Clinical trial NCT04863417: Study to Evaluate the Safety, Local and Systemic Tolerability, and Pharmacokinetics of Multiple-Dose Topical Administration of PF-07038124 in Japanese Healthy Participants
Official title: A PHASE 1, RANDOMIZED, DOUBLE-BLIND, VEHICLE-CONTROLLED, PARALLEL COHORT STUDY TO EVALUATE THE SAFETY, TOLERABILITY, SKIN IRRITATION POTENTIAL AND PHARMACOKINETICS OF MULTIPLE-DOSE, TOPICAL ADMINISTRATION OF PF-07038124 TO JAPANESE HEALTHY PARTICIPANTS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2021-04-28
Enrollment: 12
Sex: ALL
Minimum age (years): 20
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety, tolerability, skin irritation potential, and PK of PF-07038124 in Japanese healthy adult participants.


Eligibility criteria: Inclusion Criteria:

1. Male and female participants must be 20 to 55 years of age, inclusive, at the time of signing the ICD.
2. Male and female participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and 12-lead ECG.
3. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
4. Participants must have 4 biologically Japanese grandparents who were born in Japan.
5. BMI of 17.5 to 25 kg/m2; and a total body weight \>50 kg (110 lb).
6. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol.

Exclusion Criteria:

1. 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.
2. Participants who have a history of or have active forms of dermatitides/eczematous conditions (eg, contact dermatitis, seborrhhoeic, discoid, gravitational, asteatotic and dishydrotic eczema) or other inflammatory skin diseases(eg, psoriasis, viral infection, fungal infection, bacterial infection) that would interfere with evaluation of the test site reaction.
3. Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).
4. History of HIV infection, hepatitis B, or hepatitis C; positive testing for HIV, HBsAg, HBcAb, HCVAb, or syphilis at screening. Hepatitis B vaccination is allowed.
5. Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
6. Acute disease state (unstable medical condition such as nausea, vomiting, fever or diarrhea, etc) within 7 days of Day 1.
7. Have undergone significant trauma or major surgery within 4 weeks of screening.
8. Use of prescription or nonprescription drugs and dietary and herbal supplements within 14 days or 5 half lives (whichever is longer) prior to the first dose of study intervention.
9. Previous administration with an investigational drug within 4 months (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).
10. A positive urine drug test at screening and/or Day -1.
11. Screening supine BP ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), following at least 5 minutes of supine rest.
12. Baseline 12 lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results (eg, baseline QTcF interval \>450 msec, complete LBBB, signs of an acute or indeterminate age myocardial infarction, ST T interval changes suggestive of myocardial ischemia, second or third degree AV block, or serious bradyarrhythmia's or tachyarrhythmias).
13. 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:

    * AST or ALT level ≥1.5 × 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.
14. A positive COVID-19 test at screening.
15. 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).
16. Blood donation (excluding plasma donations) of approximately ≥400 mL within 3 months or ≥200 mL within a month prior to dosing. Additionally, approximately ≥400 mL within 4 months for female participants.
17. History of serious adverse reactions or hypersensitivity to any topical drug; or known allergy to any of the study intervention or any components in the study intervention or history of hypersensitivity; or allergic reactions to any of the study preparations.
18. Not willing to refrain from shaving (Note: shaving around face is permitted), 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.
19. History of sensitivity to heparin or heparin induced thrombocytopenia only if heparin is planned to flush intravenous catheters.
20. Unwilling or unable to comply with the criteria in the Lifestyle Considerations section of this protocol.
21. 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.

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: Day 1 up to maximum of 31 days after last dose of study drug (maximum up to 41 days)
measure: Number of Participants With Clinically Significant Changes in Vital Signs During the Study
timeFrame: Day 1 up to Day 11
measure: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) During the Study
timeFrame: Day 1 up to Day 11
measure: Number of Participants With Clinically Significant Laboratory Abnormalities
timeFrame: Day 1 up to Day 11
measure: Number of Participants Categorized According to Draize Scores (Maximum Score) for Local Skin Irritation Assessment During the Study, Regardless of Visit and Assessment Location
timeFrame: Through Day 1 to Day 11 (prior to application from Day 1-10 and 24 hours post application on Day 10)
Secondary outcomes:
measure: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-07038124
timeFrame: 0 to 24 hours post dose on Day 1 and Day 10
measure: Maximum Observed Plasma Concentration (Cmax) of PF-07038124
timeFrame: Day 1 and 10: Pre-dose (0 hour), 1, 2, 4, 6, 8 and 12, 24 hours post-dose
Other outcomes:
Locations:
city: Hachioji
country: Japan
facility: P-one clinic, Keikokai medical corporation
state: Tokyo
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: