Study on safety assessment and measuring, in the blood, cortisol level after HPA stimulation and amount of the drug cortexolone 17a-propionate (CB-03-01) applied in form of cream every 12 hours for two weeks in subjects 9 to <12 year of age with acne vulgaris

Phase 1

Active, not recruiting

• Conditions: Acne vulgaris; MedDRA version: 20.0Level: LLTClassification code 10000519Term: Acne vulgarisSystem Organ Class: 100000004858; Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

• Registration Number: EUCTR2016-000616-15-PL
• Lead Sponsor: Cassiopea S.P.A.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-04-07
• Last Update Posted: 15 October 2018

Recruitment & Eligibility

• Status: Not Recruiting
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

1. Subject is male or female, 9 to <12 years of age at the time of consent/assent.
2. Subject must provide written informed assent and be accompanied by the parent or legal guardian at the time of assent/consent signing. The parent or legal guardian must provide written informed consent for the subject.
3. Females of childbearing potential1 must be using highly effective birth control methods2,3 with a negative urine pregnancy test (UPT) at the Screening and Baseline Visits.
4. Subject has moderate to severe facial acne vulgaris (Grade 3 or 4) as determined by the Investigator’s Global Assessment (IGA) [0 (clear) to 4 (severe) scale] and obvious acne on the trunk (i.e., shoulders, upper chest, and/or back) at the Screening Visit.
5. Subject has facial acne vulgaris with a minimum of 15 inflammatory lesions (papules, pustules, and nodules/cysts) and a minimum of 15 non-inflammatory lesions (open and closed comedones) at the Screening Visit.
6. Subject must be in general good health in the opinion of the investigator, with normal renal function as defined per protocol4 and no clinically relevant abnormalities present at the screening physical examination, in the subject’s medical history, or from safety laboratory tests (hematology, serum chemistry, and urinalysis).
7. Subject has normal adrenal function measured with a Cosyntropin Stimulation Test (CST) at Screening, defined as a normal pre-stimulation cortisol level and a 30-minute post-stimulation cortisol level of >18 µg/dL.
8. Subject and parent/guardian are able to communicate with the staff and are willing to comply with study instructions, reside at and/or return to the clinic for required visits.
Are the trial subjects under 18? yes
Number of subjects for this age range: 24
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Subject is pregnant, lactating, or is planning to become pregnant during the study.
2. Subject has a Body Mass Index (BMI) for age percentile >95% .
3. Except for the use of contraceptives, subject reported use of any prescription drug or herbal product within two (2) weeks of Visit 2 (Baseline), any non-prescription drug or vitamin or mineral supplements within one (1) week of Visit 2 (Baseline); any known enzyme-inducer,enzyme-inhibitor, or reported chronic exposure to enzyme-inducers such as paint solvents or pesticides within 30 days of Visit 2 (Baseline).
4. Subject has used topical anti-acne medications containing retinoids such as tazarotene, adapalene, or tretinoin within four (4) weeks of Visit 2 (Baseline).
5. Subject has used the following systemic anti-acne medications: antibiotics within two (2) weeks of Visit 2 (Baseline), spironolactone within four (4) weeks of Visit 2 (Baseline), or retinoid therapy within three (3) months of Visit 2 (Baseline).
6. Subject has used topical corticosteroids (including inhaled and intranasal corticosteroids) within two (2) weeks of the CST at Visit 1 (Screening) and/or between Visit 1 (Screening) CST and Visit 2 (Baseline).
7. Subject has used systemic corticosteroids (including intramuscular and intralesional injections) within four (4) weeks of the CST at Visit 1 (Screening) and/or between the Visit 1 (Screening) CST and Visit 2 (Baseline).
8. Subject has used light treatments, microdermabrasion or chemical peels to the face, chest, and/or back within eight (8) weeks of Visit 2 (Baseline).
9. 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.
10. Subject has any condition which, in the investigator’s opinion, would make it unsafe for the subject to participate in this research study.
11. Subject has the need or plans to be exposed to artificial tanning devices or excessive sunlight during the study.
12. Subject cannot avoid any type of strenuous exercise (swimming, running, team sports, etc.) or the use of hot tubs/saunas from Visit 2 (Baseline) to the end of the study (Visit 4).
13. Subject has any clinically significant medical abnormality or chronic disease of the cardiovascular, gastrointestinal, respiratory, hepatic, or renal systems. This includes conditions (e.g., gastrointestinal surgery) that may interfere with metabolism or excretion.
14. Subject has a history of alcohol and/or drug abuse in the investigator's judgment or has a positive urine drug screen result at Visit 1 (Screening).
15. Subject is unable to communicate or cooperate with the investigator due to language problems, poor mental development, or impaired cerebral function.
16. Subject is known to be hypersensitive to the test article or any components in the test article (see Section 6.1).
17. Subject has received an investigational drug or been treated with an investigational device within 30 days prior to Visit 2 (Baseline).
18. Subject is currently enrolled in an investigational drug or device study.
19. Subject has an irregular sleep schedule (cortisol levels exhibit physiological diurnal variation) as judged by the investigator.
20. Subject has experienced significant blood loss, as judged by the investigator, within 60 days or has donated plasma within 72 hours prior to Visit 2 (Baseline).
21. Subject tests positive at screening for human immunodefic

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objectives of this study are to determine a) the adrenal suppression potential and b) the trough plasma concentrations associated with topical application of CB-03-01 cream, 1% in subjects with acne vulgaris.;Secondary Objective: Not applicable;Primary end point(s): Hypothalamic-Pituitary-Adrenal (HPA) Axis Response to Cosyntropin: Measurement of serum cortisol concentrations after stimulation of the adrenal cortex with Cosyntropin (CST) at Screening and Day 14 (or EOS). HPA axis suppression is defined as a post-stimulation serum cortisol level <18 µg/dL at Day 14 (or EOS).<br>• Trough Plasma Concentrations: Trough measurements of cortexolone 17a-propionate and cortexolone concentration in plasma at Screening, Baseline, Day 7 and Day 14.;Timepoint(s) of evaluation of this end point: Screening, baseline, Day 7 and Day 14

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - Safety laboratory testing (hematology, clinical chemistry, and urinalysis) at Screening and Day 14 (or EOS).<br>- Local and systemic AEs at every visit (Baseline, Days 7 and 14).<br>The severity of the following LSRs [for face and trunk, separately]: telangiectasia, skin atrophy, striae rubrae, erythema, edema, scaling/dryness, stinging/burning, and pruritus at Baseline (pre- and post-test article application), Day 7, and Day 14.<br>- Physical examination/vital signs at Screening and Day 14 (or EOS).<br>- UPTs (for all females of childbearing potential) at Screening, Baseline, and Day 14 (or EOS).<br>- ECG at Screening and Day 14 (or EOS).;Timepoint(s) of evaluation of this end point: Screening, baseline, Day 7 and Day 14