A First-in-human Study of Multiple Doses of Topically Administered PF-07295324 and PF-07259955

• ClinicalTrials.gov Identifier: NCT05206604
• Recruitment Status: Completed
• First Posted: January 25, 2022
• Last Update Posted: September 10, 2022
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Healthy	Drug: PF-07295324; Drug: PF-07259955	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A PHASE 1, RANDOMIZED, DOUBLE-BLIND, SPONSOR-OPEN, VEHICLE-CONTROLLED, FIRST-IN-HUMAN, MULTIPLE-DOSE STUDY, TO INVESTIGATE THE SAFETY, TOLERABILITY, AND PHARMACOKINETICS, OF TOPICALLY ADMINISTERED PF-07295324 AND PF-07259955, IN HEALTHY ADULT PARTICIPANTS
• Actual Study Start Date: February 9, 2022
• Actual Primary Completion Date: August 12, 2022
• Actual Study Completion Date: August 12, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: PF-07295324; Ointment	Drug: PF-07295324; Ointment
Experimental: PF-07259955; Cream	Drug: PF-07259955; Cream

Outcome Measures

Primary Outcome Measures :

1. AEs following multiple ascending dose (MAD) [ Time Frame: Day 1 up to Day 10 ]
   Frequency, severity and causal relationship of treatment emergent adverse events (TEAEs) and withdrawals due to TEAEs
2. Incidence and severity of application site Adverse Events (AEs) as assessed by Draize score. [ Time Frame: Day 1 up to Day 10 ]
   Frequency and severity of skin irritation potential based on Draize scoring
3. Incidence of laboratory abnormalities [ Time Frame: Day 1 up to Day 10 ]
   Number of subjects with laboratory abnormalities
4. Number of subjects with change from baseline in vital signs [ Time Frame: day 1 and day 10 ]
   Number of subjects with change from baseline of blood pressure and pulse rate

Secondary Outcome Measures :

1. Time to reach maximum plasma concentration (Cmax) [ Time Frame: Day 1 and Day 10 ]
   Maximum observed plasma concentration (Cmax)
2. Time to reach plasma Cmax (Tmax) [ Time Frame: Day 1 and Day 10 ]
   Time to reach maximum observed plasma concentration (Tmax)
3. Average Plasma Concentration (Cave) [ Time Frame: Day 1 and Day 10 ]
   Average Plasma Concentration over the duration of dosing interval, where dosing interval is 12 hours.
4. Minimum Observed Plasma Trough Concentration (Ctrough) [ Time Frame: Day 1 and Day 10 ]
   Minimum plasma concentration over the dosing interval τau (12 hour) from first dose to last dose
5. Area Under the Curve From Time Zero to End of Dosing Interval (AUCτau) [ Time Frame: Day 1 and Day 10 ]
   Area under the concentration curve from time 0 to end of dosing interval (AUCτau), where dosing interval is 12 hours.
6. Observed Accumulation Ratio for Cmax (Rac,Cmax) [ Time Frame: Day 10 ]
   Accumulation ratio based on maximum plasma concentration (Cmax) calculated as: Rac,Cmax = Cmax at steady state (ss) divided by Cmax at first dose.
7. Observed Accumulation Ratio for AUCτau (Rac, AUCτau) [ Time Frame: Day 10 ]
   Accumulation ratio calculated as, Rac obtained from Area Under the Concentration Time Curve (AUCτau) from time 0-τau (Day 10) divided by AUC from time 0-τau (Day 1).
8. Multiple Dose PK half-life (t½) [ Time Frame: Day 10 ]
   Plasma elimination half-life is the time measured for the plasma concentration to decrease by one half.
9. Apparent Volume of Distribution (Vz/F) [ Time Frame: Day 10 ]
   Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
10. Apparent Oral Clearance (CL/F) [ Time Frame: Day 10 ]
    Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed and a quantitative measure of the rate at which the drug is removed from the blood.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Locations

United States, Connecticut

New Haven Clinical Research Unit

New Haven, Connecticut, United States, 06511

Sponsors and Collaborators

Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

More Information

Additional Information:

To obtain contact information for a study center near you, click here. 

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT05206604
• Other Study ID Numbers: C4711001
• First Posted: January 25, 2022
• Last Update Posted: September 10, 2022
• Last Verified: September 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No