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Completed

NCT Number: NCT04604496

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

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

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Key information

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

University of Miami Division of Clinical Pharmacology, Miami, Florida, United States

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Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

PF-06882961 20MG

Drug

PF-06882961 in 20 mg oral tablet will be administered on Day 1

Primary outcomes

  1. Maximum Plasma Concentration (Cmax)

    Time frame: Predose (0 hours), 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24, 36 and 48 hours post dose on Day 1.

    Maximum observed plasma PF-06882961 concentration.

  2. Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf)

    Time frame: Predose (0 hours), 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24, 36 and 48 hours post dose on Day 1.

    Area under the plasma PF-06882961 concentration-time profile from time 0 extrapolated to infinite time.

  3. Area Under the Plasma Concentration-Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast)

    Time frame: Predose (0 hours), 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24, 36 and 48 hours post dose on Day 1.

    Area under the plasma PF-06882961 concentration-time profile from time 0 extrapolated to the time of the last quantifiable concentration.

  4. Fraction of Unbound Drug in Plasma (fu)

    Time frame: Predose (0 hours), and 4 hours post dose on Day 1.

    fu = Cu/C (where Cu represents unbound concentration and C represents total concentration).

Secondary outcomes

  1. Number of Participants Reporting Treatment-emergent Adverse Events (AEs)

    Time frame: Baseline to Day 30

    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.

  2. Number of Participants With Clinical Laboratory Abnormalities

    Time frame: Baseline to Day 3

    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.

  3. Number of Participants With Categorical Vital Signs Data

    Time frame: Baseline to Day 3

    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.

  4. Number of Participants With Categorical Electrocardiogram (ECG) Data

    Time frame: Baseline to Day 3

    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.

    • 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.
    • 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

Sponsors and collaborators

Lead sponsor

Pfizer

Industry

Registry information

Official study 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.

Important dates

Study start
2020
Primary completion
2022
Study completion
2022
First posted
Oct 27, 2020
Registry last updated
Mar 21, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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