Normal Healthy
Conditions
Brief summary
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.
Interventions
DRUGPF-06423264
Multiple ascending dose of PF-06423264
OTHERPlacebo
Multiple dose of placebo
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Treatment Emergent Treatment-Related Adverse Events (AEs) or other safety concerns | Baseline (Day 0) up to 28 days after last dose of study medication | 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. |
| Number of Participants with Draize-like scoring and clinical observation | Baseline (Day 1) up to Day 42+3 | 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. |
| Number of Participants With Clinical Laboratory Abnormalities | Baseline (Day 0) up to 28 days after last dose | 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 \[urine mucus and leucocytes\]). |
| Number of Participants With Abnormal Electrocardiogram (ECG) | Baseline (Day 0) up to 28 days after last dose | 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. |
| Number of Participants With Categorical Vital Signs Data | Baseline (Day 0) up to 28 days after last dose | Number of participants with maximum increase from Baseline in sitting SBP and DBP of greater than or equal to 30 mmHg was reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) for PF-06423264 | 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 | Maximum Observed Plasma Concentration (Cmax) |
| Time to Reach Maximum Observed Concentration for PF-06423264 | 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 Plasma Concentration (Tmax) |
| Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for PF-06423264 | 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 concentration curve from time 0 to end of dosing interval (AUCtau), where dosing interval was 12 hours. |
| Plasma Decay Half-Life (t1/2) for PF-06423264 | 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) |
| Apparent Volume of Distribution (Vz/F) for PF-06423264 | 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 | 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. |
| Apparent Total Body Clearance (CL/F) for | 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 | 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. |
| Observed Accumulation Ratio (Rac) for PF-06423264 | 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 | 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). |
| change from baseline in sebum lipid components and sebum excretion | Baseline (Day 0) up to 16 days after last dose of study medication | 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 |
Countries
Belgium
Outcome results
None listed