title: A randomized, double-blind, multicenter, placebo-controlled study to evaluate the efficacy and safety of oral salmon calcitonin in the treatment of osteoporosis in postmenopausal women taking calcium and vitamin D.
abstract: This randomized, double-blind, placebo-controlled phase III study was conducted to assess the efficacy and safety of oral calcitonin (SMC021) for the treatment of postmenopausal osteoporosis. A total of 4665 postmenopausal women with osteoporosis were randomized 1:1 to receive calcium and vitamin D plus either SMC021 tablets (0.8mg/d) or placebo for 36months. The primary endpoint was the proportion of patients with a new vertebral fracture. The two groups were well balanced at baseline with regards to demographic and clinical data. No effect of SMC021 on preventing new vertebral fractures was observed, nor was any effect seen on new hip or non-vertebral fractures. Women receiving SMC021 had a mean 1.02% (±0.12%) increase in lumbar spine bone mineral density (BMD) compared with a mean 0.18% (±0.12%) increase in the placebo group by the end of the study (p<0.0001). Similarly, small increases in BMD were observed at the femoral neck and hip in both groups. Levels of the biomarkers of bone turnover, urinary CTX-I and CTX-II, were 15% lower in the SMC021 group than in the placebo arm at 12 and 24months, but not at 36months. No change in quality of life between groups, assessed by the Qualeffo-14 questionnaire, was observed in either group between baseline and month 36. Pharmacokinetics analysis confirmed exposure to SMC021, but the drug levels were markedly lower than expected. Approximately 92% of subjects in each treatment group experienced an adverse event (AE), the majority of which were mild or moderate in intensity. AEs associated with SMC021 were primarily of gastrointestinal origin and included nausea, vomiting and abdominal pain, as well as hot flushes which were the reason for the slightly higher drop-out rate in the active treatment arm compared to placebo. The number of severe AEs was low in both groups. Thirty-five deaths were reported but none were considered treatment-related. Due to the lack of efficacy in preventing fractures, the development of the orally formulated calcitonin was terminated despite the promising results in earlier studies.
authors.affiliation: Nordic Bioscience Biomarkers & Research, Nordic Bioscience A/S, Herlev Hovedgade 205-207, DK-2730 Herlev, Denmark. Electronic address: kh@nordicbioscience.com.
authors.forename: Kim
authors.initials: K
authors.lastname: Henriksen
authors.affiliation: Nordic Bioscience Clinical Development, Nordic Bioscience A/S, Herlev Hovedgade 205-207, DK-2730 Herlev, Denmark.
authors.forename: Inger
authors.initials: I
authors.lastname: Byrjalsen
authors.affiliation: Nordic Bioscience Clinical Development, Nordic Bioscience A/S, Herlev Hovedgade 205-207, DK-2730 Herlev, Denmark.
authors.forename: Jeppe R
authors.initials: JR
authors.lastname: Andersen
authors.affiliation: Nordic Bioscience Clinical Development, Nordic Bioscience A/S, Herlev Hovedgade 205-207, DK-2730 Herlev, Denmark.
authors.forename: Asger R
authors.initials: AR
authors.lastname: Bihlet
authors.affiliation: Center for Clinical and Basic Research (CCBR), Rio de Janeiro, Brazil.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Russo
authors.affiliation: Center for Clinical and Basic Research (CCBR), Vejle, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Alexandersen
authors.affiliation: Center for Clinical and Basic Research (CCBR), Tallinn, Estonia.
authors.forename: Ivo
authors.initials: I
authors.lastname: Valter
authors.affiliation: Nordic Bioscience Biomarkers & Research, Nordic Bioscience A/S, Herlev Hovedgade 205-207, DK-2730 Herlev, Denmark.
authors.forename: Per
authors.initials: P
authors.lastname: Qvist
authors.affiliation: Center for Clinical and Basic Research (CCBR), Hong Kong, China.
authors.forename: Edith
authors.initials: E
authors.lastname: Lau
authors.affiliation: Nordic Bioscience Clinical Development, Nordic Bioscience A/S, Herlev Hovedgade 205-207, DK-2730 Herlev, Denmark.
authors.forename: Bente J
authors.initials: BJ
authors.lastname: Riis
authors.affiliation: Nordic Bioscience Clinical Development, Nordic Bioscience A/S, Herlev Hovedgade 205-207, DK-2730 Herlev, Denmark.
authors.forename: Claus
authors.initials: C
authors.lastname: Christiansen
authors.affiliation: Nordic Bioscience Biomarkers & Research, Nordic Bioscience A/S, Herlev Hovedgade 205-207, DK-2730 Herlev, Denmark.
authors.forename: Morten A
authors.initials: MA
authors.lastname: Karsdal
mesh_terms: D000284:Administration, Oral; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D015519:Bone Density; D016723:Bone Remodeling / Q000187:drug effects; D002116:Calcitonin / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002118:Calcium / Q000627:therapeutic use*; D003710:Demography; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D015994:Incidence; D015663:Osteoporosis, Postmenopausal / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D058866:Osteoporotic Fractures / Q000150:complications / Q000188:drug therapy / Q000453:epidemiology / Q000503:physiopathology; D010919:Placebos; D011788:Quality of Life; D012307:Risk Factors; D016896:Treatment Outcome; D014807:Vitamin D / Q000627:therapeutic use*
chemical_list: D015415:Biomarkers; D010919:Placebos; D014807:Vitamin D; C028815:salmon calcitonin; D002116:Calcitonin; D002118:Calcium
keywords: Calcitonin; Efficacy; Fractures; Osteoporosis; Safety