First-in-Human Study to Evaluate Safety and Tolerability of Single and Multiple Ascending Doses of Janus Kinase-1 Inhibitor PF-04965842 in Healthy Western and Japanese Subjects

June 19, 2014 updated by: Pfizer

A Phase 1, Within Cohort, Randomized, Double Blind, Third-Party Open, Placebo-Controlled, Single- And Multiple Dose Escalation, Parallel Group Study To Evaluate The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of Pf-04965842 In Healthy Western and Japanese Subjects

This single- and multiple-ascending dose study is the first evaluation of PF-04965842, a Janus kinase1 (JAK1) inhibitor, in humans. The goal is to assess the safety, tolerability, pharmacokinetics and pharmacodynamics in healthy Western and Japanese 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.

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.
79

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

  • United States
    • Connecticut
      • New Haven, Connecticut, United States, 06511
        • Pfizer Investigational Site

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:

  • Healthy male and/or female subjects between the ages of 18 and 55 years, inclusive.
  • Females must be of non-child bearing potential and either at least 1 year post menopausal (FSH ≥40 IU/L), or have documented hysterectomy (with or without bilateral oophrectomy) at least 6 months prior to study day
  • Subjects willing to defer receiving prophylactic immunizations (e.g. influenza or pneumococcal vaccines) during the study.
  • Absolute lymphocyte count must be greater than or equal to the lower limit of the laboratory reference range.
  • Subjects enrolled in Cohort 8 must have four Japanese grandparents born in Japan.

Exclusion Criteria:

  • Evidence or history of clinically significant hematological, renal, , pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing).
  • History of hepatitis or positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBc Ab) or hepatitis C antibodies (HCV).
  • Clinically significant abnormality on chest X-ray performed at screening or within 3 months of screening date; or history of tuberculosis or active or latent or inadequately treated infection.

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: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

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.
Experimental: SAD Cohorts 1-8 Experimental Arm
Drug: PF-04965842
Subjects will receive single doses of 3, 10, 30, 100, 200, 400, or 800 mg of PF-04695842 (solution or suspension) in a dose escalation format.
Drug: PF-04965842
Subjects will receive doses of 30, 100 or 200 mg (solution or suspension) once daily for 10 days.
Drug: PF-04965842
Subjects will receive doses of 100 or 200 mg (suspension or solution) twice daily for 10 days.
Drug: PF-04965842
Subjects will receive 200 mg dose (suspension or solution) twice daily for 10 days.
Drug: PF-04965842
Subjects will receive 400 mg dose (suspension or solution) once daily for 10 days.
Placebo Comparator: SAD Cohorts 1-8 Placebo Arm
Drug: Placebo
Subjects will receive single doses of PF-04695842 matching placebo (solution or suspension) in a dose escalation format.
Drug: Placebo
Subjects will receive PF-04965842 matching placebo (solution or suspension) once daily for 10 days.
Drug: Placebo
Subjects will receive PF-04965842 matching placebo doses (suspension or solution) twice daily for 10 days.
Drug: Placebo
Subjects will receive PF-04965842 matching placebo dose (suspension or solution) twice daily for 10 days.
Drug: Placebo
Subjects will receive PF-04965842 matching placebo dose (suspension or solution) once daily for 10 days.
Experimental: MAD Cohorts 3 through 5 Experimental Arm
Drug: PF-04965842
Subjects will receive single doses of 3, 10, 30, 100, 200, 400, or 800 mg of PF-04695842 (solution or suspension) in a dose escalation format.
Drug: PF-04965842
Subjects will receive doses of 30, 100 or 200 mg (solution or suspension) once daily for 10 days.
Drug: PF-04965842
Subjects will receive doses of 100 or 200 mg (suspension or solution) twice daily for 10 days.
Drug: PF-04965842
Subjects will receive 200 mg dose (suspension or solution) twice daily for 10 days.
Drug: PF-04965842
Subjects will receive 400 mg dose (suspension or solution) once daily for 10 days.
Placebo Comparator: MAD Cohorts 3 through 5 Placebo Arm
Drug: Placebo
Subjects will receive single doses of PF-04695842 matching placebo (solution or suspension) in a dose escalation format.
Drug: Placebo
Subjects will receive PF-04965842 matching placebo (solution or suspension) once daily for 10 days.
Drug: Placebo
Subjects will receive PF-04965842 matching placebo doses (suspension or solution) twice daily for 10 days.
Drug: Placebo
Subjects will receive PF-04965842 matching placebo dose (suspension or solution) twice daily for 10 days.
Drug: Placebo
Subjects will receive PF-04965842 matching placebo dose (suspension or solution) once daily for 10 days.
Experimental: MAD Cohorts 6 and 7 Experimental Arm
Drug: PF-04965842
Subjects will receive single doses of 3, 10, 30, 100, 200, 400, or 800 mg of PF-04695842 (solution or suspension) in a dose escalation format.
Drug: PF-04965842
Subjects will receive doses of 30, 100 or 200 mg (solution or suspension) once daily for 10 days.
Drug: PF-04965842
Subjects will receive doses of 100 or 200 mg (suspension or solution) twice daily for 10 days.
Drug: PF-04965842
Subjects will receive 200 mg dose (suspension or solution) twice daily for 10 days.
Drug: PF-04965842
Subjects will receive 400 mg dose (suspension or solution) once daily for 10 days.
Placebo Comparator: MAD Cohorts 6 and 7 Placebo Arm
Drug: Placebo
Subjects will receive single doses of PF-04695842 matching placebo (solution or suspension) in a dose escalation format.
Drug: Placebo
Subjects will receive PF-04965842 matching placebo (solution or suspension) once daily for 10 days.
Drug: Placebo
Subjects will receive PF-04965842 matching placebo doses (suspension or solution) twice daily for 10 days.
Drug: Placebo
Subjects will receive PF-04965842 matching placebo dose (suspension or solution) twice daily for 10 days.
Drug: Placebo
Subjects will receive PF-04965842 matching placebo dose (suspension or solution) once daily for 10 days.
Experimental: MAD Cohort 8 Experimental Arm
Drug: PF-04965842
Subjects will receive single doses of 3, 10, 30, 100, 200, 400, or 800 mg of PF-04695842 (solution or suspension) in a dose escalation format.
Drug: PF-04965842
Subjects will receive doses of 30, 100 or 200 mg (solution or suspension) once daily for 10 days.
Drug: PF-04965842
Subjects will receive doses of 100 or 200 mg (suspension or solution) twice daily for 10 days.
Drug: PF-04965842
Subjects will receive 200 mg dose (suspension or solution) twice daily for 10 days.
Drug: PF-04965842
Subjects will receive 400 mg dose (suspension or solution) once daily for 10 days.
Placebo Comparator: MAD Cohort 8 Placebo Arm
Drug: Placebo
Subjects will receive single doses of PF-04695842 matching placebo (solution or suspension) in a dose escalation format.
Drug: Placebo
Subjects will receive PF-04965842 matching placebo (solution or suspension) once daily for 10 days.
Drug: Placebo
Subjects will receive PF-04965842 matching placebo doses (suspension or solution) twice daily for 10 days.
Drug: Placebo
Subjects will receive PF-04965842 matching placebo dose (suspension or solution) twice daily for 10 days.
Drug: Placebo
Subjects will receive PF-04965842 matching placebo dose (suspension or solution) once daily for 10 days.
Experimental: MAD Cohort 9 Experimental Arm
Drug: PF-04965842
Subjects will receive single doses of 3, 10, 30, 100, 200, 400, or 800 mg of PF-04695842 (solution or suspension) in a dose escalation format.
Drug: PF-04965842
Subjects will receive doses of 30, 100 or 200 mg (solution or suspension) once daily for 10 days.
Drug: PF-04965842
Subjects will receive doses of 100 or 200 mg (suspension or solution) twice daily for 10 days.
Drug: PF-04965842
Subjects will receive 200 mg dose (suspension or solution) twice daily for 10 days.
Drug: PF-04965842
Subjects will receive 400 mg dose (suspension or solution) once daily for 10 days.
Placebo Comparator: MAD Cohort 9 Placebo Arm
Drug: Placebo
Subjects will receive single doses of PF-04695842 matching placebo (solution or suspension) in a dose escalation format.
Drug: Placebo
Subjects will receive PF-04965842 matching placebo (solution or suspension) once daily for 10 days.
Drug: Placebo
Subjects will receive PF-04965842 matching placebo doses (suspension or solution) twice daily for 10 days.
Drug: Placebo
Subjects will receive PF-04965842 matching placebo dose (suspension or solution) twice daily for 10 days.
Drug: Placebo
Subjects will receive PF-04965842 matching placebo dose (suspension or solution) once daily for 10 days.

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
Incidence and severity of treatment emergent adverse events and withdrawals due to treatment emergent adverse events
Time Frame: 6 weeks
6 weeks
Changes from baseline vital signs (blood pressure, pulse rate, oral temperature and respiration rate) and physical examinations
Time Frame: 6 weeks
6 weeks
Changes from baseline in 12 lead ECG parameters
Time Frame: 6 weeks
Quantitative changes in ECG intervals
6 weeks
Incidence and magnitude of treatment emergent clinical laboratory abnormalities including hematology (with white blood cell count differentials, platelets, PT and aPTT), chemistry, fasting glucose, urinalysis
Time Frame: 6 weeks
6 weeks
Change from baseline in immunoglobulin levels
Time Frame: 6 weeks
Quantitative IgG, IgA, IgM, and IgE levels
6 weeks
24-hour urine creatinine clearance (Single Ascending Dose Period)
Time Frame: Baseline, Day 1
Baseline, Day 1
24-hour urine creatinine clearance (Multiple Ascending Dose Period)
Time Frame: Baseline, Day 1
Baseline, Day 1

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
Complement Level: C3
Time Frame: 6 weeks
6 weeks
Complement Level: C4
Time Frame: 6 weeks
6 weeks
Complement Level: C3A
Time Frame: 6 weeks
Cohorts 1-7 and Cohort 9
6 weeks
Complement Level: Bb
Time Frame: 6 weeks
Cohorts 1-7 and Cohort 9
6 weeks
Single Ascending Dose: Dose-normalized Area Under the Curve From Time Zero to Infinity (AUCinf(dn))
Time Frame: 8 days
8 days
Multiple Ascending Dose: Accumulation Ratio based on Cmax (Rac(Cmax))
Time Frame: 6 weeks
6 weeks
Urinary Pharmacokinetics; for twice-a-day dosing, amount of PF-0496842 excreted unchanged in 12 hours (AE12)
Time Frame: 6 weeks
6 weeks
Urinary Pharmacokinetics; for twice-a-day dosing, percent of PF-0496842 excreted unchanged in 12 hours (AE12%)
Time Frame: 6 weeks
6 weeks
Multiple Ascending Dose: Apparent Volume of Distribution at Steady State (Vz/F)
Time Frame: 6 weeks
Vz/F is the distribution of a drug between plasma and the rest of the body following oral adminstration.
6 weeks
Multiple Ascending Dose: Apparent Total Body Clearance (CL/F)
Time Frame: 6 weeks
6 weeks
Urinary Pharmacokinetics; for once-a-day dosing, amount of PF-0496842 excreted unchanged in 24 hours (AE24)
Time Frame: 6 weeks
6 weeks
Urinary Pharmacokinetics; for once-a-day dosing, percent of PF-0496842 excreted unchanged in 24 hours (AE24%)
Time Frame: 6 weeks
6 weeks
Renal Clearance (CLr)
Time Frame: 6 weeks
6 weeks
High-Sensitivity C-Reactive Protein (hsCRP)
Time Frame: 6 weeks
6 weeks
Neutrophil counts
Time Frame: 6 weeks
6 weeks
Reticulocyte counts
Time Frame: 6 weeks
6 weeks
Complement Level: CH50
Time Frame: 6 weeks
6 weeks
Single Ascending Dose: Apparent Total Body Clearance (CL/F)
Time Frame: 8 days
8 days
Multiple Ascending Dose: Maximum Observed Plasma Concentration (Cmax)
Time Frame: 6 weeks
6 weeks
Multiple Ascending Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time Frame: 6 weeks
6 weeks
Multiple Ascending Dose: Dose-normalized Maximum Observed Plasma Concentration (Cmax(dn))
Time Frame: 6 weeks
6 weeks
Multiple Ascending Dose: Area Under the Curve to the end of the dosing period (AUCtau(dn))
Time Frame: 6 weeks
6 weeks
Multiple Ascending Dose: Accumulation Ratio based on AUC predicted (Rss)
Time Frame: 6 weeks
6 weeks
Multiple Ascending Dose: Accumulation Ration based on AUC observed (Rac)
Time Frame: 6 weeks
6 weeks
Multiple Ascending Dose: Plasma Decay Half-Life (t1/2)
Time Frame: 6 weeks
Plasma decay half-life is the time measured for the plasma concentration to decrease by one-half.
6 weeks
Multiple Ascending Dose: Peak to Trough Fluctuation (PTF)
Time Frame: 6 weeks
6 weeks
Single Ascending Dose: Dose-normalized Area Under the Curve to the end of the dosing period (AUCtau(dn))
Time Frame: 8 days
8 days
Single Ascending Dose: Area Under the Curve From Time Zero to Infinity (AUCinf)
Time Frame: 8 days
8 days
Single Ascending Dose: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
Time Frame: 8 days
8 days
Single Ascending Dose: Dose-normalized Maximum Observed Plasma Concentration (Cmax(dn))
Time Frame: 8 days
8 days
Single Ascending Dose: Area Under the Curve to the end of the dosing period (AUCtau)
Time Frame: 8 days
8 days
Single Ascending Dose: Dose-normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast(dn))
Time Frame: 8 days
Dose-normalized area under the plasma concentration time-curve from zero to the last measured concentration (AUClast(dn))
8 days
Single Ascending Dose: Plasma Decay Half-Life (t1/2)
Time Frame: 8 days
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
8 days
Multiple Ascending Dose: Area Under the Curve to the end of the dosing period (AUCtau)
Time Frame: 6 weeks
6 weeks
Single Ascending Dose: Apparent Volume of Distribution (Vz/F)
Time Frame: 8 days
8 days
Single Ascending Dose: Maximum Observed Plasma Concentration (Cmax)
Time Frame: 8 days
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.

General Publications

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

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.
May 1, 2013

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.
June 1, 2014

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.
June 1, 2014

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).
April 15, 2013

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.
April 15, 2013

First Posted (Estimate)

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.
April 18, 2013

Study Record Updates

Last Update Posted (Estimate)

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.
June 20, 2014

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.
June 19, 2014

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.
June 1, 2014

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.
  • B7451001

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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