Evidence map›Paper›PMID 26542280›Full record

Trial reportPituitary2016

Osilodrostat, a potent oral 11β-hydroxylase inhibitor: 22-week, prospective, Phase II study in Cushing's disease.

Maria Fleseriu, Rosario Pivonello, Jacques Young, Amir H Hamrahian, Mark E Molitch, Chikara Shimizu, Tomoaki Tanaka, Akira Shimatsu, Tracy White, Annie Hilliard and 4 more

Registry-linked trialOpen access · hybridAbstract readClinical Trial, Phase IIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Pituitary, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01331239 (A Proof of Concept, Open-label, Forced Titration, Multi-center Study to Assess the Safety/Tolerability and Efficacy of 10-weeks Treatment of LCI699 in Patients With Cushing's Disease), which is not on this map. Cited by 72 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed, 4 pooled it
7.8field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01331239 phase2completednot on this map

A Proof of Concept, Open-label, Forced Titration, Multi-center Study to Assess the Safety/Tolerability and Efficacy of 10-weeks Treatment of LCI699 in Patients With Cushing's Disease

TypeinterventionalSponsorNovartis PharmaceuticalsRan2011 to 2019Enrolled31ConditionsCushings Disease, Cushing DiseaseArmsLCI699
3 · Its place in the literature

Who cites it

72 citing papers in PubMed, 4 syntheses or guidelines pooled it, 153 citations in OpenAlex.

  1. Pooled it
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  5. Trial
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  12. Review
  13. Real-World Osilodrostat Effectiveness and Safety in Nonpituitary Cushing Syndrome.The Journal of clinical endocrinology and metabolism · 2026
    Observational
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12 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 12 institutions in 5 countries.

Maria FleseriuNorthwest Pituitary Center, Departments of Medicine and Neurological Surgery, Oregon Health and Science University, Portland, OR, USA. fleseriu@ohsu.edu.
Rosario PivonelloDipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università Federico II di Napoli, Naples, Italy.
Jacques YoungDepartment of Endocrinology, Hôpital Bicêtre, Université Paris-Sud, Assistance Publique Hôpitaux de Paris, Paris, France.
Amir H HamrahianDepartment of Endocrinology, Diabetes, and Metabolism, Cleveland Clinic Foundation, Cleveland, OH, USA.
Mark E MolitchDivision of Endocrinology, Metabolism and Molecular Medicine, Northwestern University, Chicago, IL, USA.
Chikara ShimizuDivision of Laboratory and Transfusion Medicine, Hokkaido University Hospital, Sapporo, Japan.
Tomoaki TanakaDivision of Endocrinology and Metabolism, Chiba University Hospital, Chiba-city, Japan.
Akira ShimatsuClinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto, Japan.
Tracy WhiteNovartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
Annie HilliardNovartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
Chuan TianNovartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
Nicholas SauterNovartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
Beverly M K BillerNeuroendocrine Clinical Center, Massachusetts General Hospital, Boston, MA, USA.
Xavier BertagnaDepartment of Endocrinology, Centre de Référence des Maladies Rares de la Surrénale, Hôpital Cochin, Faculté de Médecine Paris Descartes, Université Paris 5, Paris, France.
Novartis (Switzerland) · CHNovartis (United States) · USAssistance Publique – Hôpitaux de Paris · FRChiba University Hospital · JPCleveland Clinic · USHokkaido University Hospital · JPKyoto Medical Center · JPMassachusetts General Hospital · USNorthwestern University · USOregon Health & Science University · USUniversité Paris Cité · FRUniversity of Naples Federico II · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeIn a 10-week proof-of-concept study (LINC 1), the potent oral 11β-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.

methodsPhase 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.

resultsOverall 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.

conclusionsOsilodrostat 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.

Indexed as

Administration, OralAdrenocorticotropic HormoneAdultAgedEnzyme InhibitorsFemaleFollow-Up StudiesHumansHydrocortisoneImidazolesMaleMiddle AgedPituitary ACTH HypersecretionPyridinesTreatment OutcomeAdrenocorticotropic HormoneEnzyme InhibitorsHydrocortisoneImidazolesOsilodrostatPyridines11β-hydroxylaseCortisolCushing’sLCI699Osilodrostat

Identifiers

PMID26542280
PMCPMC4799251
OpenAlexW2117280636

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.