A STUDY TO COMPARE THE PHARMACOKINETICS OF PF-06835919 IN PARTICIPANTS WITH AND WITHOUT HEPATIC IMPAIRMENT

Study Overview
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Brief Summary
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The study is proposed to characterize the effect of varying degrees of hepatic impairment on the plasma PK of PF-06835919

Official Title
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A PHASE 1, NON-RANDOMIZED, OPEN-LABEL, SINGLE-DOSE, PARALLEL-COHORT STUDY TO COMPARE THE PHARMACOKINETICS OF PF-06835919 IN ADULT PARTICIPANTS WITH VARYING DEGREES OF HEPATIC IMPAIRMENT RELATIVE TO PARTICIPANTS WITHOUT HEPATIC IMPAIRMENT

Conditions
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Hepatic Impairment, Healthy Participants

Intervention / Treatment
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* Drug: PF-06835919 25 mg


Participation Criteria
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Eligibility Criteria
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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 35.4 kg/m2; and a total body weight >50 kg (110 lb). Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent document (ICD) and in this protocol. Exclusion Criteria: Any condition possibly affecting drug absorption (eg, prior bariatric surgery, gastrectomy, ileal resection). (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. Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behaviour or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this 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 06835919. A positive urine drug test, for illicit drugs, and/or a positive breath alcohol test at Screening. However, participants who have been medially prescribed opiates/opiods or benzodiazepines and report the use of these drugs to the investigator at the screening visit will be allowed to participate. Male participants with partners who are currently pregnant. 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. 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 the protocol. Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or Pfizer employees, including their family members, directly involved in the conduct of the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PF-06835919 with severe hepatic impairement<br>This arm includes participants with severe hepatic impairment who will receive a 25mg oral dose of PF-06835919 | Drug: PF-06835919 25 mg<br>* PF-06835919 in 25 mg oral tablet will be administered on Day 1<br>|
| Experimental: PF-06835919 with moderate hepatic impairement<br>This arm includes participants with moderate hepatic impairment who will receive a 25mg oral dose of PF-06835919 | Drug: PF-06835919 25 mg<br>* PF-06835919 in 25 mg oral tablet will be administered on Day 1<br>|
| Experimental: PF-06835919 with mild hepatic impairement<br>This arm includes participants with mild hepatic impairment who will receive a 25mg oral dose of PF-06835919 | Drug: PF-06835919 25 mg<br>* PF-06835919 in 25 mg oral tablet will be administered on Day 1<br>|
| Experimental: PF-06835919 without hepatic impairment<br>This arm includes participants without hepatic impairment who will receive a 25mg oral dose of PF-06835919 | Drug: PF-06835919 25 mg<br>* PF-06835919 in 25 mg oral tablet will be administered on Day 1<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC[inf]) |  | Hour 0, 0.5, 1, 2, 4, 6, 8, 10, 12 on Day 1, Hour 24, 36 on Day 2, Hour 48 on Day 3, Hour 72 on Day 4, Hour 96 on Day 5, Hour 120 on Day 6 | 
| Maximum Plasma Concentration (C[max]) |  | Hour 0, 0.5, 1, 2, 4, 6, 8, 10, 12 on Day 1, Hour 24, 36 on Day 2, Hour 48 on Day 3, Hour 72 on Day 4, Hour 96 on Day 5, Hour 120 on Day 6 | 
| Unbound Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC[inf,u]) |  | Hour 2 on Day 1 | 
| Unbound Maximum Plasma Concentration (C[max,u]) |  | Hour 2 on Day 1 | 
| Fraction of Drug Unbound (f[u]) |  | Hour 2 on Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participantss Reporting Treatment-emergent AEs |  | Baseline (Day 1) up to 30 days after last dose of study medication | 
| Number of Participants with Clinically Significant Change from Baseline in Laboratory Tests |  | Baseline (Day 1) up to 30 days after last dose of study medication | 
| Number of Participants with Clinically Significant Change from Baseline in Vital Signs |  | Baseline (Day 1) up to 30 days after last dose of study medication | 
| Njumber of Participants with Clinically Significant Change from Baseline in 12-Lead ECGs |  | Baseline (Day 1) up to 30 days after last dose of study medication | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-alcoholic Fatty Liver Disease, Non-alcoholic steatohepatitis