A Dose-response Study With Strontium Malonate in Postmenopausal Women

A Dose-response Study With Strontium Malonate in Postmenopausal Women. A 12 Week, Multi National, Double Blind, Randomized, 5 Arms, Parallel Group Placebo Controlled Open Label Active Controlled, Phase II Study With 3 Dose Levels of Strontium Malonate and Protelos Within Post Menopausal Women With a BMDT-score Below -1

The primary objective of the study is to compare dose-response effect of three dose levels of strontium malonate to placebo on bone resorption quantified by S-CTX-1 following 12 weeks of treatment.

275 post menopausal women are treated with either 750 mg strontium malonate, 1000 mg strontium malonate, 2000 mg strontium malonate, 2 g Protelos® or placebo.

Patients are treated for 12 weeks. A follow up period of 4 weeks is planned for the main study and a follow up period of 8 weeks is planned for approximately 20% of the patients to follow post treatment CTX-1 activity.

Apart from S-CTS-1 also response on other bio markers are evaluated as well as BMD.

Inclusion Criteria:

• Postmenopausal women (at least 12 months since last menstruation).
• BMD (L2-4) T-score between -1 and -3 (at least 20% of the enrolled patients must have a BMD (L2-4) T-score below -2,5).
• 50 years of age.
• BMI<30 kg/m2.
• Total S-Ca level within normal range.
• Ability to read and understand the information given.
• The patient has signed an informed consent form according to ICH E6 and local requirements before any study specific procedure is carried out.
• Ability to comply with study procedures.

Exclusion Criteria:

• History of prior fragility fracture (any fracture in wrist, hip or spine appearing after 40 years of age).
• History of alcohol or drug abuse.
• Metabolic bone disease (e.g. pagets disease, bone cancer).
• History of VTE/DVT.
• History of kidney transplant.
• Bilateral oophorectomy.
• Relevant and treated reduced kidney or liver function.
• Any malignancy within the last 5 years (except basal cell carcinoma)
• Any chronic condition likely to affect absorption (e.g. Crohns disease, gluten enteropathy).
• Known genetic pre-disposition to VTE/DVT
• Known hypersensitivity to any of the active substances or excipients.
• 25-OH-vitamin D level below 25 nmol/L
• Any previous treatment with bisphosphonates, Strontium or fluoride.
• Treatment during the last 3 months affecting calcium balance or bone metabolism (e.g. thiazides, corticosteroids, calcitonin, HRT, SERMs, PTH, phosphorus).
• Treatment during the last week with tetracycline, ciprofloxacin or loop diuretics.
• PTH out of normal range
• Use of any drug known to influence the coagulation process (aspirin and other NSAID allowed)
• Prothrombin time out of normal range (sec or INR)
• Inclusion in another clinical study within 30 days before randomization or during this study