Comparison of Oral Octreotide Capsules to Injectable Somatostatin Analogs in Acromegaly

Phase 3

Completed

Conditions: Acromegaly

Interventions: Drug: Octreotide capsules

Registration Number: NCT02685709

Lead Sponsor: 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).

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 146

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

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
RCT phase - Injectables	Octreotide capsules	Injectable somatostatin analogs (octreotide or lanreotide)
Combination phase (sub-study)	Octreotide capsules	Octreotide capsules plus cabergoline
Run-in phase	Octreotide capsules	Oral octreotide capsules
RCT phase - Oral	Octreotide capsules	Oral octreotide capsules

Primary Outcome Measures

Name	Time	Method
Proportion of Patients Who Are Biochemically Controlled Throughout the RCT Phase	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

Name	Time	Method
Proportion of Patients With Clinical and Biochemical Control at the End of the RCT Phase	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	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	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	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	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	Change from Week 26 to week 62	Change in GH levels from the start of the randomized phase through the end of RCT phase.

Trial Locations

Locations (53): University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States
Keck Medical Center of University of Southern California
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Los Angeles, California, United States
Cedars-Sinai Medical Center
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Los Angeles, California, United States
Stanford University School of Medicine
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Stanford, California, United States
University of Colorado Denver
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Aurora, Colorado, United States
Emory University
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Atlanta, Georgia, United States
Northwestern University
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Chicago, Illinois, United States
John H. Stroger, Jr. Hospital of Cook County
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Chicago, Illinois, United States
Johns Hopkins University
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Baltimore, Maryland, United States
Massachusetts General Hospital
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Boston, Massachusetts, United States
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University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States