Healthy
Conditions
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.
Interventions
DRUGPF-07295324
Ointment
DRUGPF-07259955
Cream
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
Participants are eligible to be included in the study only if all of the following criteria apply: Age and Sex: 1. Healthy (except obese) female participants of non-childbearing potential and/or male participants, at the time of screening, must be 18 to 60 years of age, inclusive, at the time of signing the informed consent document (ICD). 2. Male and female of non-child bearing potential participants, who are healthy as determined by medical evaluation including medical history, physical examination, vital assessments, 12 lead ECGs, and laboratory tests. 3. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures. Weight: 4. Body mass index (BMI) of 17.5 to 35 kg/m2; and a total body weight \>50 kg (110 lb). 5. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICD and the protocol.
Exclusion criteria
Participants are excluded from the study if any of the following criteria apply: Medical Conditions: 1. Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, immunological/rheumatological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing). 2. Participants who have any visible skin damage or skin condition (eg sunburn, excessively deep tans, uneven skin tones, tattoos, scars, excessive hair, numerous freckles, or other disfigurations) in or around the application site which, in the opinion of the investigative personnel, will interfere with the evaluation of the test site reaction. 3. Participants who have a history of or have active AD/eczema/urticaria. 4. Evidence of active or latent or inadequately treated infection with Mycobacterium tuberculosis (TB) as defined by both of the following: * A positive QuantiFERON TB Gold In-tube or equivalent test (QFT). * History of either untreated or inadequately treated latent or active TB infection, or current treatment for the same. 5. History of HIV infection, hepatitis B, or hepatitis C; positive testing for HIV, hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb) or hepatitis C antibody (HCVAb). Hepatitis B vaccination is allowed. As an exception a positive HBsAb test due to hepatitis B vaccination is permissible. 6. Have a history of systemic infection requiring hospitalization, parenteral antimicrobial therapy, or as otherwise judged clinically significant by the investigator within 6 months prior to Day 1. 7. A history (single episode) of disseminated herpes zoster or disseminated herpes simplex, or a recurrent (more than one episode of) localized, dermatomal herpes zoster. 8. Acute disease state (unstable medical condition such as nausea, vomiting, fever or diarrhea, etc) within 7 days of Day 1. 9. Have any malignancies or have a history of malignancies with the exception of adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin. 10. Have a first-degree relative with hereditary immunodeficiency. 11. A history of any lymphoproliferative disorder (such as Epstein Barr Virus \[EBV\] -related lymphoproliferative disorder), history of lymphoma, leukemia, malignancies or signs and symptoms suggestive of current lymphatic disease. 12. Have undergone significant trauma or major surgery within 4 weeks of screening. 13. Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality or other conditions or situations related to COVID-19 pandemic (eg. Contact with positive case, residence, or travel to an area with high incidence) that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study. Prior/Concomitant Therapy: 14. Use of prescription or nonprescription drugs and dietary and herbal supplements within 7 days or 5 half lives (whichever is longer) prior to the first dose of study intervention. (Refer to Section 6.8 Concomitant Therapy for additional details). 15. Participants who are vaccinated with vaccines that have live components (or live attenuated vaccines) within the 6 weeks prior to the first dose of PF-07295324/vehicle or PF-07259955/vehicle or who are expected to be vaccinated during treatment or during follow-up period. NOTE regarding COVID vaccines with authorization or approval for emergency use: There is no requirement for washout of COVID vaccines prior to the first dose of PF-07295324/vehicle or PF-07259955/vehicle if the vaccine is not live attenuated (eg, mRNA, utilizing a viral vector,inactivated virus).There is no protocol-specified requirement for the interruption of IP dosing prior to or after vaccination if the COVID vaccine is not live attenuated. 16. Participants in any cohort of this study can only be randomized and receive the IP in only 1 cohort of this study. Prior/Concurrent Clinical Study Experience: 17. Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half lives preceding the first dose of study intervention used in this study (whichever is longer). Diagnostic Assessments: 18. A positive urine drug test. 19. Screening supine BP ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), following at least 5 minutes of supine rest. If BP is ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), the BP should be repeated 2 more times and the average of the 3 BP values should be used to determine the participant's eligibility. 20. Baseline 12 lead electrocardiogram (ECG) that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results (eg, baseline corrected QT (QTc) interval \>450 msec, complete left bundle branch block \[LBBB\], signs of an acute or indeterminate age myocardial infarction, ST T interval changes suggestive of myocardial ischemia, second or third degree atrioventricular \[AV\] block, or serious bradyarrhythmias or tachyarrhythmias). If the baseline uncorrected QT interval is \>450 msec, this interval should be rate corrected using the Fridericia method and the resulting QTcF should be used for decision making and reporting. If QTc exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated 2 more times and the average of the 3 QTc or QRS values should be used to determine the participant's eligibility. Computer interpreted ECGs should be overread by a physician experienced in reading ECGs before excluding participants. 21. Participants with ANY of the following abnormalities in clinical laboratory tests at screening, as assessed by the study specific laboratory and confirmed by a single repeat test, if deemed necessary: * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level ≥1.5 × upper limit of normal (ULN); * Total bilirubin level ≥1.5 × ULN; participants with a history of Gilbert's syndrome may have direct bilirubin measured and would be eligible for this study provided the direct bilirubin level is ≤ ULN. Other Exclusions: 22. History of alcohol abuse or binge drinking and/or any other illicit drug use or dependence within 6 months of Screening. Binge drinking is defined as a pattern of 5 (male) and 4 (female) or more alcoholic drinks in about 2 hours. As a general rule, alcohol intake should not exceed 14 units per week (1 unit = 8 ounces (240 mL) beer, 1 ounce (30 mL) of 40% spirit or 3 ounces (90 mL) of wine). 23. Use of tobacco/nicotine containing products more than 5 cigarettes/day. 24. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to dosing. 25. History of serious adverse reactions or hypersensitivity to any topical drug; or known allergy to any of the test product(s) or any components in the test product(s) or history of hypersensitivity; or allergic reactions to any of the study preparations as described in the PF-07295324 IB and PF-07259955 IB. 26. Not willing to refrain from shaving, the use of depilatories or other hair-removal activities, antiperspirants, lotions, skin creams, fragrances or perfumes, or body oils (eg, baby oil; coconut oil), use of hair products, hair gels, and hair oil in the treatment areas for 48 hours prior to admission to the CRU and for the duration of the stay in the CRU. 27. Unwilling or unable to comply with the criteria in the Lifestyle Considerations section of this protocol. 28. Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Pre-assignment details
Twenty-four participants were enrolled in the study, with 6 participants assigned to each of the 4 cohorts. All 24 participants were treated: 23 completed the study and 1 discontinued from the study due to non-compliance with study intervention.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 PF-07295324 0.12% Ointment BID Healthy participants in Cohort 1 randomized to active received 0.12% PF-07295324 ointment BID on approximately 20% BSA or 4000 cm\^2 of skin area for 10 days. | 4 |
| Cohort 1 PF-07295324 Vehicle Ointment BID Healthy participants in Cohort 1 randomized to vehicle received vehicle ointment BID on approximately 20% BSA or 4000 cm\^2 of skin area for 10 days. | 2 |
| Cohort 2 PF-07259955 2% Cream BID Healthy participants in Cohort 2 randomized to active received 2% PF-07259955 cream BID on approximately 20% BSA or 4000 cm\^2 of skin area for 10 days. | 4 |
| Cohort 2 PF-07259955 Vehicle Cream BID Healthy participants in Cohort 2 randomized to vehicle received vehicle cream BID on approximately 20% BSA or 4000 cm\^2 of skin area for 10 days. | 2 |
| Cohort 3 PF-07295324 0.12% Ointment BID Healthy participants in Cohort 3 randomized to active received 0.12% PF-07295324 ointment BID on approximately 20% BSA or 4000 cm\^2 of skin area for 10 days. | 4 |
| Cohort 3 PF-07295324 Vehicle Ointment BID Healthy participants in Cohort 3 randomized to vehicle received vehicle ointment BID on approximately 20% BSA or 4000 cm\^2 of skin area for 10 days. | 2 |
| Cohort 4 PF-07295324 0.12% Ointment QD Healthy participants in Cohort 4 randomized to active received 0.12% PF-07295324 ointment QD on approximately 20% BSA or 4000 cm\^2 of skin area for 10 days. | 4 |
| Cohort 4 PF-07295324 Vehicle Ointment QD Healthy participants in Cohort 4 randomized to vehicle received vehicle ointment QD on approximately 20% BSA or 4000 cm\^2 of skin area for 10 days. | 2 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Non-compliance with study drug | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Cohort 1 PF-07295324 0.12% Ointment BID | Cohort 1 PF-07295324 Vehicle Ointment BID | Cohort 2 PF-07259955 2% Cream BID | Cohort 2 PF-07259955 Vehicle Cream BID | Cohort 3 PF-07295324 0.12% Ointment BID | Cohort 3 PF-07295324 Vehicle Ointment BID | Cohort 4 PF-07295324 0.12% Ointment QD | Cohort 4 PF-07295324 Vehicle Ointment QD | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized 18 - 44 Years | 2 Participants | 2 Participants | 3 Participants | 0 Participants | 3 Participants | 1 Participants | 2 Participants | 2 Participants | 15 Participants |
| Age, Customized 45 - 60 Years | 2 Participants | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 9 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 1 Participants | 3 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants | 10 Participants |
| Race/Ethnicity, Customized Multiracial | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 3 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants | 1 Participants | 2 Participants | 0 Participants | 11 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 4 Participants |
| Sex: Female, Male Male | 4 Participants | 2 Participants | 4 Participants | 1 Participants | 3 Participants | 1 Participants | 3 Participants | 2 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 2 | 0 / 4 | 0 / 2 | 0 / 4 | 0 / 2 | 0 / 4 | 0 / 2 |
| other Total, other adverse events | 3 / 4 | 1 / 2 | 1 / 4 | 1 / 2 | 3 / 4 | 2 / 2 | 2 / 4 | 0 / 2 |
| serious Total, serious adverse events | 0 / 4 | 0 / 2 | 0 / 4 | 0 / 2 | 0 / 4 | 0 / 2 | 0 / 4 | 0 / 2 |
Outcome results
Primary
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
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.
Time frame: Baseline up to the end of follow up (ie, up to 44 days)
Population: All participants randomly assigned to study intervention and who are applied at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 PF-07295324 0.12% Ointment BID | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with treatment-related AEs | 3 Participants |
| Cohort 1 PF-07295324 0.12% Ointment BID | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 0 Participants |
| Cohort 1 PF-07295324 0.12% Ointment BID | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with treatment-related SAEs | 0 Participants |
| Cohort 1 PF-07295324 0.12% Ointment BID | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with AEs | 3 Participants |
| Cohort 1 PF-07295324 Vehicle Ointment BID | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with treatment-related SAEs | 0 Participants |
| Cohort 1 PF-07295324 Vehicle Ointment BID | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with AEs | 1 Participants |
| Cohort 1 PF-07295324 Vehicle Ointment BID | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with treatment-related AEs | 1 Participants |
| Cohort 1 PF-07295324 Vehicle Ointment BID | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 0 Participants |
| Cohort 2 PF-07259955 2% Cream BID | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with treatment-related AEs | 1 Participants |
| Cohort 2 PF-07259955 2% Cream BID | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with treatment-related SAEs | 0 Participants |
| Cohort 2 PF-07259955 2% Cream BID | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with AEs | 1 Participants |
| Cohort 2 PF-07259955 2% Cream BID | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 0 Participants |
| Cohort 2 PF-07259955 Vehicle Cream BID | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with treatment-related SAEs | 0 Participants |
| Cohort 2 PF-07259955 Vehicle Cream BID | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with AEs | 1 Participants |
| Cohort 2 PF-07259955 Vehicle Cream BID | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with treatment-related AEs | 0 Participants |
| Cohort 2 PF-07259955 Vehicle Cream BID | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 0 Participants |
| Cohort 3 PF-07295324 0.12% Ointment BID | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with treatment-related AEs | 3 Participants |
| Cohort 3 PF-07295324 0.12% Ointment BID | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with treatment-related SAEs | 0 Participants |
| Cohort 3 PF-07295324 0.12% Ointment BID | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with AEs | 3 Participants |
| Cohort 3 PF-07295324 0.12% Ointment BID | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 0 Participants |
| Cohort 3 PF-07295324 Vehicle Ointment BID | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with treatment-related AEs | 1 Participants |
| Cohort 3 PF-07295324 Vehicle Ointment BID | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 0 Participants |
| Cohort 3 PF-07295324 Vehicle Ointment BID | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with treatment-related SAEs | 0 Participants |
| Cohort 3 PF-07295324 Vehicle Ointment BID | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with AEs | 2 Participants |
| Cohort 4 PF-07295324 0.12% Ointment QD | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with treatment-related AEs | 1 Participants |
| Cohort 4 PF-07295324 0.12% Ointment QD | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with AEs | 2 Participants |
| Cohort 4 PF-07295324 0.12% Ointment QD | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 0 Participants |
| Cohort 4 PF-07295324 0.12% Ointment QD | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with treatment-related SAEs | 0 Participants |
| Cohort 4 PF-07295324 Vehicle Ointment QD | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with treatment-related AEs | 0 Participants |
| Cohort 4 PF-07295324 Vehicle Ointment QD | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with AEs | 0 Participants |
| Cohort 4 PF-07295324 Vehicle Ointment QD | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with treatment-related SAEs | 0 Participants |
| Cohort 4 PF-07295324 Vehicle Ointment QD | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 0 Participants |
Primary
Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Findings
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.
Time frame: At screening, on Days 1, 2, 5, 7, 10, 11, at discharge (Day 12), and at early termination if applicable
Population: All participants randomly assigned to study intervention and who are applied at least 1 dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 PF-07295324 0.12% Ointment BID | Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Findings | 0 Participants |
| Cohort 1 PF-07295324 Vehicle Ointment BID | Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Findings | 0 Participants |
| Cohort 2 PF-07259955 2% Cream BID | Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Findings | 0 Participants |
| Cohort 2 PF-07259955 Vehicle Cream BID | Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Findings | 0 Participants |
| Cohort 3 PF-07295324 0.12% Ointment BID | Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Findings | 0 Participants |
| Cohort 3 PF-07295324 Vehicle Ointment BID | Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Findings | 0 Participants |
| Cohort 4 PF-07295324 0.12% Ointment QD | Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Findings | 0 Participants |
| Cohort 4 PF-07295324 Vehicle Ointment QD | Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Findings | 0 Participants |
Primary
Number of Participants With Laboratory Abnormalities
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.
Time frame: At screening, admission (Day -1), on Days 5, 7, 10, at discharge (Day 12), and at early termination if applicable
Population: All participants randomly assigned to study intervention and who are applied at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 PF-07295324 0.12% Ointment BID | Number of Participants With Laboratory Abnormalities | Eosinophils/Leukocytes >1.2*upper limit of normal (ULN) | 0 Participants |
| Cohort 1 PF-07295324 0.12% Ointment BID | Number of Participants With Laboratory Abnormalities | Neutrophils/Leukocytes <0.8*LLN | 0 Participants |
| Cohort 1 PF-07295324 0.12% Ointment BID | Number of Participants With Laboratory Abnormalities | Urate >1.2*ULN | 0 Participants |
| Cohort 1 PF-07295324 0.12% Ointment BID | Number of Participants With Laboratory Abnormalities | Monocytes/Leukocytes >1.2*ULN | 1 Participants |
| Cohort 1 PF-07295324 0.12% Ointment BID | Number of Participants With Laboratory Abnormalities | URINE Bilirubin >=1 | 0 Participants |
| Cohort 1 PF-07295324 0.12% Ointment BID | Number of Participants With Laboratory Abnormalities | Potassium >1.1*ULN | 0 Participants |
| Cohort 1 PF-07295324 0.12% Ointment BID | Number of Participants With Laboratory Abnormalities | Leukocyte Esterase >=1 | 0 Participants |
| Cohort 1 PF-07295324 0.12% Ointment BID | Number of Participants With Laboratory Abnormalities | Bicarbonate < 0.9*LLN | 0 Participants |
| Cohort 1 PF-07295324 0.12% Ointment BID | Number of Participants With Laboratory Abnormalities | Neutrophils <0.8*lower limit of normal (LLN) | 0 Participants |
| Cohort 1 PF-07295324 Vehicle Ointment BID | Number of Participants With Laboratory Abnormalities | Urate >1.2*ULN | 0 Participants |
| Cohort 1 PF-07295324 Vehicle Ointment BID | Number of Participants With Laboratory Abnormalities | Monocytes/Leukocytes >1.2*ULN | 1 Participants |
| Cohort 1 PF-07295324 Vehicle Ointment BID | Number of Participants With Laboratory Abnormalities | Neutrophils <0.8*lower limit of normal (LLN) | 0 Participants |
| Cohort 1 PF-07295324 Vehicle Ointment BID | Number of Participants With Laboratory Abnormalities | Leukocyte Esterase >=1 | 0 Participants |
| Cohort 1 PF-07295324 Vehicle Ointment BID | Number of Participants With Laboratory Abnormalities | URINE Bilirubin >=1 | 0 Participants |
| Cohort 1 PF-07295324 Vehicle Ointment BID | Number of Participants With Laboratory Abnormalities | Neutrophils/Leukocytes <0.8*LLN | 0 Participants |
| Cohort 1 PF-07295324 Vehicle Ointment BID | Number of Participants With Laboratory Abnormalities | Bicarbonate < 0.9*LLN | 0 Participants |
| Cohort 1 PF-07295324 Vehicle Ointment BID | Number of Participants With Laboratory Abnormalities | Potassium >1.1*ULN | 0 Participants |
| Cohort 1 PF-07295324 Vehicle Ointment BID | Number of Participants With Laboratory Abnormalities | Eosinophils/Leukocytes >1.2*upper limit of normal (ULN) | 0 Participants |
| Cohort 2 PF-07259955 2% Cream BID | Number of Participants With Laboratory Abnormalities | Urate >1.2*ULN | 0 Participants |
| Cohort 2 PF-07259955 2% Cream BID | Number of Participants With Laboratory Abnormalities | URINE Bilirubin >=1 | 0 Participants |
| Cohort 2 PF-07259955 2% Cream BID | Number of Participants With Laboratory Abnormalities | Potassium >1.1*ULN | 0 Participants |
| Cohort 2 PF-07259955 2% Cream BID | Number of Participants With Laboratory Abnormalities | Eosinophils/Leukocytes >1.2*upper limit of normal (ULN) | 1 Participants |
| Cohort 2 PF-07259955 2% Cream BID | Number of Participants With Laboratory Abnormalities | Leukocyte Esterase >=1 | 0 Participants |
| Cohort 2 PF-07259955 2% Cream BID | Number of Participants With Laboratory Abnormalities | Bicarbonate < 0.9*LLN | 0 Participants |
| Cohort 2 PF-07259955 2% Cream BID | Number of Participants With Laboratory Abnormalities | Neutrophils <0.8*lower limit of normal (LLN) | 0 Participants |
| Cohort 2 PF-07259955 2% Cream BID | Number of Participants With Laboratory Abnormalities | Monocytes/Leukocytes >1.2*ULN | 1 Participants |
| Cohort 2 PF-07259955 2% Cream BID | Number of Participants With Laboratory Abnormalities | Neutrophils/Leukocytes <0.8*LLN | 0 Participants |
| Cohort 2 PF-07259955 Vehicle Cream BID | Number of Participants With Laboratory Abnormalities | Neutrophils/Leukocytes <0.8*LLN | 0 Participants |
| Cohort 2 PF-07259955 Vehicle Cream BID | Number of Participants With Laboratory Abnormalities | Eosinophils/Leukocytes >1.2*upper limit of normal (ULN) | 0 Participants |
| Cohort 2 PF-07259955 Vehicle Cream BID | Number of Participants With Laboratory Abnormalities | Monocytes/Leukocytes >1.2*ULN | 1 Participants |
| Cohort 2 PF-07259955 Vehicle Cream BID | Number of Participants With Laboratory Abnormalities | Neutrophils <0.8*lower limit of normal (LLN) | 0 Participants |
| Cohort 2 PF-07259955 Vehicle Cream BID | Number of Participants With Laboratory Abnormalities | Urate >1.2*ULN | 1 Participants |
| Cohort 2 PF-07259955 Vehicle Cream BID | Number of Participants With Laboratory Abnormalities | Potassium >1.1*ULN | 1 Participants |
| Cohort 2 PF-07259955 Vehicle Cream BID | Number of Participants With Laboratory Abnormalities | Bicarbonate < 0.9*LLN | 0 Participants |
| Cohort 2 PF-07259955 Vehicle Cream BID | Number of Participants With Laboratory Abnormalities | URINE Bilirubin >=1 | 0 Participants |
| Cohort 2 PF-07259955 Vehicle Cream BID | Number of Participants With Laboratory Abnormalities | Leukocyte Esterase >=1 | 0 Participants |
| Cohort 3 PF-07295324 0.12% Ointment BID | Number of Participants With Laboratory Abnormalities | Eosinophils/Leukocytes >1.2*upper limit of normal (ULN) | 0 Participants |
| Cohort 3 PF-07295324 0.12% Ointment BID | Number of Participants With Laboratory Abnormalities | Urate >1.2*ULN | 1 Participants |
| Cohort 3 PF-07295324 0.12% Ointment BID | Number of Participants With Laboratory Abnormalities | Potassium >1.1*ULN | 0 Participants |
| Cohort 3 PF-07295324 0.12% Ointment BID | Number of Participants With Laboratory Abnormalities | Neutrophils/Leukocytes <0.8*LLN | 0 Participants |
| Cohort 3 PF-07295324 0.12% Ointment BID | Number of Participants With Laboratory Abnormalities | Leukocyte Esterase >=1 | 0 Participants |
| Cohort 3 PF-07295324 0.12% Ointment BID | Number of Participants With Laboratory Abnormalities | Bicarbonate < 0.9*LLN | 1 Participants |
| Cohort 3 PF-07295324 0.12% Ointment BID | Number of Participants With Laboratory Abnormalities | Neutrophils <0.8*lower limit of normal (LLN) | 0 Participants |
| Cohort 3 PF-07295324 0.12% Ointment BID | Number of Participants With Laboratory Abnormalities | URINE Bilirubin >=1 | 0 Participants |
| Cohort 3 PF-07295324 0.12% Ointment BID | Number of Participants With Laboratory Abnormalities | Monocytes/Leukocytes >1.2*ULN | 0 Participants |
| Cohort 3 PF-07295324 Vehicle Ointment BID | Number of Participants With Laboratory Abnormalities | Eosinophils/Leukocytes >1.2*upper limit of normal (ULN) | 0 Participants |
| Cohort 3 PF-07295324 Vehicle Ointment BID | Number of Participants With Laboratory Abnormalities | Bicarbonate < 0.9*LLN | 0 Participants |
| Cohort 3 PF-07295324 Vehicle Ointment BID | Number of Participants With Laboratory Abnormalities | Potassium >1.1*ULN | 0 Participants |
| Cohort 3 PF-07295324 Vehicle Ointment BID | Number of Participants With Laboratory Abnormalities | Neutrophils <0.8*lower limit of normal (LLN) | 0 Participants |
| Cohort 3 PF-07295324 Vehicle Ointment BID | Number of Participants With Laboratory Abnormalities | Monocytes/Leukocytes >1.2*ULN | 0 Participants |
| Cohort 3 PF-07295324 Vehicle Ointment BID | Number of Participants With Laboratory Abnormalities | Urate >1.2*ULN | 0 Participants |
| Cohort 3 PF-07295324 Vehicle Ointment BID | Number of Participants With Laboratory Abnormalities | Leukocyte Esterase >=1 | 1 Participants |
| Cohort 3 PF-07295324 Vehicle Ointment BID | Number of Participants With Laboratory Abnormalities | Neutrophils/Leukocytes <0.8*LLN | 0 Participants |
| Cohort 3 PF-07295324 Vehicle Ointment BID | Number of Participants With Laboratory Abnormalities | URINE Bilirubin >=1 | 0 Participants |
| Cohort 4 PF-07295324 0.12% Ointment QD | Number of Participants With Laboratory Abnormalities | Monocytes/Leukocytes >1.2*ULN | 1 Participants |
| Cohort 4 PF-07295324 0.12% Ointment QD | Number of Participants With Laboratory Abnormalities | Neutrophils <0.8*lower limit of normal (LLN) | 0 Participants |
| Cohort 4 PF-07295324 0.12% Ointment QD | Number of Participants With Laboratory Abnormalities | Urate >1.2*ULN | 0 Participants |
| Cohort 4 PF-07295324 0.12% Ointment QD | Number of Participants With Laboratory Abnormalities | Neutrophils/Leukocytes <0.8*LLN | 0 Participants |
| Cohort 4 PF-07295324 0.12% Ointment QD | Number of Participants With Laboratory Abnormalities | URINE Bilirubin >=1 | 1 Participants |
| Cohort 4 PF-07295324 0.12% Ointment QD | Number of Participants With Laboratory Abnormalities | Potassium >1.1*ULN | 0 Participants |
| Cohort 4 PF-07295324 0.12% Ointment QD | Number of Participants With Laboratory Abnormalities | Bicarbonate < 0.9*LLN | 0 Participants |
| Cohort 4 PF-07295324 0.12% Ointment QD | Number of Participants With Laboratory Abnormalities | Leukocyte Esterase >=1 | 0 Participants |
| Cohort 4 PF-07295324 0.12% Ointment QD | Number of Participants With Laboratory Abnormalities | Eosinophils/Leukocytes >1.2*upper limit of normal (ULN) | 0 Participants |
| Cohort 4 PF-07295324 Vehicle Ointment QD | Number of Participants With Laboratory Abnormalities | Monocytes/Leukocytes >1.2*ULN | 0 Participants |
| Cohort 4 PF-07295324 Vehicle Ointment QD | Number of Participants With Laboratory Abnormalities | Potassium >1.1*ULN | 0 Participants |
| Cohort 4 PF-07295324 Vehicle Ointment QD | Number of Participants With Laboratory Abnormalities | Neutrophils <0.8*lower limit of normal (LLN) | 1 Participants |
| Cohort 4 PF-07295324 Vehicle Ointment QD | Number of Participants With Laboratory Abnormalities | Bicarbonate < 0.9*LLN | 0 Participants |
| Cohort 4 PF-07295324 Vehicle Ointment QD | Number of Participants With Laboratory Abnormalities | Leukocyte Esterase >=1 | 0 Participants |
| Cohort 4 PF-07295324 Vehicle Ointment QD | Number of Participants With Laboratory Abnormalities | Eosinophils/Leukocytes >1.2*upper limit of normal (ULN) | 0 Participants |
| Cohort 4 PF-07295324 Vehicle Ointment QD | Number of Participants With Laboratory Abnormalities | URINE Bilirubin >=1 | 0 Participants |
| Cohort 4 PF-07295324 Vehicle Ointment QD | Number of Participants With Laboratory Abnormalities | Urate >1.2*ULN | 0 Participants |
| Cohort 4 PF-07295324 Vehicle Ointment QD | Number of Participants With Laboratory Abnormalities | Neutrophils/Leukocytes <0.8*LLN | 1 Participants |
Primary
Number of Participants With Vital Signs Abnormalities
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.
Time frame: At screening, on Days 1, 2, 5, 7, 10, 11, at discharge (Day 12), and at early termination if applicable
Population: All participants randomly assigned to study intervention and who are applied at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 PF-07295324 0.12% Ointment BID | Number of Participants With Vital Signs Abnormalities | Systolic blood pressure decrease >=30 mmHg | 1 Participants |
| Cohort 1 PF-07295324 0.12% Ointment BID | Number of Participants With Vital Signs Abnormalities | Diastolic blood pressure increase >=20 mmHg | 1 Participants |
| Cohort 1 PF-07295324 0.12% Ointment BID | Number of Participants With Vital Signs Abnormalities | Diastolic blood pressure decrease >=20 mmHg | 1 Participants |
| Cohort 1 PF-07295324 Vehicle Ointment BID | Number of Participants With Vital Signs Abnormalities | Systolic blood pressure decrease >=30 mmHg | 0 Participants |
| Cohort 1 PF-07295324 Vehicle Ointment BID | Number of Participants With Vital Signs Abnormalities | Diastolic blood pressure increase >=20 mmHg | 0 Participants |
| Cohort 1 PF-07295324 Vehicle Ointment BID | Number of Participants With Vital Signs Abnormalities | Diastolic blood pressure decrease >=20 mmHg | 1 Participants |
| Cohort 2 PF-07259955 2% Cream BID | Number of Participants With Vital Signs Abnormalities | Diastolic blood pressure decrease >=20 mmHg | 0 Participants |
| Cohort 2 PF-07259955 2% Cream BID | Number of Participants With Vital Signs Abnormalities | Diastolic blood pressure increase >=20 mmHg | 1 Participants |
| Cohort 2 PF-07259955 2% Cream BID | Number of Participants With Vital Signs Abnormalities | Systolic blood pressure decrease >=30 mmHg | 0 Participants |
| Cohort 2 PF-07259955 Vehicle Cream BID | Number of Participants With Vital Signs Abnormalities | Diastolic blood pressure increase >=20 mmHg | 0 Participants |
| Cohort 2 PF-07259955 Vehicle Cream BID | Number of Participants With Vital Signs Abnormalities | Systolic blood pressure decrease >=30 mmHg | 0 Participants |
| Cohort 2 PF-07259955 Vehicle Cream BID | Number of Participants With Vital Signs Abnormalities | Diastolic blood pressure decrease >=20 mmHg | 0 Participants |
| Cohort 3 PF-07295324 0.12% Ointment BID | Number of Participants With Vital Signs Abnormalities | Systolic blood pressure decrease >=30 mmHg | 0 Participants |
| Cohort 3 PF-07295324 0.12% Ointment BID | Number of Participants With Vital Signs Abnormalities | Diastolic blood pressure increase >=20 mmHg | 0 Participants |
| Cohort 3 PF-07295324 0.12% Ointment BID | Number of Participants With Vital Signs Abnormalities | Diastolic blood pressure decrease >=20 mmHg | 0 Participants |
| Cohort 3 PF-07295324 Vehicle Ointment BID | Number of Participants With Vital Signs Abnormalities | Diastolic blood pressure decrease >=20 mmHg | 0 Participants |
| Cohort 3 PF-07295324 Vehicle Ointment BID | Number of Participants With Vital Signs Abnormalities | Systolic blood pressure decrease >=30 mmHg | 0 Participants |
| Cohort 3 PF-07295324 Vehicle Ointment BID | Number of Participants With Vital Signs Abnormalities | Diastolic blood pressure increase >=20 mmHg | 0 Participants |
| Cohort 4 PF-07295324 0.12% Ointment QD | Number of Participants With Vital Signs Abnormalities | Diastolic blood pressure increase >=20 mmHg | 0 Participants |
| Cohort 4 PF-07295324 0.12% Ointment QD | Number of Participants With Vital Signs Abnormalities | Systolic blood pressure decrease >=30 mmHg | 0 Participants |
| Cohort 4 PF-07295324 0.12% Ointment QD | Number of Participants With Vital Signs Abnormalities | Diastolic blood pressure decrease >=20 mmHg | 0 Participants |
| Cohort 4 PF-07295324 Vehicle Ointment QD | Number of Participants With Vital Signs Abnormalities | Systolic blood pressure decrease >=30 mmHg | 0 Participants |
| Cohort 4 PF-07295324 Vehicle Ointment QD | Number of Participants With Vital Signs Abnormalities | Diastolic blood pressure increase >=20 mmHg | 0 Participants |
| Cohort 4 PF-07295324 Vehicle Ointment QD | Number of Participants With Vital Signs Abnormalities | Diastolic blood pressure decrease >=20 mmHg | 0 Participants |
Primary
Skin Irritation Assessments Using Draize Scoring
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.
Time frame: Screening up to Day 12 or early termination if applicable
Population: All participants randomly assigned to study intervention and who are applied at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 PF-07295324 0.12% Ointment BID | Skin Irritation Assessments Using Draize Scoring | Draize Score = 0 | 2 Participants |
| Cohort 1 PF-07295324 0.12% Ointment BID | Skin Irritation Assessments Using Draize Scoring | Draize Score = 4 | 0 Participants |
| Cohort 1 PF-07295324 0.12% Ointment BID | Skin Irritation Assessments Using Draize Scoring | Draize Score = 3 | 0 Participants |
| Cohort 1 PF-07295324 0.12% Ointment BID | Skin Irritation Assessments Using Draize Scoring | Draize Score = 2 | 2 Participants |
| Cohort 1 PF-07295324 0.12% Ointment BID | Skin Irritation Assessments Using Draize Scoring | Draize Score = 1 | 0 Participants |
| Cohort 1 PF-07295324 Vehicle Ointment BID | Skin Irritation Assessments Using Draize Scoring | Draize Score = 1 | 0 Participants |
| Cohort 1 PF-07295324 Vehicle Ointment BID | Skin Irritation Assessments Using Draize Scoring | Draize Score = 0 | 2 Participants |
| Cohort 1 PF-07295324 Vehicle Ointment BID | Skin Irritation Assessments Using Draize Scoring | Draize Score = 2 | 0 Participants |
| Cohort 1 PF-07295324 Vehicle Ointment BID | Skin Irritation Assessments Using Draize Scoring | Draize Score = 3 | 0 Participants |
| Cohort 1 PF-07295324 Vehicle Ointment BID | Skin Irritation Assessments Using Draize Scoring | Draize Score = 4 | 0 Participants |
| Cohort 2 PF-07259955 2% Cream BID | Skin Irritation Assessments Using Draize Scoring | Draize Score = 2 | 0 Participants |
| Cohort 2 PF-07259955 2% Cream BID | Skin Irritation Assessments Using Draize Scoring | Draize Score = 0 | 4 Participants |
| Cohort 2 PF-07259955 2% Cream BID | Skin Irritation Assessments Using Draize Scoring | Draize Score = 4 | 0 Participants |
| Cohort 2 PF-07259955 2% Cream BID | Skin Irritation Assessments Using Draize Scoring | Draize Score = 1 | 0 Participants |
| Cohort 2 PF-07259955 2% Cream BID | Skin Irritation Assessments Using Draize Scoring | Draize Score = 3 | 0 Participants |
| Cohort 2 PF-07259955 Vehicle Cream BID | Skin Irritation Assessments Using Draize Scoring | Draize Score = 0 | 2 Participants |
| Cohort 2 PF-07259955 Vehicle Cream BID | Skin Irritation Assessments Using Draize Scoring | Draize Score = 2 | 0 Participants |
| Cohort 2 PF-07259955 Vehicle Cream BID | Skin Irritation Assessments Using Draize Scoring | Draize Score = 1 | 0 Participants |
| Cohort 2 PF-07259955 Vehicle Cream BID | Skin Irritation Assessments Using Draize Scoring | Draize Score = 3 | 0 Participants |
| Cohort 2 PF-07259955 Vehicle Cream BID | Skin Irritation Assessments Using Draize Scoring | Draize Score = 4 | 0 Participants |
| Cohort 3 PF-07295324 0.12% Ointment BID | Skin Irritation Assessments Using Draize Scoring | Draize Score = 4 | 0 Participants |
| Cohort 3 PF-07295324 0.12% Ointment BID | Skin Irritation Assessments Using Draize Scoring | Draize Score = 3 | 0 Participants |
| Cohort 3 PF-07295324 0.12% Ointment BID | Skin Irritation Assessments Using Draize Scoring | Draize Score = 2 | 0 Participants |
| Cohort 3 PF-07295324 0.12% Ointment BID | Skin Irritation Assessments Using Draize Scoring | Draize Score = 0 | 4 Participants |
| Cohort 3 PF-07295324 0.12% Ointment BID | Skin Irritation Assessments Using Draize Scoring | Draize Score = 1 | 0 Participants |
| Cohort 3 PF-07295324 Vehicle Ointment BID | Skin Irritation Assessments Using Draize Scoring | Draize Score = 3 | 0 Participants |
| Cohort 3 PF-07295324 Vehicle Ointment BID | Skin Irritation Assessments Using Draize Scoring | Draize Score = 2 | 0 Participants |
| Cohort 3 PF-07295324 Vehicle Ointment BID | Skin Irritation Assessments Using Draize Scoring | Draize Score = 1 | 0 Participants |
| Cohort 3 PF-07295324 Vehicle Ointment BID | Skin Irritation Assessments Using Draize Scoring | Draize Score = 4 | 0 Participants |
| Cohort 3 PF-07295324 Vehicle Ointment BID | Skin Irritation Assessments Using Draize Scoring | Draize Score = 0 | 2 Participants |
| Cohort 4 PF-07295324 0.12% Ointment QD | Skin Irritation Assessments Using Draize Scoring | Draize Score = 2 | 0 Participants |
| Cohort 4 PF-07295324 0.12% Ointment QD | Skin Irritation Assessments Using Draize Scoring | Draize Score = 3 | 0 Participants |
| Cohort 4 PF-07295324 0.12% Ointment QD | Skin Irritation Assessments Using Draize Scoring | Draize Score = 0 | 4 Participants |
| Cohort 4 PF-07295324 0.12% Ointment QD | Skin Irritation Assessments Using Draize Scoring | Draize Score = 4 | 0 Participants |
| Cohort 4 PF-07295324 0.12% Ointment QD | Skin Irritation Assessments Using Draize Scoring | Draize Score = 1 | 0 Participants |
| Cohort 4 PF-07295324 Vehicle Ointment QD | Skin Irritation Assessments Using Draize Scoring | Draize Score = 0 | 2 Participants |
| Cohort 4 PF-07295324 Vehicle Ointment QD | Skin Irritation Assessments Using Draize Scoring | Draize Score = 1 | 0 Participants |
| Cohort 4 PF-07295324 Vehicle Ointment QD | Skin Irritation Assessments Using Draize Scoring | Draize Score = 3 | 0 Participants |
| Cohort 4 PF-07295324 Vehicle Ointment QD | Skin Irritation Assessments Using Draize Scoring | Draize Score = 4 | 0 Participants |
| Cohort 4 PF-07295324 Vehicle Ointment QD | Skin Irritation Assessments Using Draize Scoring | Draize Score = 2 | 0 Participants |
Secondary
Apparent Clearance (CL/F) of PF-07295324 on Day 10
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).
Time frame: 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
Population: All participants randomly assigned to study intervention who received an application of PF-07295324 and who had at least 1 of the PK parameters of interest calculated.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Cohort 1 PF-07295324 0.12% Ointment BID | Apparent Clearance (CL/F) of PF-07295324 on Day 10 | NA L/hr |
| Cohort 2 PF-07259955 2% Cream BID | Apparent Clearance (CL/F) of PF-07295324 on Day 10 | NA L/hr |
Secondary
Apparent Volume of Distribution (Vz/F) of PF-07295324 on Day 10
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.
Time frame: 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
Population: All participants randomly assigned to study intervention who received an application of PF-07295324 and who had at least 1 of the PK parameters of interest calculated. None of the participants had reportable parameter values.
Secondary
Area Under the Concentration-Time Profile From Time Zero to the Dosing Interval Tau (AUCtau) of PF-07295324 on Days 1 and 10
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.
Time frame: On Days 1 and 10 at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after application
Population: All participants randomly assigned to study intervention who received an application of PF-07295324 and who had at least 1 of the PK parameters of interest calculated. In overall number of participants analyzed, the total number of participants in each treatment group was presented, and in number analyzed, the number of participants contributing to the data was presented.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 PF-07295324 0.12% Ointment BID | Area Under the Concentration-Time Profile From Time Zero to the Dosing Interval Tau (AUCtau) of PF-07295324 on Days 1 and 10 | Day 1 | 0.0001000 ng*hr/mL | Geometric Coefficient of Variation 0 |
| Cohort 1 PF-07295324 0.12% Ointment BID | Area Under the Concentration-Time Profile From Time Zero to the Dosing Interval Tau (AUCtau) of PF-07295324 on Days 1 and 10 | Day 10 | 0.001262 ng*hr/mL | Geometric Coefficient of Variation 1539186 |
| Cohort 1 PF-07295324 Vehicle Ointment BID | Area Under the Concentration-Time Profile From Time Zero to the Dosing Interval Tau (AUCtau) of PF-07295324 on Days 1 and 10 | Day 1 | 0.0001000 ng*hr/mL | Geometric Coefficient of Variation 0 |
| Cohort 1 PF-07295324 Vehicle Ointment BID | Area Under the Concentration-Time Profile From Time Zero to the Dosing Interval Tau (AUCtau) of PF-07295324 on Days 1 and 10 | Day 10 | NA ng*hr/mL | — |
| Cohort 2 PF-07259955 2% Cream BID | Area Under the Concentration-Time Profile From Time Zero to the Dosing Interval Tau (AUCtau) of PF-07295324 on Days 1 and 10 | Day 1 | 0.0001000 ng*hr/mL | Geometric Coefficient of Variation 0 |
| Cohort 2 PF-07259955 2% Cream BID | Area Under the Concentration-Time Profile From Time Zero to the Dosing Interval Tau (AUCtau) of PF-07295324 on Days 1 and 10 | Day 10 | 0.002037 ng*hr/mL | Geometric Coefficient of Variation 82741202 |
Secondary
AUCtau of PF-07259955 on Days 1 and 10
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.
Time frame: On Days 1 and 10 at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after application
Population: All participants randomly assigned to study intervention who received an application of PF-07259955 and who had at least 1 of the PK parameters of interest calculated.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 PF-07295324 0.12% Ointment BID | AUCtau of PF-07259955 on Days 1 and 10 | Day 1 | 0.0001000 ng*hr/mL | Geometric Coefficient of Variation 0 |
| Cohort 1 PF-07295324 0.12% Ointment BID | AUCtau of PF-07259955 on Days 1 and 10 | Day 10 | 46.48 ng*hr/mL | Geometric Coefficient of Variation 38 |
Secondary
Average Plasma Concentration (Cavg) of PF-07295324 on Days 1 and 10
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.
Time frame: On Days 1 and 10 at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after application
Population: All participants randomly assigned to study intervention who received an application of PF-07295324 and who had at least 1 of the PK parameters of interest calculated. In overall number of participants analyzed, the total number of participants in each treatment group was presented, and in number analyzed, the number of participants contributing to the data was presented.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 PF-07295324 0.12% Ointment BID | Average Plasma Concentration (Cavg) of PF-07295324 on Days 1 and 10 | Day 10 | 0.0005518 ng/mL | Geometric Coefficient of Variation 7950 |
| Cohort 1 PF-07295324 Vehicle Ointment BID | Average Plasma Concentration (Cavg) of PF-07295324 on Days 1 and 10 | Day 10 | NA ng/mL | — |
| Cohort 2 PF-07259955 2% Cream BID | Average Plasma Concentration (Cavg) of PF-07295324 on Days 1 and 10 | Day 10 | 0.0007061 ng/mL | Geometric Coefficient of Variation 30808 |
| Unknown | Average Plasma Concentration (Cavg) of PF-07295324 on Days 1 and 10 | Day 1 | — ng/mL | — |
Secondary
Cavg of PF-07259955 on Days 1 and 10
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.
Time frame: On Days 1 and 10 at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after application
Population: All participants randomly assigned to study intervention who received an application of PF-07259955 and who had at least 1 of the PK parameters of interest calculated.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 PF-07295324 0.12% Ointment BID | Cavg of PF-07259955 on Days 1 and 10 | Day 10 | 3.873 ng/mL | Geometric Coefficient of Variation 38 |
| Unknown | Cavg of PF-07259955 on Days 1 and 10 | Day 1 | — ng/mL | — |
Secondary
CL/F of PF-07259955 on Day 10
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).
Time frame: 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
Population: All participants randomly assigned to study intervention who received an application of PF-07259955 and who had at least 1 of the PK parameters of interest calculated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 PF-07295324 0.12% Ointment BID | CL/F of PF-07259955 on Day 10 | 3441 L/hr | Geometric Coefficient of Variation 38 |
Secondary
Cmax of PF-07259955 on Days 1 and 10
Cmax was defined as maximum plasma concentration. It was observed directly from data.
Time frame: On Days 1 and 10 at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after application
Population: All participants randomly assigned to study intervention who received an application of PF-07259955 and who had at least 1 of the PK parameters of interest calculated.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 PF-07295324 0.12% Ointment BID | Cmax of PF-07259955 on Days 1 and 10 | Day 1 | 0.001161 ng/mL | Geometric Coefficient of Variation 16729163 |
| Cohort 1 PF-07295324 0.12% Ointment BID | Cmax of PF-07259955 on Days 1 and 10 | Day 10 | 4.942 ng/mL | Geometric Coefficient of Variation 42 |
Secondary
Ctrough of PF-07259955 on Days 1 and 10
Ctrough was defined as pre-dose concentration. It was observed directly from data.
Time frame: Pre-dose on Days 1 and 10
Population: All participants randomly assigned to study intervention who received an application of PF-07259955 and who had at least 1 of the PK parameters of interest calculated.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 PF-07295324 0.12% Ointment BID | Ctrough of PF-07259955 on Days 1 and 10 | Day 1 | 0.0001000 ng/mL | Geometric Coefficient of Variation 0 |
| Cohort 1 PF-07295324 0.12% Ointment BID | Ctrough of PF-07259955 on Days 1 and 10 | Day 10 | 4.077 ng/mL | Geometric Coefficient of Variation 41 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of PF-07295324 on Days 1 and 10
Cmax was defined as maximum plasma concentration. It was observed directly from data.
Time frame: On Days 1 and 10 at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after application
Population: All participants randomly assigned to study intervention who received an application of PF-07295324 and who had at least 1 of the PK parameters of interest calculated.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 PF-07295324 0.12% Ointment BID | Maximum Observed Plasma Concentration (Cmax) of PF-07295324 on Days 1 and 10 | Day 1 | 0.0001000 ng/mL | Geometric Coefficient of Variation 0 |
| Cohort 1 PF-07295324 0.12% Ointment BID | Maximum Observed Plasma Concentration (Cmax) of PF-07295324 on Days 1 and 10 | Day 10 | 0.001655 ng/mL | Geometric Coefficient of Variation 19579 |
| Cohort 1 PF-07295324 Vehicle Ointment BID | Maximum Observed Plasma Concentration (Cmax) of PF-07295324 on Days 1 and 10 | Day 1 | 0.0001000 ng/mL | Geometric Coefficient of Variation 0 |
| Cohort 1 PF-07295324 Vehicle Ointment BID | Maximum Observed Plasma Concentration (Cmax) of PF-07295324 on Days 1 and 10 | Day 10 | 0.001502 ng/mL | Geometric Coefficient of Variation 13373 |
| Cohort 2 PF-07259955 2% Cream BID | Maximum Observed Plasma Concentration (Cmax) of PF-07295324 on Days 1 and 10 | Day 1 | 0.0001000 ng/mL | Geometric Coefficient of Variation 0 |
| Cohort 2 PF-07259955 2% Cream BID | Maximum Observed Plasma Concentration (Cmax) of PF-07295324 on Days 1 and 10 | Day 10 | 0.002006 ng/mL | Geometric Coefficient of Variation 40943 |
Secondary
Observed Accumulation Ratio for AUCtau (Rac[AUCtau]) of PF-07295324 on Day 10
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.
Time frame: On Days 1 and 10 at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after application
Population: All participants randomly assigned to study intervention who received an application of PF-07295324 and who had at least 1 of the PK parameters of interest calculated.
Secondary
Observed Accumulation Ratio for Cmax (Rac[Cmax]) of PF-07295324 on Day 10
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.
Time frame: On Days 1 and 10 at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after application
Population: All participants randomly assigned to study intervention who received an application of PF-07295324 and who had at least 1 of the PK parameters of interest calculated.
Secondary
Pre-Dose Concentration (Ctrough) of PF-07295324 on Days 1 and 10
Ctrough was defined as pre-dose concentration. It was observed directly from data.
Time frame: Pre-dose on Days 1 and 10
Population: All participants randomly assigned to study intervention who received an application of PF-07295324 and who had at least 1 of the PK parameters of interest calculated.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 PF-07295324 0.12% Ointment BID | Pre-Dose Concentration (Ctrough) of PF-07295324 on Days 1 and 10 | Day 10 (0 hour) | 0.00010008 ng/mL | Geometric Coefficient of Variation 0 |
| Cohort 1 PF-07295324 0.12% Ointment BID | Pre-Dose Concentration (Ctrough) of PF-07295324 on Days 1 and 10 | Day 1 | 0.0001000 ng/mL | Geometric Coefficient of Variation 0 |
| Cohort 1 PF-07295324 0.12% Ointment BID | Pre-Dose Concentration (Ctrough) of PF-07295324 on Days 1 and 10 | Day 10 (12 hour) | 0.0001000 ng/mL | Geometric Coefficient of Variation 0 |
| Cohort 1 PF-07295324 Vehicle Ointment BID | Pre-Dose Concentration (Ctrough) of PF-07295324 on Days 1 and 10 | Day 10 (12 hour) | 0.0001000 ng/mL | Geometric Coefficient of Variation 0 |
| Cohort 1 PF-07295324 Vehicle Ointment BID | Pre-Dose Concentration (Ctrough) of PF-07295324 on Days 1 and 10 | Day 1 | 0.0001000 ng/mL | Geometric Coefficient of Variation 0 |
| Cohort 1 PF-07295324 Vehicle Ointment BID | Pre-Dose Concentration (Ctrough) of PF-07295324 on Days 1 and 10 | Day 10 (0 hour) | 0.0003784 ng/mL | Geometric Coefficient of Variation 3451 |
| Cohort 2 PF-07259955 2% Cream BID | Pre-Dose Concentration (Ctrough) of PF-07295324 on Days 1 and 10 | Day 10 (0 hour) | 0.0004395 ng/mL | Geometric Coefficient of Variation 8008 |
| Cohort 2 PF-07259955 2% Cream BID | Pre-Dose Concentration (Ctrough) of PF-07295324 on Days 1 and 10 | Day 1 | 0.0001000 ng/mL | Geometric Coefficient of Variation 0 |
Secondary
Rac(AUCtau) of PF-07259955 on Day 10
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.
Time frame: On Days 1 and 10 at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after application
Population: All participants randomly assigned to study intervention who received an application of PF-07259955 and who had at least 1 of the PK parameters of interest calculated.
Secondary
Rac(Cmax) of PF-07259955 on Day 10
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.
Time frame: On Days 1 and 10 at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after application
Population: All participants randomly assigned to study intervention who received an application of PF-07259955 and who had at least 1 of the PK parameters of interest calculated.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Cohort 1 PF-07295324 0.12% Ointment BID | Rac(Cmax) of PF-07259955 on Day 10 | NA ratio |
Secondary
t½ of PF-07259955 on Day 10
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.
Time frame: 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
Population: All participants randomly assigned to study intervention who received an application of PF-07259955 and who had at least 1 of the PK parameters of interest calculated. None of the participants had reportable parameter values.
Secondary
Terminal Half-Life (t1/2) of PF-07295324 on Day 10
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.
Time frame: 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
Population: All participants randomly assigned to study intervention who received an application of PF-07295324 and who had at least 1 of the PK parameters of interest calculated. None of the participants had reportable parameter values.
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07295324 on Days 1 and 10
Tmax was defined as time to reach maximum observed plasma concentration. It was observed directly from data.
Time frame: On Days 1 and 10 at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after application
Population: All participants randomly assigned to study intervention who received an application of PF-07295324 and who had at least 1 of the PK parameters of interest calculated. In overall number of participants analyzed, the total number of participants in each treatment group was presented, and in number analyzed, the number of participants contributing to the data was presented.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1 PF-07295324 0.12% Ointment BID | Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07295324 on Days 1 and 10 | Day 10 | NA hour |
| Cohort 1 PF-07295324 Vehicle Ointment BID | Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07295324 on Days 1 and 10 | Day 10 | NA hour |
| Cohort 2 PF-07259955 2% Cream BID | Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07295324 on Days 1 and 10 | Day 10 | NA hour |
| Unknown | Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07295324 on Days 1 and 10 | Day 1 | — hour |
Secondary
Tmax of PF-07259955 on Days 1 and 10
Tmax was defined as time to reach maximum observed plasma concentration. It was observed directly from data.
Time frame: On Days 1 and 10 at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after application
Population: All participants randomly assigned to study intervention who received an application of PF-07259955 and who had at least 1 of the PK parameters of interest calculated.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1 PF-07295324 0.12% Ointment BID | Tmax of PF-07259955 on Days 1 and 10 | Day 10 | 8.00 hour |
| Unknown | Tmax of PF-07259955 on Days 1 and 10 | Day 1 | — hour |
Secondary
Vz/F of PF-07259955 on Day 10
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.
Time frame: 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
Population: All participants randomly assigned to study intervention who received an application of PF-07259955 and who had at least 1 of the PK parameters of interest calculated. None of the participants had reportable parameter values.