Effect Of Hepatic Impairment on the Pharmacokinetics, Safety and Tolerability of PF-06865571 In Subjects With Hepatic Impairment and in Healthy Subjects

• ClinicalTrials.gov Identifier: NCT04091061
• Recruitment Status: Completed
• First Posted: September 16, 2019
• Results First Posted: April 13, 2021
• Last Update Posted: April 13, 2021
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: September 13, 2019
• First Posted Date: September 16, 2019
• Results First Submitted Date: March 18, 2021
• Results First Posted Date: April 13, 2021
• Last Update Posted Date: April 13, 2021
• Actual Study Start Date: October 3, 2019
• Actual Primary Completion Date: April 7, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 18, 2021)

• Maximum Observed Plasma Concentration (Cmax) [ Time Frame: For Cohort 1, pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48 hours post dose. For Cohorts 2-4, pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 hours post dose. ]
  Cmax of PF-06865571 was observed directly from data.
• Area Under the Curve From Time 0 to Last Quantifiable Concentration (AUClast) [ Time Frame: For Cohort 1, pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48 hours post dose. For Cohorts 2-4, pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 hours post dose. ]
  AUClast of PF-06865571 was determined by linear/log trapezoidal method.
• Area Under the Curve From Time 0 to Extrapolated Infinite Time (AUCinf) [ Time Frame: For Cohort 1, pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48 hours post dose. For Cohorts 2-4, pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 hours post dose. ]
  AUCinf = Area under the plasma concentration versus time curve (AUC) from time 0 (pre-dose) to extrapolated infinite time (0-inf).

Original Primary Outcome Measures (submitted: September 13, 2019)

• Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) [ Time Frame: Hour 0, 0.5, 1, 2, 4, 6, 8, 10, 12, and 16 on Day 1, Hour 24 and 36 on Day 2, Hour 48 on Day 3 and Hour 72 on Day 4 ]
• Area under the plasma concentration-time AUC([last)] [ Time Frame: Hour 0, 0.5, 1, 2, 4, 6, 7, 8, 10, 12, 14, and 16 on Day 1, Hour 24 and 36 on Day 2, Hour 48 on Day 3 and Hour 72 on Day 4 ]
• Maximum plasma concentration [C(max)] [ Time Frame: Hour 0, 0.5, 1, 2, 4, 6, 8, 10, 12, and 16 on Day 1, Hour 24 and 36 on Day 2, Hour 48 on Day 3 and Hour 72 on Day 4 ]

Current Secondary Outcome Measures (submitted: March 18, 2021)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Up to Day 32 (31 days after investigational product administration) ]
  An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who receives study drug. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs were events following start of treatment.
• Number of Participants With Clinical Laboratory Abnormalities [ Time Frame: Up to Day 4 (3 days after investigational product administration) ]
  The following parameters were analyzed for laboratory examination: hematology, clinical chemistry, and urinalysis. The abnormalities with at least 1 participant are presented here.
• Number of Participants With Categorical Vital Signs Data [ Time Frame: Up to Day 4 (3 days after investigational product administration) ]
  Vital signs (systolic and diastolic blood pressure, and pulse rate) were obtained with participants after having sat calmly for at least 5 minutes.
• Number of Participants With Categorical Electrocardiogram (ECG) [ Time Frame: Up to Day 4 (3 days after investigational product administration) ]
  QT interval corrected using Fridericia's formula (QTcF) was obtained with participants. All scheduled ECGs were performed after the participant had rested quietly for at least 10 minutes in a supine position.

Original Secondary Outcome Measures (submitted: September 13, 2019)

• Number of Subjects Reporting Treatment-emergent AEs [ Time Frame: Baseline to Day 30 ]
• Number of Subjects with Clinically Significant Change from Baseline in Laboratory tests [ Time Frame: Baseline to Day 4 ]
• Number of Subjects with Clinically Significant Change from Baseline in Vital Signs [ Time Frame: Baseline to Day 4 ]
• Number of Subjects with Clinically Significant Change from Baseline in 12-lead ECGs [ Time Frame: Baseline to Day 4 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Effect Of Hepatic Impairment on the Pharmacokinetics, Safety and Tolerability of PF-06865571 In Subjects With Hepatic Impairment and in Healthy Subjects
• Official Title: A PHASE 1, NON-RANDOMIZED, OPEN-LABEL, SINGLE-DOSE, PARALLEL-COHORT STUDY TO COMPARE THE PHARMACOKINETICS OF PF 06865571 IN ADULT PARTICIPANTS WITH VARYING DEGREES OF HEPATIC IMPAIRMENT RELATIVE TO PARTICIPANTS WITHOUT HEPATIC IMPAIRMENT
• Brief Summary: The current study is proposed to evaluate whether there is any clinically meaningful effect of hepatic impairment on the plasma PK of PF-06865571.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Basic Science

Condition

• Hepatic Impairment
• Healthy Volunteers

Intervention

Drug: PF-06865571 100 mg

PF-06865571 in 100 mg oral tablet will be administered on Day 1

Study Arms

• Experimental: PF-06865571 Moderate Hepatic Impairment
  This arm includes participants with moderate hepatic impairment who will receive an oral dose of PF-06865571 100 mg on Day 1
  Intervention: Drug: PF-06865571 100 mg
• Experimental: PF-06865571 Severe Hepatic Impairment
  This arm includes participants with severe hepatic impairment who will receive an oral dose of PF-06865571 100 mg on Day 1
  Intervention: Drug: PF-06865571 100 mg
• Experimental: PF-06865571 Mild Hepatic Impairment
  This arm includes participants with mild hepatic impairment who will receive an oral dose of PF-06865571 100 mg on Day 1
  Intervention: Drug: PF-06865571 100 mg
• Experimental: PF-06865571 Healthy Participants
  This arm includes healthy participants who will receive an oral dose of PF-06865571 100 mg on Day 1
  Intervention: Drug: PF-06865571 100 mg

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 13, 2019): 24
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: April 7, 2020
• Actual Primary Completion Date: April 7, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• 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, 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.
• Capable of giving signed informed consent.

Exclusion Criteria

• Any condition possibly affecting drug absorption (eg, prior bariatric surgery,gastrectomy, ileal resection).
• 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 behavior 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.
• 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-06865571.
• A positive urine drug test, for illicit drugs on Day -1,
• At Screening or Day -1, a positive breath alcohol test.
• 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.
• Unwilling or unable to comply with the criteria in the Lifestyle Considerations.
• 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04091061
• Other Study ID Numbers: C2541009
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

• Current Responsible Party: Pfizer
• Original Responsible Party: Same as current
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: March 2021