(4.15) Oral octreotide capsules for treatment of acromegaly: a post hoc analysis of biochemical efficacy and safety using a pooled phase 3 clinical trial dataset

The efficacy and safety of oral octreotide capsules (OOC) was assessed in patients with acromegaly who had previously tolerated and responded to the injectable somatostatin receptor ligands (iSRLs), octreotide and lanreotide, in three phase 3 clinical trials (CH-ACM-01, OPTIMAL, MPOWERED). Despite differences in trial design, OOC were well-tolerated and demonstrated consistent maintenance and durability of biochemical response across all trials.

Examine the biochemical response and safety of OOC through a pooled analysis of phase 3 clinical trial datasets.

Methods:

Patients were aged ≥18 years with acromegaly and were biochemically controlled with iSRL therapy (defined as insulin growth factor 1 [IGF-I < 1.3] × upper limit of normal [ULN] and mean integrated growth hormone [GH] < 2.5 ng/mL for CH-ACM-01 and MPOWERED, and IGF-I ≤1.0 × ULN for OPTIMAL) prior to OOC initiation. Data analyzed were from the following periods: baseline until the end of the double-blind placebo-controlled phase of OPTIMAL (36 wks); the run-in phase of MPOWERED (26 wks); end of dose escalation (2-5 mos; efficacy data) and end of fixed dose phase (up to 7 mos, safety data) for CH-ACM-01.  Effect of prior iSRL dose was analyzed using a random effects meta-analysis.  

Results:

Efficacy and safety results were available for 318 and 329 patients, respectively. Baseline IGF-I ≤1.0 × ULN was maintained in 72% (n=155/214) transitioning to OOC therapy, while baseline IGF-I >1.0 and < 1.3 × ULN was maintained or improved in 64% (n=52/81) of patients. Final OOC dose was 40, 60, or 80 mg in 114 (36%), 69 (22%), and 135 (42%) patients. The proportion of patients with last IGF-I ≤1, >1 to < 1.3, and ≥1.3 x ULN on 80mg was 23%, 54%, and 78%. Response rates to OOC were not associated with prior iSRL dose (p >0.05). The most common OOC-related adverse events (AEs) ≥ 5% were nausea (n=72), diarrhea (n=39), flatulence (n=20), abdominal pain (n=18), dyspepsia (n=17), and headache (n=27). Median time to onset (days, [IQR]) of first OOC-related GI AEs was 2 (1-31) for flatulence, 7 (1-67) for nausea, 15 (2-70) for diarrhea, 46.5 (5.5-142) for abdominal pain, and 18 (1-82) for dyspepsia. Mean HbA1c remained consistent from baseline to month 6 and the last measurement across trials (6% for all time points).

Discussion/Conclusion:

OOC resulted in improved or maintained biochemical control in most patients previously responding to iSRL therapy. Safety of OOC derived from pooled analysis was consistent with first-generation iSRLs with no notable increases in GI AEs or those related to glycemic control. These results further support OOC as a viable option for treating acromegaly.