A First-in-human Study of Multiple Doses of Topically Administered PF-07295324 and PF-07259955
- Conditions
- Healthy
- Interventions
- Drug: PF-07295324Drug: PF-07259955
- Registration Number
- NCT05206604
- Lead Sponsor
- Pfizer
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 24
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description PF-07295324 PF-07295324 Ointment PF-07259955 PF-07259955 Cream
- Primary Outcome Measures
Name Time Method Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Findings 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 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) 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 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 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 Outcome Measures
Name Time Method 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 Cmax was defined as maximum plasma concentration. It was observed directly from data.
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 Tmax was defined as time to reach maximum observed plasma concentration. It was observed directly from data.
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 AUCtau was defined as area under the plasma concentration-time profile from time zero to time tau, the dosing interval. tau = 12 hours for BID dosing cohorts and tau = 24 hours for QD dosing cohorts.
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 Cavg was defined as average plasma concentration. It was determined by AUCtau/tau; where tau was the dosing interval and AUCtau was area under the plasma concentration-time profile from time zero to time tau, the dosing interval. tau = 12 hours for BID dosing cohorts and tau = 24 hours for QD dosing cohorts.
Pre-Dose Concentration (Ctrough) of PF-07295324 on Days 1 and 10 Pre-dose on Days 1 and 10 Ctrough was defined as pre-dose concentration. It was observed directly from data.
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 Rac(Cmax) was defined as observed accumulation ratio for Cmax and was determined by Cmax on Day 10/Cmax on Day 1. Cmax was defined as maximum plasma concentration. Accumulation ratios was not calculated due to Day 1 Cmax values below the limit of quantification.
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 Rac(AUCtau) was defined as observed accumulation ratio for AUCtau. AUCtau was defined as area under the plasma concentration-time profile from time zero to time tau, the dosing interval. tau = 12 hours for BID dosing cohorts and tau = 24 hours for QD dosing cohorts. Rac\[AUCtau\] was calculated by AUCtau on Day 10/AUCtau on Day 1 and accumulation ratios was not calculated due to Day 1 AUCtau values below the limit of quantification.
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 t1/2 was defined as terminal half-life. It was determined by Loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log linear concentration time curve.
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 CL/F was defined as aparent clearance. It was determined by Dose/AUCtau. AUCtau was area under the plasma concentration-time profile from time zero to time tau, the dosing interval (12 hours for BID cohorts and 24 hours for QD cohorts).
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 Cavg was defined as average plasma concentration. It was determined by AUCtau/tau; where tau was the dosing interval and AUCtau was area under the plasma concentration-time profile from time zero to time tau, the dosing interval. tau = 12 hours for BID dosing cohorts.
Ctrough of PF-07259955 on Days 1 and 10 Pre-dose on Days 1 and 10 Ctrough was defined as pre-dose concentration. It was observed directly from data.
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 Vz/F was defined as apparant volume of distribution. It was determined by Dose/(AUCtau \* kel). AUCtau was area under the plasma concentration-time profile from time zero to time tau, the dosing interval (12 hours for BID cohorts and 24 hours for QD cohorts). kel was the terminal phase rate constant calculated by a linear regression of the log linear concentration time curve.
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 Cmax was defined as maximum plasma concentration. It was observed directly from data.
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 Tmax was defined as time to reach maximum observed plasma concentration. It was observed directly from data.
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 AUCtau was defined as area under the plasma concentration-time profile from time zero to time tau, the dosing interval. tau = 12 hours for BID dosing cohorts.
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(Cmax) was defined as observed accumulation ratio for Cmax and was determined by Cmax on Day 10/Cmax on Day 1. Cmax was defined as maximum plasma concentration.
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 Rac(AUCtau) was defined as observed accumulation ratio for AUCtau. AUCtau was defined as area under the plasma concentration-time profile from time zero to time tau, the dosing interval. tau = 12 hours for BID dosing cohorts. Accumulation ratios was not calculated due to Day 1 AUCtau values below the limit of quantification.
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 t1/2 was defined as terminal half-life. It was determined by Loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log linear concentration time curve.
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 CL/F was defined as aparent clearance. It was determined by Dose/AUCtau. AUCtau was area under the plasma concentration-time profile from time zero to time tau, the dosing interval (12 hours for BID cohorts and 24 hours for QD cohorts).
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 Vz/F was defined as apparant volume of distribution. It was determined by Dose/(AUCtau \* kel). AUCtau was area under the plasma concentration-time profile from time zero to time tau, the dosing interval (12 hours for BID cohorts and 24 hours for QD cohorts). kel was the terminal phase rate constant calculated by a linear regression of the log linear concentration time curve.
Trial Locations
- Locations (1)
New Haven Clinical Research Unit
🇺🇸New Haven, Connecticut, United States