Hepatic ImpairmentPhase 1NCT04016077

A Study to Evaluate the Pharmacokinetics, Safety and Tolerability of PF-06651600 in Subjects With Hepatic Impairment and Healthy Volunteers

A Phase 1 study testing PF-06651600 30 mg in people with Hepatic Impairment and Healthy Participants, run by Pfizer at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The purpose of this study is to characterize the effect of hepatic impairment on the pharmacokinetic(s) (PK) of PF-06651600 following administration of multiple once daily doses of PF-06651600. The safety and tolerability of PF-06651600 will also be evaluated in this study. Read more about this study

Who is it for?: Ages 18 to 70 yearsHealthy volunteers can take part
Conditions the study is for: Hepatic Impairment, Healthy Participants
What is being tested?: PF-06651600 30 mg
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 18 participants
Where: 2 sitesUnited States
Study dates: 19 Jul 2019to 5 Mar 2020
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 70 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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 40 kg/m2; and a total body weight >50 kg (110 lb)
Additional Inclusion Criteria for Participants with Normal Hepatic Function:
Healthy male or female participants
No known or suspected hepatic disease
Additional Inclusion Criteria for Participants with Impaired Hepatic Function:

Show all 9Show fewer

Stable hepatic impairment, defined as no clinically significant change in disease status within the last 30 days prior to the Screening visit
No other ongoing clinically significant abnormalities based on medical history, physical examination, vital signs, 12-lead ECG, and clinical laboratory tests except for the abnormal findings that are related to the participant's hepatic impairment.
Satisfy the criteria for Class A or Class B of the Child-Pugh classification (mild: Child-Pugh Scores 5-6 points, and moderate: Child Pugh Scores 7-9 points), within 28 days of investigational product administration.

Who cannot join

Has active acute or chronic infection requiring treatment or history of systemic infection requiring hospitalization, incl. herpes zoster, herpes simplex, tuberculosis
Infection with hepatitis B, hepatitis C or HIV
Any condition affecting drug absorption, distribution, metabolism and excretion (eg, status post porta-caval shunt surgery, prior bariatric surgery, gastrectomy, ileal resection)
Has malignancy, lymphoproliferative disorder, surgery or other condition not allowed per protocol
Additional Exclusion Criteria for Participants with Normal Hepatic Function:
Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, gynecologic or allergic disease
Additional Exclusion Criteria for Participants with Impaired Hepatic Function:
Has encephalopathy, severe ascites and/or pleural effusion, Child-Pugh score >9 or medical conditions (like hepatorenal syndrome, gastrointestinal hemorrhage, etc.) excluded per protocol

Trial locations and contacts

2 sites in 1 country.

United States2 sites

University of Miami Division of Clinical Pharmacology
Miami, Florida, 33136
Orlando Clinical Research Center
Orlando, Florida, 32809

Other trials in United States

About this study

Official title: A PHASE 1, NON-RANDOMIZED, OPEN LABEL, MULTIPLE DOSE STUDY TO EVALUATE THE PHARMACOKINETICS, SAFETY AND TOLERABILITY OF PF 06651600 IN SUBJECTS WITH HEPATIC IMPAIRMENT AND IN HEALTHY SUBJECTS WITH NORMAL HEPATIC FUNCTION

Conditions: Hepatic Impairment, Healthy Participants
Being tested: PF-06651600 30 mg
Keywords: PF-06651600, Pharmacokinetics, Hepatic impairment

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PF-06651600 30 mgDrug
PF-06651600 in 10 mg oral tablets will be administered on days 1 to 10.

Study groups in NCT04016077
Study group	Role	What they receive
PF-06651600 Moderate Hepatic Impairment	Experimental	This arm includes participants with moderate hepatic impairment who will receive oral doses of PF-06651600 30 mg on Day 1 through Day 10. Receives: Drug: PF-06651600 30 mg
PF-06651600 Healthy participants	Experimental	This arm includes healthy adult participants who will receive oral doses of PF-06651600 30 mg on Day 1 through Day 10. Receives: Drug: PF-06651600 30 mg
PF-06651600 Mild Hepatic Impairment	Experimental	This arm is in Part 2 which will be conducted if the decision criterion to proceed to Part 2 is met. The arm includes participants with mild hepatic impairment who will receive oral doses of PF-06651600 30 mg on Day 1 through Day 10. Receives: Drug: PF-06651600 30 mg

What is being measured

The primary outcome is the main question the study is designed to answer.

Area Under the Plasma Concentration-time Profile From Time 0 to 24 Hours (AUC24) for PF-06651600
AUC24 of PF-06651600 pre and post dose.
Measured: Hour 0 (pre-dose) on Days 7, 8 and 9, and hour 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 14, 24 hours post-dose on Day 10
Maximum Plasma Concentration (Cmax) for PF-06651600
Cmax is maximum observed plasma concentration.
Measured: Hour 0 (pre-dose) on Days 7, 8 and 9, and hour 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 14, 24 hours post-dose on Day 10

Secondary outcomes (4)

Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) (All Causalities and Treatment-related)
AEs with all causalities were any untoward medical occurrences in a study participant administered a product which did not necessarily had causal relationship with the treatment or usage. An SAE was an AE resulting in any of the following endpoints or deemed significant for any other reason: death; life threatening (immediate risk of death); inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; or considered to be an important medical event. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-emergent are events between first dose of study drug and up to 35 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
Measured: Baseline (Day 0) up to 28 days after last dose of study medication (Day 39)
Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)
Laboratory parameters included: hematology (hemoglobin, hematocrit, erythrocytes, leukocytes, neutrophils, prothrombin time, prothrombin intl. normalized ratio), chemistry (bilirubin, direct bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, albumin, sodium, potassium, calcium, bicarbonate and glucose), urinalysis (glucose, ketones, protein, hemoglobin, urobilinogen, bilirubin and nitrite). Each parameter was evaluated against commonly used and widely accepted criteria.
Measured: Baseline (Day 0) up to 28 days after last dose of study medication (Day 39)
Number of Participants With Out of Range Vital Signs
Vital signs included supine blood pressure, pulse rate and temperature. The pre-specified out of range criterion for supine diastolic blood pressure was change from baseline equal to or over than (≥) 20 millimeter of mercury (mmHg). Clinical significance of vital signs and out of range criterion were determined at the investigator's discretion.
Measured: Baseline (Day 0) up to 28 days after last dose of study medication (Day 39)
Number of Adverse Events Leading to Discontinuation
Adverse events result in participants discontinuations from the study drug.
Measured: Baseline (Day 0) up to 28 days after last dose of study medication (Day 39)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

19 Jul 20195 Mar 2020

First posted11 Jul 2019
Study start19 Jul 2019
Primary completion5 Mar 2020
Study completion5 Mar 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Hepatic ImpairmentStudies of the same condition, open and under way.
More trials run by PfizerThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Basic science
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 18 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04016077
Sponsor's protocol ID: B7981016
Status last verified: Apr 2021
First submitted: 8 Jul 2019
Last updated: 8 Apr 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No: 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.

Publications

Wojciechowski J, S Purohit V, Huh Y, Banfield C, Nicholas T. Evolution of Ritlecitinib Population Pharmacokinetic Models During Clinical Drug Development. Clin Pharmacokinet. 2023 Dec;62(12):1765-1779. doi: 10.1007/s40262-023-01318-3. Epub 2023 Nov 2.
PubMed 37917289
Purohit V, Huh Y, Wojciechowski J, Plotka A, Salts S, Antinew J, Dimitrova A, Nicholas T. Leveraging Prior Healthy Participant Pharmacokinetic Data to Evaluate the Impact of Renal and Hepatic Impairment on Ritlecitinib Pharmacokinetics. AAPS J. 2023 Mar 28;25(3):32. doi: 10.1208/s12248-023-00792-8.
PubMed 36977960

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 8 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A PHASE 1, NON-RANDOMIZED, OPEN LABEL, MULTIPLE DOSE STUDY TO EVALUATE THE PHARMACOKINETICS, SAFETY AND TOLERABILITY OF PF 06651600 IN SUBJECTS WITH HEPATIC IMPAIRMENT AND IN HEALTHY SUBJECTS WITH NORMAL HEPATIC FUNCTION
ClinicalTrials.gov ID: NCT04016077
Acronym / sponsor ID: B7981016
Conditions: Hepatic Impairment, Healthy Participants
Keywords: PF-06651600, Pharmacokinetics, Hepatic impairment
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 18 participants (actual)
Lead sponsor: PfizerIndustry (pharma, biotech, devices)
Study start: 19 Jul 2019 (actual)
Primary completion: 5 Mar 2020 (actual)
Study completion: 5 Mar 2020 (actual)
First posted: 11 Jul 2019 (actual)
Results: Posted 8 Apr 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Basic science
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
PF-06651600 Moderate Hepatic Impairment	Experimental	Drug: PF-06651600 30 mgThis arm includes participants with moderate hepatic impairment who will receive oral doses of PF-06651600 30 mg on Day 1 through Day 10.
PF-06651600 Healthy participants	Experimental	Drug: PF-06651600 30 mgThis arm includes healthy adult participants who will receive oral doses of PF-06651600 30 mg on Day 1 through Day 10.
PF-06651600 Mild Hepatic Impairment	Experimental	Drug: PF-06651600 30 mgThis arm is in Part 2 which will be conducted if the decision criterion to proceed to Part 2 is met. The arm includes participants with mild hepatic impairment who will receive oral doses of PF-06651600 30 mg on Day 1 through Day 10.

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

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 40 kg/m2; and a total body weight >50 kg (110 lb)
Healthy male or female participants
No known or suspected hepatic disease
Stable hepatic impairment, defined as no clinically significant change in disease status within the last 30 days prior to the Screening visit

Key exclusion criteria (8 listed)

Has active acute or chronic infection requiring treatment or history of systemic infection requiring hospitalization, incl. herpes zoster, herpes simplex, tuberculosis
Infection with hepatitis B, hepatitis C or HIV
Any condition affecting drug absorption, distribution, metabolism and excretion (eg, status post porta-caval shunt surgery, prior bariatric surgery, gastrectomy, ileal resection)
Has malignancy, lymphoproliferative disorder, surgery or other condition not allowed per protocol
Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, gynecologic or allergic disease

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PF-06651600 30 mgPF-06651600 in 10 mg oral tablets will be administered on days 1 to 10.	Drug	PF-06651600 Healthy participants, PF-06651600 Mild Hepatic Impairment, PF-06651600 Moderate Hepatic Impairment

Primary outcome

Area Under the Plasma Concentration-time Profile From Time 0 to 24 Hours (AUC24) for PF-06651600
Time frame: Hour 0 (pre-dose) on Days 7, 8 and 9, and hour 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 14, 24 hours post-dose on Day 10
AUC24 of PF-06651600 pre and post dose.
Maximum Plasma Concentration (Cmax) for PF-06651600
Time frame: Hour 0 (pre-dose) on Days 7, 8 and 9, and hour 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 14, 24 hours post-dose on Day 10
Cmax is maximum observed plasma concentration.

4 secondary outcomes

Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) (All Causalities and Treatment-related)
Time frame: Baseline (Day 0) up to 28 days after last dose of study medication (Day 39)
Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)
Time frame: Baseline (Day 0) up to 28 days after last dose of study medication (Day 39)
Number of Participants With Out of Range Vital Signs
Time frame: Baseline (Day 0) up to 28 days after last dose of study medication (Day 39)
Number of Adverse Events Leading to Discontinuation
Time frame: Baseline (Day 0) up to 28 days after last dose of study medication (Day 39)

Results and safety

Results posted to the registry on 8 Apr 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Moderate Hepatic Impairment	10	10
Normal Hepatic Function	8	8

Primary outcome: Area Under the Plasma Concentration-time Profile From Time 0 to 24 Hours (AUC24) for PF-06651600

Time frame: Hour 0 (pre-dose) on Days 7, 8 and 9, and hour 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 14, 24 hours post-dose on Day 10. Geometric mean (Geometric Coefficient of Variation). Unit: nanogram*hour per milliliter (ng*hr/mL)

Measure	Moderate Hepatic Impairment n = 8	Normal Hepatic Function n = 8
Value	454.5 (45)	383.6 (16)

Moderate Hepatic Impairment vs Normal Hepatic Function: Ratio of Geometric Means: 118.50 (90% CI 87.96 to 159.64), ANOVA

Population analysed: The analysis population was defined as all participants treated who have at least 1 of the pharmacokinetic (PK) parameters of primary interest.

Primary outcome: Maximum Plasma Concentration (Cmax) for PF-06651600

Measure	Moderate Hepatic Impairment n = 8	Normal Hepatic Function n = 8
Value	194.3 (49)	186.9 (24)

Moderate Hepatic Impairment vs Normal Hepatic Function: Ratio of Geometric Means: 104.00 (90% CI 74.48 to 145.23), ANOVA

Population analysed: The analysis population was defined as all participants treated who have at least 1 of the PK parameters of primary interest.

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Baseline (Day 0) up to Day 39 (28 days after last dose of study medication).. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Moderate Hepatic Impairment	1 of 10 (10%)	3 of 10 (30%)	0 of 10
Normal Hepatic Function	0 of 8 (0%)	2 of 8 (25%)	0 of 8

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Apr 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 37917289Wojciechowski J, S Purohit V, Huh Y, Banfield C, Nicholas T. Evolution of Ritlecitinib Population Pharmacokinetic Models During Clinical Drug Development. Clin Pharmacokinet. 2023 Dec;62(12):1765-1779. doi: 10.1007/s40262-023-01318-3. Epub 2023 Nov 2.
Derived from this study: PubMed 36977960Purohit V, Huh Y, Wojciechowski J, Plotka A, Salts S, Antinew J, Dimitrova A, Nicholas T. Leveraging Prior Healthy Participant Pharmacokinetic Data to Evaluate the Impact of Renal and Hepatic Impairment on Ritlecitinib Pharmacokinetics. AAPS J. 2023 Mar 28;25(3):32. doi: 10.1208/s12248-023-00792-8.
To obtain contact information for a study center near you, click here.Link provided by the sponsor.
Individual participant dataSharing planned: No. 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.

Related trials for Hepatic Impairment

Not yet recruitingPhase 1
A Study to Assess the Pharmacokinetics and Safety of Revumenib in Participants With Advanced Cancer and Hepatic or Renal Impairment
Relapsed/Refractory (R/R) Hematologic Malignancies, Acute Leukemia
RecruitingPhase 1
A Study of Efimosfermin Alfa in Adults With Hepatic Impairment
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Not yet recruitingPhase 1
A Study of Zovaglutide (ZT002 Injection) in Participants With Hepatic Impairment and Healthy Participants
Overweight, Obesity
Not yet recruitingPhase 1
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Hepatic Impairment, Healthy Adult Participants
RecruitingPhase 1
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Pfizer CT.gov Call Center study director

Pfizer

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing PF-06651600 30 mg in people with Hepatic Impairment and Healthy Participants, run by Pfizer at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Apr 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Area Under the Plasma Concentration-time Profile From Time 0 to 24 Hours (AUC24) for PF-06651600 (time frame: Hour 0 (pre-dose) on Days 7, 8 and 9, and hour 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 14, 24 hours post-dose on Day 10). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04016077, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Apr 2021.