Topical Multiple Ascending Dose Study for PF-06423264

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

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.

Study Overview

• Status: Terminated
• Conditions: Normal Healthy
• Intervention / Treatment: Drug: PF-06423264; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, B-1070
    • Pfizer Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Masking: Double

Number of Arms

18

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.
• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): May 23, 2016
• Primary Completion (Actual): May 23, 2017
• Study Completion (Actual): May 23, 2017

Study Registration Dates

• First Submitted: May 17, 2016
• First Submitted That Met QC Criteria: May 17, 2016
• First Posted (Estimate): May 20, 2016

Study Record Updates

• Last Update Posted (Actual): June 21, 2017
• Last Update Submitted That Met QC Criteria: June 20, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Other Study ID Numbers: B7561002; 2014-003736-39 (EudraCT Number)