PMID- 31251549
OWN - NLM
STAT- MEDLINE
DCOM- 20200114
LR  - 20200114
IS  - 1545-9616 (Print)
IS  - 1545-9616 (Linking)
VI  - 18
IP  - 6
DP  - 2019 Jun 1
TI  - Pharmacokinetic Profile, Safety, and Tolerability of Clascoterone (Cortexolone 
      17-alpha propionate, CB-03-01) Topical Cream, 1% in Subjects With Acne Vulgaris: 
      An Open-Label Phase 2a Study.
PG  - 563
LID - S1545961619P0563X [pii]
AB  - Clascoterone (cortexolone 17alpha-propionate, CB-03-01) 1% cream, a topical, androgen 
      receptor (AR) inhibitor under investigation for the treatment of acne vulgaris, 
      is rapidly metabolized to cortexolone in human plasma. The primary objectives of 
      this study were to determine the pharmacokinetic (PK) properties and adrenal 
      suppression potential of clascoterone topical cream, 1% in subjects with acne 
      vulgaris. Study Design: This study was an open-label, multicenter study in 42 
      subjects >/=12 years of age with moderate-to-severe acne (Grade 3-4 on the 
      Investigator's Global Assessment [IGA]), on the face, chest and/or back. Cohort 
      1(>18 years of age) and Cohort 2 (12-18 years of age) applied clascoterone 
      topical cream, 1% twice daily (BID) for 14 days. Primary safety endpoints 
      included hypothalamic-pituitary-adrenal (HPA) axis response to cosyntropin via a 
      Cosyntropin Stimulation Test (CST) upon screening (day 1) and at day 14 (HPA axis 
      suppression was defined as a post-stimulation serum cortisol level <18 mug/dL at 
      day 14); and PK evaluation including concentration-time profiles of clascoterone 
      and cortexolone in plasma-PK parameters were determined using "non-compartmental" 
      analysis. Secondary safety endpoints included clinical laboratory testing, local 
      and systemic adverse events (AEs), physical examination/vital signs, and 
      electrocardiogram (ECG). Results: 42 subjects (Cohort 1=20, Cohort 2= 22) 
      enrolled. Cohort 1 was comprised of 15 females (15/20, 75%) and 5 males (5/20, 
      25%), non-Hispanic/Latino (20/20, 100%), mean age is 24.4 years. Cohort 2 was 
      comprised of 12 females (12/22, 54.5%) and 10 males (10/22, 45.5%), 
      non-Hispanic/Latino (21/22, 95.5%), and mean age is 15.6 years. Three subjects 
      (3/42,7%), 1 adult and 2 adolescents, demonstrated an abnormal HPA axis response 
      with post-stimulation serum cortisol levels ranging from 14.9 to 17.7 mug/dL at 
      day 14. All returned to normal HPA axis function, four weeks after day 14. None 
      showed clinical evidence of adrenal suppression. Clascoterone plasma 
      concentrations achieved PK steady-state by day 5. Clascoterone systemic exposure 
      was similar between both cohorts. At steady-state, plasma concentrations 
      increased ~1.8 to 2.1 fold versus first dose with mean (coefficient of variation 
      [CV] %) maximum plasma concentrations of 4.4 ng/mL (67%) and 4.6 ng/mL (103%) in 
      Cohort 1 and Cohort 2, respectively. Cortexolone plasma concentrations trended 
      below the lower limit of quantitation (0.5 ng/mL) in both cohorts. Local skin 
      reactions (LSRs) were mostly mild, with only one moderate case of pruritus. There 
      were nine AEs categorized as follows: definitely related (N=2), probably related 
      (N=4), unlikely/not related (N=3), to clascoterone. Conclusion: This study 
      demonstrates the safety and tolerability of clascoterone topical cream, 1% in 
      adolescents and adults with acne vulgaris treated BID for 14 consecutive days. J 
      Drugs Dermatol. 2019;18(6):563-568.
FAU - Mazzetti, Alessandro
AU  - Mazzetti A
FAU - Moro, Luigi
AU  - Moro L
FAU - Gerloni, Mara
AU  - Gerloni M
FAU - Cartwright, Martina
AU  - Cartwright M
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PL  - United States
TA  - J Drugs Dermatol
JT  - Journal of drugs in dermatology : JDD
JID - 101160020
RN  - 0 (Androgen Receptor Antagonists)
RN  - 0 (Propionates)
RN  - WDT5SLP0HQ (Cortodoxone)
RN  - XN7MM8XG2M (Clascoterone)
SB  - IM
MH  - Acne Vulgaris/blood/diagnosis/*drug therapy
MH  - Adolescent
MH  - Adult
MH  - Androgen Receptor Antagonists/administration & dosage/adverse 
      effects/*pharmacokinetics
MH  - Child
MH  - Cortodoxone/administration & dosage/adverse effects/*analogs & 
      derivatives/pharmacokinetics
MH  - Female
MH  - Humans
MH  - Hypothalamo-Hypophyseal System/drug effects
MH  - Male
MH  - Pituitary-Adrenal System/drug effects
MH  - Propionates/administration & dosage/adverse effects/*pharmacokinetics
MH  - Severity of Illness Index
MH  - Skin Cream/administration & dosage/adverse effects/*pharmacokinetics
MH  - Treatment Outcome
MH  - Young Adult
EDAT- 2019/06/30 06:00
MHDA- 2020/01/15 06:00
CRDT- 2019/06/29 06:00
PHST- 2019/06/29 06:00 [entrez]
PHST- 2019/06/30 06:00 [pubmed]
PHST- 2020/01/15 06:00 [medline]
AID - S1545961619P0563X [pii]
PST - ppublish
SO  - J Drugs Dermatol. 2019 Jun 1;18(6):563.