Comparison of Oral Octreotide Capsules to Injectable Somatostatin Analogs in Acromegaly

NCT02685709 | Completed Phase 3 Results DMC

• 2 other identifiers: OOC-ACM-3022015-002854-11
• Study Type: interventional
• Target: 146
• Locations: 13 countries
• Sites: 53

Brief Summary

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).

Conditions

Acromegaly

Keywords

Octreotide Capsules; Acromegaly; somatostatin receptor ligands (SRLs); Mpowered; OOC-ACM-302

Outcome Measures

Primary Outcomes (1)

• Proportion of Patients Who Are Biochemically Controlled Throughout the RCT Phase

  Proportion of patients who are biochemically controlled throughout the RCT phase. A patient was considered biochemically controlled if IGF-1 Time Weighted Average (TWA) during the RCT phase is \<1.3 ULN

  62 weeks

Secondary Outcomes (6)

• Proportion of Patients With Clinical and Biochemical Control at the End of the RCT Phase

  Week 62/ End of treatment; EOT

• Proportion of Patients Who Maintain or Reduce the Overall Number of Active Acromegaly Symptoms at the End of the RCT Phase

  62 weeks

• Proportion of Patients Who Maintain or Improve Their Overall Acromegaly Index of Severity (AIS) Score at the End of the RCT Phase

  62 weeks

• Proportion of Patients of Those Completing the RCT Phase Who Entered the Study Extension Phase

  62 weeks

• Change in IGF-1 Levels in the RCT Phase

  Change from Week 26 to week 62

Other Outcomes (11)

• Proportion of Patients Reporting Injection Site Reactions in the Acro-TSQ During the RCT Phase

  62 weeks

• Proportion of Patients Reporting Interference With Daily Activities in Acro-TSQ During the RCT Phase

  62 weeks

• Proportion of Patients on Octreotide Capsules Who Are Biochemically Controlled at the End of the RCT Phase- Landmark Analysis

  Average of weeks 58 and 62

Study Arms (4)

Run-in phase

EXPERIMENTAL

Oral octreotide capsules

Drug: Octreotide capsules

RCT phase - Oral

EXPERIMENTAL

Oral octreotide capsules

Drug: Octreotide capsules

RCT phase - Injectables

ACTIVE COMPARATOR

Injectable somatostatin analogs (octreotide or lanreotide)

Drug: Octreotide capsules

Combination phase (sub-study)

EXPERIMENTAL

Octreotide capsules plus cabergoline

Drug: Octreotide capsules

Interventions

Octreotide capsules DRUG

Also known as: Injection SRLs

Combination phase (sub-study); RCT phase - Injectables; RCT phase - Oral; Run-in phase

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Chiasma, Inc.: lead

Study Sites (53)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Keck Medical Center of University of Southern California

Los Angeles, California, 90033, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

John H. Stroger, Jr. Hospital of Cook County

Chicago, Illinois, 60612, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Rutgers - Robert Wood Johnson Medical School

New Brunswick, New Jersey, 08903, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43203, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Allegheny Endocrinology Associates

Pittsburgh, Pennsylvania, 15212, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Houston Methodist Research Institute

Houston, Texas, 77030, United States

Location

Universitätsklinik für Innere Medizin Klinische Abteilung für Endokrinologie und Diabetologie

Graz, A-8036, Austria

Location

Medizinische Universität Wien

Vienna, A-1090, Austria

Location

Hospices Civils de Lyon

Bron, 69677, France

Location

Hôpital Bicêtre APHP

Le Kremlin-Bicêtre, 94275, France

Location

Praxis für Endokrinologie und Diabetologie Dr M Droste

Oldenburg, 26122, Germany

Location

Magyar Honvedseg Egeszsegugyi Kozpont

Budapest, H-1062, Hungary

Location

University of Pecs

Pécs, H-7624, Hungary

Location

Szegedi Tudományegyetem, I. Belgyógyászati Klinika

Szeged, H-6720, Hungary

Location

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

Monserrato, 09042, Italy

Location

Università di Pisa Dipartimento di Medicina Clinica e Sperimentale

Pisa, 56124, Italy

Location

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

Rome, 00168, Italy

Location

Hospital of LUHS Kauno Klinikos

Kaunas, LT-50009, Lithuania

Location

Vaidotas Urbanavicius Individuali Imonė

Vilnius, LT-10207, Lithuania

Location

Katedra i Klinika Endokrynologii i Chorob Wewnetrznych Gdanski Uniwersytet Medyczny

Gdansk, 80-211, Poland

Location

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

Wroclaw, 50-367, Poland

Location

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

Bucharest, 011863, Romania

Location

Antrium Multidisciplinary Medical Clinic

Barnaul, 656043, Russia

Location

Interregional Clinical Diagnostic Center

Kazan', 420101, Russia

Location

Regional State Budgetary Healthcare Institution Regional State Hospital

Krasnoyarsk, 660022, Russia

Location

Sechenov Moscow First State Medical University

Moscow, 119881, Russia

Location

"Atlas" Medical Center

Moscow, 121170, Russia

Location

Vladimirsky Moscow Regional Research Clinical Institute

Moscow, 129110, Russia

Location

Novosibirsk State Regional Clinical Hospital

Novosibirsk, 630087, Russia

Location

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

Saint Petersburg, 194156, Russia

Location

"Centre Diabetes" LLC

Samara, 443041, Russia

Location

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

Belgrade, 11 000, Serbia

Location

Hospital Universitario de la Ribera

Alzira, 46600, Spain

Location

Hospital Universitari Germans Trias i Pujol

Barcelona, 08916, Spain

Location

Hospital General Universitario Gregorio Maranon

Madrid, 28007, Spain

Location

Complejo Hospitalario Universitario de Santiago de Compostela

Santiago de Compostela, 15706, Spain

Location

Campus Del Hospital Universitario Virgen del Rocio

Seville, 46013, Spain

Location

University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital

Birmingham, B15 2GW, United Kingdom

Location

Central Manchester University Hospitals NHS Foundation Trust, Manchester Royal Infirmary

Manchester, M13 9WL, United Kingdom

Location

Royal Victoria Infirmary

Newcastle upon Tyne, NE1 4LP, United Kingdom

Location

Royal Hallamshire Hospital

Sheffield, S10 2JF, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 25664604 BACKGROUND

• 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.

  PMID: 26610414 BACKGROUND

• 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.

  PMID: 34953531 DERIVED

Related Links

• Click here for more information about Chiasma

MeSH Terms

Conditions

Acromegaly

Interventions

Octreotide

Condition Hierarchy (Ancestors)

Bone Diseases, Endocrine; Bone Diseases; Musculoskeletal Diseases; Hyperpituitarism; Pituitary Diseases; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Asi Haviv, VP Clinical development
• Organization: Amryt

Asi@amrytpharma.com

972 8 9393888

Study Officials

• Maria Fleseriu, M.D., FACE

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

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2016
• First Posted: February 19, 2016
• Study Start: February 1, 2016
• Primary Completion: October 1, 2020
• Study Completion: August 1, 2021
• Last Updated: April 22, 2022
• Results First Posted: April 22, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

RU (9); SE (1); ES (5); LI (2); DE (1); IT (3); US (18); PL (2); RO (1); GB (4); HU (3); AU (2); FR (2)