Evidence mapPaperPMID 39183039Full record

Trial reportEndocrine journal2024

Osilodrostat treatment in patients with Cushing's disease of Asian or non-Asian origin: a pooled analysis of two Phase III randomized trials (LINC 3 and LINC 4).

Akira Shimatsu, Beverly Mk Biller, Maria Fleseriu, Rosario Pivonello, Eun Jig Lee, Rattana Leelawattana, Jung Hee Kim, Rama Walia, Yerong Yu, Zhihong Liao and 3 more

2 registry-linked trialsAbstract readClinical Trial, Phase IIIRandomized Controlled Trial
In one paragraph

Trial report in Endocrine journal, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
field-weighted citation impact
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.

NCT02180217 phase3completednot on this map

Phase III, Multi-center, Double-blind, Randomized Withdrawal Study of LCI699 Following a 24 Week, Single-arm, Open-label Dose Titration and Treatment Period to Evaluate the Safety and Efficacy of LCI699 for the Treatment of Patients With Cushing's Disease

TypeinterventionalSponsorNovartis PharmaceuticalsRan2014 to 2019Enrolled137ConditionsCushings DiseaseArmsosilodrostat, LCI699 matching placebo
NCT02697734 phase3completednot on this map

A Phase III, Multi-center, Randomized, Double-blind, 48 Week Study With an Initial 12 Week Placebo-controlled Period to Evaluate the Safety and Efficacy of Osilodrostat in Patients With Cushing's Disease

TypeinterventionalSponsorNovartis PharmaceuticalsRan2016 to 2020Enrolled73ConditionsCushing's DiseaseArmsosilodrostat, osilodrostat Placebo
3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  4. Review
  5. Article
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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

13 authors.

Akira ShimatsuOmi Medical Center, Kusatsu 525-8585, Japan.
Beverly Mk BillerNeuroendocrine and Pituitary Tumor Clinical Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Maria FleseriuPituitary Center, Departments of Medicine and Neurological Surgery, Oregon Health & Science University, Portland, OR 97239, USA.
Rosario PivonelloDipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università Federico II di Napoli, Naples 80131, Italy.
Eun Jig LeeDepartment of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, South Korea.
Rattana LeelawattanaDivision of Endocrinology, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand.
Jung Hee KimDepartment of Internal Medicine, Seoul National University College of Medicine, Seoul 03080, South Korea.
Rama WaliaDepartment of Endocrinology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh 160012, India.
Yerong YuDepartment of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu 610041, China.
Zhihong LiaoDivision of Endocrinology, Sun Yat-sen University, Guangzhou 510275, China.
Andrea PiacentiniRecordati SpA, Milan 20148, Italy.
Alberto M PedroncelliRecordati AG, Basel 4057, Switzerland.
Peter J SnyderPerelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cushing's disease is associated with increased morbidity and mortality. Osilodrostat, a potent oral 11β-hydroxylase inhibitor, provided rapid, sustained mean urinary free cortisol (mUFC) normalization in Cushing's disease patients in two Phase III studies (LINC 3, NCT02180217; LINC 4, NCT02697734). Here, we evaluate the efficacy and safety of osilodrostat in Cushing's disease in patients of Asian origin compared with patients of non-Asian origin. Pooled data from LINC 3 and LINC 4 were analyzed. Outcomes were evaluated separately for Asian and non-Asian patients. For the analysis, 210 patients were included; 56 (27%) were of Asian origin. Median (minimum-maximum) osilodrostat dose was 3.8 (1-25) and 7.3 (1-47) mg/day in Asian and non-Asian patients, respectively. mUFC control was achieved at weeks 48 and 72 in 64.3% and 68.1% of Asian and 68.2% and 75.8% of non-Asian patients. Improvements in cardiovascular and metabolic-related parameters, physical manifestations of hypercortisolism, and quality of life were similar in both groups. Most common adverse events (AEs) were adrenal insufficiency (44.6%) in Asian and nausea (45.5%) in non-Asian patients. AEs related to hypocortisolism and pituitary tumor enlargement occurred in more Asian (58.9% and 21.4%) than non-Asian patients (40.3% and 9.1%). Of Asian and non-Asian patients, 23.2% and 13.6%, respectively, discontinued because of AEs. Asian patients with Cushing's disease generally required numerically lower osilodrostat doses than non-Asian patients to achieve beneficial effects. Hypocortisolism-related AEs were reported in more Asian than non-Asian patients. Together, these findings suggest that Asian patients are more sensitive to osilodrostat than non-Asian patients.

Indexed as

Asian PeoplePituitary ACTH HypersecretionAdultAgedFemaleHumansHydrocortisoneImidazolesMaleMiddle AgedPyridinesTreatment OutcomeYoung AdultHydrocortisoneImidazolesOsilodrostatPyridinesClinical trialCushing’s syndromeEfficacyRaceSafety

Identifiers

PMID39183039
PMCPMC11778389

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.