Comparison of Oral Octreotide Capsules to Injectable Somatostatin Analogs in Acromegaly
- Registration Number
- NCT02685709
- Lead Sponsor
- Chiasma, Inc.
- 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).
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 146
- 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)
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description RCT phase - Injectables Octreotide capsules Injectable somatostatin analogs (octreotide or lanreotide) Combination phase (sub-study) Octreotide capsules Octreotide capsules plus cabergoline Run-in phase Octreotide capsules Oral octreotide capsules RCT phase - Oral Octreotide capsules Oral octreotide capsules
- Primary Outcome Measures
Name Time Method Proportion of Patients Who Are Biochemically Controlled Throughout the RCT Phase 62 weeks 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
- Secondary Outcome Measures
Name Time Method Proportion of Patients With Clinical and Biochemical Control at the End of the RCT Phase Week 62/ End of treatment; EOT Proportion of patients with clinical and biochemical control at the end of the RCT phase. Patients were considered biochemically and clinically controlled if they met both of the following criteria:
* Their IGF-1 TWA during the RCT phase was \<1.3 times ULN
* Their AIS score at week 62/EOT was maintained or reduced compared to week 26 (start of RCT phase)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 reduce the overall number of active acromegaly symptoms at the end of the RCT phase (week 62/ EOT) , compared to week 26 (start of the RCT phase
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 who maintain or improve their overall Acromegaly index of severity (AIS) score at the end of the RCT phase (improvement defined as a reduction of at least one point in the AIS score), compared to week 26 (start of the RCT phase)
Proportion of Patients of Those Completing the RCT Phase Who Entered the Study Extension Phase 62 weeks Proportion of patients of those completing the RCT phase (at a time octreotide capsules were not commercially available at the specific country), who entered the Study Extension phase, overall and by treatment group
Change in IGF-1 Levels in the RCT Phase Change from Week 26 to week 62 Change in IGF-1 levels from the start of the randomized phase to the end of RCT phase.
Complete Responder (CR) is defined as IGF-1 ≤ 1 x ULN; Partial Responder (PR) is defined as 1 x ULN \< IGF-1 \< 1.3 x ULN, and Non-Responder (NR): IGF-1 ≥ 1.3 x ULNChange in GH Levels in the RCT Phase Change from Week 26 to week 62 Change in GH levels from the start of the randomized phase through the end of RCT phase.
Trial Locations
- Locations (53)
Katedra i Klinika Endokrynologii i Chorob Wewnetrznych Gdanski Uniwersytet Medyczny
🇵🇱Gdańsk, Poland
Rutgers - Robert Wood Johnson Medical School
🇺🇸New Brunswick, New Jersey, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
University of Colorado Denver
🇺🇸Aurora, Colorado, United States
Houston Methodist Research Institute
🇺🇸Houston, Texas, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Keck Medical Center of University of Southern California
🇺🇸Los Angeles, California, United States
Magyar Honvedseg Egeszsegugyi Kozpont
🇭🇺Budapest, Hungary
Central Manchester University Hospitals NHS Foundation Trust, Manchester Royal Infirmary
🇬🇧Manchester, United Kingdom
"Centre Diabetes" LLC
🇷🇺Samara, Russian Federation
Royal Victoria Infirmary
🇬🇧Newcastle upon Tyne, United Kingdom
Universitätsklinik für Innere Medizin Klinische Abteilung für Endokrinologie und Diabetologie
🇦🇹Graz, Austria
Campus Del Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Emory University
🇺🇸Atlanta, Georgia, United States
John H. Stroger, Jr. Hospital of Cook County
🇺🇸Chicago, Illinois, United States
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Hôpital Bicêtre APHP
🇫🇷Le Kremlin-Bicêtre, France
Hospices Civils de Lyon
🇫🇷Bron, France
University of Pecs
🇭🇺Pecs, Hungary
Szegedi Tudományegyetem, I. Belgyógyászati Klinika
🇭🇺Szeged, Hungary
Policlinico di Monserrato U.O.C. Endocrinologia e Diabetologia
🇮🇹Monserrato, Italy
Hospital of LUHS Kauno Klinikos
🇱🇹Kaunas, Lithuania
Vaidotas Urbanavicius Individuali Imonė
🇱🇹Vilnius, Lithuania
Università di Pisa Dipartimento di Medicina Clinica e Sperimentale
🇮🇹Pisa, Italy
Fondazione Policlinico Universitario A. Gemelli Università Cattolica del S.Cuore S.C. Endocrinologia e Malattie del Metabolismo
🇮🇹Rome, Italy
Interregional Clinical Diagnostic Center
🇷🇺Kazan, Russian Federation
"Atlas" Medical Center
🇷🇺Moscow, Russian Federation
Regional State Budgetary Healthcare Institution Regional State Hospital
🇷🇺Krasnoyarsk, Russian Federation
Novosibirsk State Regional Clinical Hospital
🇷🇺Novosibirsk, Russian Federation
Sechenov Moscow First State Medical University
🇷🇺Moscow, Russian Federation
Hospital Universitari Germans Trias i Pujol
🇪🇸Barcelona, Spain
Clinical Centre of Serbia, Clinic for Endocrinology Diabetes and Metabolic Diseases
🇷🇸Belgrade, Serbia
Antrium Multidisciplinary Medical Clinic
🇷🇺Barnaul, Russian Federation
Stanford University School of Medicine
🇺🇸Stanford, California, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Hospital Universitario de la Ribera
🇪🇸Alzira, Spain
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Royal Hallamshire Hospital
🇬🇧Sheffield, United Kingdom
The Ohio State University Wexner Medical Center
🇺🇸Columbus, Ohio, United States
Vladimirsky Moscow Regional Research Clinical Institute
🇷🇺Moscow, Russian Federation
Praxis für Endokrinologie und Diabetologie Dr M Droste
🇩🇪Oldenburg, Germany
Allegheny Endocrinology Associates
🇺🇸Pittsburgh, Pennsylvania, United States
University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital
🇬🇧Birmingham, United Kingdom
Hospital General Universitario Gregorio Maranon
🇪🇸Madrid, Spain
Federal State Budgetary Institution "V. A. Almazov Federal North-West Medical Research Centre" of the Ministry of Health of the Russian Federation
🇷🇺Saint-Petersburg, Russian Federation
Complejo Hospitalario Universitario de Santiago de Compostela
🇪🇸Santiago de Compostela, Spain
Samodzielny Publiczny Szpital Kliniczny nr 1 we Wroclawiu, Klinika Endokrynologii, Diabetologii i Leczenia Izotopami
🇵🇱Wroclaw, Poland
Medizinische Universität Wien
🇦🇹Wien, Austria
"C.I. Parhon" National Institute of Endocrinology I Clinical Endocrinology Department - Endemic goitier and its complications
🇷🇴Bucharest, Romania
Baylor College of Medicine
🇺🇸Houston, Texas, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States