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

Pfizer

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: PF-04965842; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01835197

B7451001

Details and patient eligibility

About

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.

Enrollment: 79 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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79 participants in 10 patient groups, including a placebo group

SAD Cohorts 1-8 Experimental Arm

Experimental group

Treatment:

Drug: PF-04965842

Drug: PF-04965842

Drug: PF-04965842

Drug: PF-04965842

Drug: PF-04965842

SAD Cohorts 1-8 Placebo Arm

Placebo Comparator group

Treatment:

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

MAD Cohorts 3 through 5 Experimental Arm

Experimental group

Treatment:

Drug: PF-04965842

Drug: PF-04965842

Drug: PF-04965842

Drug: PF-04965842

Drug: PF-04965842

MAD Cohorts 3 through 5 Placebo Arm

Placebo Comparator group

Treatment:

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

MAD Cohorts 6 and 7 Experimental Arm

Experimental group

Treatment:

Drug: PF-04965842

Drug: PF-04965842

Drug: PF-04965842

Drug: PF-04965842

Drug: PF-04965842

MAD Cohorts 6 and 7 Placebo Arm

Placebo Comparator group

Treatment:

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

MAD Cohort 8 Experimental Arm

Experimental group

Treatment:

Drug: PF-04965842

Drug: PF-04965842

Drug: PF-04965842

Drug: PF-04965842

Drug: PF-04965842

MAD Cohort 8 Placebo Arm

Placebo Comparator group

Treatment:

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

MAD Cohort 9 Experimental Arm

Experimental group

Treatment:

Drug: PF-04965842

Drug: PF-04965842

Drug: PF-04965842

Drug: PF-04965842

Drug: PF-04965842

MAD Cohort 9 Placebo Arm

Placebo Comparator group

Treatment:

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: Placebo