| Eligibility |
Inclusion Criteria:
- Women who are capable of understanding and giving written, voluntary informed consent
before the clinical study screening visit
- Women with the ability to self-administer a daily injection or having a designee who
will give the injections
- Women who are postmenopausal with at least one year since their last menstruation. If
a subject's menopausal status at screening is in question, because of history or
because the subject had a hysterectomy without oophorectomy, a follicle-stimulating
hormone (FSH) level >40 mIU/mL will satisfy the definition of postmenopausal status.
- Women 45-54 years of age with the following T-score and/or vertebral fracture
- T-score >=3.0 standard deviations (SD) below mean peak bone mass of young women
at the lumbar spine, femoral neck, or total hip Or
- T-score >=2.5 SD below mean peak bone mass of young women at the lumbar spine,
femoral neck, or total hip with a prevalent vertebral fracture verified by the
central imaging organization before the subject is enrolled into the study
- Women >=55 years of age with the following T-score and/or vertebral fracture:
o T-score >=2.5 SD below mean peak bone mass of young women at the lumbar spine,
femoral neck, or total hip Or
- T-score >=2.0 SD below mean peak bone mass of young women at the lumbar spine, femoral
neck, or total hip with a vertebral fracture verified by the central imaging
organization before the subject is enrolled into the study
The following types of vertebral fractures should not be considered for subject enrollment
into this study:
- Pathological fractures due to malignant disease or infection
- Fractures due to excessive trauma sufficient to cause a fracture in young individuals
with normal bone mass
Exclusion Criteria:
A. Vertebral Deformity (assessed as described in Appendix 2 of the protocol, are sufficient
for exclusion):
· Vertebral deformities
- Patient has 5 or more vertebral (thoracic and lumbar) fractures
- Patient has 2 or more lumbar vertebral deformities (L1 to L4)
B. DXA Imaging:
· Inability to have a DXA scan performed, e.g.:
- A history of a lumbar laminectomy which interferes with the DXA measurement of the
lumbar vertebrae
- The presence of pedicle screws
- The patient cannot lay flat on her back for the required time to provide accurate
imaging
- Patient is not able to have an A/P lumbar vertebral DXA performed
- Patient has a history of vertebroplasty
- Any other excessive degenerative disease which interferes with the DXA measurement of
the lumbar vertebrae or hip
C. History of or Concurrent Illness:
- Disorders of Immunity
- HIV
- Significant* immunological disorders
- Endocrine system
- Any history of hyper- or hypoparathyroidism
- Cushing's disease
- Hyperthyroidism (within 12 months)
- Significant* endocrine disorders
- Gastrointestinal system
- Significant* gastrointestinal disorders
- Kidney and collecting system
- Clinically significant* history of nephrolithiasis or urolithiasis
- Current impaired renal function and/or verified kidney calcification*
- Significant* renal disorders
- Liver, biliary tract and pancreatic systems
- Active hepatitis or pancreatitis
- Significant* hepatic or pancreatic disorders
- Musculoskeletal system
- Any history of other metabolic bone diseases within the past 5 years, (e.g.,
Paget´s disease, osteogenesis imperfecta, osteomalacia)
- Subjects with chronic, active joint disease and/or joint infection
- Neoplasia - Any history of bone cancer or any cancer within the previous 5 years, with
the exception of squamous or basal cell carcinoma**
(**)Patients who have had either squamous or basal cell carcinoma of the skin can enroll
if:
1. The lesion(s) were fully resected with clear margins described in a written report by
a pathologist, and
2. The patient has had no recurrence of lesions for at least one year from the time of
the original resection.
· Nervous system
- Significant* neurological or psychiatric disease
· Vascular, respiratory and cardiac system
- Significant* unstable cardiac or pulmonary disease
(*) Significance will be determined by the investigator on the basis of history,
physical exam, and/or laboratory screens. Significant disorders necessitate ongoing
changes in therapeutic medication or frequent monitoring.
D. Concurrent Medication:
Patients cannot be enrolled into this clinical trial if they have received any of the
following therapies at any time:
- Any PTH or PTH analogs [e.g., rhPTH(1-84), PTH(1-34), PTHrP and analogs]
- Fluoride
- Strontium
Patients must have been off the following agents for the specified times before
entering the screening phase of this clinical trial:
- Any investigational drug (>30 days)
- Anabolic steroids or androgens (>6 consecutive months)
- Active Vitamin D3 metabolites and analogs, e.g., calcitriol (>90 days)
- Provera (medroxyprogesterone) (According to label instructions)
- Systemic corticosteroids, more than 5mg/day formulation equivalent to 5mg/day
prednisone (>12 consecutive month or as acute bolus for nonrecurring condition).
A patient who has been enrolled in the study and needs to receive an acute bolus
of steroids (oral or injectable) for a self-limited illness may continue
treatment in the study if the following requirements are met:
- The maximal dose of steroid (prednisone equivalent) is limited to no more
than 225 mg (7.5 mg each day for 30 days)
- The illness is acute in nature and is not expected to recur during the
remaining treatment period of the study
- Inhaled corticosteroids equivalent to <1200 µg of beclomethasone
- Bisphosphonates, including investigational bisphosphonates
- If the patient has received bisphosphonates for >90 days during 12 months
immediately before screening, the patient is excluded from this study.
- If the patient has received bisphosphonates for more than 12 months at any
time.
*The patient may be enrolled if she:
Has taken bisphosphonates for >=30 days but <=90 days, and has completed washout of
equivalent time.
No washout is necessary if the patient has taken bisphosphonates <30 days.
- Intravenous (IV) pamidronate
- Patient can have received 1 dose of pamidronate in >3 to 12 months
immediately preceding the screening visit. Patient should not have received
this 1 dose within the three months immediately prior to the screening visit
- Patient must not have received >2 doses at any time before screening.
- Cyclical Etidronate
- Patient should not have an exposure equal to 9 months on a standard dose
(e.g., 400 mg).
- Exposure to cyclical etidronate must be <=6 months on a standard dose (e.g.,
400 mg/day) prior to the screening visit.
- Phenytoin for seizure control:
- If the patient has received phenytoin <5 years before, the patient is
excluded from this study
- The patient may continue in the screening process if:
>=15 years have passed since the last dose of phenytoin or if use was between 5-15
years before the screening visit and the patient received phenytoin for <2 months
Patients may be enrolled if they have been stabilized on the following therapy for the
specified amount of time:
- Thyroid Hormone (<0.1 mg/day thyroxine) therapy for >=6 months
- If taking >= 0.1 mg/day but <= 0.2 mg/day, must have serum TSH level >= 0.1
mU/L. Patients will be excluded if they are taking doses of >0.2 mg/day.
- If a patient has had a minimal change in L-thyroxine dose of <=0.025 mg/day
within 6 months of enrollment, and has been on this new dose for >=2 months,
she may continue. The patient must have the history documented with
L-thyroxine in the CRF.
- If a patient requires an increase or decrease in her thyroid replacement
dose, after she has been enrolled in this clinical study, each increment or
decrement should be <=0.025 mg/day, and increments should not occur more
frequently than once per month, as recommended by a physician who is caring
for the patient. The patient must have a TSH and thyroxine level within 3
months of the dose change to ensure that the patient does not become
hyperthyroid, or hypothyroid.
- Thiazide (Stable dosage of thiazide for >=3 consecutive months)
All patients must stop the following therapies at least 4 weeks before starting the
stabilization period and will remain off these therapies for the remainder of the
clinical study. The informed consent must be signed prior to the washout of any
therapy. Screening laboratories must be performed only after the washout is complete.
However, imaging studies (BMD, X-rays) may be performed prior to starting the
calcitonin, estrogen, or Selective Estrogen Receptor Modulation (SERM) washout.
· Calcitonin
- Estrogen replacement therapy by oral, transdermal, or intramuscular
administration
- Vaginal application of estrogen-containing creams (If conjugated estrogen or
estradiol: <=0.5 g twice each week [total of 1.0 g weekly] this medication is
allowed)
- SERM drugs, e.g., tamoxifen, raloxifene, Evista
- Cytostatics, e.g., azathioprine, recombinant human tumor necrosis fusion (Fc)
protein, monoclonal antibody against tumor necrosis factor (e.g., remicade
[infliximab]
- Medication known to affect the metabolism of bone (the Principal Investigator
should discuss this with the PMO before the patient is excluded from enrollment).
E. Miscellaneous Concurrent Medications
· Methotrexate,which interferes with DNA synthesis, repair and cellular replication.
· Immunomodulatory agents with antiproliferative activity.
· Intra-articular injections
- Patients may receive a maximum of 1 intra-articular injection (ONE JOINT ONLY) every
6 months while participating in this study. The dose of corticosteroid injected should
not exceed the anti-inflammatory equivalent dose of Prednisone 40-mg suspension. The
dose and volume should be adjusted downward as appropriate to the size of the joint.
F. Laboratory Values and Physical Examination Findings:
-For laboratory values, the levels shown below are the upper limits for exclusions
based on specific test results. For weight, the limit is the lower limit.
· Serum calcium >10.7 mg/dL (>2.67 mmol/L)
· Serum creatinine > 1.5 mg/dL (132.6 µmol/L)
· Urinary calcium to creatinine ratio >=1.0 (mmol/mmol)
- Total serum alkaline phosphatase >130 U/L (Serum total alkaline phosphatase value
given is for the U.S.; >311 U/L (Argentina), >159 U/L (Mexico).
- Body weight <40 kg
G. Substance Abuse:
· Subjects are excluded for a history of alcohol and/or drug abuse as determined by
the investigator
H. Compliance:
Subjects are excluded if they exhibit suspected or confirmed poor compliance in
completing clinical study evaluations and/or clinical study required questionnaires.
|
