Comparison of Oral Octreotide Capsules to Injectable Somatostatin Analogs in Acromegaly (MPOWERED)
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| ClinicalTrials.gov Identifier: NCT02685709 |
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Recruitment Status :
Completed
First Posted : February 19, 2016
Results First Posted : April 22, 2022
Last Update Posted : April 22, 2022
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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).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Acromegaly | Drug: Octreotide capsules | Phase 3 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 146 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | February 2016 |
| Actual Primary Completion Date : | October 2020 |
| Actual Study Completion Date : | August 2021 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Run-in phase
Oral octreotide capsules
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Drug: Octreotide capsules
Other Name: Injection SRLs |
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Experimental: RCT phase - Oral
Oral octreotide capsules
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Drug: Octreotide capsules
Other Name: Injection SRLs |
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Active Comparator: RCT phase - Injectables
Injectable somatostatin analogs (octreotide or lanreotide)
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Drug: Octreotide capsules
Other Name: Injection SRLs |
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Experimental: Combination phase (sub-study)
Octreotide capsules plus cabergoline
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Drug: Octreotide capsules
Other Name: Injection SRLs |
- Proportion of Patients Who Are Biochemically Controlled Throughout the RCT Phase [ Time Frame: 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
- Proportion of Patients With Clinical and Biochemical Control at the End of the RCT Phase [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 ULN
- Change in GH Levels in the RCT Phase [ Time Frame: Change from Week 26 to week 62 ]Change in GH levels from the start of the randomized phase through the end of RCT phase.
- Proportion of Patients Reporting Injection Site Reactions in the Acro-TSQ During the RCT Phase [ Time Frame: 62 weeks ]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.
- Proportion of Patients Reporting Interference With Daily Activities in Acro-TSQ During the RCT Phase [ Time Frame: 62 weeks ]
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.
- Proportion of Patients on Octreotide Capsules Who Are Biochemically Controlled at the End of the RCT Phase- Landmark Analysis [ Time Frame: Average of weeks 58 and 62 ]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
- Proportion of Week 26 Responders on Octreotide Capsules Who Are Biochemically Controlled at the End of the RCT Phase- Landmark Sensitivity Analysis [ Time Frame: 62 weeks ]Proportion of patients on Octreotide Capsules Who Are Biochemically Controlled at the End of the RCT Phase- Landmark sensitivity analysis- Week 26 responders
- Proportion of Patients Biochemically Controlled at the End of Run-in [ Time Frame: 26 weeks ]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
- Proportion of Patients With a Reduction in the Overall Number of Active Acromegaly Symptoms at the End of the Run-in Phase [ Time Frame: 26 weeks ]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
- Proportion of Patients With Improved Acromegaly Index of Severity (AIS) Score at the End of the Run-in Phase [ Time Frame: 26 weeks ]
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).
- EuroQol - 5 Dimensions - 5 Levels (EQ-5D-5L) Index Scores During the Run-in Phase [ Time Frame: 26 weeks ]
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.
- Change From Baseline to End of RCT Phase in WPAI [ Time Frame: 26 weeks ]
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).
- Change From Baseline to End of Run-in Phase in WPAI [ Time Frame: 62 weeks ]
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).
- Change in Acromegaly Treatment Satisfaction Questionnaire (ACRO-TSQ) Scores From Baseline to End of Run-in in Randomized Patients. [ Time Frame: 26 weeks ]
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.
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| Ages Eligible for Study: | 18 Years to 75 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02685709
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| Study Chair: | Maria Fleseriu, M.D., FACE | Northwest Pituitary Center, Oregon Health & Science University , Portland, OR, USA |
Documents provided by Chiasma, Inc.:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Chiasma, Inc. |
| ClinicalTrials.gov Identifier: | NCT02685709 |
| Other Study ID Numbers: |
OOC-ACM-302 2015-002854-11 ( EudraCT Number ) |
| First Posted: | February 19, 2016 Key Record Dates |
| Results First Posted: | April 22, 2022 |
| Last Update Posted: | April 22, 2022 |
| Last Verified: | March 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
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Octreotide Capsules Acromegaly somatostatin receptor ligands (SRLs) Mpowered OOC-ACM-302 |
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Acromegaly Bone Diseases, Endocrine Bone Diseases Musculoskeletal Diseases Hyperpituitarism Pituitary Diseases Hypothalamic Diseases Brain Diseases |
Central Nervous System Diseases Nervous System Diseases Endocrine System Diseases Octreotide Gastrointestinal Agents Antineoplastic Agents, Hormonal Antineoplastic Agents |