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HealthyPhase 1NCT03637790

Drug Interaction Study Evaluating the Effect of Rifampin on PK and Safety of PF 04965842.

A Phase 1 study testing PF-04965842 and rifampin in people with Healthy, run by Pfizer at 1 site in Belgium.

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

This is a Phase 1 open label, 2 period, single fixed sequence study designed to evaluate the effect of repeat dose oral rifampin on single dose PF 04965842 PK after a single 200 mg oral dose in healthy subjects. Read more about this study

Who is it for?
Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for
Healthy
What is being tested?
PF-04965842 and rifampin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
1 siteBelgium
Study dates
13 Sep 2018to 14 Dec 2018
Phase
Phase 1
Are there results?
None posted in the registry

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 55 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Subjects must meet all of the following inclusion criteria to be eligible for enrollment in the study:
  • Healthy female subjects and/or male subjects who, at the time of screening, are between the ages of 18 and 55 years, inclusive. Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure (BP) and pulse rate measurement, 12 lead ECG, or clinical laboratory tests.
  • Female subjects of non childbearing potential must meet at least 1 of the following criteria:
  • Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; status may be confirmed with a serum follicle stimulating hormone (FSH) level confirming the postmenopausal state;
  • Have undergone a documented hysterectomy and/or bilateral oophorectomy;
  • Have medically confirmed ovarian failure. All other female subjects (including female subjects with tubal ligations) are considered to be of childbearing potential.
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  • Body mass index (BMI) of 17.5 to 30.5 kg/m2 and a total body weight >50 kg (110 lb).
  • Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
  • Subjects who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures.

Who cannot join

  • Subjects with any of the following characteristics/conditions will not be included in the study:
  • Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing). Evidence of acute exacerbation of dermatological condition (eg, AD, eczema or psoriasis) or visible rash present during physical examination. Subjects with history of psoriasis, AD or eczema can be included in the study.
  • Subjects, who according to the product label for rifampin, would be at increased risk if dosed with rifampin.
  • Any condition possibly affecting drug absorption (eg, gastrectomy).
  • A positive urine drug test.
  • History of regular alcohol consumption exceeding 14 drinks/week for female subjects or 21 drinks/week for male subjects (1 drink = 5 ounces [150 mL] of wine or 12 ounces [360 mL] of beer or 1.5 ounces [45 mL] of hard liquor) within 6 months before screening.
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  • Treatment 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 (whichever is longer).
  • Screening supine systolic BP <90 mm Hg or >140 mm Hg following at least 5 minutes of supine rest OR Screening supine diastolic BP <50 mm Hg or >90 mm Hg following at least 5 minutes of supine rest.
  • If a subject meets any of these criteria, the BP should be repeated 2 more times and the average of the 3 BP values should be used to determine the subject's eligibility.
  • Screening supine 12 lead ECG demonstrating a corrected QT (QTc) interval >450 msec or a QRS interval >120 msec. If QTc exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated 2 more times and the average of the 3 QTc or QRS values should be used to determine the subject's eligibility.
  • Pregnant female subjects; breastfeeding female subjects; fertile male subjects and female subjects of childbearing potential who are unwilling or unable to use 1 highly effective method of contraception as outlined in this protocol Contraception section for the duration of the study and for at least 28 days after the last dose of investigational product.
  • Subjects with ANY of the following abnormalities in clinical laboratory tests at screening, as assessed by the study specific laboratory and confirmed by a single repeat test, if deemed necessary:
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level 1.5 × upper limit of normal (ULN);
  • Total bilirubin level 1 × ULN; subjects with a history of Gilbert's syndrome may have direct bilirubin measured and would be eligible for this study provided the direct bilirubin level is ULN.
  • Use of CYP2C19 inhibitors (eg, fluconazole, fluoxetine, fluvoxamine, ticlopidine omeprazole, voriconazole, cimetidine, esomeprazole, and felbamate) or inducers (eg, rifampin, ritonavir, efavirenz, enzalutamide, phenytoin, and St. John's Wort) within 28 days or 5 half lives (whichever is longer) prior to dosing.
  • Use of CYP2C9 inhibitors (eg, amiodarone, felbamate, fluconazole, miconazole, piperine, diosmin, disulfiram, fluvastatin, fluvoxamine, voriconazole, efavirenz, isoniazid) or inducers (eg, aprepitant, carbamazepine, enzalutamide, rifampin, ritonavir, nevirapine, phenobarbital, and St. John's Wort) within 28 days or 5 half lives (whichever is longer) prior to dosing.
  • Use of CYP3A4 inhibitors (eg, ketoconazole, ciprofloxacin, diltiazem) or other inducers (eg, phenytoin, carbamazepine) within 28 days or 5 half lives (whichever is longer) prior to dosing.
  • Known relevant history of elevated liver function tests (LFTs) or impaired liver function.
  • History of active or latent or inadequately treated tuberculosis (TB) infection, or a positive QuantiFERON TB Gold test.
  • Any history of chronic infections, any history of recurrent infections, any history of latent infections, or any acute infection within 2 weeks of screening.
  • History of disseminated herpes zoster, or disseminated herpes simplex, or recurrent localized dermatomal herpes zoster.
  • History of systemic infection requiring hospitalization, parenteral antimicrobial therapy, or considered clinically significant by the investigator within 6 months prior to screening.
  • History of receiving a live vaccine within 6 weeks prior to the first dose of investigational product, or is expected to receive a live vaccine within 6 weeks after the last dose of investigational product.
  • Have a known immunodeficiency disorder or a first degree relative with a hereditary immunodeficiency.
  • History or evidence of any malignancies with the exception of adequately treated or excised non metastatic basal cell or squamous cell cancer of the skin, or cervical carcinoma in situ.
  • Use of prescription or nonprescription drugs and dietary supplements within 7 days or 5 half lives (whichever is longer) prior to the first dose of investigational product. As an exception, acetaminophen/paracetamol may be used at doses of < 1 g/day. Limited use of nonprescription medications that are not believed to affect subject safety or the overall results of the study may be permitted on a case by case basis following approval by the sponsor.
  • Herbal supplements and hormonal methods of contraception (including oral and transdermal contraceptives, injectable progesterone, progestin subdermal implants, progesterone releasing intrauterine devices [IUDs], vaginal ring, and postcoital contraceptive methods) and hormone replacement therapy must have been discontinued at least 28 days prior to the first dose of investigational product.
  • Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to dosing.
  • History of sensitivity to heparin or heparin induced thrombocytopenia.
  • History of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C; positive testing for HIV, hepatitis B surface antigen (HepBsAg), hepatitis B core antibody (HepBcAb), or hepatitis C antibody (HCVAb). A positive hepatitis B surface antibody (HepBsAb) finding as a result of subject vaccination is permissible.
  • A current or past medical history of conditions associated with thrombocytopenia, coagulopathy or platelet dysfunction.
  • Unwilling or unable to comply with the criteria in the Lifestyle Requirements section of this protocol.
  • Subjects who are 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 subjects who are Pfizer employees, including their family members, directly involved in the conduct of the study.
  • 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 subject inappropriate for entry into this study.
  • Use of tobacco or nicotine containing products in excess of the equivalent of 5 cigarettes per day or 2 chews of tobacco per day.

Trial locations and contacts

1 site in 1 country.

Belgium1 site

  • Pfizer Clinical Research Unit

    Brussels, B-1070

Other trials in Belgium

About this study

Official title: A PHASE 1, OPEN-LABEL, FIXED-SEQUENCE STUDY TO ESTIMATE THE EFFECT OF REPEAT-DOSE RIFAMPIN ON THE PHARMACOKINETICS OF PF-04965842 IN HEALTHY SUBJECTS

This is a Phase 1 open label, 2 period, single fixed sequence study designed to evaluate the effect of repeat dose oral rifampin on single dose PF 04965842 PK after a single 200 mg oral dose in healthy subjects. A total of 12 healthy male and/or female subjects will be enrolled in the study so that at least 10 subjects will complete the study.

Subject will report to the clinical research unit (CRU) at least 12 hours prior to Day 1 dosing in Period 1 and will be required to stay in the CRU for 11 days and 10 nights. Genotyping samples for CYP2C19 and CYP2C9 will be collected predose in Period 1 only. In Period 1, subjects will be administered a single oral 200 mg dose of PF 04965842 in the morning on Day 1 under fasted conditions. No food will be allowed for at least 4 hours postdose and undergo serial blood sample collection for 24 hours postdose to characterize the PK profile of PF 04965842.

In Period 2, subjects will receive rifampin 600 mg QD in the mornings of Day 1 to Day 7, approximately 1 hour before the morning meal. On the morning of Day 8, after an overnight fast of approximately 9 hours, subjects will be administered rifampin 600 mg 1 hour prior to administration of a single 200 mg oral dose of PF 04965842. Subjects will remain in a fasted state for 4 hours after dosing with PF 04965842 and undergo serial blood sample collection for 24 hours post PF 04965842 dosing to characterize the PK profile of PF 04965842. Subjects will be discharged from the CRU on Day 9 of Period 2 after all study procedures are completed. The subject will be required to return to the CRU for on site follow up visits 7 14 days, and have a follow up phone contact 28 35 days after the last dose of PF 04965842.

Conditions
Healthy
Being tested
PF-04965842, rifampin
Keywords
healthy volunteers

What participants receive

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

  • PF-04965842Drug

    single oral 200 mg dose of PF 04965842 in the morning on Day 1 under fasted conditions.In Period 2, subjects will receive rifampin 600 mg QD in the mornings of Day 1 to Day 7, approximately 1 hour before the morning meal. On the morning of Day 8, after an overnight fast of approximately 9 hours, subjects will be administered rifampin 600 mg 1 hour prior to administration of a single 200 mg oral dose of PF 04965842.

  • rifampinOther

    In Period 2, subjects will receive rifampin 600 mg QD in the mornings of Day 1 to Day 7, approximately 1 hour before the morning meal. On the morning of Day 8, after an overnight fast of approximately 9 hours, subjects will be administered rifampin 600 mg 1 hour prior to administration of a single 200 mg oral dose of PF 04965842

Study groups in NCT03637790
Study groupRoleWhat they receive
PF 04965842OtherIn Period 1, subjects will be administered a single oral 200 mg dose of PF 04965842 in the morning on Day 1 under fasted conditions.
Receives: Drug: PF-04965842
Rifampin and PF 04965842OtherIn Period 2, subjects will receive rifampin 600 mg QD in the mornings of Day 1 to Day 7, approximately 1 hour before the morning meal. On the morning of Day 8, after an overnight fast of approximately 9 hours, subjects will be administered rifampin 600 mg 1 hour prior to administration of a single 200 mg oral dose of PF 04965842.
Receives: Drug: PF-04965842; Other: rifampin

What is being measured

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

  1. Plasma PF 04965842 Cmax PK

    Maximum observed plasma concentration for PF 04965842

    Measured: Day 1 on period 1 and Days 1, 8 and 9 on period 2

  2. AUCinf for PF 04965842

    Area under the curve from time zero to extrapolated infinite time tor PF 04965842

    Measured: Day 1 on period 1 and Days 1, 8 and 9 on period 2

Secondary outcomes (4)

  1. Number of subjects with adverse events (AEs).

    Number of subjects with adverse events (AEs).

    Measured: Screening up to 28-35 days after the last dose of PF 04965842 in period 2

  2. Number of subjects with laboratory tests findings of potential clinical importance

    Number of subjects with laboratory tests findings of potential clinical importance

    Measured: Screening up to 7-14 days after the last dose of PF 04965842 in period 2

  3. Number of subjects with clinically significant abnormal vital signs

    Number of subjects with clinically significant abnormal vital signs

    Measured: Screening up to 7-14 days after the last dose of PF 04965842 in period 2

  4. Number of subjects with clinically significant abnormal Electrocardiograms (ECGs)

    Number of subjects with clinically significant abnormal Electrocardiograms (ECGs).

    Measured: Screening up to 7-14 days after the last dose of PF 04956842 in period 2.

Timeline

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

  1. First posted20 Aug 2018
  2. Study start13 Sep 2018
  3. Primary completion14 Dec 2018
  4. Study completion14 Dec 2018

Resources

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
Other
Allocation
Randomised
Intervention model
Sequential
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03637790
Sponsor's protocol ID
B7451019
Other IDs
2018-002167-25, 2018
Status last verified
Feb 2020
First submitted
16 Aug 2018
Last updated
28 Feb 2020
Results posted
No
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

  • Wang X, Dowty ME, Wouters A, Tatulych S, Connell CA, Le VH, Tripathy S, O'Gorman MT, Winton JA, Yin N, Valdez H, Malhotra BK. Assessment of the Effects of Inhibition or Induction of CYP2C19 and CYP2C9 Enzymes, or Inhibition of OAT3, on the Pharmacokinetics of Abrocitinib and Its Metabolites in Healthy Individuals. Eur J Drug Metab Pharmacokinet. 2022 May;47(3):419-429. doi: 10.1007/s13318-021-00745-6. Epub 2022 Feb 28.

    PubMed 35226304

  • 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

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing PF-04965842 and rifampin in people with Healthy, run by Pfizer at 1 site in Belgium.

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 35 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 28 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Belgium. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Plasma PF 04965842 Cmax PK (time frame: Day 1 on period 1 and Days 1, 8 and 9 on period 2). 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 NCT03637790, 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 28 Feb 2020.

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