Safety, Tolerability, and Pharmacokinetics of BAP5191 in Healthy Adults Following Topical Application of Repeat Doses

Study Overview
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Brief Summary
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All enrolled participants will be randomized to 3 cohorts with 8 participants each and will receive BAP5191 and placebo topically on a square of 121 cm2 each in the left and right scapula region daily for 28 days, with a 28-d safety follow-up. The squares will be covered with a semi-occlusive patch. The doses will escalate from Cohort 1 to Cohort 2 to Cohort 3.

Official Title
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A Phase 1, Double Blind, Randomized, Placebo-Controlled First in Human Study, to Assess the Safety, Tolerability and Pharmacokinetics of BAP5191 Following Topical Application of Repeat Doses in Healthy Adult Participants

Conditions
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Healthy

Intervention / Treatment
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* Drug: BAP5191


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Healthy adult participants,18 to 65 years of age. Women of childbearing potential (WOCBP) must agree to use a highly effective form of contraception, from at least 7 days prior to first administration to 28 days after last administration. Male participants with WOCBP partner must be willing to use condoms from first IMP application to 90 days after last application. Body Mass Index (BMI) between 18 and 29.9 kg/m2. Body weight must be greater than 50 kg. Clinical laboratory parameters, vital signs, pulse oximetry, and ECG within the reference range from population studies, or showing no clinically relevant deviations. Key Exclusion Criteria: Chronic use of immunosuppressants within 3 years prior to the first administration of the study drug. History of prior leishmaniasis or extensive travel to endemic regions within 1 year prior to the first administration of the study drug. Presence or history of severe adverse reaction to any drug, or sensitivity to components of the study medication or to adhesive bandages or tape. Skin diseases, excessive hair, tattoos, pigmentation, scars or moles that could interfere with patch application and skin assessment at the site of application.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>1 mg/mL (0.1%) BAC6027 formulation; placebo | Drug: BAP5191<br>* Placebo<br>|
| Experimental: Cohort 2<br>5 mg/mL (0.5%) BAC6027 formulation; placebo | Drug: BAP5191<br>* Placebo<br>|
| Experimental: Cohort 3<br>10 mg/mL (1.0%) BAC6027 formulation; placebo | Drug: BAP5191<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| General safety (number, frequency, severity, seriousness and duration of adverse events) | Summarized statistics on adverse events will be reported under categories such as total adverse events, serious adverse events, treatment emerging adverse events. | From day 0 to day 55 | 
| Blood pressure from baseline | Change of blood pressure from baseline. Systolic and diastolic blood pressure will be assessed. | From day 0 to day 55 | 
| Heart rate from baseline | Change of pulse rate from baseline. | From day 0 to day 55 | 
| Respiratory rate from baseline | Change of respiratory rate from baseline. | From day 0 to day 55 | 
| Temperature from baseline | Change of tympanic temperature from baseline. | From day 0 to day 55 | 
| ECG parameters from baseline | Change in 12-lead electrocardiogram (ECG) parameters (PR Interval, QRS Complex, QT Interval, QTC Interval) from baseline. | From day 0 to day 55 | 
| Local skin tolerability: dermal response score | Summarized statistics of tolerability assessment based on dermal response score and other effects score. The dermal response score ranges from score 0 (better, No evidence of irritation) to score 7 (worse, Strong reaction spreading beyond test site). | From day 0 to day 55 | 
| Local skin tolerability: other effects score | Summarized statistics of tolerability assessment based on dermal response score and other effects score. The other effects score ranges from score 0 (better, None observed) to score 4 (worse, Glazing with fissures, Film of dried serous exudates covering all or part of the patch site, Small petechial erosions and/or scabs). | From day 0 to day 55 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax of BAC6027 | Peak Plasma Concentration (Cmax) of BAC6027, if detectable. | during the procedure, day 0 - day 31 | 
| Tmax of BAC6027 | Time to reach Cmax (Tmax), in case of plasma concentration determined. | during the procedure, day 0 - day 31 | 
| AUC of BAC6027 | Area under the curve (AUC) of the plasma concentration determined. | during the procedure, day 0 - day 31 | 
| AUC (0-t), of BAC6027 | Concentration from time zero to the last quantifiable concentration at time t, in case plasma concentration can be determined. | during the procedure, day 0 - day 31 | 
| T1/2 of BAC6027 | The plasma elimination half-life, In case plasma concentration can be determined. | during the procedure, day 0 - day 31 | 
| AUC (0-∞) of BAC6027 | The AUC of the plasma concentration from time zero to infinity with extrapolation of the terminal phase, In case plasma concentration can be determined. | during the procedure, day 0 - day 31 |