PMID- 32378529
OWN - NLM
STAT- MEDLINE
DCOM- 20210730
LR  - 20210730
IS  - 1348-4540 (Electronic)
IS  - 0918-8959 (Linking)
VI  - 67
IP  - 8
DP  - 2020 Aug 28
TI  - A multicenter, phase 2 study to evaluate the efficacy and safety of osilodrostat, 
      a new 11beta-hydroxylase inhibitor, in Japanese patients with endogenous Cushing's 
      syndrome other than Cushing's disease.
PG  - 841-852
LID - 10.1507/endocrj.EJ19-0617 [doi]
AB  - This phase 2, single-arm, open-label, dose-titration, multicenter study evaluated 
      osilodrostat (11beta-hydroxylase inhibitor) in Japanese patients with endogenous 
      Cushing's syndrome (CS) caused by adrenal tumor/hyperplasia or ectopic 
      adrenocorticotropic hormone syndrome. The primary endpoint was percent change 
      from baseline to week 12 in mean urinary free cortisol (mUFC) at the individual 
      patient level. Of the nine patients enrolled in the study, seven completed the 
      12-week core treatment period and two discontinued at or prior to week 12 due to 
      adverse events (AEs). Of the seven patients who completed 12 weeks of study 
      treatment, two completed 48 weeks of study treatment. Median osilodrostat 
      exposure was 12 weeks. Median (range) average dose including dose interruption (0 
      mg/day) was 2.143 (1.16-7.54) mg/day. Median (range, population) percentage 
      change in mUFC was -94.47% (-99.0% to -52.6%, n = 7) at week 12. At week 12, 6/9 
      patients were complete responders (mUFC </= upper limit of normal [ULN]) and 1/9 
      was a partial responder (mUFC > ULN but decreased by >/=50% from baseline). Most 
      frequent AEs were adrenal insufficiency (n = 7), gamma-glutamyl transferase 
      increase, malaise, and nasopharyngitis (n = 3 each). Serious AEs were seen in 
      four patients. No deaths occurred in this study. In conclusion, osilodrostat 
      treatment led to a reduction in mUFC in all nine patients with endogenous CS 
      other than Cushing's disease (CD), regardless of disease type, with >80% 
      reduction seen in 6/7 patients at week 12. The safety profile was consistent with 
      previous reports in CD patients, and the reported AEs were manageable.
FAU - Tanaka, Tomoaki
AU  - Tanaka T
AD  - Department of Molecular Diagnosis, Chiba University Hospital/Chiba University 
      Graduate School of Medicine, Chiba 260-8670, Japan.
FAU - Satoh, Fumitoshi
AU  - Satoh F
AD  - Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University 
      Hospital, Sendai 980-8574, Japan.
FAU - Ujihara, Makoto
AU  - Ujihara M
AD  - Department of Internal Medicine, National Hospital Organization Yokohama Medical 
      Center, Yokohama 245-8575, Japan.
FAU - Midorikawa, Sanae
AU  - Midorikawa S
AD  - Department of Radiation Health Management, Fukushima Medical University School of 
      Medicine, Fukushima 960-1295, Japan.
FAU - Kaneko, Tomomi
AU  - Kaneko T
AD  - Global Drug Development Division, Novartis Pharma K.K., Tokyo 105-6333, Japan.
FAU - Takeda, Tamami
AU  - Takeda T
AD  - Global Drug Development Division, Novartis Pharma K.K., Tokyo 105-6333, Japan.
FAU - Suzuki, Akina
AU  - Suzuki A
AD  - Global Drug Development Division, Novartis Pharma K.K., Tokyo 105-6333, Japan.
FAU - Sato, Masahiko
AU  - Sato M
AD  - Global Drug Development Division, Novartis Pharma K.K., Tokyo 105-6333, Japan.
FAU - Shimatsu, Akira
AU  - Shimatsu A
AD  - Clinical Research Institute, National Hospital Organization Kyoto Medical Center, 
      Kyoto 612-8555/Advanced Medical Care Center, Kusatsu General Hospital, Kusatsu 
      525-8585, Japan.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
DEP - 20200501
PL  - Japan
TA  - Endocr J
JT  - Endocrine journal
JID - 9313485
RN  - 0 (Imidazoles)
RN  - 0 (Pyridines)
RN  - 5YL4IQ1078 (Osilodrostat)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Cushing Syndrome/*drug therapy
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Female
MH  - Humans
MH  - Imidazoles/administration & dosage/*therapeutic use
MH  - Japan
MH  - Male
MH  - Middle Aged
MH  - Pituitary ACTH Hypersecretion/drug therapy
MH  - Pyridines/administration & dosage/*therapeutic use
MH  - Treatment Outcome
MH  - Young Adult
OTO - NOTNLM
OT  - 11beta-hydroxylase inhibitor
OT  - Cushing's disease
OT  - Cushing's syndrome
OT  - Osilodrostat
EDAT- 2020/05/08 06:00
MHDA- 2021/07/31 06:00
CRDT- 2020/05/08 06:00
PHST- 2020/05/08 06:00 [pubmed]
PHST- 2021/07/31 06:00 [medline]
PHST- 2020/05/08 06:00 [entrez]
AID - 10.1507/endocrj.EJ19-0617 [doi]
PST - ppublish
SO  - Endocr J. 2020 Aug 28;67(8):841-852. doi: 10.1507/endocrj.EJ19-0617. Epub 2020 
      May 1.