Safety and Efficacy of Multiple Dosing Regimens of BPS804 in Postmenopausal Women With Low Bone Mineral Density

• Change from baseline to month 9 in bone mineral density at the lumbar spine for the individual BPS804 groups and pooled placebo arms. [ Time Frame: 9 months ] [ Designated as safety issue: No ]
• The number (percent) of subjects experiencing adverse events or serious adverse events [ Time Frame: 9 months ] [ Designated as safety issue: Yes ]

• Change from baseline during 9 months of serological bone biomarkers for the individual BPS804 groups and pooled placebo arms. [ Time Frame: 9 months ] [ Designated as safety issue: No ]
• Characterization of the PK profile of BPS804: area under the plasma concentration-time curve (AUC) [ Time Frame: 260 days ] [ Designated as safety issue: No ]
• Characterization of the PK profile of BPS804: time to reach the maximum Characterization of the PK profile of BPS804: maximum plasma concentration (Cmax) [ Time Frame: 260 days ] [ Designated as safety issue: No ]
• Characterization of the PK profile: time to reach the maximum concentration (Tmax) [ Time Frame: 260 days ] [ Designated as safety issue: No ]
• Characterization of the PK profile of BPS804: half-life (T1/2) [ Time Frame: 260 days ] [ Designated as safety issue: No ]

This study is designed to provide information on the safety, tolerability, pharmacokinetics (PK) and bone biomarker response following multiple BPS804 administration in multiple dosing regimens. This information will permit a comparison of the possible risks and benefits of different dosing regimens of the study drug to enable optimal doses and dose intervals to be tested in subsequent studies.

• Osteopenia
• Osteoporosis

• Drug: BPS804
• Drug: Placebo

• Experimental: BPS804 dosing frequency 1
  Intervention: Drug: BPS804
• Placebo Comparator: placebo dosing frequency 1
  Intervention: Drug: Placebo
• Experimental: BPS804 dosing frequency 2
  Intervention: Drug: BPS804
• Placebo Comparator: placebo dosing frequency 2
  Intervention: Drug: Placebo
• Experimental: BPS804 dosing frequency 3
  Intervention: Drug: BPS804
• Placebo Comparator: Placebo dosing frequency 3
  Intervention: Drug: Placebo

Inclusion Criteria:

• Postmenopausal women (natural or surgically induced menopause)
• Low bone mineral density (BMD), as defined by a T score or equivalent BMD absolute value (g/cm2) for lumbar spine of between -2.0 and -3.5, inclusive
• Body mass index (BMI) must be within the range of 18 to 35kg/m2. Subjects must weigh between 45 and 120kg inclusive to participate.
• 25-(OH) vitamin D serum level of ≥ 15ng/ml
• Serum calcium within normal limits

Exclusion Criteria:

• Subjects with suspected neural foraminal stenosis (e.g., cervical, spinal, lumbar), or history of Bell's palsy, cranial nerve disorders, temporomandibular joint and muscle disorders.
• Subjects who have an increased baseline risk of osteosarcoma: Paget's disease of the bone or unexplained and clinically significant elevations of alkaline phosphatase and/or subjects who have received radiation therapy involving the skeleton.
• Subjects with any known bone diseases other than postmenopausal osteoporosis.
• Subjects with a history of an osteoporotic fracture (e.g., vertebral fracture, fragility fracture of the wrist, radius, humerus, hip, or pelvis).

• Subjects who are regularly using or have regularly used agents affecting bone metabolism:

  • Calcitonin, estrogen, SERMs (raloxifene, Tamoxifen, etc.), Tibolone progestin, or androgens within the last three (3) months prior to screening.
  • Any oral bisphosphonate, lithium chloride, fluoride or systemic glucocorticosteroids (p.o. or i.v.) where the total dose exceeds 750 mg of prednisone or equivalent within the last year prior to screening.
  • Any previous use of denusomab (ProliaTM), parathyroid hormone (ForteoTM), and/or PTH analogs, strontium ranelate, or parenteral formulations of bisphosphonates.
• Current disease(s) known to influence calcium metabolism including hyperparathyroidism, hypoparathyroidism, hypocalcemia or hypercalcemia.
• Any disease, abnormality or deformation of the spine (e.g., scoliosis, ankylosing spondylitis, osteophytes) or hip (e.g., joint prosthesis) which would preclude the proper acquisition of a lumbar spine DXA (L1-L4) or femur DXA, respectively.

Other protocol-defined inclusion/exclusion criteria may apply