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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02685709
Other study ID # OOC-ACM-302
Secondary ID 2015-002854-11
Status Completed
Phase Phase 3
First received
Last updated
Start date February 2016
Est. completion date August 2021

Study information

Verified date March 2022
Source Chiasma, Inc.
Contact n/a
Is FDA regulated No
Health authority
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 (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).


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 information / eligibility

Status Completed
Enrollment 146
Est. completion date August 2021
Est. primary completion date October 2020
Accepts healthy volunteers No
Gender All
Age group 18 Years to 75 Years
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Octreotide capsules


Locations

Country Name City State
Austria Universitätsklinik für Innere Medizin Klinische Abteilung für Endokrinologie und Diabetologie Graz
Austria Medizinische Universität Wien Wien
France Hospices Civils de Lyon Bron
France Hôpital Bicêtre APHP Le Kremlin-Bicêtre
Germany Praxis für Endokrinologie und Diabetologie Dr M Droste Oldenburg
Hungary Magyar Honvedseg Egeszsegugyi Kozpont Budapest
Hungary University of Pecs Pecs
Hungary Szegedi Tudományegyetem, I. Belgyógyászati Klinika Szeged
Italy Policlinico di Monserrato U.O.C. Endocrinologia e Diabetologia Monserrato
Italy 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
Lithuania Hospital of LUHS Kauno Klinikos Kaunas
Lithuania Vaidotas Urbanavicius Individuali Imone Vilnius
Poland Katedra i Klinika Endokrynologii i Chorob Wewnetrznych Gdanski Uniwersytet Medyczny Gdansk
Poland Samodzielny Publiczny Szpital Kliniczny nr 1 we Wroclawiu, Klinika Endokrynologii, Diabetologii i Leczenia Izotopami Wroclaw
Romania "C.I. Parhon" National Institute of Endocrinology I Clinical Endocrinology Department - Endemic goitier and its complications Bucharest
Russian Federation Antrium Multidisciplinary Medical Clinic Barnaul
Russian Federation Interregional Clinical Diagnostic Center Kazan
Russian Federation Regional State Budgetary Healthcare Institution Regional State Hospital Krasnoyarsk
Russian Federation "Atlas" Medical Center Moscow
Russian Federation Sechenov Moscow First State Medical University Moscow
Russian Federation Vladimirsky Moscow Regional Research Clinical Institute Moscow
Russian Federation Novosibirsk State Regional Clinical Hospital Novosibirsk
Russian Federation 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 "Centre Diabetes" LLC Samara
Serbia Clinical Centre of Serbia, Clinic for Endocrinology Diabetes and Metabolic Diseases Belgrade
Spain Hospital Universitario de la Ribera Alzira
Spain Hospital Universitari Germans Trias i Pujol Barcelona
Spain Hospital General Universitario Gregorio Maranon Madrid
Spain Complejo Hospitalario Universitario de Santiago de Compostela Santiago de Compostela
Spain Campus Del Hospital Universitario Virgen del Rocio Sevilla
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 Kingdom Royal Hallamshire Hospital Sheffield
United States Emory University Atlanta Georgia
United States University of Colorado Denver Aurora Colorado
United States Johns Hopkins University Baltimore Maryland
United States University of Alabama at Birmingham Birmingham Alabama
United States Massachusetts General Hospital Boston Massachusetts
United States John H. Stroger, Jr. Hospital of Cook County Chicago Illinois
United States Northwestern University Chicago Illinois
United States The Ohio State University Wexner Medical Center Columbus Ohio
United States Baylor College of Medicine Houston Texas
United States Houston Methodist Research Institute 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 Rutgers - Robert Wood Johnson Medical School New Brunswick New Jersey
United States Columbia University Medical Center New York New York
United States Thomas Jefferson University Philadelphia Pennsylvania
United States Allegheny Endocrinology Associates Pittsburgh Pennsylvania
United States Washington University School of Medicine Saint Louis Missouri
United States Stanford University School of Medicine Stanford California

Sponsors (1)

Lead Sponsor Collaborator
Chiasma, Inc.

Countries where clinical trial is conducted

United States,  Austria,  France,  Germany,  Hungary,  Italy,  Lithuania,  Poland,  Romania,  Russian Federation,  Serbia,  Spain,  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. J Clin Endocrinol Metab. 2020 Dec 1;105(12):. — View 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. Review. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Other Proportion of Patients Reporting Injection Site Reactions in the Acro-TSQ During the RCT Phase Proportion of patients reporting injection site reactions (ISRs). Acromegaly treatment satisfaction questionnaire (ACRO-TSQ) is a validated PRO tool assessing overall convenience and satisfaction with treatment and patient perception of symptomatic control and adverse drug. It includes 6 scales: Symptom Interference, (4 items); Treatment Convenience, (6 items); Injection Site Interference (2 items); GI Interference (3 items); Treatment Satisfaction, (3 items); and Emotional Reaction (3 items). Each scale score can range from 0 to 100, with 0 representing the lowest (highest burden/lower satisfaction) and 100 representing the best possible score (lowest burden/highest satisfaction) for each of the 6 scales. Positive ACRO-TSQ change scores indicate improvement while negative change scores indicate worsening. 62 weeks
Other Proportion of Patients Reporting Interference With Daily Activities in Acro-TSQ During the RCT Phase Proportion of patients reporting interference with daily activities in the Acromegaly Treatment Satisfaction Questionnaire (Acro-TSQ) during the RCT phase.
Acro-TSQ is a validated PRO tool assessing overall convenience and satisfaction with treatment and patient perception of symptomatic control and adverse drug. It includes 6 scales: Symptom Interference, (4 items); Treatment Convenience, (6 items); Injection Site Interference (2 items); GI Interference (3 items); Treatment Satisfaction, (3 items); and Emotional Reaction (3 items). Each scale score can range from 0 to 100, with 0 representing the lowest (highest burden/lower satisfaction) and 100 representing the best possible score (lowest burden/highest satisfaction) for each of the 6 scales. Positive Acro-TSQ change scores indicate improvement while negative change scores indicate worsening.
62 weeks
Other Proportion of Patients on Octreotide Capsules Who Are Biochemically Controlled at the End of the RCT Phase- Landmark Analysis Proportion of patients on octreotide capsules who are biochemically controlled at the end of the RCT phase defined as IGF-1< 1.3 x ULN based on average of weeks 58 and 62 Average of weeks 58 and 62
Other Proportion of Week 26 Responders on Octreotide Capsules Who Are Biochemically Controlled at the End of the RCT Phase- Landmark Sensitivity Analysis Proportion of patients on Octreotide Capsules Who Are Biochemically Controlled at the End of the RCT Phase- Landmark sensitivity analysis- Week 26 responders 62 weeks
Other Proportion of Patients Biochemically Controlled at the End of Run-in Proportion of patients biochemically controlled at the end of the Run-in phase, defined as average IGF-1 levels during weeks 24 and 26 < 1.3xULN 26 weeks
Other Proportion of Patients With a Reduction in the Overall Number of Active Acromegaly Symptoms at the End of the Run-in Phase Proportion of patients with a reduction in the overall number of active acromegaly symptoms at the end of the Run-in phase compared to Baseline 26 weeks
Other Proportion of Patients With Improved Acromegaly Index of Severity (AIS) Score at the End of the Run-in Phase Proportion of patients with improved AIS score at the end of the Run-in phase compared to Baseline Acromegaly index of severity (AIS) at the end of Run-in phase compared to Baseline.
The Acromegaly Index of Severity (AIS) symptom score is calculated based on the presence and severity of 5 acromegaly signs/symptoms: headache, swelling of extremities, joint pain, sweating, and fatigue. Each symptom was graded from no symptoms (score 0), to mild symptoms (1), moderate (2), or severe symptoms (3).
26 weeks
Other EuroQol - 5 Dimensions - 5 Levels (EQ-5D-5L) Index Scores During the Run-in Phase Change from baselines in EQ-5D-5L Index scores in randomized participants during the Run-in phase.
EQ-5D-5L (five severity levels EQ-5D) is a standardized instrument completed by the patient for use as a measure of health outcome applicable to a wide range of health conditions. It comprises 5 dimensions of health: mobility, ability to self care, ability to undertake usual activities, pain and discomfort, and anxiety and depression. Based on qualitative and quantitative studies conducted by the EuroQol Group, there are 5 levels under each domain: 'no problems' (assigned a value of 1), 'slight problems' (assigned a value of 2), 'moderate problems' (assigned a value of 3), 'severe problems' (assigned a value of 4), and 'unable to/extreme problems' (assigned a value of 5). An EQ-5D Index score is calculated based on the responses to these 5 dimensions of health. Weights for use in the index calculation are not universally available. Higher values represent better health states.
26 weeks
Other Change From Baseline to End of RCT Phase in WPAI Work Productivity and Activity Impairment Questionnaire- RCT phase. WPAI:SHP is a standardized and validated PRO questionnaire to measure health outcomes in clinical trial settings. It measures time missed from work, impairment of work and regular activities due to overall health and symptoms, relative to measures of general health perceptions, role (physical), role (emotional), pain, symptom severity, and global measures of work and interference with regular activity.
The WPAI yields 4 types of scores: (1) absenteeism (work time missed); (2) presenteeism (impairment at work/reduced on-the-job effectiveness); (3) work productivity loss (overall work impairment/absenteeism plus presenteeism); and (4) activity impairment. Each of the 4 WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity (i.e., worse outcomes).
26 weeks
Other Change From Baseline to End of Run-in Phase in WPAI Work Productivity and Activity Impairment Questionnaire- Run-in phase. WPAI:SHP is a standardized and validated PRO questionnaire to measure health outcomes in clinical trial settings. It measures time missed from work, impairment of work and regular activities due to overall health and symptoms, relative to measures of general health perceptions, role (physical), role (emotional), pain, symptom severity, and global measures of work and interference with regular activity.
The WPAI yields 4 types of scores: (1) absenteeism (work time missed); (2) presenteeism (impairment at work/reduced on-the-job effectiveness); (3) work productivity loss (overall work impairment/absenteeism plus presenteeism); and (4) activity impairment. Each of the 4 WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity (i.e., worse outcomes).
62 weeks
Other Change in Acromegaly Treatment Satisfaction Questionnaire (ACRO-TSQ) Scores From Baseline to End of Run-in in Randomized Patients. Change in Acromegaly treatment satisfaction questionnaire (ACRO-TSQ) PRO questionnaire from baseline to end of Run-in phase in randomized patients.
Acro-TSQ is a validated PRO tool assessing overall convenience and satisfaction with treatment and patient perception of symptomatic control and adverse drug. It includes 6 scales: Symptom Interference, (4 items); Treatment Convenience, (6 items); Injection Site Interference (2 items); GI Interference (3 items); Treatment Satisfaction, (3 items); and Emotional Reaction (3 items). Each scale score can range from 0 to 100, with 0 representing the lowest (highest burden/lower satisfaction) and 100 representing the best possible score (lowest burden/highest satisfaction) for each of the 6 scales. Positive Acro-TSQ change scores indicate improvement while negative change scores indicate worsening.
26 weeks
Primary 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 Proportion of Patients With Clinical and Biochemical Control at the End of the RCT Phase 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)
Week 62/ End of treatment; EOT
Secondary Proportion of Patients Who Maintain or Reduce the Overall Number of Active Acromegaly Symptoms at the End of the RCT Phase 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 62 weeks
Secondary Proportion of Patients Who Maintain or Improve Their Overall Acromegaly Index of Severity (AIS) Score at the End 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 (improvement defined as a reduction of at least one point in the AIS score), compared to week 26 (start of the RCT phase) 62 weeks
Secondary Proportion of Patients of Those Completing the RCT Phase Who Entered the Study Extension Phase 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 62 weeks
Secondary Change in IGF-1 Levels in the RCT Phase 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 ULN
Change from Week 26 to week 62
Secondary Change in GH Levels in the RCT Phase Change in GH levels from the start of the randomized phase through the end of RCT phase. Change from Week 26 to week 62
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