Hepatic ImpairmentPhase 1NCT03626415

A Hepatic Impairment Study for PF-04965842.

A Phase 1 study testing PF-04965842 in people with Hepatic Impairment, 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.

Trial summary

This is a Phase 1 non randomized, open label, single dose, parallel cohort study to investigate the effect of hepatic impairment on the PK, safety and tolerability of PF 04965842. 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
What is being tested?: PF-04965842
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 24 participants
Where: 2 sitesUnited States
Study dates: 1 Oct 2018to 30 Apr 2019
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

Body mass index (BMI) of 17.5 to 40 kg/m2; and a total body weight >50 kg (110 pounds).
Subjects who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures.
Additional Inclusion Criteria for subjects with hepatic impairment:
Satisfy the criteria for Class A or Class B of the Child Pugh classification (mild: Child Pugh Scores 5 to 6 points, and moderate: Child Pugh Scores 7 to 9 points), within 14 days of investigational product administration.
A diagnosis of hepatic dysfunction due to hepatocellular disease (and not secondary to any acute ongoing hepatocellular process) documented by medical history, physical examination, liver biopsy, hepatic ultrasound, computerized tomography scan, or magnetic resonance imaging (MRI).

Who cannot join

Subjects with clinically significant infections within the past 3 months (for example, those requiring hospitalization, or as judged by the Investigator), evidence of any infection (including influenza) within the past 7 days, history of disseminated herpes simplex infection or recurrent (>1 episode) or disseminated herpes zoster.
Subjects with a malignancy or with a history of malignancy, with the exception of adequately treated or excised non metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ.
Additional exclusion criteria for subjects with hepatic impairment:
Hepatic carcinoma or hepatorenal syndrome or limited predicted life expectancy (defined as less than 1 year).
Subjects who have previously had a transplanted kidney, liver, or heart.
At Screening, persistent severe, uncontrolled hypertension.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

Orlando Clinical Research Center
Orlando, Florida, 32809
Prism Clinical Research, LLC
Saint Paul, Minnesota, 55114

Other trials in United States

About this study

Official title: A PHASE 1, NON-RANDOMIZED, OPEN-LABEL, SINGLE-DOSE STUDY TO COMPARE THE PHARMACOKINETICS, SAFETY AND TOLERABILITY OF PF-04965842 IN ADULT SUBJECTS WITH MILD AND MODERATE HEPATIC IMPAIRMENT RELATIVE TO SUBJECTS WITH NORMAL HEPATIC FUNCTION

This is a Phase 1 non randomized, open label, single dose, parallel cohort study to investigate the effect of hepatic impairment on the PK, safety and tolerability of PF 04965842.

Read the detailed description

A minimum of 24 subjects with normal, mild or moderate hepatic function will be enrolled into the study, with approximately 8 subjects in each cohort. The Child Pugh classification score will be utilized to assess entry criteria and to assign subjects into the appropriate hepatic impairment group. For individual subjects, the total maximum duration of study participation from the Screening visit to the end of clinical research unit (CRU) stay is approximately 31 days and approximately 63 days from the Screening visit to the Follow up contact.

Conditions: Hepatic Impairment
Being tested: PF-04965842

What participants receive

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

PF-04965842Drug
PF 04965842 is an orally bioavailable small molecule that selectively inhibits JAK1.

Study groups in NCT03626415
Study group	Role	What they receive
PF-04965842	Experimental	PF 04965842 is an orally bioavailable small molecule that selectively inhibits JAK1. Receives: Drug: PF-04965842

What is being measured

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

Maximum Observed Plasma Concentration (Cmax) for PF-04965842
Cmax is maximum plasma concentration. It was observed directly from data.
Measured: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24, 36, 48, 72 hours post-dose in each cohort
Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUCinf) for PF-04965842
AUCinf is area under the concentration-time curve (AUC) from time 0 (pre-dose) extrapolated to infinite time.
Measured: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24, 36, 48, 72 hours post-dose in each cohort

Secondary outcomes (4)

Number of Participants With Treatment-Emergent Adverse Events (AEs) for PF-04965842
Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-emergent adverse events (TEAEs) were those with initial onset or increasing in severity between the first dose of investigational product and up to 36 days post-dose.
Measured: From screening (within 28 days prior to Day 1) till up to 36 days post-dose, the total maximum duration was approximately 63 days for individual participants.
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)
Laboratory tests included tests that were performed under the categories of hematology, chemistry, urinalysis, other, and additional tests needed for Hy's law.
Measured: Screening (within 28 days prior to Day 1), Day -1, 2, 24, 72 hours post-dose.
Number of Participants With Electrocardiogram (ECG) Findings of Potential Clinical Importance for PF-04965842
12-Lead ECGs were collected after the participants rested quietly for at least 10 minutes in a supine position. Clinical significance of ECG recordings was determined at the investigator's discretion.
Measured: Screening (within 28 days prior to Day 1), Day -1, 2, 72 hours post-dose.
Number of Participants With Vital Sign Findings of Potential Clinical Importance for PF-04965842
Vital signs (pulse rate, systolic and diastolic blood pressure) were obtained with participant following at least 5 minutes of supine rest. Clinical significance of vital signs was determined at the investigator's discretion.
Measured: Screening (within 28 days prior to Day 1), 0 (pre-dose), and 72 hours post-dose.

Timeline

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

1 Oct 201830 Apr 2019

First posted13 Aug 2018
Study start1 Oct 2018
Primary completion30 Apr 2019
Study completion30 Apr 2019

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
Intervention model: Parallel groups
Model description: Recruitment for subjects with moderate and mild hepatic impairment (Cohorts 1 and 2) will initiate first and these subjects will be enrolled in parallel.
Masking: None (open label)
Enrolment: 24 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03626415
Sponsor's protocol ID: B7451020
Status last verified: Apr 2020
First submitted: 8 Aug 2018
Last updated: 18 May 2020
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, Malhotra BK, Wang X, Fostvedt L, Valdez H, Nicholas T. Population Pharmacokinetics of Abrocitinib in Healthy Individuals and Patients with Psoriasis or Atopic Dermatitis. Clin Pharmacokinet. 2022 May;61(5):709-723. doi: 10.1007/s40262-021-01104-z. Epub 2022 Jan 21.
PubMed 35061234
Wang EQ, Le V, O'Gorman M, Tripathy S, Dowty ME, Wang L, Malhotra BK. Effects of Hepatic Impairment on the Pharmacokinetics of Abrocitinib and Its Metabolites. J Clin Pharmacol. 2021 Oct;61(10):1311-1323. doi: 10.1002/jcph.1858. Epub 2021 Apr 17.
PubMed 33749838

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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All Hepatic Impairment trials

Study at a glance

From the registry record, last updated by the sponsor on 18 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A PHASE 1, NON-RANDOMIZED, OPEN-LABEL, SINGLE-DOSE STUDY TO COMPARE THE PHARMACOKINETICS, SAFETY AND TOLERABILITY OF PF-04965842 IN ADULT SUBJECTS WITH MILD AND MODERATE HEPATIC IMPAIRMENT RELATIVE TO SUBJECTS WITH NORMAL HEPATIC FUNCTION
ClinicalTrials.gov ID: NCT03626415
Acronym / sponsor ID: B7451020
Conditions: Hepatic Impairment
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 24 participants (actual)
Lead sponsor: PfizerIndustry (pharma, biotech, devices)
Study start: 1 Oct 2018 (actual)
Primary completion: 30 Apr 2019 (actual)
Study completion: 30 Apr 2019 (actual)
First posted: 13 Aug 2018 (actual)
Results: Posted 18 May 2020

Clinical summary

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

This is a Phase 1 non randomized, open label, single dose, parallel cohort study to investigate the effect of hepatic impairment on the PK, safety and tolerability of PF 04965842.

Detailed description

Study design

Primary purpose: Basic science
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 1
Model description: Recruitment for subjects with moderate and mild hepatic impairment (Cohorts 1 and 2) will initiate first and these subjects will be enrolled in parallel.

Arm	Type	Receives
PF-04965842	Experimental	Drug: PF-04965842PF 04965842 is an orally bioavailable small molecule that selectively inhibits JAK1.

Who may qualify

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

Key inclusion criteria (5 listed)

Body mass index (BMI) of 17.5 to 40 kg/m2; and a total body weight >50 kg (110 pounds).
Subjects who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures.
Satisfy the criteria for Class A or Class B of the Child Pugh classification (mild: Child Pugh Scores 5 to 6 points, and moderate: Child Pugh Scores 7 to 9 points), within 14 days of investigational product administration.
A diagnosis of hepatic dysfunction due to hepatocellular disease (and not secondary to any acute ongoing hepatocellular process) documented by medical history, physical examination, liver biopsy, hepatic ultrasound, computerized tomography scan, or magnetic resonance imaging (MRI).

Key exclusion criteria (6 listed)

Subjects with clinically significant infections within the past 3 months (for example, those requiring hospitalization, or as judged by the Investigator), evidence of any infection (including influenza) within the past 7 days, history of disseminated herpes simplex infection or recurrent (>1 episode) or disseminated herpes zoster.
Subjects with a malignancy or with a history of malignancy, with the exception of adequately treated or excised non metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ.
Hepatic carcinoma or hepatorenal syndrome or limited predicted life expectancy (defined as less than 1 year).
Subjects who have previously had a transplanted kidney, liver, or heart.
At Screening, persistent severe, uncontrolled hypertension.

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-04965842PF 04965842 is an orally bioavailable small molecule that selectively inhibits JAK1.	Drug	PF-04965842

Primary outcome

Maximum Observed Plasma Concentration (Cmax) for PF-04965842
Time frame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24, 36, 48, 72 hours post-dose in each cohort
Cmax is maximum plasma concentration. It was observed directly from data.
Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUCinf) for PF-04965842
Time frame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24, 36, 48, 72 hours post-dose in each cohort
AUCinf is area under the concentration-time curve (AUC) from time 0 (pre-dose) extrapolated to infinite time.

4 secondary outcomes

Number of Participants With Treatment-Emergent Adverse Events (AEs) for PF-04965842
Time frame: From screening (within 28 days prior to Day 1) till up to 36 days post-dose, the total maximum duration was approximately 63 days for individual participants.
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)
Time frame: Screening (within 28 days prior to Day 1), Day -1, 2, 24, 72 hours post-dose.
Number of Participants With Electrocardiogram (ECG) Findings of Potential Clinical Importance for PF-04965842
Time frame: Screening (within 28 days prior to Day 1), Day -1, 2, 72 hours post-dose.
Number of Participants With Vital Sign Findings of Potential Clinical Importance for PF-04965842
Time frame: Screening (within 28 days prior to Day 1), 0 (pre-dose), and 72 hours post-dose.

Results and safety

Results posted to the registry on 18 May 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
PF-04965842 (Normal Hepatic Function Cohort)	8	8
PF-04965842 (Mild Hepatic Impairment Cohort)	8	8
PF-04965842 (Moderate Hepatic Impairment Cohort)	8	8

Primary outcome: Maximum Observed Plasma Concentration (Cmax) for PF-04965842

Time frame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24, 36, 48, 72 hours post-dose in each cohort. Geometric mean (Geometric Coefficient of Variation). Unit: nanogram per milliliter (ng/mL)

Measure	PF-04965842 (Normal Hepatic Function Cohort) n = 8	PF-04965842 (Mild Hepatic Impairment Cohort) n = 8	PF-04965842 (Moderate Hepatic Impairment Cohort) n = 8
Value	1352 (44)	1276 (41)	1426 (63)

PF-04965842 (Normal Hepatic Function Cohort) vs PF-04965842 (Mild Hepatic Impairment Cohort): Ratio of Adjusted Geometric Mean: 94.40 (90% CI 62.96 to 141.55), ANOVA
PF-04965842 (Normal Hepatic Function Cohort) vs PF-04965842 (Moderate Hepatic Impairment Cohort): Ratio of Adusted Geometric Means: 105.53 (90% CI 70.38 to 158.24), ANOVA

Population analysed: The pharmacokinetic concentration population was defined as all participants who received 1 dose of PF-04965842 and in whom at least 1 plasma concentration value was reported.

Primary outcome: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUCinf) for PF-04965842

Time frame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24, 36, 48, 72 hours post-dose in each cohort. Geometric mean (Geometric Coefficient of Variation). Unit: nanogram*hour per milliliter (ng*hr/mL)

Measure	PF-04965842 (Normal Hepatic Function Cohort) n = 8	PF-04965842 (Mild Hepatic Impairment Cohort) n = 8	PF-04965842 (Moderate Hepatic Impairment Cohort) n = 8
Value	5587 (74)	7449 (29)	8603 (55)

PF-04965842 (Normal Hepatic Function Cohort) vs PF-04965842 (Mild Hepatic Impairment Cohort): Ratio of Adjusted Geometric Means: 133.33 (90% CI 86.17 to 206.28), ANOVA
PF-04965842 (Normal Hepatic Function Cohort) vs PF-04965842 (Moderate Hepatic Impairment Cohort): Ratio of Adjusted Geometric Mean: 153.99 (90% CI 99.52 to 238.25), ANOVA

Population analysed: The pharmacokinetic parameter analysis population was defined as all participants dosed who had at least 1 of the pharmocokinetics parameters of primary interest.

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: From screening (within 28 days prior to Day 1) till up to 36 days post-dose, the total maximum duration was approximately 63 days for individual participants.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
PF-04965842 (Normal Hepatic Function Cohort)	0 of 8 (0%)	2 of 8 (25%)	0 of 8
PF-04965842 (Mild Hepatic Impairment Cohort)	0 of 8 (0%)	3 of 8 (37.5%)	0 of 8
PF-04965842 (Moderate Hepatic Impairment Cohort)	0 of 8 (0%)	0 of 8 (0%)	0 of 8

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 May 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 35061234Wojciechowski J, Malhotra BK, Wang X, Fostvedt L, Valdez H, Nicholas T. Population Pharmacokinetics of Abrocitinib in Healthy Individuals and Patients with Psoriasis or Atopic Dermatitis. Clin Pharmacokinet. 2022 May;61(5):709-723. doi: 10.1007/s40262-021-01104-z. Epub 2022 Jan 21.
Derived from this study: PubMed 33749838Wang EQ, Le V, O'Gorman M, Tripathy S, Dowty ME, Wang L, Malhotra BK. Effects of Hepatic Impairment on the Pharmacokinetics of Abrocitinib and Its Metabolites. J Clin Pharmacol. 2021 Oct;61(10):1311-1323. doi: 10.1002/jcph.1858. Epub 2021 Apr 17.
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.

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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-04965842 in people with Hepatic Impairment, 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 5 inclusion and 6 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 18 May 2020. 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 18 May 2020). 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?

Maximum Observed Plasma Concentration (Cmax) for PF-04965842 (time frame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24, 36, 48, 72 hours post-dose in each cohort). 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 NCT03626415, 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 18 May 2020.