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

Healthy Clinical Trial

Official 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01981681
• Other study ID #: B5391002
• Secondary ID: 2013-004231-68
• Status: Completed
• Phase: Phase 1
• First received: November 5, 2013
• Last updated: July 15, 2014
• Start date: November 2013
• Est. completion date: June 2014

Study information

• Verified date: July 2014
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 47
• Est. completion date: June 2014
• Est. primary completion date: June 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• PF-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.
• PF-06263726
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.
• PF-06263726
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.
• Placebo
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.
• PF-06263726
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.
• Placebo
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.

Locations

Country	Name	City	State
Belgium	Pfizer Investigational Site	Brussels

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Draize toxicity assessment score.	Changes from baseline on Draize toxicity assessment score.	Day 8, Day 28	Yes
Primary	Changes from baseline vital signs (blood pressure, pulse rate, oral temperature and respiration rate) and physical examinations.		Day 23, Day 28	Yes
Primary	Changes from baseline in 12 lead electrocardiogram (ECG) parameters.	Quantitative changes in ECG intervals.	Day 23, Day 28	Yes
Primary	Incidence and severity of treatment emergent adverse events and withdrawals due to treatment emergent adverse events.		Day 23, Day 28	Yes
Primary	Incidence and magnitude of treatment emergent clinical laboratory abnormalities including hematology, chemistry, fasting glucose, urinalysis.		Day 23, Day 28	Yes
Secondary	Cohorts 3 and 4: Maximum Observed Plasma Concentration (Cmax)		Day 1, Day 14	Yes
Secondary	Cohorts 3 and 4: Time to Reach Maximum Observed Plasma Concentration (Tmax)		Day 1, Day 14	No
Secondary	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	Yes
Secondary	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	No
Secondary	Cohorts 3 and 4: Dose-Normalized Maximum Observed Plasma Concentration [Cmax (dn)]		Day 1, Day 14	No
Secondary	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	No
Secondary	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	No
Secondary	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	No

External Links

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