An Evaluation of the Adrenal Suppression Potential and Pharmacokinetic Properties of CB-03-01 Cream in Subjects With Acne Vulgaris

Study Overview
=================
Brief Summary
-----------------
This study is designed to determine the hypothalamic-pituitary-adrenal (HPA) axis suppression potential and pharmacokinetic (PK) properties of CB-03-01 Cream, 1%, applied every twelve hours for two weeks, in subjects with acne vulgaris ages 12 years or older.

Official Title
-----------------
An Open Label Evaluation of the Adrenal Suppression Potential and Pharmacokinetic Properties of Cortexolone 17α-Propionate (CB-03-01) Cream Applied Every Twelve Hours for Two Weeks in Subjects With Acne Vulgaris

Conditions
-----------------
Acne Vulgaris

Intervention / Treatment
-----------------
* Drug: cortexolone 17α-propionate


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subject has moderate to severe facial acne vulgaris as determined by the Investigator's Global Assessment (IGA) and obvious acne on the chest and/or back at study start. Subject has facial acne vulgaris (including the nose) with a minimum number of inflammatory lesions (papules, pustules, and nodules/cysts) and a minimum number of non-inflammatory lesions (open and closed comedones) at study start. Females must be post-menopausal, surgically sterile or using highly effective birth control methods with a negative urine pregnancy test (UPT) at study start. Subject must be in general good health in the opinion of the investigator, with normal renal function, based on screening physical examination, medical history, and clinical laboratory values. Exclusion Criteria: Subject is pregnant, lactating, or is planning to become pregnant during the study. Subject is 12-20 years of age and has a Body Mass Index (BMI) for age percentile > 85%. Subject is > 20 years of age and has a BMI > 32.0 kg/m2. Subject has used tobacco, smoking cessation products, or products containing nicotine within three months prior to study start. Except for the use of contraceptives, subject has used any prescription drug or herbal product within 14 days prior to dosing, any non-prescription drug or vitamin or mineral supplements within 7 days prior to study start; any known enzyme-inducer, enzyme-inhibitor, or reported chronic exposure to enzyme-inducers such as paint solvents or pesticides within 30 days of study start. Subject has used topical anti-acne medications containing retinoids such as tazarotene, adapalene or tretinoin, within four weeks of study start. Subject has used the following systemic anti-acne medications: antibiotics within two weeks of study start, spironolactone within four weeks of study start, or retinoid therapy within three months of study start. Subject has any skin or medical condition, including facial hair that could interfere with the evaluation of the test article or requires the use of interfering topical or systemic therapy. Subject has the need or plans to be exposed to artificial tanning devices or excessive sunlight during the study. Subject has used light treatments, microdermabrasion or chemical peels to the face, chest and back within eight weeks of study start. Subject cannot avoid any type of strenuous exercise (swimming, running, team sports, etc.,) or the use of hot tubs/saunas from study start to the end of the study. Subject has received an investigational drug or been treated with an investigational device within 30 days prior to study start. Subject is currently enrolled in an investigational drug or device study. Subject has used topical corticosteroids (including inhaled and intranasal corticosteroids) within two weeks of study start. Subject has used systemic corticosteroids (including intramuscular and intralesional injections) within four weeks of study start. Subject has an irregular sleep schedule or works night shifts. Subject has experienced significant blood loss within 60 days or has donated plasma within 72 hours prior to study start. Subject tests positive at Screening for human immunodeficiency virus (HIV) or is known to be seropositive for HIV. Subject tests positive at Screening for hepatitis B surface antigen, hepatitis C antibody or has a history of a positive result. Subject had major surgery within 30 days prior to study start or plans to have surgery during the study. Subject has participated in a previous CB-03-01 study.

Ages Eligible for Study
-----------------
Minimum Age: 12 Years

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

Accepts Healthy Volunteers
-----------------
No

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

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cortexolone 17α-Propionate<br>Topical cream, 1.0% concentration, applied every twelve hours | Drug: cortexolone 17α-propionate<br> <br> * Other names: clascoterone (USAN, INN);|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HPA Axis Response to Cosyntropin | Measurement of serum cortisol concentrations after stimulation of the adrenal cortex with cosyntropin injection (Cosyntropin Stimulation Test - CST). Prior to CST, a pre-CST blood sample is taken between 7AM to 9AM. Thirty minutes after CST, a post-CST blood sample is collected. HPA axis suppression is defined as a post-stimulation serum cortisol level ≤ 18 μg/dL at Day 14. | Baseline and Day 14 | 
| PK Profiles (Cmax) of Cortexolone 17α-propionate | Max concentration (Cmax) of cortexolone 17α-propionate in plasma following the first application (i.e., Day 1, 0-12 hours) and last application (i.e., Day 14, 0-12 hours). | Baseline and Day 14 | 
| PK Profiles (AUC) of Cortexolone 17α-propionate | Area under the plasma concentration curve (0-12 hours) of cortexolone 17α-propionate at baseline (i.e., Day 1, after first application [0-12 hours]) and at Day 14 (i.e., Day 14, after last application [0-12 hours]). | Baseline and Day 14 | 
| PK Profiles (Cavg) of Cortexolone 17α-propionate | Average concentration of cortexolone 17α-propionate in plasma calculated as the ratio of the AUC(0-12 hours) and the dosing interval (i.e., 12 hours) at baseline (i.e., Day 1, after first application) and at Day 14 (after last application). | Baseline and Day 14 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Cassiopea, clascoterone, cortexolone 17α-propionate, anti-androgen, CB-01-03