Oral Salmon Calcitonin Superior to Nasal Formulation, Placebo

Nancy A. Melville

September 23, 2011

September 23, 2011 (San Diego, California) — Oral recombinant salmon calcitonin tablets are more effective at improving lumbar spine bone mineral density (BMD) after 48 weeks than placebo or a nasal formulation of the hormone, according to the results of a phase 3 multinational double-blind trial.

In the study, presented here at the American Society for Bone and Mineral Research 2011 Annual Meeting, researchers compared the tablet form of salmon calcitonin (Tarsa Therapeutics) with a nasal formulation and placebo in 565 postmenopausal women from 6 countries.

The women, 45 years or older, had BMD T scores of –2.5 or less at the lumbar spine, femoral neck, or total hip, or a T score of 2.0 or less and a previous vertebral fracture.

They were randomized in a 4:3:2 ratio to receive, for 48 weeks, oral recombinant salmon calcitonin tablets 200 µg daily plus nasal placebo, oral placebo plus 200 IU of commercially available synthetic nasal salmon calcitonin, or oral placebo plus nasal placebo.

At baseline and at weeks 24 and 48, replicate dual-emission X-ray absorptiometry scans showed the oral formulation to be better than the nasal formulation at increasing BMD (change, 0.77%; 95% confidence interval [CI], 0.09 to 1.45; P = .026).

In the oral group (n = 189), lumbar spine BMD increased 1.53% (P < .001). In the nasal group (n = 140), the increase was 0.76% (P = .014), and in the placebo group (n = 82), the increase was 0.47% (not significant).

The per-protocol population results were similar, with an increase of 1.05% (95% CI, 0.32 to 1.78; P = .005), and consistent with the change in BMD.

At the exit visit, fasting carboxy-terminal collagen crosslink (CTx) serum levels, indicating bone resorption, decreased by 29.9%, 11.4%, and 11.8% in the oral, nasal, and placebo groups, respectively (P < .001 for oral vs nasal).

Among the groups, there were no significant differences in tolerability. The most common adverse events in each group were gastrointestinal issues. Most adverse events were mild or moderate in severity; there were few serious adverse events or fractures.

"These data are robust and consistent with a modest increase in lumbar spine BMD, and the safety profile between oral or nasal formulations and placebo did not differ," said lead author Neil C. Binkley, MD, associate director of the Institute on Aging at the University of Wisconsin–Madison.

"There was a suppression of bone turnover measures by CTx at week 24 that persisted to the end of the study," he said. "The final conclusion is that oral salmon calcitonin may provide an additional option for the treatment of postmenopausal osteoporosis."

"Salmon calcitonin is as much as 30 to 50 times more potent than human calcitonin in suppressing osteoplast absorption. The oral formulation that is being developed might improve convenience and compliance," Dr. Binkley explained.

The formulation is a combination of an organic acid and peptide, which are simultaneously released. It is designed with a coating that prevents opening in the acidic environment of the stomach, but subsequently dissolves in the neutral upper bowel, Dr. Binkley said.

Laura A.G. Armas, MD, who moderated the session, speculated that one reason for the improved efficacy of the oral over the nasal form of salmon calcitonin is its formulation.

"It is likely that the formulation used for the oral tablet is more bioavailable than the nasal form," said Dr. Armas, who is assistant professor at Creighton University's Osteoporosis Research Center, in Omaha, Nebraska.

"It is encouraging to see new forms of osteoporosis treatment options becoming available for clinical use. I will be very interested in further research trials on oral salmon calcitonin."

Dr. Binkley reports receiving research grants from Tarsa Therapeutics. Dr. Armas has disclosed no relevant financial relationships.

American Society for Bone and Mineral Research (ASBMR) 2011 Annual Meeting: Abstract 1134. Presented September 18, 2011.

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