NPC-12G Gel 0.2% Sirolimus PK Bridging Study

Study Overview
=================
Brief Summary
-----------------
This study is designed to describe the relative systemic bioavailability of topical and oral sirolimus formulations.

Official Title
-----------------
Open-label, Fixed-sequence, Two-period Comparative Bioavailability Study of Sirolimus From Topical Application of NPC-12G Gel to Oral Rapamune® Following Single Administration in Healthy Subjects Under Fasting Conditions

Conditions
-----------------
Bioavailability Study

Intervention / Treatment
-----------------
* Drug: NPC-12G Gel 0.2%
* Drug: Rapamune® 2 mg tablet


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria Male or female, non-smoker (no use within 3 months prior to screening), ≥ 18 and ≤ 65 years of age, with BMI > 18.5 and < 30.0 kg/m2 and body weight ≥ 50.0 kg for males and ≥ 45.0 kg for females Females of childbearing potential who are sexually active with a male partner must be willing to use one of acceptable contraceptive method throughout the study and for 12 weeks after the last study drug administration Exclusion Criteria Any sign of eczema/dermatitis, skin lesion, wound, or infection at the application site, or any other conditions that would prevent a safe application of the gel formulation. Laser or surgery at the gel application site within 2 weeks before the gel application. Positive alcohol breath test, urine drug screen or urine cotinine test at screeningation History of allergic reactions or hypersensitivity to sirolimus, sirolimus derivatives, or excipient of NPC-12G Gel Use of any drugs known to induce or inhibit CYP3A4 metabolism within 30 days prior to the first study drug administration Positive pregnancy test at screening Breast-feeding subject History of active tuberculosis or exposure to endemic areas within 8 weeks prior to QuantiFERON®-TB testing performed at screening Positive QuantiFERON®-TB test with positive chest X-ray, indicating possible tuberculosis infection Immunization with a live attenuated vaccine within 1 month prior to dosing or planned vaccination during the study and up to 3 weeks after the last study drug administration

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NPC-12G Gel 0.2% (Period 1)<br>A single 800 mg quantity weight (1.6 mg sirolimus) dose will be applied to the central face on Day 1. | Drug: NPC-12G Gel 0.2%<br>* Period 1<br>* Other names: 2 mg of sirolimus in 1 g of gel;|
| Active Comparator: Rapamune Tablet (Period 2)<br>Rapamune® (sirolimus) 2 mg tablet for oral dosing. | Drug: Rapamune® 2 mg tablet<br>* Period 2<br>* Other names: Sirolimus;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-48 |  | Sampling: Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, 24, and 48 hours post-dose | 
| Cmax |  | Sampling: Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, 24, and 48 hours post-dose | 
| Tmax |  | Sampling: Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, 24, and 48 hours post-dose |