Octreotide hydrogel implant safe, effective in acromegaly

American Association of Clinical Endocrinologists 20th Annual Meeting

SAN DIEGO — Patients with acromegaly who received a 52-mg octreotide hydrogel implant for 6 months achieved consistent biochemical control and reduced tumor size, according to results of a study presented here.

The phase 2, open-label, randomized study evaluated the safety and efficacy of a subcutaneous 52-mg octreotide hydrogel implant (Endo Pharmaceuticals) for the treatment of acromegaly. Octreotide is contained in the middle of a cartridge made of hydrogel, the same material found in soft contact lenses, which is implanted subcutaneously in the upper forearm.

The small study included 11 patients (mean age, 47 years) at a single center in Brazil who were randomly assigned to receive one (n=5) or two (n=6) 52-mg implants. The implants were inserted on day 1 of the study and removed at month 6. Patients were then followed for the 6 months and for 1 month after the implants were removed.

“This is the first study to evaluate the effectiveness and safety of octreotide hydrogel implant,” Theodore Danoff, MD, PhD, vice president of clinical development, endocrinology/urology, Endo Pharmaceuticals, said during a late-breaking session.

According to the results, the octreotide hydrogel implant suppressed mean insulin-like growth factor I levels during the 6 months; however, levels increased after the implants were removed. One patient in the one-implant group achieved normalization of IGF-I for the entirety of the study, as did two patients in the two-implant group. Those who did not achieve IGF-I normalization had a mean 40% reduction in IGF-I levels.

An oral glucose tolerance test was performed at insertion and at month 6, and growth hormone levels were assessed at 0, 30, 60, 90 and 120 minutes after the OGTT. The researchers found that patients also achieved “good suppression” of GH concentrations throughout the study; again, levels increased once the implants were removed. One patient in the one-implant group and three in the two-implant group achieved GH concentrations <1 ng/mL.

Tumor size was reduced by 23% among patients who received one implant and by 38% in patients who received two implants.

The researchers also measured quality of life, using a series of questions that examined efficacy, satisfaction with treatment, discomfort and other factors. Danoff said patient ratings of efficacy and satisfaction were high and patient ratings of discomfort, pain and disruption of daily activities was low.

“Patients were highly satisfied and felt it was effective for their treatment,” Danoff said.

Regarding safety, all patients reported at least one adverse event. Most adverse events related to treatment were gastrointestinal related. Four of the five patients who received one implant and three of the six patients who received two implants had diarrhea, mostly during the first week of therapy and it resolved within 1 week.

“Based on the results of this, we move forward to a phase 3 study, which is studying an 84-mg implant, and that is currently ongoing,” Danoff said.

For more information:

• Danoff T. Recent and late breaking clinical trials. Effectiveness and safety of an octreotide hydrogel implant in patients with acromegaly. Presented at: American Association of Clinical Endocrinologists 20th Annual Meeting; April 13-17, 2011; San Diego.

Disclosure: Dr. Danoff is an employee of Endo Pharmaceuticals.

Endo Pharmaceuticals presented an abstract demonstrating the effect of a 6-month subcutaneous octreotide hydrogel implant in acromegaly. This was a small study of 11 subjects in Brazil who were randomized to two doses of the octreotide implant. All patients had previously demonstrated response to octreotide. In the study, IGF-I levels normalized in one of five subjects with one implant and two of six with two implants over the 6 months. The implant was well tolerated, and this therapy may well have a role as an alternative vehicle for octreotide therapy. A phase 3 study is necessary to determine more thoroughly the efficacy in acromegaly patients, as this current study showed limited IGF-I normalization in a population that had already demonstrated somatostatin analog responsiveness. In addition, a phase 3 study will provide further information as to the routine use of an implantable octreotide pellet. The subcutaneous octreotide implant may provide improved patient compliance and hence may be an important addition to our medical therapy for acromegaly.

– Laurence Katznelson, MD
Medical Director,
Pituitary Center, Stanford Medical Center

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