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

NCT01835197 | Completed Phase 1

• 1 other identifier: B7451001
• Study Type: interventional
• Target: 79
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy

Keywords

Phase 1; Randomized; Double Blind; Placebo-Controlled; Single- & Multiple Dose Escalation; Safety; Tolerability; PK; PD; Pf-04965842

Outcome Measures

Primary Outcomes (7)

• Changes from baseline vital signs (blood pressure, pulse rate, oral temperature and respiration rate) and physical examinations

  6 weeks

• Changes from baseline in 12 lead ECG parameters

  Quantitative changes in ECG intervals

  6 weeks

• Incidence and severity of treatment emergent adverse events and withdrawals due to treatment emergent adverse events

  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

  6 weeks

• Change from baseline in immunoglobulin levels

  Quantitative IgG, IgA, IgM, and IgE levels

  6 weeks

• 24-hour urine creatinine clearance (Single Ascending Dose Period)

  Baseline, Day 1

• 24-hour urine creatinine clearance (Multiple Ascending Dose Period)

  Baseline, Day 1

Secondary Outcomes (36)

• Complement Level: C3

  6 weeks

• Complement Level: C4

  6 weeks

• Complement Level: C3A

  6 weeks

• Complement Level: Bb

  6 weeks

• Single Ascending Dose: Dose-normalized Area Under the Curve From Time Zero to Infinity (AUCinf(dn))

  8 days

Study Arms (10)

SAD Cohorts 1-8 Experimental Arm

EXPERIMENTAL

Drug: PF-04965842

SAD Cohorts 1-8 Placebo Arm

PLACEBO COMPARATOR

Drug: Placebo

MAD Cohorts 3 through 5 Experimental Arm

EXPERIMENTAL

Drug: PF-04965842

MAD Cohorts 3 through 5 Placebo Arm

PLACEBO COMPARATOR

Drug: Placebo

MAD Cohorts 6 and 7 Experimental Arm

EXPERIMENTAL

Drug: PF-04965842

MAD Cohorts 6 and 7 Placebo Arm

PLACEBO COMPARATOR

Drug: Placebo

MAD Cohort 8 Experimental Arm

EXPERIMENTAL

Drug: PF-04965842

MAD Cohort 8 Placebo Arm

PLACEBO COMPARATOR

Drug: Placebo

MAD Cohort 9 Experimental Arm

EXPERIMENTAL

Drug: PF-04965842

MAD Cohort 9 Placebo Arm

PLACEBO COMPARATOR

Drug: Placebo

Interventions

PF-04965842 DRUG

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.

SAD Cohorts 1-8 Experimental Arm

Placebo DRUG

Subjects will receive single doses of PF-04695842 matching placebo (solution or suspension) in a dose escalation format.

SAD Cohorts 1-8 Placebo Arm

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

Pfizer Investigational Site

New Haven, Connecticut, 06511, United States

Location

Related Publications (2)

• 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.

  PMID: 35061234 DERIVED

• Peeva E, Hodge MR, Kieras E, Vazquez ML, Goteti K, Tarabar SG, Alvey CW, Banfield C. Evaluation of a Janus kinase 1 inhibitor, PF-04965842, in healthy subjects: A phase 1, randomized, placebo-controlled, dose-escalation study. Br J Clin Pharmacol. 2018 Aug;84(8):1776-1788. doi: 10.1111/bcp.13612. Epub 2018 May 24.

  PMID: 29672897 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Interventions

abrocitinib

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2013
• First Posted: April 18, 2013
• Study Start: May 1, 2013
• Primary Completion: June 1, 2014
• Study Completion: June 1, 2014
• Last Updated: June 20, 2014

Record last verified: 2014-06

Locations

US (1)