Safety and Efficacy of LCI699 for the Treatment of Patients With Cushing's Disease
Summary
The study aimed to confirm long-term efficacy and safety of LCI699 for the treatment of patients with Cushing's disease. It was a pivotal trial which supported the registration of LCI699 for the treatment of patients with Cushing's disease in the US and the EU. This is a phase lll, multi-center, double-blind, randomized withdrawal study of LCI699 following a 24 week, single-arm, open-label dose titration and treatment period which evaluated the safety and efficacy of LCI699 for the treatment of patients with Cushing's disease.
Timeline
- Start
- 2014-10-06
- Primary completion
- 2018-02-21
- Completion
- 2019-12-04
Outcome
Met primary endpoint
paper More patients maintained a complete response with osilodrostat versus with placebo at week 34 (31 [86%] vs ten [29%]; odds ratio 13·7 [95% CI 3·7-53·4]; p<0·0001). PMID 32730798 ↗
registry NUMBER Osilodrostat (LCI699): 86.1 Percentage of participants NCT02180217 ↗
Publications
- Fleseriu M, Pivonello R, Lacroix A, Biller BMK, Feelders R, Gadelha M, Bertherat J, Belaya Z, Piacentini A, Pedroncelli AM, Newell-Price J. Osilodrostat dose impact on efficacy/safety in Cushing's disease: large, pooled analysis of LINC 2, 3, and 4. Eur J Endocrinol. 2025 Oct 30;193(5):606-617. doi: 10.1093/ejendo/lvaf207.
- Newell-Price J, Fleseriu M, Pivonello R, Feelders RA, Gadelha MR, Lacroix A, Witek P, Heaney AP, Piacentini A, Pedroncelli AM, Biller BMK. Improved Clinical Outcomes During Long-term Osilodrostat Treatment of Cushing Disease With Normalization of Late-night Salivary Cortisol and Urinary Free Cortisol. J Endocr Soc. 2024 Nov 12;9(1):bvae201. doi: 10.1210/jendso/bvae201. eCollection 2024 Nov 26.
- Pivonello R, Fleseriu M, Newell-Price J, Shimatsu A, Feelders RA, Kadioglu P, Tabarin A, Brue TC, Geer EB, Piacentini A, Pedroncelli AM, Biller BMK. Improvement in clinical features of hypercortisolism during osilodrostat treatment: findings from the Phase III LINC 3 trial in Cushing's disease. J Endocrinol Invest. 2024 Oct;47(10):2437-2448. doi: 10.1007/s40618-024-02359-6. Epub 2024 May 2.
- Gadelha M, Snyder PJ, Witek P, Bex M, Belaya Z, Turcu AF, Feelders RA, Heaney AP, Paul M, Pedroncelli AM, Auchus RJ. Long-term efficacy and safety of osilodrostat in patients with Cushing's disease: results from the LINC 4 study extension. Front Endocrinol (Lausanne). 2023 Aug 23;14:1236465. doi: 10.3389/fendo.2023.1236465. eCollection 2023.
- Fontaine-Sylvestre C, Letourneau-Guillon L, Moumdjian RA, Berthelet F, Lacroix A. Corticotroph tumor progression during long-term therapy with osilodrostat in a patient with persistent Cushing's disease. Pituitary. 2021 Apr;24(2):207-215. doi: 10.1007/s11102-020-01097-1. Epub 2020 Oct 19.
- Pivonello R, Fleseriu M, Newell-Price J, Bertagna X, Findling J, Shimatsu A, Gu F, Auchus R, Leelawattana R, Lee EJ, Kim JH, Lacroix A, Laplanche A, O'Connell P, Tauchmanova L, Pedroncelli AM, Biller BMK; LINC 3 investigators. Efficacy and safety of osilodrostat in patients with Cushing's disease (LINC 3): a multicentre phase III study with a double-blind, randomised withdrawal phase. Lancet Diabetes Endocrinol. 2020 Sep;8(9):748-761. doi: 10.1016/S2213-8587(20)30240-0. Epub 2020 Jul 27.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | osilodrostat | Small molecule | 1 mg | Oral |
| Subject | osilodrostat | Small molecule | 5 mg | Oral |
| Subject | osilodrostat | Small molecule | 10 mg | Oral |
| Subject | osilodrostat | Small molecule | 20 mg | Oral |
| Subject | osilodrostat | Small molecule | 30 mg | Oral |