Osilodrostat, a potent oral 11ß-hydroxylase inhibitor: 22-week, prospective, Phase II study in Cushing's disease.
Pituitary
; 19(2): 138-48, 2016 Apr.
Article
em En
| MEDLINE
| ID: mdl-26542280
ABSTRACT
PURPOSE:
In a 10-week proof-of-concept study (LINC 1), the potent oral 11ß-hydroxylase inhibitor osilodrostat (LCI699) normalized urinary free cortisol (UFC) in 11/12 patients with Cushing's disease. The current 22-week study (LINC 2; NCT01331239) further evaluated osilodrostat in patients with Cushing's disease.METHODS:
Phase II, open-label, prospective study of two patient cohorts. Follow-up cohort 4/12 patients previously enrolled in LINC 1, offered re-enrollment if baseline mean UFC was above ULN. Expansion cohort 15 newly enrolled patients with baseline UFC > 1.5 × ULN. In the follow-up cohort, patients initiated osilodrostat twice daily at the penultimate efficacious/tolerable dose in LINC 1; dose was adjusted as needed. In the expansion cohort, osilodrostat was initiated at 4 mg/day (10 mg/day if baseline UFC > 3 × ULN), with dose escalated every 2 weeks to 10, 20, 40, and 60 mg/day until UFC ≤ ULN. Main efficacy endpoint was the proportion of responders (UFC ≤ ULN or ≥50% decrease from baseline) at weeks 10 and 22.RESULTS:
Overall response rate was 89.5% (n/N = 17/19) at 10 weeks and 78.9% (n/N = 15/19) at 22 weeks; at week 22, all responding patients had UFC ≤ ULN. The most common AEs observed during osilodrostat treatment were nausea, diarrhea, asthenia, and adrenal insufficiency (n = 6 for each). New or worsening hirsutism (n = 2) and/or acne (n = 3) were reported among four female patients, all of whom had increased testosterone levels.CONCLUSIONS:
Osilodrostat treatment reduced UFC in all patients; 78.9% (n/N = 15/19) had normal UFC at week 22. Treatment with osilodrostat was generally well tolerated.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Piridinas
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Hipersecreção Hipofisária de ACTH
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Imidazóis
Tipo de estudo:
Clinical_trials
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Observational_studies
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Prognostic_studies
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article