Topical Multiple Ascending Dose Study for PF-06423264

Study Overview
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Brief Summary
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The current study is the first clinical trial proposed with PF-06423264. It is designed to evaluate the safety, tolerability, and pharmacokinetics (PK) following administration of multiple ascending doses of PF-06423264 to healthy adult subjects with or without oily skin.

Official Title
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A Phase 1, Randomized, Double-blind, Placebo-controlled Study To Assess The Safety, Tolerability And Pharmacokinetics Of Multiple Ascending Doses Of Pf-06423264 Administered Topically To Sequential Cohorts Of Healthy Subjects With And Without Oily Skin

Conditions
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Normal Healthy

Intervention / Treatment
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* Drug: PF-06423264
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males and female of non-childbearing potential; Body Mass Index 17.5-35.5 kg/m2; Body weight >50 kg; Exclusion Criteria: Evidence of history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergises, but excluding untreated, asymptomatic, seasonal allergies at time of dosing)

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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A_Cohort 1_Active<br>Multiple ascending dose of PF-06423264 | Drug: PF-06423264<br>* Multiple ascending dose of PF-06423264<br>|
| Placebo Comparator: Part A_Cohort 1_Placebo<br>Multiple dose of placebo | Other: Placebo<br>* Multiple dose of placebo<br>* Other names: Placebo comparator;|
| Experimental: Part A_Cohort 2_Active<br>Multiple ascending dose of PF-06423264 | Drug: PF-06423264<br>* Multiple ascending dose of PF-06423264<br>|
| Placebo Comparator: Part A_Cohort 2_Placebo<br>Multiple dose of placebo | Other: Placebo<br>* Multiple dose of placebo<br>* Other names: Placebo comparator;|
| Experimental: Part A_Cohort 3_Active<br>Multiple ascending dose of PF-06423264 | Drug: PF-06423264<br>* Multiple ascending dose of PF-06423264<br>|
| Placebo Comparator: Part A_Cohort 3_Placebo<br>Multiple dose of placebo | Other: Placebo<br>* Multiple dose of placebo<br>* Other names: Placebo comparator;|
| Experimental: Part A_Cohort 4_Active<br>Multiple ascending dose of PF-06423264 | Drug: PF-06423264<br>* Multiple ascending dose of PF-06423264<br>|
| Placebo Comparator: Part A_Cohort 4_Placebo<br>Multiple dose of placebo | Other: Placebo<br>* Multiple dose of placebo<br>* Other names: Placebo comparator;|
| Experimental: Part A_Cohort 5_Active<br>Multiple ascending dose of PF-06423264 | Drug: PF-06423264<br>* Multiple ascending dose of PF-06423264<br>|
| Placebo Comparator: Part A_Cohort 5_Placebo<br>Multiple dose of placebo | Other: Placebo<br>* Multiple dose of placebo<br>* Other names: Placebo comparator;|
| Experimental: Part A_Cohort 6_Active<br>Multiple ascending dose of PF-06423264 | Drug: PF-06423264<br>* Multiple ascending dose of PF-06423264<br>|
| Placebo Comparator: Part A_Cohort 6_Placebo<br>Multiple dose of placebo | Other: Placebo<br>* Multiple dose of placebo<br>* Other names: Placebo comparator;|
| Experimental: Part A_Cohort 7_Active<br>Multiple ascending dose of PF-06423264 | Drug: PF-06423264<br>* Multiple ascending dose of PF-06423264<br>|
| Placebo Comparator: Part A_Cohort 7_Placebo<br>Multiple ascending dose of placebo | Other: Placebo<br>* Multiple dose of placebo<br>* Other names: Placebo comparator;|
| Experimental: Part B_Cohort 1_Active<br>Multiple doses of PF-06423264 | Drug: PF-06423264<br>* Multiple ascending dose of PF-06423264<br>|
| Placebo Comparator: Part B_Cohort 1_Placebo<br>Multiple doses of placebo | Other: Placebo<br>* Multiple dose of placebo<br>* Other names: Placebo comparator;|
| Experimental: Part B_Cohort 2_Active<br>Multiple doses of PF-06423264 | Drug: PF-06423264<br>* Multiple ascending dose of PF-06423264<br>|
| Placebo Comparator: Part B_Cohort 2_Placebo<br>Multiple doses of placebo | Other: Placebo<br>* Multiple dose of placebo<br>* Other names: Placebo comparator;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Treatment Emergent Treatment-Related Adverse Events (AEs) or other safety concerns | Assessment by adverse event monitoring, 12 lead ECGs, telemetry, vital signs and clinical safety laboratory measurements. Treatment-related AE was any untoward medical occurrence attributed to study drug in a subject who received study drug. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. Relatedness to Drug was assessed by the investigator (Yes/No). Subjects with multiple occurrences of an AE within a category were counted once within the category. | Baseline (Day 0) up to 28 days after last dose of study medication | 
| Number of Participants with Draize-like scoring and clinical observation | Modified Draize-like scoring and clinical observation. Severity estimated by clinical signs and scoring; ranged 0-4: 0= No reaction visible, 1= Trace reaction - barely perceptible pinkness, 2= Mild reaction - readily visible pinkness, 3= Moderate reaction - definite redness, 4= Strong to severe reaction - very intense redness. | Baseline (Day 1) up to Day 42+3 | 
| Number of Participants With Clinical Laboratory Abnormalities | Following parameters were analyzed for laboratory examination: hematology (hemoglobin, hematocrit, red blood cell count, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); liver function (aspartate aminotransferase, alanine aminotransferase, total bilirubin, lactate dehydrogenase, alkaline phosphatase, albumin, total protein); renal function (blood urea nitrogen, creatinine, uric acid); electrolytes (sodium, potassium, chloride, calcium, phosphate, bicarbonate); clinical chemistry (glucose, creatine kinase); immunology (CRP); urinalysis (dipstick [urine specific gravity, decimal logarithm of reciprocal of hydrogen ion activity {pH} of urine, glucose, protein, blood, ketones, bilirubin], microscopy [urine RBC, WBC, urate crystals, calcium, oxalate, miscellaneous [urine mucus and leucocytes]). | Baseline (Day 0) up to 28 days after last dose | 
| Number of Participants With Abnormal Electrocardiogram (ECG) | Criteria for potential clinical concern in ECG parameters: Maximum QTcF interval (Fridericia's Correction) in range of 450 to less than 480 msec, maximum QTc interval increase from baseline in range of 30 to less than 60 msec and >=60 msec. | Baseline (Day 0) up to 28 days after last dose | 
| Number of Participants With Categorical Vital Signs Data | Number of participants with maximum increase from Baseline in sitting SBP and DBP of greater than or equal to 30 mmHg was reported. | Baseline (Day 0) up to 28 days after last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) for PF-06423264 | Maximum Observed Plasma Concentration (Cmax) | 0, 0.5, 1, 2, 4, 5, 6, 8, 12, 24 hours post dose on Day 1 and 0, 0.5, 1, 2, 4, 5, 6, 8, 12, 24, 36, and 48 hours post dose on Day 14 | 
| Time to Reach Maximum Observed Concentration for PF-06423264 | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 0, 0.5, 1, 2, 4, 5, 6, 8, 12, 24 hours post dose on Day 1 and 0, 0.5, 1, 2, 4, 5, 6, 8, 12, 24, 36, and 48 hours post dose on Day 14 | 
| Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for PF-06423264 | Area under the concentration curve from time 0 to end of dosing interval (AUCtau), where dosing interval was 12 hours. | 0, 0.5, 1, 2, 4, 5, 6, 8, 12, 24 hours post dose on Day 1 and 0, 0.5, 1, 2, 4, 5, 6, 8, 12, 24, 36, and 48 hours post dose on Day 14 | 
| Plasma Decay Half-Life (t1/2) for PF-06423264 | Plasma Decay Half-Life (t1/2) | 0, 0.5, 1, 2, 4, 5, 6, 8, 12, 24 hours post dose on Day 1 and 0, 0.5, 1, 2, 4, 5, 6, 8, 12, 24, 36, and 48 hours post dose on Day 14 | 
| Apparent Volume of Distribution (Vz/F) for PF-06423264 | 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. | 0, 0.5, 1, 2, 4, 5, 6, 8, 12, 24 hours post dose on Day 1 and 0, 0.5, 1, 2, 4, 5, 6, 8, 12, 24, 36, and 48 hours post dose on Day 14 | 
| Apparent Total Body Clearance (CL/F) for | 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 apparent total body 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. | 0, 0.5, 1, 2, 4, 5, 6, 8, 12, 24 hours post dose on Day 1 and 0, 0.5, 1, 2, 4, 5, 6, 8, 12, 24, 36, and 48 hours post dose on Day 14 | 
| Observed Accumulation Ratio (Rac) for PF-06423264 | Rac was calculated as, area under the curve from time zero to end of dosing interval on Day Y (AUCtau) divided by area under the curve from time zero to end of dosing interval on Day X(AUCtau). | 0, 0.5, 1, 2, 4, 5, 6, 8, 12, 24 hours post dose on Day 1 and 0, 0.5, 1, 2, 4, 5, 6, 8, 12, 24, 36, and 48 hours post dose on Day 14 | 
| change from baseline in sebum lipid components and sebum excretion | change from baseline in sebum lipid components and sebum excretion as assessed with Sebutape strips and Sebumeter measurements on the forehead of subjects with oily skin | Baseline (Day 0) up to 16 days after last dose of study medication |