Comparison of Oral Octreotide Capsules to Injectable Somatostatin Analogs in Acromegaly

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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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

Conditions
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Acromegaly

Intervention / Treatment
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* Drug: Octreotide capsules


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Run-in phase<br>Oral octreotide capsules | Drug: Octreotide capsules<br> <br> * Other names: Injection SRLs;|
| Experimental: RCT phase - Oral<br>Oral octreotide capsules | Drug: Octreotide capsules<br> <br> * Other names: Injection SRLs;|
| Active Comparator: RCT phase - Injectables<br>Injectable somatostatin analogs (octreotide or lanreotide) | Drug: Octreotide capsules<br> <br> * Other names: Injection SRLs;|
| Experimental: Combination phase (sub-study)<br>Octreotide capsules plus cabergoline | Drug: Octreotide capsules<br> <br> * Other names: Injection SRLs;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Octreotide Capsules, Acromegaly, somatostatin receptor ligands (SRLs), Mpowered, OOC-ACM-302