Acne Vulgaris
Conditions
Keywords
Cassiopea, clascoterone, cortexolone 17α-propionate, anti-androgen, CB-01-03
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.
Interventions
Sponsors
Intrepid Therapeutics, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in HPA Axis Response to Cosyntropin | Baseline and Day 14 | 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. |
| PK Profiles (Cmax) of Cortexolone 17α-propionate | Baseline and Day 14 | 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). |
| PK Profiles (AUC) of Cortexolone 17α-propionate | Baseline and Day 14 | 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 \[0-12 hours\]). |
| PK Profiles (Cavg) of Cortexolone 17α-propionate | Baseline and Day 14 | 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). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cortexolone 17α-Propionate (Cohort 1) Topical cream, 1.0% concentration, applied every twelve hours. | 20 |
| Cortexolone 17α-Propionate (Cohort 2) Cohort 2 enrolled adolescent subjects 12 to less than 18 years of age. Topical cream, 1.0% concentration, applied every twelve hours. | 22 |
| Total | 42 |
Baseline characteristics
| Characteristic | Cortexolone 17α-Propionate (Cohort 2) | Total | Cortexolone 17α-Propionate (Cohort 1) |
|---|---|---|---|
| Age, Continuous | 15.6 years STANDARD_DEVIATION 1.33 | 19.8 years STANDARD_DEVIATION 6.02 | 24.4 years STANDARD_DEVIATION 5.84 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants | 41 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 21 Participants | 38 Participants | 17 Participants |
| Sex: Female, Male Female | 12 Participants | 27 Participants | 15 Participants |
| Sex: Female, Male Male | 10 Participants | 15 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 22 |
| other Total, other adverse events | 5 / 20 | 3 / 22 |
| serious Total, serious adverse events | 0 / 20 | 0 / 22 |
Outcome results
Primary
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.
Time frame: Baseline and Day 14
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cortexolone 17α-Propionate (Cohort 1) | Change in HPA Axis Response to Cosyntropin | Baseline (pre-CST) | 17.0 mcg/dL | Standard Deviation 5.98 |
| Cortexolone 17α-Propionate (Cohort 1) | Change in HPA Axis Response to Cosyntropin | Baseline (post-CST) | 27.7 mcg/dL | Standard Deviation 3.43 |
| Cortexolone 17α-Propionate (Cohort 1) | Change in HPA Axis Response to Cosyntropin | Day 14 (pre-CST) | 18.1 mcg/dL | Standard Deviation 7.02 |
| Cortexolone 17α-Propionate (Cohort 1) | Change in HPA Axis Response to Cosyntropin | Day 14 (post-CST) | 26.7 mcg/dL | Standard Deviation 5.56 |
| Cortexolone 17α-Propionate (Cohort 2) | Change in HPA Axis Response to Cosyntropin | Day 14 (post-CST) | 22.8 mcg/dL | Standard Deviation 2.99 |
| Cortexolone 17α-Propionate (Cohort 2) | Change in HPA Axis Response to Cosyntropin | Baseline (pre-CST) | 16.8 mcg/dL | Standard Deviation 4.71 |
| Cortexolone 17α-Propionate (Cohort 2) | Change in HPA Axis Response to Cosyntropin | Day 14 (pre-CST) | 15.4 mcg/dL | Standard Deviation 3.98 |
| Cortexolone 17α-Propionate (Cohort 2) | Change in HPA Axis Response to Cosyntropin | Baseline (post-CST) | 24.6 mcg/dL | Standard Deviation 3.12 |
Primary
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 \[0-12 hours\]).
Time frame: Baseline and Day 14
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cortexolone 17α-Propionate (Cohort 1) | PK Profiles (AUC) of Cortexolone 17α-propionate | AUCτ - Day 1 | 22.02 hr*ng/mL | Standard Deviation 13.67 |
| Cortexolone 17α-Propionate (Cohort 1) | PK Profiles (AUC) of Cortexolone 17α-propionate | AUCτ - Day 14 | 37.14 hr*ng/mL | Standard Deviation 22.92 |
| Cortexolone 17α-Propionate (Cohort 2) | PK Profiles (AUC) of Cortexolone 17α-propionate | AUCτ - Day 1 | 22.55 hr*ng/mL | Standard Deviation 22.57 |
| Cortexolone 17α-Propionate (Cohort 2) | PK Profiles (AUC) of Cortexolone 17α-propionate | AUCτ - Day 14 | 30.97 hr*ng/mL | Standard Deviation 24.65 |
Primary
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).
Time frame: Baseline and Day 14
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cortexolone 17α-Propionate (Cohort 1) | PK Profiles (Cavg) of Cortexolone 17α-propionate | Cavg - Day 1 | 1.84 ng/mL | Standard Deviation 1.14 |
| Cortexolone 17α-Propionate (Cohort 1) | PK Profiles (Cavg) of Cortexolone 17α-propionate | Cavg - Day 14 | 3.10 ng/mL | Standard Deviation 1.91 |
| Cortexolone 17α-Propionate (Cohort 2) | PK Profiles (Cavg) of Cortexolone 17α-propionate | Cavg - Day 1 | 1.88 ng/mL | Standard Deviation 1.88 |
| Cortexolone 17α-Propionate (Cohort 2) | PK Profiles (Cavg) of Cortexolone 17α-propionate | Cavg - Day 14 | 2.58 ng/mL | Standard Deviation 2.05 |
Primary
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).
Time frame: Baseline and Day 14
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cortexolone 17α-Propionate (Cohort 1) | PK Profiles (Cmax) of Cortexolone 17α-propionate | Cmax - Day 1 (ng/mL) | 3.23 ng/mL | Standard Deviation 2.01 |
| Cortexolone 17α-Propionate (Cohort 1) | PK Profiles (Cmax) of Cortexolone 17α-propionate | Cmax - Day 14 (ng/mL) | 4.46 ng/mL | Standard Deviation 3 |
| Cortexolone 17α-Propionate (Cohort 2) | PK Profiles (Cmax) of Cortexolone 17α-propionate | Cmax - Day 1 (ng/mL) | 3.58 ng/mL | Standard Deviation 4.3 |
| Cortexolone 17α-Propionate (Cohort 2) | PK Profiles (Cmax) of Cortexolone 17α-propionate | Cmax - Day 14 (ng/mL) | 4.61 ng/mL | Standard Deviation 4.74 |