 IN PARTICIPANTS WITH AND WITHOUT VARYING DEGREES OF HEPATIC IMPAIREMENT
Official title: A Phase 1, Non-randomized, Open-label, Single-dose, Parallel Cohort Study to Compare the Pharmacokinetics of PF-06882961 in Adult Participants With Varying Degrees of Hepatic Impairment Relative to Participants Without Hepatic Impairment.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatic Impairment
Healthy Volunteers
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2020-10-27
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The current study is proposed to evaluate whether there is any clinically meaningful effect of hepatic impairment on the plasma Pharmacokinetic (PK) of PF-06882961


Eligibility criteria: Inclusion Criteria:

* Male and female participants between the ages of 18 (or the minimum country-specific age of consent if \>18) and 70 years, inclusive, at the screening visit:
* Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
* Body mass index (BMI) of 17.5 to 38.0 kg/m2, inclusive; and a total body weight \>50 kg (110 lb), at the screening visit; with a single repeat assessment of total body weight (and hence BMI), on a separate day permitted to assess eligibility, if needed.

Exclusion Criteria:

* Any condition possibly affecting drug absorption (eg, prior bariatric surgery, gastrectomy, ileal resection); NOTE: Participants who have undergone cholecystectomy and/or appendectomy are eligible for this study as long as the surgery occurred more than 6 months prior to Screening;
* At screening, participants with a positive result for human immunodeficiency virus (HIV) antibodies, as assessed by sponsor-identified central laboratory, with a single repeat permitted to assess eligibility, if needed;
* A positive COVID-19 test at screening;
* A diagnosis of type 2 diabetes mellitus (T2DM) that is documented by medical history;
* Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN2), or participants with suspected MTC per the investigator's judgement;
* Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study;
* Use of prior/concomitant therapies
* Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of investigational product used in this study (whichever is longer);
* Participants with known prior participation (ie, randomized and received at least 1 dose of investigational product) in a study involving PF-06882961;
* Participants with ANY of the following abnormalities in clinical laboratory tests at Visit 1, as assessed by the study specific laboratory and confirmed by a single repeat test, if deemed necessary:

HbA1c ≥6.5%; FPG ≥126 mg/Dl; eGFR\<60 mL/min/1.73m2;

* A positive urine drug test, for illicit drugs at screening, as assessed by sponsor-identified central laboratory. However, participants in Cohorts 2-4, only, who have been medically prescribed opiates/opioids or benzodiazepines and report the use of these drugs to the investigator at the Screening visit will be allowed to participate; NOTE: repeat urine drug testing is not permitted in this study;
* At screening or Day -1, a positive breath alcohol test, as assessed using kits provided by sponsor-identified central laboratory, with a single repeat on a separate day permitted to assess eligibility, if needed;
* Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to dosing and until the follow-up contact; 13. History of sensitivity to heparin or heparin-induced thrombocytopenia, only if heparin is used to flush intravenous catheters used during serial blood collections;
* Unwilling or unable to comply with the criteria in the Lifestyle Considerations section of this protocol;
* Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.

Primary outcomes:
measure: Maximum Plasma Concentration (Cmax)
timeFrame: Predose (0 hours), 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24, 36 and 48 hours post dose on Day 1.
measure: Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf)
timeFrame: Predose (0 hours), 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24, 36 and 48 hours post dose on Day 1.
measure: Area Under the Plasma Concentration-Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast)
timeFrame: Predose (0 hours), 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24, 36 and 48 hours post dose on Day 1.
measure: Fraction of Unbound Drug in Plasma (fu)
timeFrame: Predose (0 hours), and 4 hours post dose on Day 1.
Secondary outcomes:
measure: Number of Participants Reporting Treatment-emergent Adverse Events (AEs)
timeFrame: Baseline to Day 30
measure: Number of Participants With Clinical Laboratory Abnormalities
timeFrame: Baseline to Day 3
measure: Number of Participants With Categorical Vital Signs Data
timeFrame: Baseline to Day 3
measure: Number of Participants With Categorical Electrocardiogram (ECG) Data
timeFrame: Baseline to Day 3
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami Division of Clinical Pharmacology
state: Florida
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Florida
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: