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Completed

NCT Number: NCT01981681

A Phase 1 Study To Evaluate Tolerability, Safety, And Pharmacokinetics Of Topical PF-06263276 In Healthy Subjects

PF-06263276 is a first in class inhibitor of the Janus kinase (JAK) enzymes 1, 2, 3 and tyrosine kinase 2 (TYK2) that is being developed for the treatment of chronic plaque psoriasis. The goal of the study is to assess the safety, local tolerability, and pharmacokinetics in healthy subjects.

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Key information

Conditions

Age range

18 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Pfizer Investigational Site

Brussels, B-1070, Belgium

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Healthy male and/or female subjects of non-childbearing potential 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 and pulse rate measurement, 12-lead ECG and clinical laboratory tests.
  • Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
  • Subjects willing to avoid tanning beds and sun exposure of the back during the study.

Exclusion criteria

  • Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of application).
  • Subjects with any active skin condition at the application site possibly affecting drug absorption (e.g. rash, sun burn, scars, tattoos).
  • Subjects with a Draize score >0 of the test area (back) immediately prior to first treatment application.
  • Subjects using topical prescription or nonprescription drugs/over the counter preparations on the back within 14 days of the first treatment application.
  • Subjects not willing to avoid application of treatmentssuch as lotions or creams to the back throughout the study until follow-up.

Treatment and study plan

PF-06263726

Drug

Subjects will receive dose strength of 2% PF-06263276 (1.14 mg) and matching placebo in topical formulation (2.5 µL/cm2) to be applied twice daily to two separate contralateral 20 cm2 areas on the back.

Placebo

Drug

Subjects will receive dose strength of 2% PF-06263276 (11.4 mg) matching placebo in topical formulation (2.5 µL/cm2) to be applied twice daily to a 200 cm2 area on the back.

Primary outcomes

  1. Draize toxicity assessment score.

    Time frame: Day 8, Day 28

    Changes from baseline on Draize toxicity assessment score.

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

    Time frame: Day 23, Day 28

  3. Changes from baseline in 12 lead electrocardiogram (ECG) parameters.

    Time frame: Day 23, Day 28

    Quantitative changes in ECG intervals.

  4. Incidence and severity of treatment emergent adverse events and withdrawals due to treatment emergent adverse events.

    Time frame: Day 23, Day 28

  5. Incidence and magnitude of treatment emergent clinical laboratory abnormalities including hematology, chemistry, fasting glucose, urinalysis.

    Time frame: Day 23, Day 28

Secondary outcomes

  1. Cohorts 3 and 4: Maximum Observed Plasma Concentration (Cmax)

    Time frame: Day 1, Day 14

  2. Cohorts 3 and 4: Time to Reach Maximum Observed Plasma Concentration (Tmax)

    Time frame: Day 1, Day 14

  3. Cohorts 3 and 4: Area Under the Curve From Time Zero to 12 hours [AUC (0-12)]

    Time frame: Day 1, Day 14

    AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t)

  4. Cohorts 3 and 4: Dose-Normalized Area Under the Curve From Time Zero to 12 hours [AUC (0-12)]

    Time frame: Day 1, Day 14

    AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t)

  5. Cohorts 3 and 4: Dose-Normalized Maximum Observed Plasma Concentration [Cmax (dn)]

    Time frame: Day 1, Day 14

  6. Cohorts 3 and 4: Plasma Decay Half-Life (t1/2)

    Time frame: Day 14

    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

  7. Cohorts 3 and 4: Apparent Volume of Distribution (Vz/F)

    Time frame: Day 14

    Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.

  8. Cohorts 3 and 4: Apparent Oral Clearance (CL/F)

    Time frame: Day 14

    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.

Sponsors and collaborators

Lead sponsor

Pfizer

Industry

Registry information

Official study title

A Phase 1, Randomized, Third-Party Open, Placebo-Controlled, Multiple Dose Escalation, Parallel Group Study To Evaluate Local Tolerability, Safety And Pharmacokinetics Of Topically Applied PF-06263276 In Healthy Subjects

Important dates

Study start
2013
Primary completion
2014
Study completion
2014
First posted
Nov 11, 2013
Registry last updated
Jul 17, 2014

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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