Clinical trial NCT01406548: Safety and Efficacy of Multiple Dosing Regimens of BPS804 in Post Menopausal Women With Low Bone Mineral Density
Official title: A Randomized, Double-blind, Placebo-controlled, Multiple Dose Study to Assess the Safety and Efficacy of Multiple Dosing Regimens of BPS804 in Post Menopausal Women With Low Bone Mineral Density
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Osteopenia
Osteoporosis
Keywords: Osteopenia
osteoporosis
low bone mineral density
Lead sponsor: Ultragenyx Pharmaceutical Inc
Sponsor class: INDUSTRY
Collaborators: name: Mereo BioPharma
name: Novartis
First posted: 2011-08-01
Enrollment: 44
Sex: FEMALE
Minimum age (years): 45
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: This study was conducted and previously posted by Novartis. The record was transferred to Ultragenyx in February 2021.

Eligibility criteria: 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

Primary outcomes:
measure: Change from baseline to month 9 in bone mineral density at the lumbar spine for the individual BPS804 groups and pooled placebo arms.
timeFrame: 9 months
measure: The number (percent) of subjects experiencing adverse events or serious adverse events
timeFrame: 9 months
Secondary outcomes:
measure: Change from baseline during 9 months of serological bone biomarkers for the individual BPS804 groups and pooled placebo arms.
timeFrame: 9 months
measure: Characterization of the PK profile of BPS804: area under the plasma concentration-time curve (AUC)
timeFrame: 260 days
measure: Characterization of the PK profile of BPS804: time to reach the maximum Characterization of the PK profile of BPS804: maximum plasma concentration (Cmax)
timeFrame: 260 days
measure: Characterization of the PK profile: time to reach the maximum concentration (Tmax)
timeFrame: 260 days
measure: Characterization of the PK profile of BPS804: half-life (T1/2)
timeFrame: 260 days
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Novartis Investigative Site
state: California
city: Miami
country: United States
facility: Novartis Investigative Site
state: Florida
city: Miami
country: United States
facility: Novartis Investigative Site
state: Florida
city: Berlin
country: United States
facility: Novartis Investigative Site
state: New Jersey
city: Duncansville
country: United States
facility: Novartis Investigative Site
state: Pennsylvania
Study officials:
affiliation: Ultragenyx Pharmaceutical Inc
name: Medical Director
role: STUDY_DIRECTOR
References: