Improvement in clinical features of hypercortisolism during osilodrostat treatment: findings from the Phase III LINC 3 trial in Cushing's disease.
Cushing’s disease
Diabetes
Dyslipidaemia
Hypertension
Osilodrostat
Urinary free cortisol
Journal
Journal of endocrinological investigation
ISSN: 1720-8386
Titre abrégé: J Endocrinol Invest
Pays: Italy
ID NLM: 7806594
Informations de publication
Date de publication:
02 May 2024
02 May 2024
Historique:
received:
08
06
2023
accepted:
09
03
2024
medline:
2
5
2024
pubmed:
2
5
2024
entrez:
2
5
2024
Statut:
aheadofprint
Résumé
Cushing's disease is associated with substantial morbidity and impaired quality of life (QoL) resulting from excess cortisol exposure. The current study explored improvements in clinical signs and additional specific manifestations of hypercortisolism during osilodrostat (potent oral 11β-hydroxylase inhibitor) therapy by degree of control of mean urinary free cortisol (mUFC). LINC 3 (NCT02180217) was a prospective, open-label, 48-week study of osilodrostat (starting dose: 2 mg bid; maximum: 30 mg bid) that enrolled 137 adults with Cushing's disease and mUFC > 1.5 times the upper limit of normal (ULN). mUFC (normal range 11‒138 nmol/24 h), cardiometabolic parameters (blood pressure, weight, waist circumference, body mass index, total cholesterol, fasting plasma glucose, glycated haemoglobin), physical manifestations of hypercortisolism (facial rubor, striae, fat distribution, bruising, hirsutism [females], muscle atrophy) and QoL were evaluated. mUFC was defined as controlled if ≤ ULN, partially controlled if > ULN but ≥ 50% reduction from baseline, and uncontrolled if > ULN and < 50% reduction from baseline. Concomitant medications were permitted throughout the study. At weeks 24 and 48, respectively, mUFC was controlled in 93 (67.9%) and 91 (66.4%) patients, partially controlled in 20 (14.6%) and 13 (9.5%), and uncontrolled in 24 (17.5%) and 33 (24.1%). Overall, mean improvements from baseline in cardiometabolic at week 24 were greater in patients with controlled or partially controlled versus uncontrolled mUFC; at week 48, improvements occurred irrespective of mUFC control. Generally, physical manifestations and QoL progressively improved from baseline irrespective of mUFC control. Improvements in clinical signs and additional specific manifestations of hypercortisolism associated with Cushing's disease occurred alongside decreases in mUFC. Trial registration NCT02180217 (first posted July 2014).
Identifiants
pubmed: 38696122
doi: 10.1007/s40618-024-02359-6
pii: 10.1007/s40618-024-02359-6
doi:
Banques de données
ClinicalTrials.gov
['NCT02180217']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024. The Author(s).
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