Comparison of Oral Octreotide Capsules to Injectable Somatostatin Analogs in Acromegaly

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

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).

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.

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