Comparison of Oral Octreotide Capsules to Injectable Somatostatin Analogs in Acromegaly

NCT ID: NCT02685709

Last Updated: 2022-04-22

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

146 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-02-29

Study Completion Date

2021-08-31

Brief Summary

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Octreotide capsule is a novel, orally-administered formulation of the commercially-available injectable drug octreotide. In a recent phase 3 trial (OPTMAL; NCT03252353), oral octreotide capsules demonstrated sustained biochemical response up to 13 months in patients with acromegaly previously managed with somatostatin analog injections (ref).

The objective of this study was to compare the efficacy, safety, and patient reported outcomes (PROs) between oral octreotide capsules and injectable somatostatin receptor ligands (SRLs).

Detailed Description

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This was phase 3, randomized, open-label, active controlled, multicenter study to evaluate the maintenance of response, safety and patient reported outcomes (PROs) in acromegaly patients treated with octreotide capsules and in patients treated with standard of care parenteral somatostatin receptor ligands (SRLs), who previously tolerated and demonstrated biochemical control on both treatments.

The core study consisted of three phases: a Screening phase, Run-in phase and a Randomized Controlled Treatment (RCT) phase.

Eligible patients who were biochemically controlled on parenteral SRLs were switched to octreotide capsules for a 26-week period Run-in phase. During this phase the effective dose for each patient was determined through dose titration.

Patients whose acromegaly has been controlled biochemically on octreotide capsules at the end of the Run-in phase entered a 36-week open-label RCT phase, where they randomized to continue on octreotide capsules or switch back to their injectable SRL treatment (as received prior to Screening).

Following the completion of the core study (Screening, Run-in and RCT phases), eligible patients were offered to enter the Study Extension phase and receive octreotide capsules until product marketing or study termination.

A Sub-study, performed in selected non-European sites, allowed patients with inadequate biochemical control on octreotide capsules during the Run-in phase to enter a Combination phase and receive co-administration of octreotide capsules with cabergoline tablets for a total of 36 weeks.

Conditions

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Acromegaly

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Run-in phase

Oral octreotide capsules

Group Type EXPERIMENTAL

Octreotide capsules

Intervention Type DRUG

RCT phase - Oral

Oral octreotide capsules

Group Type EXPERIMENTAL

Octreotide capsules

Intervention Type DRUG

RCT phase - Injectables

Injectable somatostatin analogs (octreotide or lanreotide)

Group Type ACTIVE_COMPARATOR

Octreotide capsules

Intervention Type DRUG

Combination phase (sub-study)

Octreotide capsules plus cabergoline

Group Type EXPERIMENTAL

Octreotide capsules

Intervention Type DRUG

Interventions

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Octreotide capsules

Intervention Type DRUG

Other Intervention Names

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Injection SRLs

Eligibility Criteria

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Inclusion Criteria

* Confirmed diagnosis of acromegaly
* Treatment with Somatostatin analogs injections (octreotide or lanreotide) for at least 6 months
* Biochemical control (IGF -1 \< 1.3 x ULN and GH \< 2.5ng/mL)

Exclusion Criteria

* Injections of long-acting somatostatin analogs, at a dosing interval \> 8 weeks.
* Pituitary radiotherapy within 5 years
* Pituitary surgery within six months
* Patients who previously participated in CH-ACM-01 study
* Any clinically significant uncontrolled concomitant disease
* Symptomatic cholelithiasis
* Previous treatment with:
* Pegvisomant, within 12 weeks
* Dopamine agonists, within 6 weeks
* Pasireotide, within 12 weeks
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Chiasma, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Maria Fleseriu, M.D., FACE

Role: STUDY_CHAIR

Northwest Pituitary Center, Oregon Health & Science University , Portland, OR, USA

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

Keck Medical Center of University of Southern California

Los Angeles, California, United States

Site Status

Cedars-Sinai Medical Center

Los Angeles, California, United States

Site Status

Stanford University School of Medicine

Stanford, California, United States

Site Status

University of Colorado Denver

Aurora, Colorado, United States

Site Status

Emory University

Atlanta, Georgia, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

John H. Stroger, Jr. Hospital of Cook County

Chicago, Illinois, United States

Site Status

Johns Hopkins University

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Rutgers - Robert Wood Johnson Medical School

New Brunswick, New Jersey, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

The Ohio State University Wexner Medical Center

Columbus, Ohio, United States

Site Status

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Site Status

Allegheny Endocrinology Associates

Pittsburgh, Pennsylvania, United States

Site Status

Baylor College of Medicine

Houston, Texas, United States

Site Status

Houston Methodist Research Institute

Houston, Texas, United States

Site Status

Universitätsklinik für Innere Medizin Klinische Abteilung für Endokrinologie und Diabetologie

Graz, , Austria

Site Status

Medizinische Universität Wien

Vienna, , Austria

Site Status

Hospices Civils de Lyon

Bron, , France

Site Status

Hôpital Bicêtre APHP

Le Kremlin-Bicêtre, , France

Site Status

Praxis für Endokrinologie und Diabetologie Dr M Droste

Oldenburg, , Germany

Site Status

Magyar Honvedseg Egeszsegugyi Kozpont

Budapest, , Hungary

Site Status

University of Pecs

Pécs, , Hungary

Site Status

Szegedi Tudományegyetem, I. Belgyógyászati Klinika

Szeged, , Hungary

Site Status

Policlinico di Monserrato U.O.C. Endocrinologia e Diabetologia

Monserrato, , Italy

Site Status

Università di Pisa Dipartimento di Medicina Clinica e Sperimentale

Pisa, , Italy

Site Status

Fondazione Policlinico Universitario A. Gemelli Università Cattolica del S.Cuore S.C. Endocrinologia e Malattie del Metabolismo

Rome, , Italy

Site Status

Hospital of LUHS Kauno Klinikos

Kaunas, , Lithuania

Site Status

Vaidotas Urbanavicius Individuali Imonė

Vilnius, , Lithuania

Site Status

Katedra i Klinika Endokrynologii i Chorob Wewnetrznych Gdanski Uniwersytet Medyczny

Gdansk, , Poland

Site Status

Samodzielny Publiczny Szpital Kliniczny nr 1 we Wroclawiu, Klinika Endokrynologii, Diabetologii i Leczenia Izotopami

Wroclaw, , Poland

Site Status

"C.I. Parhon" National Institute of Endocrinology I Clinical Endocrinology Department - Endemic goitier and its complications

Bucharest, , Romania

Site Status

Antrium Multidisciplinary Medical Clinic

Barnaul, , Russia

Site Status

Interregional Clinical Diagnostic Center

Kazan', , Russia

Site Status

Regional State Budgetary Healthcare Institution Regional State Hospital

Krasnoyarsk, , Russia

Site Status

Sechenov Moscow First State Medical University

Moscow, , Russia

Site Status

"Atlas" Medical Center

Moscow, , Russia

Site Status

Vladimirsky Moscow Regional Research Clinical Institute

Moscow, , Russia

Site Status

Novosibirsk State Regional Clinical Hospital

Novosibirsk, , Russia

Site Status

Federal State Budgetary Institution "V. A. Almazov Federal North-West Medical Research Centre" of the Ministry of Health of the Russian Federation

Saint Petersburg, , Russia

Site Status

"Centre Diabetes" LLC

Samara, , Russia

Site Status

Clinical Centre of Serbia, Clinic for Endocrinology Diabetes and Metabolic Diseases

Belgrade, , Serbia

Site Status

Hospital Universitario de la Ribera

Alzira, , Spain

Site Status

Hospital Universitari Germans Trias i Pujol

Barcelona, , Spain

Site Status

Hospital General Universitario Gregorio Maranon

Madrid, , Spain

Site Status

Complejo Hospitalario Universitario de Santiago de Compostela

Santiago de Compostela, , Spain

Site Status

Campus Del Hospital Universitario Virgen del Rocio

Seville, , Spain

Site Status

University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital

Birmingham, , United Kingdom

Site Status

Central Manchester University Hospitals NHS Foundation Trust, Manchester Royal Infirmary

Manchester, , United Kingdom

Site Status

Royal Victoria Infirmary

Newcastle upon Tyne, , United Kingdom

Site Status

Royal Hallamshire Hospital

Sheffield, , United Kingdom

Site Status

Countries

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United States Austria France Germany Hungary Italy Lithuania Poland Romania Russia Serbia Spain United Kingdom

References

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Melmed S, Popovic V, Bidlingmaier M, Mercado M, van der Lely AJ, Biermasz N, Bolanowski M, Coculescu M, Schopohl J, Racz K, Glaser B, Goth M, Greenman Y, Trainer P, Mezosi E, Shimon I, Giustina A, Korbonits M, Bronstein MD, Kleinberg D, Teichman S, Gliko-Kabir I, Mamluk R, Haviv A, Strasburger C. Safety and efficacy of oral octreotide in acromegaly: results of a multicenter phase III trial. J Clin Endocrinol Metab. 2015 Apr;100(4):1699-708. doi: 10.1210/jc.2014-4113. Epub 2015 Feb 9.

Reference Type BACKGROUND
PMID: 25664604 (View on PubMed)

Melmed S. New therapeutic agents for acromegaly. Nat Rev Endocrinol. 2016 Feb;12(2):90-8. doi: 10.1038/nrendo.2015.196. Epub 2015 Nov 27.

Reference Type BACKGROUND
PMID: 26610414 (View on PubMed)

Fleseriu M, Dreval A, Bondar I, Vagapova G, Macut D, Pokramovich YG, Molitch ME, Leonova N, Raverot G, Grineva E, Poteshkin YE, Gilgun-Sherki Y, Ludlam WH, Patou G, Haviv A, Gordon MB, Biermasz NR, Melmed S, Strasburger CJ. Maintenance of response to oral octreotide compared with injectable somatostatin receptor ligands in patients with acromegaly: a phase 3, multicentre, randomised controlled trial. Lancet Diabetes Endocrinol. 2022 Feb;10(2):102-111. doi: 10.1016/S2213-8587(21)00296-5. Epub 2021 Dec 22.

Reference Type DERIVED
PMID: 34953531 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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http://www.chiasmapharma.com

Click here for more information about Chiasma

Other Identifiers

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2015-002854-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

OOC-ACM-302

Identifier Type: -

Identifier Source: org_study_id

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