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Comparison of Oral Octreotide Capsules to Injectable Somatostatin Analogs in Acromegaly (MPOWERED)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02685709
Recruitment Status : Completed
First Posted : February 19, 2016
Results First Posted : April 22, 2022
Last Update Posted : April 22, 2022
Sponsor:
Information provided by (Responsible Party):
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).


Condition or disease Intervention/treatment Phase
Acromegaly Drug: Octreotide capsules Phase 3

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.

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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

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Run-in phase
Oral octreotide capsules
Drug: Octreotide capsules
Other Name: Injection SRLs

Experimental: RCT phase - Oral
Oral octreotide capsules
Drug: Octreotide capsules
Other Name: Injection SRLs

Active Comparator: RCT phase - Injectables
Injectable somatostatin analogs (octreotide or lanreotide)
Drug: Octreotide capsules
Other Name: Injection SRLs

Experimental: Combination phase (sub-study)
Octreotide capsules plus cabergoline
Drug: Octreotide capsules
Other Name: Injection SRLs




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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)

  2. 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

  3. 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)

  4. 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

  5. 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


  6. 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.


Other Outcome Measures:
  1. 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.

  2. 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.


  3. 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

  4. 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

  5. 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

  6. 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

  7. 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).


  8. 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.


  9. 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).


  10. 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).


  11. 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.




Information from the National Library of Medicine

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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
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

Information from the National Library of Medicine

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


Locations
Show Show 53 study locations
Sponsors and Collaborators
Chiasma, Inc.
Investigators
Layout table for investigator information
Study Chair: Maria Fleseriu, M.D., FACE Northwest Pituitary Center, Oregon Health & Science University , Portland, OR, USA
  Study Documents (Full-Text)

Documents provided by Chiasma, Inc.:
Study Protocol  [PDF] January 16, 2020
Statistical Analysis Plan  [PDF] May 15, 2019

Additional Information:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
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
Keywords provided by Chiasma, Inc.:
Octreotide Capsules
Acromegaly
somatostatin receptor ligands (SRLs)
Mpowered
OOC-ACM-302
Additional relevant MeSH terms:
Layout table for MeSH terms
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