Evidence map›Paper›PMID 38696122›Full record

Trial reportJournal of endocrinological investigation2024

Improvement in clinical features of hypercortisolism during osilodrostat treatment: findings from the Phase III LINC 3 trial in Cushing's disease.

R Pivonello, M Fleseriu, J Newell-Price, A Shimatsu, R A Feelders, P Kadioglu, A Tabarin, T C Brue, E B Geer, A Piacentini and 2 more

Registry-linked trialOpen access · hybridAbstract readClinical Trial, Phase IIIMulticenter Study
In one paragraph

Trial report in Journal of endocrinological investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02180217 (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), which is not on this map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
3.2field-weighted citation impact, top 7% 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.

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
3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 10 citations in OpenAlex.

  1. Trial
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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

12 authors at 11 institutions in 7 countries.

R PivonelloDipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Diabetologia, Andrologia e Nutrizione, Università Federico II di Napoli, Naples, Italy. rosario.pivonello@unina.it.ORCID http://orcid.org/0000-0002-9632-1348
M FleseriuPituitary Center, Departments of Medicine and Neurological Surgery, Oregon Health & Science University, Portland, OR, USA.ORCID http://orcid.org/0000-0001-9284-6289
J Newell-PriceDepartment of Oncology and Metabolism, The Medical School, University of Sheffield, Sheffield, UK.ORCID http://orcid.org/0000-0002-0835-5493
A ShimatsuAdvanced Medical Care Center, Omi Medical Center, Kusatsu, Japan.ORCID http://orcid.org/0000-0002-9688-006X
R A FeeldersDepartment of Internal Medicine, Endocrine Section, Erasmus Medical Center, Rotterdam, Netherlands.
P KadiogluDivision of Endocrinology, Metabolism and Diabetes, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul, Turkey.ORCID http://orcid.org/0000-0002-8329-140X
A TabarinCHU de Bordeaux, Bordeaux, France.
T C BrueAix-Marseille Université, Institut National de la Santé et de la Recherche Médicale, Marseille Medical Genetics, and Assistance Publique Hôpitaux de Marseille, Department of Endocrinology, Hôpital de la Conception, Centre de Référence des Maladies Rares de l'Hypophyse, Marseille, France.ORCID http://orcid.org/0000-0001-8482-6691
E B GeerMultidisciplinary Pituitary & Skull Base Tumor Center, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0000-0003-3722-1889
A PiacentiniRecordati SpA, Milan, Italy.
A M PedroncelliRecordati AG, Basel, Switzerland.
B M K BillerNeuroendocrine and Pituitary Tumor Clinical Center, Massachusetts General Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0003-4359-4622
Centre Hospitalier Universitaire de Bordeaux · FRErasmus MC · NLHôpital de la Conception · FRIstanbul University-Cerrahpaşa · TRIsuzu Advanced Engineering Center (Japan) · JPMassachusetts General Hospital · USMemorial Sloan Kettering Cancer Center · USOregon Health & Science University · USRecordati (Italy) · ITUniversity of Naples Federico II · ITUniversity of Sheffield · GB

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Michael Jason de la Cruz · 1985 to 2026
$347.4M
NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

purposeCushing'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).

methodsLINC 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.

resultsAt 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.

conclusionsImprovements 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).

Indexed as

Pituitary ACTH HypersecretionQuality of LifeAdultCushing SyndromeFemaleHumansHydrocortisoneImidazolesMaleMiddle AgedProspective StudiesPyridinesTreatment OutcomeYoung AdultHydrocortisoneImidazolesOsilodrostatPyridinesCushing’s diseaseDiabetesDyslipidaemiaHypertensionOsilodrostatUrinary free cortisol

Identifiers

PMID38696122
PMCPMC11392997
OpenAlexW4396583046

What Socratic holds

Textmetadata
LicenceCC BY
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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.