Clinical trial NCT02685709: Comparison of Oral Octreotide Capsules to Injectable Somatostatin Analogs in Acromegaly
Official title: A Phase 3, Randomized, Active Controlled Study to Evaluate Maintenance of Response, Safety and Patient Reported Outcomes in Acromegaly Patients Treated With Octreotide Capsules vs. Parenteral Somatostatin Receptor Ligands
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acromegaly
Keywords: Octreotide Capsules
Acromegaly
somatostatin receptor ligands (SRLs)
Mpowered
OOC-ACM-302
Lead sponsor: Chiasma, Inc.
Sponsor class: INDUSTRY
First posted: 2016-02-19
Enrollment: 146
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Proportion of Patients Who Are Biochemically Controlled Throughout the RCT Phase
timeFrame: 62 weeks
Secondary outcomes:
measure: Proportion of Patients With Clinical and Biochemical Control at the End of the RCT Phase
timeFrame: Week 62/ End of treatment; EOT
measure: Proportion of Patients Who Maintain or Reduce the Overall Number of Active Acromegaly Symptoms at the End of the RCT Phase
timeFrame: 62 weeks
measure: Proportion of Patients Who Maintain or Improve Their Overall Acromegaly Index of Severity (AIS) Score at the End of the RCT Phase
timeFrame: 62 weeks
measure: Proportion of Patients of Those Completing the RCT Phase Who Entered the Study Extension Phase
timeFrame: 62 weeks
measure: Change in IGF-1 Levels in the RCT Phase
timeFrame: Change from Week 26 to week 62
measure: Change in GH Levels in the RCT Phase
timeFrame: Change from Week 26 to week 62
Other outcomes:
measure: Proportion of Patients Reporting Injection Site Reactions in the Acro-TSQ During the RCT Phase
timeFrame: 62 weeks
measure: Proportion of Patients Reporting Interference With Daily Activities in Acro-TSQ During the RCT Phase
timeFrame: 62 weeks
measure: Proportion of Patients on Octreotide Capsules Who Are Biochemically Controlled at the End of the RCT Phase- Landmark Analysis
timeFrame: Average of weeks 58 and 62
measure: Proportion of Week 26 Responders on Octreotide Capsules Who Are Biochemically Controlled at the End of the RCT Phase- Landmark Sensitivity Analysis
timeFrame: 62 weeks
measure: Proportion of Patients Biochemically Controlled at the End of Run-in
timeFrame: 26 weeks
measure: Proportion of Patients With a Reduction in the Overall Number of Active Acromegaly Symptoms at the End of the Run-in Phase
timeFrame: 26 weeks
measure: Proportion of Patients With Improved Acromegaly Index of Severity (AIS) Score at the End of the Run-in Phase
timeFrame: 26 weeks
measure: EuroQol - 5 Dimensions - 5 Levels (EQ-5D-5L) Index Scores During the Run-in Phase
timeFrame: 26 weeks
measure: Change From Baseline to End of RCT Phase in WPAI
timeFrame: 26 weeks
measure: Change From Baseline to End of Run-in Phase in WPAI
timeFrame: 62 weeks
measure: Change in Acromegaly Treatment Satisfaction Questionnaire (ACRO-TSQ) Scores From Baseline to End of Run-in in Randomized Patients.
timeFrame: 26 weeks
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Los Angeles
country: United States
facility: Keck Medical Center of University of Southern California
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
city: Aurora
country: United States
facility: University of Colorado Denver
state: Colorado
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: John H. Stroger, Jr. Hospital of Cook County
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New Brunswick
country: United States
facility: Rutgers - Robert Wood Johnson Medical School
state: New Jersey
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny Endocrinology Associates
state: Pennsylvania
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: Houston Methodist Research Institute
state: Texas
city: Graz
country: Austria
facility: Universitätsklinik für Innere Medizin Klinische Abteilung für Endokrinologie und Diabetologie
city: Wien
country: Austria
facility: Medizinische Universität Wien
city: Bron
country: France
facility: Hospices Civils de Lyon
city: Le Kremlin-Bicêtre
country: France
facility: Hôpital Bicêtre APHP
city: Oldenburg
country: Germany
facility: Praxis für Endokrinologie und Diabetologie Dr M Droste
city: Budapest
country: Hungary
facility: Magyar Honvedseg Egeszsegugyi Kozpont
city: Pecs
country: Hungary
facility: University of Pecs
city: Szeged
country: Hungary
facility: Szegedi Tudományegyetem, I. Belgyógyászati Klinika
city: Monserrato
country: Italy
facility: Policlinico di Monserrato U.O.C. Endocrinologia e Diabetologia
city: Pisa
country: Italy
facility: Università di Pisa Dipartimento di Medicina Clinica e Sperimentale
city: Rome
country: Italy
facility: Fondazione Policlinico Universitario A. Gemelli Università Cattolica del S.Cuore S.C. Endocrinologia e Malattie del Metabolismo
city: Kaunas
country: Lithuania
facility: Hospital of LUHS Kauno Klinikos
city: Vilnius
country: Lithuania
facility: Vaidotas Urbanavicius Individuali Imonė
city: Gdańsk
country: Poland
facility: Katedra i Klinika Endokrynologii i Chorob Wewnetrznych Gdanski Uniwersytet Medyczny
city: Wroclaw
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny nr 1 we Wroclawiu, Klinika Endokrynologii, Diabetologii i Leczenia Izotopami
city: Bucharest
country: Romania
facility: "C.I. Parhon" National Institute of Endocrinology I Clinical Endocrinology Department - Endemic goitier and its complications
city: Barnaul
country: Russian Federation
facility: Antrium Multidisciplinary Medical Clinic
city: Kazan
country: Russian Federation
facility: Interregional Clinical Diagnostic Center
city: Krasnoyarsk
country: Russian Federation
facility: Regional State Budgetary Healthcare Institution Regional State Hospital
city: Moscow
country: Russian Federation
facility: Sechenov Moscow First State Medical University
city: Moscow
country: Russian Federation
facility: "Atlas" Medical Center
city: Moscow
country: Russian Federation
facility: Vladimirsky Moscow Regional Research Clinical Institute
city: Novosibirsk
country: Russian Federation
facility: Novosibirsk State Regional Clinical Hospital
city: Saint-Petersburg
country: Russian Federation
facility: Federal State Budgetary Institution "V. A. Almazov Federal North-West Medical Research Centre" of the Ministry of Health of the Russian Federation
city: Samara
country: Russian Federation
facility: "Centre Diabetes" LLC
city: Belgrade
country: Serbia
facility: Clinical Centre of Serbia, Clinic for Endocrinology Diabetes and Metabolic Diseases
city: Alzira
country: Spain
facility: Hospital Universitario de la Ribera
city: Barcelona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Santiago de Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago de Compostela
city: Sevilla
country: Spain
facility: Campus Del Hospital Universitario Virgen del Rocio
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital
city: Manchester
country: United Kingdom
facility: Central Manchester University Hospitals NHS Foundation Trust, Manchester Royal Infirmary
city: Newcastle upon Tyne
country: United Kingdom
facility: Royal Victoria Infirmary
city: Sheffield
country: United Kingdom
facility: Royal Hallamshire Hospital
Study officials:
affiliation: Northwest Pituitary Center, Oregon Health & Science University , Portland, OR, USA
name: Maria Fleseriu, M.D., FACE
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.