STUDY OF PF-06882961 IN PARTICIPANTS WITH AND WITHOUT VARYING DEGREES OF HEPATIC IMPAIREMENT

Healthy Volunteers Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04604496
• Other study ID #: C3421014
• Status: Completed
• Phase: Phase 1
• Start date: December 30, 2020
• Est. completion date: January 10, 2022

Study information

• Verified date: September 2023
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: January 10, 2022
• Est. primary completion date: January 10, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Volunteers
• Hepatic Impairment
• Liver Diseases

Intervention

Drug:
• PF-06882961 20MG
PF-06882961 in 20 mg oral tablet will be administered on Day 1

Locations

Country	Name	City	State
United States	University of Miami Division of Clinical Pharmacology	Miami	Florida
United States	Orlando Clinical Research Center	Orlando	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Plasma Concentration (Cmax)	Maximum observed plasma PF-06882961 concentration.	Predose (0 hours), 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24, 36 and 48 hours post dose on Day 1.
Primary	Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf)	Area under the plasma PF-06882961 concentration-time profile from time 0 extrapolated to infinite time.	Predose (0 hours), 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24, 36 and 48 hours post dose on Day 1.
Primary	Area Under the Plasma Concentration-Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast)	Area under the plasma PF-06882961 concentration-time profile from time 0 extrapolated to the time of the last quantifiable concentration.	Predose (0 hours), 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24, 36 and 48 hours post dose on Day 1.
Primary	Fraction of Unbound Drug in Plasma (fu)	fu = Cu/C (where Cu represents unbound concentration and C represents total concentration).	Predose (0 hours), and 4 hours post dose on Day 1.
Secondary	Number of Participants Reporting Treatment-emergent Adverse Events (AEs)	Adverse events (AEs): any untoward medical occurrence in a clinical investigation participant administered a product or medical device, without regard to causality. Treatment-emergent AEs (TEAEs): AEs which occurred for the first time during the effective duration of treatment or AEs that increased in severity during treatment. AEs included SAEs and non-serious AEs. Serious AEs (SAEs) were any untoward medical occurrence at any dose that resulted in death; was life-threatening; required inpatient hospitalization or caused prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduction normal life functions). Treatment-related TEAEs were any untoward medical occurrence attributed to study treatment. Relatedness to study treatment was determined by the investigator.	Baseline to Day 30
Secondary	Number of Participants With Clinical Laboratory Abnormalities	Protocol-required safety laboratory assessments included: hemoglobin <0.8 x lower limit of normal (LLN), hematocrit <0.8 x LLN, erythrocytes <0.8 x LLN, ery. mean corpuscular volume >1.1 x upper limit of normal (ULN), ery. mean corpuscular hemoglobin >1.1 x ULN, platelets <0.5 x LLN, eosinophils >1.2 x ULN, activated partial thromboplastin time >1.1 x ULN, prothrombin time >1.1 x ULN, prothrombin intl. normalized ratio >1.1 x ULN; bilirubin/direct bilirubin/indirect bilirubin >1.5 x ULN, aspartate aminotransferase/alanine aminotransferase/gamma glutamyl transferase >3.0 x ULN, albumin <0.8 x LLN, urate >1.2 x ULN, bicarbonate >1.1 x ULN, triacylglycerol lipase >1.5 x ULN; urine hemoglobin/urine urobilinogen/urine nitrite/urine leukocyte esterase =1.	Baseline to Day 3
Secondary	Number of Participants With Categorical Vital Signs Data	Vital signs categorical criteria: 1) supine systolic blood pressure (SBP) <90 millimeters of mercury (mmHg); 2) supine diastolic blood pressure (DBP) <50 mmHg; 3) supine pulse rate <40 or >120 beats per minute (bpm); 4) change from baseline (increase or decrease) in supine SBP greater than or equal to (=) 30 mmHg; 5) change from baseline (increase or decrease) in supine DBP = 20 mmHg.	Baseline to Day 3
Secondary	Number of Participants With Categorical Electrocardiogram (ECG) Data	ECG categorical criteria: 1. PR interval (the interval between the start of the P wave and the start of the QRS complex, corresponding to the time between the onset of the atrial depolarization and onset of ventricular depolarization): a) greater than or equal to (=) 300 millisecond (msec), b) =25% increase when baseline is > 200 msec or =50% increase when baseline is less than or equal to (=) 200 msec.; 2. QRS interval (time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization): a) =140 msec, b) =50% increase from baseline.; 3. QTcF interval (QT corrected using the Fridericia formula): a) >450 msec and =480 msec, b) >480 msec and =500 msec, c) >500 msec, d) >30 msec and =60 msec increase from baseline, e) >60 msec increase from baseline	Baseline to Day 3

External Links

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