Efficacy and Safety of Octreotide Capsules (MYCAPSSA) in Acromegaly

Acromegaly Clinical Trial

— OPTIMAL  

Official title:

A Phase 3, Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate Efficacy and Safety of Octreotide Capsules in Patients Who Demonstrated Biochemical Control on Injectable Somatostatin Receptor Ligands (SRL) Treatment

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03252353
• Other study ID #: OOC-ACM-303
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: September 1, 2017
• Est. completion date: May 2022

Study information

• Verified date: November 2020
• Source: Chiasma, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

This is a double blind, randomized study that assesses the efficacy and safety of octreotide capsules vs. placebo. Eligible acromegaly patients, treated with injectable somatostatin analogs, who are biochemically controlled and have prior evidence of active disease, will be randomized to receive either octreotide capsules or placebo for up to 36 weeks. At the end of this double blind, placebo controlled period, eligible patients will receive octreotide capsules in an open-labeled extension for at least one year. Patients failing to respond (per protocol), to oral treatment, (either placebo or octreotide capsules), will be rescued with the standard of care and upon meeting the eligibility criteria could also enroll into the long term extension with octreotide capsules.

This study received agreement from the FDA, under a special protocol assessment.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 56
• Est. completion date: May 2022
• Est. primary completion date: June 13, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Documented evidence of active acromegaly

• Treatment with Somatostatin analogs injections (octreotide or lanreotide) for at least 6 months with a stable dose for at least the last three months of therapy

• Biochemically controlled

Exclusion Criteria:

• Patients taking injections of long-acting Somatostatin Receptor Ligands (SRLs) not as indicated in the label

• Pituitary surgery within six months

• Conventional or stereotactic pituitary radiotherapy any time in the past

• Patients who previously participated in CH-ACM-01 or OOC-ACM-302

• Any clinically significant uncontrolled concomitant disease

• Symptomatic cholelithiasis

• Pegvisomant, within 24 weeks

• Dopamine agonists, within 12 weeks

• Pasireotide, within 24 weeks

Related Conditions & MeSH terms

• Acromegaly

Intervention

Drug:
• octreotide capsules
octreotide capsules 40 mg/day, 60 mg/day, 80 mg/day (individual dose titration)
• Matching placebo
Matching placebo capsules

Locations

Country	Name	City	State
Australia	St Vincent's Private Hospital-NSW	Darlinghurst	New South Wales
Australia	St Vincent's Hospital-VIC	Fitzroy	Victoria
Australia	The Alfred	Melbourne	Victoria
Australia	Keogh Institute (Sir Charles Gardner)	Nedlands	Western Australia
Australia	Melbourne Health	Parkville	Victoria
Australia	Royal North Shore Public Hospital	St Leonards	New South Wales
Bulgaria	University Specialized Hospital for Active Treatment of Endocrinology "Acad. Iv. Pencev" EAD	Sofia
Canada	St Joseph's Health Care	London	Ontario
Canada	McGill University Health Centre	Montreal	Quebec
Canada	University of British Columbia	Vancouver	British Columbia
Denmark	Aarhus University Hospital	Aarhus
Denmark	Rigshospitalet The Department of Endocrinology	Copenhagen
Germany	RWTH Aachen University Hospital, Medical Clinic III Division of Endocrinology and Diabetes	Aachen
Germany	Klinikum der LMU Muenchen, Medizinische Klinik und Poliklinik IV, Endokrinologie	Munich
Hungary	Magyar Honvedseg Egeszsegugyi Kozpont, II. sz. Belgyogyaszati Osztaly	Budapest
Hungary	University of Semmelweiss, Budapest	Budapest
Hungary	Szegedi Tudományegyetem, I. Belgyógyászati Klinika	Szeged
Israel	Hadassah Ein-Karem Medical Center	Jerusalem
Israel	Rabin Medical Center, Beilinson Hospital	Petah Tikva
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Italy	Policlinico di Monserrato U.O.C. Endocrinologia e Diabetologia	Monserrato
Italy	Azienda Ospedaliero-Universitaria Pisana, Università di Pisa	Pisa
Latvia	Riga Eastern Clinical University, Hospital Gailezers Department of Endocrinology	Riga
Netherlands	Leids Universitair Medisch Centrum	Leiden
Netherlands	Erasmus Medisch Centrum	Rotterdam
New Zealand	Dunedin Hospital	Dunedin
New Zealand	Wellington Hospital	Wellington
Poland	Katedra i Klinika Endokrynologii i Chorob Wewnetrznych	Gdansk
Poland	Uniwersyteckie Centrum Okulistyki i Onkologii Samodzielny Publiczny Szpital Kliniczny Slaskiego Uniwersytetu Medycznego w Katowicach, Oddzial Endokrynologii	Katowice
Poland	Szpital Uniwersytecki w Krakowie, Oddzial Kliniczny Endokrynologii	Krakow
Poland	Klinika Chorob Wewnetrznych i Endokrynologii	Warszawa
Poland	Samodzielny Publiczny Szpital Kliniczny nr 1 we Wroclawiu, Klinika Endokrynologii, Diabetologii i Leczenia Izotopami	Wroclaw
Slovenia	Medical University Centre Ljubljana	Ljubljana
Sweden	Sahlgrenska University Hospital	Göteborg
Turkey	Ankara University, Faculty of Medicine	Ankara
Turkey	Hacettepe University Medical School	Ankara
Turkey	Ege University Medical Faculty Internal Diseases	Izmir
Turkey	Erciyes University Medical Faculty	Kayseri
United Kingdom	University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital	Birmingham
United Kingdom	Central Manchester University Hospitals NHS Foundation Trust, Manchester Royal Infirmary	Manchester
United Kingdom	Royal Victoria Infirmary	Newcastle upon Tyne
United States	The Emory Clinic	Atlanta	Georgia
United States	University of Colorado	Aurora	Colorado
United States	Johns Hopkins University Clinical Trials Unit	Baltimore	Maryland
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	John H. Stroger Jr. Hospital of Cook County	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	Ohio State University	Columbus	Ohio
United States	Baylor College of Medicine	Houston	Texas
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Keck Medical Center of University of Southern California	Los Angeles	California
United States	UCLA Medical Center	Los Angeles	California
United States	Columbia University Medical Center	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Stanford University School of Medicine	Palo Alto	California
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	Allegheny Endocrinology Associates	Pittsburgh	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Huntsman Cancer Hospital	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Chiasma, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Bulgaria,  Canada,  Denmark,  Germany,  Hungary,  Israel,  Italy,  Latvia,  Netherlands,  New Zealand,  Poland,  Slovenia,  Sweden,  Turkey,  United Kingdom, 

References & Publications (2)

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. Erratum in: J Clin Endocrinol Metab. 2016 Oct;101(10 ):3863. — View Citation

Tuvia S, Atsmon J, Teichman SL, Katz S, Salama P, Pelled D, Landau I, Karmeli I, Bidlingmaier M, Strasburger CJ, Kleinberg DL, Melmed S, Mamluk R. Oral octreotide absorption in human subjects: comparable pharmacokinetics to parenteral octreotide and effective growth hormone suppression. J Clin Endocrinol Metab. 2012 Jul;97(7):2362-9. doi: 10.1210/jc.2012-1179. Epub 2012 Apr 26. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Patients Who Maintain Their Biochemical Response at the End of the Double Blind Placebo Controlled (DPC) Period.	Maintenance of response was defined by using the average IGF-1 level of the last 2 available assessments in the DPC period. If the average IGF-1 is = 1×ULN, a patient was classified as a responder (i.e., maintained their biochemical response). If the average IGF-1 is > 1×ULN, a patient was classified as a non-responder. Patients who discontinue study medication during the DPC period for any reason was classified as non-responders for the primary analysis, regardless of their IGF-1 values.	Week 36
Secondary	Number of Patients Who Maintain Growth Hormone (GH) Response at the End of the Double Blind Placebo Controlled Period	Maintenance of GH response was defined as having mean Growth Hormone (5 measurements 30 minutes apart) < 2.5 ng/mL at the end of the double blind placebo controlled period, out of those who were responders on Somatostatin Receptor Ligands (SRLs) injections at Screening.	Week 36
Secondary	Number of Patients Who Begin Rescue Treatment	Number of Patients who Began Rescue Treatment Prior to and Including Week 36	Week 36

External Links

•   Chiasma Web Page
•   Melmed et al. JCEM 2015