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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Drug: PF-06263726
* Drug: PF-06263726
* Drug: PF-06263726
* Drug: Placebo
* Drug: PF-06263726
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 Experimental Arm<br> | Drug: PF-06263726<br>* 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.<br>|
| Experimental: Cohort 2 Experimental Arm<br> | Drug: PF-06263726<br>* Subjects will receive dose strength of 4% PF-06263276 (2.28 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.<br>|
| Experimental: Cohort 3 Experimental Arm<br> | Drug: PF-06263726<br>* Subjects will receive dose strength of 2% PF-06263276 (11.4 mg) in topical formulation (2.5 µL/cm2) to be applied twice daily to a 200 cm2 area on the back.<br>|
| Placebo Comparator: Cohort 3 Placebo Arm<br> | Drug: Placebo<br>* 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.<br>|
| Experimental: Cohort 4 Experimental Arm<br> | Drug: PF-06263726<br>* Subjects will receive dose strength of 4% PF-06263276 (22.8 mg) in topical formulation (2.5 µL/cm2) to be applied twice daily to a 200 cm2 area on the back.<br>|
| Placebo Comparator: Cohort 4 Placebo Arm<br> | Drug: Placebo<br>* Subjects will receive dose strength of 4% PF-06263276 (22.8 mg) matching placebo in topical formulation (2.5 µL/cm2) to be applied twice daily to a 200 cm2 area on the back.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Draize toxicity assessment score. | Changes from baseline on Draize toxicity assessment score. | Day 8, Day 28 | 
| Changes from baseline vital signs (blood pressure, pulse rate, oral temperature and respiration rate) and physical examinations. |  | Day 23, Day 28 | 
| Changes from baseline in 12 lead electrocardiogram (ECG) parameters. | Quantitative changes in ECG intervals. | Day 23, Day 28 | 
| Incidence and severity of treatment emergent adverse events and withdrawals due to treatment emergent adverse events. |  | Day 23, Day 28 | 
| Incidence and magnitude of treatment emergent clinical laboratory abnormalities including hematology, chemistry, fasting glucose, urinalysis. |  | Day 23, Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohorts 3 and 4: Maximum Observed Plasma Concentration (Cmax) |  | Day 1, Day 14 | 
| Cohorts 3 and 4: Time to Reach Maximum Observed Plasma Concentration (Tmax) |  | Day 1, Day 14 | 
| Cohorts 3 and 4: Area Under the Curve From Time Zero to 12 hours [AUC (0-12)] | AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t) | Day 1, Day 14 | 
| Cohorts 3 and 4: Dose-Normalized Area Under the Curve From Time Zero to 12 hours [AUC (0-12)] | AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t) | Day 1, Day 14 | 
| Cohorts 3 and 4: Dose-Normalized Maximum Observed Plasma Concentration [Cmax (dn)] |  | Day 1, Day 14 | 
| Cohorts 3 and 4: Plasma Decay Half-Life (t1/2) | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | Day 14 | 
| Cohorts 3 and 4: Apparent Volume of Distribution (Vz/F) | 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. | Day 14 | 
| Cohorts 3 and 4: Apparent Oral Clearance (CL/F) | 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. | Day 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 1, Randomized, Placebo-Controlled, Multiple Dose Escalation, Tolerability, Safety, PK, Topical, Healthy, PF-06263276