Healthy
Conditions
Keywords
Phase 1, Randomized, Placebo-Controlled, Multiple Dose Escalation, Tolerability, Safety, PK, Topical, Healthy, PF-06263276
Brief summary
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.
Interventions
DRUGPF-06263726
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.
DRUGPlacebo
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.
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Draize toxicity assessment score. | Day 8, Day 28 | Changes from baseline on Draize toxicity assessment score. |
| 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. | Day 23, Day 28 | Quantitative changes in ECG intervals. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| Cohorts 3 and 4: Plasma Decay Half-Life (t1/2) | Day 14 | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. |
| Cohorts 3 and 4: Time to Reach Maximum Observed Plasma Concentration (Tmax) | Day 1, Day 14 | — |
| Cohorts 3 and 4: Apparent Oral Clearance (CL/F) | 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. |
| Cohorts 3 and 4: Apparent Volume of Distribution (Vz/F) | 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. |
| Cohorts 3 and 4: Maximum Observed Plasma Concentration (Cmax) | Day 1, Day 14 | — |
| Cohorts 3 and 4: Area Under the Curve From Time Zero to 12 hours [AUC (0-12)] | 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) |
| Cohorts 3 and 4: Dose-Normalized Area Under the Curve From Time Zero to 12 hours [AUC (0-12)] | 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) |
| Cohorts 3 and 4: Dose-Normalized Maximum Observed Plasma Concentration [Cmax (dn)] | Day 1, Day 14 | — |
Countries
Belgium
Outcome results
None listed