A PHASE 1, RANDOMIZED, DOUBLE-BLIND, SPONSOR-OPEN, VEHICLE-CONTROLLED, FIRST-IN-HUMAN, MULTIPLE-DOSE STUDY, TO INVESTIGATE THE SAFETY, TOLERABILITY, AND PHARMACOKINETICS, OF TOPICALLY ADMINISTERED PF-07295324 AND PF-07259955, IN HEALTHY ADULT PARTICIPANTS
Overview
- Phase
- Phase 1
- Intervention
- PF-07295324
- Conditions
- Healthy
- Sponsor
- Pfizer
- Enrollment
- 24
- Locations
- 1
- Primary Endpoint
- Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Findings
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
The purpose of the study is to evaluate the safety, (local and systemic) tolerability, and pharmacokinetics following multiple doses of topically applied, maximum feasible formulations of PF-07295324 (0.12% w/w) or PF-07259955 (2% w/w), on approximately 20% body surface area (BSA), in healthy adult participants.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
PF-07295324
Ointment
Intervention: PF-07295324
PF-07259955
Cream
Intervention: PF-07259955
Outcomes
Primary Outcomes
Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Findings
Time Frame: At screening, on Days 1, 2, 5, 7, 10, 11, at discharge (Day 12), and at early termination if applicable
ECG abnormalities criteria included: 1) maximum QTc interval adjusted according Fridericia formula (QTcF) (msec): 450\<= QTcF \<480, 480\<= QTcF \<500, and QTcF \>=500; QTcF maximum increase from baseline (msec): 30\<= change \<60, and change \>=60; 2) maximum PR interval (msec): \>=300; PR increase from baseline (msec): baseline \>200 with 25% increase at maximum, baseline \<=200 with 50% increase at maximum; 3) maximum QRS (msec): \>=140; QRS increase from baseline (msec) \>=50%. Baseline was defined as the average of the last triplicate measurement prior to the first dosing. ECG abnormalities reported for at least 1 participant are presented here.
Skin Irritation Assessments Using Draize Scoring
Time Frame: Screening up to Day 12 or early termination if applicable
Application site toleration was assessed by Draize scoring. Draize scores were defined as: 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. Participants with at least 1 instance of Draize score \>0 were listed.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: Baseline up to the end of follow up (ie, up to 44 days)
An AE was any untoward medical occurrence in a clinical investigation where participant administered a product; the event did not need to have a causal relationship with the treatment. A SAE was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. AEs included both SAEs and non-serious AEs. Treatment-related AEs and SAEs were determined by the investigator.
Number of Participants With Laboratory Abnormalities
Time Frame: At screening, admission (Day -1), on Days 5, 7, 10, at discharge (Day 12), and at early termination if applicable
Hematology parameters included hemoglobin, hematocrit, red blood cell count, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet and white blood cell count, total neutrophils, eosinophils, monocytes, basophils, reticulocytes, and lymphocytes. Chemistry parameters included blood urea nitrogen, creatinine, glucose (fasting), calcium, sodium, potassium, chloride, total bicarbonate, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid, albumin, total protein. Urine parameters included pH, glucose, protein, blood, ketones, nitrites, leukocyte esterase, urobilinogen, urine bilirubin, microscopy. Only those categories in which at least 1 participant had abnormal data were reported.
Number of Participants With Vital Signs Abnormalities
Time Frame: At screening, on Days 1, 2, 5, 7, 10, 11, at discharge (Day 12), and at early termination if applicable
Criteria for abnormality in vital signs: supine pulse rate \<40 beats per minute (bpm) or \>120 bpm; supine diastolic blood pressure (DBP) \<50 mmHg, maximum increase or decrease from baseline of \>=20 mmHg; supine systolic blood pressure (SBP) \<90 mmHg, maximum increase or decrease from baseline of \>=30 mmHg. Baseline was defined as the last measurement prior to the first dosing. Vital sign abnormalities reported for at least 1 participant are presented here.
Secondary Outcomes
- Maximum Observed Plasma Concentration (Cmax) of PF-07295324 on Days 1 and 10(On Days 1 and 10 at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after application)
- Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07295324 on Days 1 and 10(On Days 1 and 10 at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after application)
- Area Under the Concentration-Time Profile From Time Zero to the Dosing Interval Tau (AUCtau) of PF-07295324 on Days 1 and 10(On Days 1 and 10 at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after application)
- Average Plasma Concentration (Cavg) of PF-07295324 on Days 1 and 10(On Days 1 and 10 at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after application)
- Pre-Dose Concentration (Ctrough) of PF-07295324 on Days 1 and 10(Pre-dose on Days 1 and 10)
- Observed Accumulation Ratio for Cmax (Rac[Cmax]) of PF-07295324 on Day 10(On Days 1 and 10 at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after application)
- Observed Accumulation Ratio for AUCtau (Rac[AUCtau]) of PF-07295324 on Day 10(On Days 1 and 10 at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after application)
- Terminal Half-Life (t1/2) of PF-07295324 on Day 10(On Days 1, 2, 5, 7, 10, 11, 12, and early termination (if applicable) at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after application)
- Apparent Clearance (CL/F) of PF-07295324 on Day 10(On Days 1, 2, 5, 7, 10, 11, 12, and early termination (if applicable) at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after application)
- Apparent Volume of Distribution (Vz/F) of PF-07295324 on Day 10(On Days 1, 2, 5, 7, 10, 11, 12, and early termination (if applicable) at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after application)
- Cmax of PF-07259955 on Days 1 and 10(On Days 1 and 10 at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after application)
- Tmax of PF-07259955 on Days 1 and 10(On Days 1 and 10 at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after application)
- AUCtau of PF-07259955 on Days 1 and 10(On Days 1 and 10 at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after application)
- Cavg of PF-07259955 on Days 1 and 10(On Days 1 and 10 at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after application)
- Ctrough of PF-07259955 on Days 1 and 10(Pre-dose on Days 1 and 10)
- Rac(Cmax) of PF-07259955 on Day 10(On Days 1 and 10 at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after application)
- Rac(AUCtau) of PF-07259955 on Day 10(On Days 1 and 10 at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after application)
- t½ of PF-07259955 on Day 10(On Days 1, 2, 5, 7, 10, 11, 12, and early termination (if applicable) at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after application)
- CL/F of PF-07259955 on Day 10(On Days 1, 2, 5, 7, 10, 11, 12, and early termination (if applicable) at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after application)
- Vz/F of PF-07259955 on Day 10(On Days 1, 2, 5, 7, 10, 11, 12, and early termination (if applicable) at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after application)