A Study to Determine the Effects of PF-04965842 on Midazolam PK in Healthy Volunteers

March 19, 2020 updated by: Pfizer

A PHASE 1, RANDOMIZED, 2-WAY CROSSOVER, MULTIPLE DOSE, OPEN LABEL STUDY OF THE EFFECT OF PF-04965842 ON MIDAZOLAM PHARMACOKINETICS IN HEALTHY VOLUNTEERS

This is a Phase 1, randomized, 2-way crossover, multiple dose, open label study of the effect of PF-04965842 on midazolam PK in healthy subjects. The study will demonstrate the effect of multiple dose PF-04965842 on the pharmacokinetics of a single, oral dose of midazolam in healthy subjects.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Subjects will be randomized to 1 of 2 treatment sequences as described below. A total of 24 healthy male and/or female subjects will be enrolled in the study so that 12 subjects will be enrolled in each treatment sequence. Each treatment sequence will consist of 2 periods in a single fixed sequence. Subjects will be screened within 28 days of the first dose of study medication. Subjects will report to the clinical research unit (CRU) the day prior to (or Day -1) Day 1 dosing in Period 1 for both treatment sequences. In Sequence 1 subjects will remain in the CRU for a total of 11 days and 10 nights (including Period 1 and Period 2). In Sequence 2, Period 1, subjects will remain in the CRU for 9 days and 8 nights. In Sequence 2, Period 2, subjects will remain in the CRU for 3 days and 2 nights. In Sequence 1, Period 1, subjects will be dosed with a single administration of midazolam 2 mg oral solution on Day 1. Midazolam PK will then be assessed over the next 24 hours (hr). Period 1 will be immediately followed by Period 2 with no washout, in which subjects will be dosed with 200 mg PF-04965842 orally once daily (QD) for 7 days. Midazolam 2 mg oral solution will be administered on the morning of Day 2 and Day 7 within 5 minutes after PF-04965842 dosing. Midazolam PK will be assessed for 24 hr following dosing.In Sequence 2, Period 1, subjects will be dosed with 200 mg PF-04965842 orally QD for 7 days. Midazolam 2 mg oral solution will be administered on the morning of Day 2 and Day 7 within 5 minutes after PF-04965842 dosing. Midazolam PK will be assessed for 24 hr following dosing. Subjects will then undergo a washout period of at least 7 days. In Period 2 subjects will be dosed with a single administration of midazolam 2 mg oral solution on Day 1. Midazolam PK will then be assessed over the next 24 hr.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
25

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Brussels, Belgium, B-1070
        • Pfizer Clinical Research Unit

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 55 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study
  • Willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures
  • Healthy female subjects and/or male subjects who, at the time of screening, are between the ages of 18 and 55 years, inclusive
  • Female subjects with child-bearing potential must not be intending to become pregnant, currently pregnant, or lactating. Conditions apply: negative pregnancy test, effective method of contraception
  • Non-childbearing potential must meet at least 1 of the following criteria: documented hysterectomy and/or bilateral oophorectomy, ovarian failure, achieved postmenopausal status confirmed with FSH
  • Body mass index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs)

Exclusion Criteria:

  • Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, GI, CV, hepatic, psych, neurological, or allergic disease (including drug allergies, but excluding seasonal)
  • Evidence or history of clinically significant dermatological condition (eg, contact dermatitis or psoriasis) or visible rash present during physical examination
  • Subjects, who according to the product label for midazolam, would be at increased risk if dosed with midazolam
  • Self-reported history or risk factors for QT prolongation or torsades de pointes, congenital deafness, family history of sudden death, and family history of long QT syndrome
  • Any condition possibly affecting drug absorption (eg, gastrectomy)
  • A positive urine drug test
  • History of regular alcohol consumption exceeding 14 for female or 21 for male drinks/week (1 drink = 5 ounces of wine or 12 ounces of beer or 1.5 ounces of hard liquor) within 6 months of screening
  • 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)
  • Following at least 5 minutes of supine rest, screening supine systolic BP <90 mm Hg or >=140 mm Hg, or screening supine diastolic BP <50 mm Hg or >=90 mm Hg. Any criteria met, BP should be repeated
  • Screening supine 12-lead ECG demonstrating: QTcF >450 msec or QRS interval >120 msec. If QTcF exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated
  • AST/SGOT or ALT/SGPT >=1.5 × ULN. Total bilirubin level >1× ULN; subjects with a hx of Gilbert's syndrome must have direct bilirubin <= ULN Known relevant history of elevated liver function tests (LFTs)
  • History of tuberculosis (TB) (active or latent) or inadequately treated TB infection. 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 baseline
  • History of disseminated herpes zoster, or disseminated herpes simplex, or recurrent localized dermatomal herpes zoster
  • History of sensitivity to heparin or heparin-induced thrombocytopenia
  • Pregnant or breastfeeding female; fertile male and WOCBP unwilling to use a highly effective method of contraception through study duration and for at least 28 days after the last dose
  • Use of medications and dietary supplements within 7 days or 5 half-lives prior to first dose, acetaminophen/paracetamol <=1 g/day exception. Herbal supplements and hormonal methods of contraception
  • Use of tobacco- or nicotine- containing products in excess of the equivalent of 5 cigarettes per day
  • Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to first dose of investigational product
  • History of hypersensitivity to midazolam or any other bezodiazapine
  • History of HIV, hepatitis B or C; positive testing for HIV, HepBsAg, HepBcAb or HCVAb. As an exception, a positive HepBsAb as a result of subject vaccination is permissible
  • Unwilling or unable to comply with the criteria in the Lifestyle Requirements section of this protocol
  • Investigator site staff members and their family members, site staff members otherwise supervised by the investigator, or subjects who are Pfizer employees, including their family members
  • Other medical or psych condition including active suicidal ideation/ behavior or lab abnormality that the investigator deems inappropriate for this study or may interfere with study results
  • Have any malignancies or have a history of 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
  • Subjects at significant risk of suicidal or violent behavior

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: OTHER
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
OTHER: Sequence 1
In Sequence 1, Period 1, subjects will be dosed with a single administration of midazolam 2 mg oral solution on Day 1. Midazolam PK will then be assessed over the next 24 hours (hr). Period 1 will be immediately followed by Period 2 with no washout, in which subjects will be dosed with 200 mg PF-04965842 orally once daily (QD) for 7 days. Midazolam 2 mg oral solution will be administered on the morning of Day 2 and Day 7 within 5 minutes after PF-04965842 dosing. Midazolam PK will be assessed for 24 hr following dosing.
Drug: PF-04965842
orally bioavailable small molecule that selectively inhibits JAK1 by blocking the adenosine triphosphate (ATP) binding site.
Other Names:
  • JAK1 Inhibitor
Drug: Midazolam
substrate which undergoes extensive metabolism by CYP3A4 and CYP3A5 and acts as a sensitive probe for evaluating drug interaction with respect to these isoenzymes
OTHER: Sequence 2
In Sequence 2, Period 1, subjects will be dosed with 200 mg PF-04965842 orally QD for 7 days. Midazolam 2 mg oral solution will be administered on the morning of Day 2 and Day 7 within 5 minutes after PF-04965842 dosing. Midazolam PK will be assessed for 24 hr following dosing. Subjects will then undergo a washout period of at least 7 days. In Period 2 subjects will be dosed with a single administration of midazolam 2 mg oral solution on Day 1. Midazolam PK will then be assessed over the next 24 hr.
Drug: PF-04965842
orally bioavailable small molecule that selectively inhibits JAK1 by blocking the adenosine triphosphate (ATP) binding site.
Other Names:
  • JAK1 Inhibitor
Drug: Midazolam
substrate which undergoes extensive metabolism by CYP3A4 and CYP3A5 and acts as a sensitive probe for evaluating drug interaction with respect to these isoenzymes

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
AUCinf of midazolam.
Time Frame: 8 days
To demonstrate the effect of multiple dose PF-04965842 on the pharmacokinetics of a single, oral dose of midazolam in healthy subjects. The lack of an effect of PF-04965842 on midazolam PK will be concluded if the 90% confidence interval for the ratio of adjusted geometric mean for AUCinf falls wholly within (80%, 125%).
8 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
AUClast of midazolam
Time Frame: 8 days
Adjusted mean differences and 90% confidence intervals for the differences will be exponentiated to provide estimates of the ratio of adjusted geometric means and 90% confidence intervals for the ratios.
8 days
Blood Pressure
Time Frame: 8 days
Number of Subjects with Data of Potential Clinical Concern
8 days
Cmax of midazolam.
Time Frame: 8 days
Adjusted mean differences and 90% confidence intervals for the differences will be exponentiated to provide estimates of the ratio of adjusted geometric means and 90% confidence intervals for the ratios.
8 days
Tmax of midazolam.
Time Frame: 8 days
Adjusted mean differences and 90% confidence intervals for the differences will be exponentiated to provide estimates of the ratio of adjusted geometric means and 90% confidence intervals for the ratios.
8 days
t1/2 of midazolam.
Time Frame: 8 days
Adjusted mean differences and 90% confidence intervals for the differences will be exponentiated to provide estimates of the ratio of adjusted geometric means and 90% confidence intervals for the ratios.
8 days
Pulse
Time Frame: 8 days
Number of Subjects with Data of Potential Clinical Concern
8 days
Temperature
Time Frame: 8 days
Number of subjects with data of potential clinical concern
8 days
Adverse Events
Time Frame: 8 days
Number of Subjects With Treatment-Related Treatment Emergent Adverse Events (TEAEs)
8 days
Laboratory tests
Time Frame: 8 days
Number of Subjects with Laboratory Test Abnormailities
8 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Pfizer

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 3, 2018

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 16, 2018

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 16, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 12, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 23, 2018

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 27, 2018

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 23, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 19, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • B7451022
  • 2018-001198-26 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD 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.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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