| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Postmenopausal osteoporosis / Osteoporosis postmenopáusica |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10031285 |
| E.1.2 | Term | Osteoporosis postmenopausal |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To determine the effect of treatment with AMG 785 versus placebo at month 12 on the percent change from baseline in bone mineral density (BMD) at the lumbar spine in postmenopausal women with low bone density. |
|
| E.2.2 | Secondary objectives of the trial |
To study the effects of up to 12 months of treatment with AMG 785 versus placebo on the percent change from baseline:
- in BMD at lumbar spine (at month 6), total hip and femoral neck (at months 6 and 12), and distal radius (at month 12), and
- in bone turnover markers (BTMs). |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
| -Quantitative Computed Tomography. Date,Ver.: 20 Mar 09, Amend.4.Object.: To investigate the effect of AMG785 on trabecular and cortical bone as assessed by QCT of the spine and/or proximal femur. -Iliac Crest Bone Biopsy. Date,Ver.: 20 Mar 09, Amend. 4. Object.: To investigate the effect of AMG 785 on bone histology and histomorphometry based on transiliac bone biopsies. -24-Hour Urine Collection. Date, Ver.: March 09, Amend. 4.Object.: To determine 24h calcium levels. |
|
| E.3 | Principal inclusion criteria |
To be eligible for enrollment subjects must meet the following criteria:
- Ambulatory, postmenopausal women (based on medical history) aged > or = 55 to < or = 85. Postmenopausal will be defined as no vaginal bleeding or spotting for at least one year. If there is uncertainty regarding menopausal status:
- Women 60 years of age and older will be considered postmenopausal
- Women 55-59 must have confirmation of serum FSH > or = 50 mIU/ml and serum estradiol < or = 20 pg/mL at screening
- Low BMD measured by Dual energy X-ray Absorptiometry (DXA) and assessed by the central imaging vendor (refer to table below for eligible BMD values).
- Subjects must have at least two evaluable vertebrae in the L1-L4 region, and at least one evaluable hip.
- Subjects must not have a BMD value at any anatomical site (lumbar spine, total hip and femoral neck) that is below the lower limit specified for that site.
- Scans will be done in duplicate and the mean of the scans from at least one anatomical site (lumbar spine, total hip or femoral neck) must meet the BMD values defined in table below.
Eligible BMD values; Lunar (g/cm2); Hologic (g/cm2)
Lumbar Spine (a); < or =0.940 and > or = 0.760; < or= 0.827and > or = 0.662
Total Hip (b); < or= 0.756 and > or =0.567; < or= 0.698 and > or = 0.515
Femoral Neck (b); < or= 0.760 and > or = 0.551; < or= 0.618 and > or =0.438
(a) Values correspond to T-scores between -2.0 and -3.5 as determined by the manufacturer
(b) Values correspond to T-scores between -2.0 and -3.5 Based on data for Caucasian women from the National Health and Nutritional Examination Survey (NHANES) 1998 |
|
| E.4 | Principal exclusion criteria |
Subjects meeting any of the following criteria are not eligible for participation in the study:
- History of vertebral fracture or fragility fracture (a fracture resulting from no or minor trauma, ie fall from standing height or less) of the wrist, humerus, hip or pelvis after age 50.
- History of metabolic or bone disease that may interfere with the interpretation of the results, such as Paget's disease, rheumatoid arthritis, osteomalacia, osteogenesis imperfecta, osteopetrosis, ankylosing spondylitis, Cushing's disease, hyperprolactinemia, and malabsorption syndrome.
- Vitamin D deficiency (defined as 25 (OH) vitamin D levels < 20 ng/mL as determined by the central laboratory. Vitamin D repletion will be permitted and subjects may be re-screened once.
- Evidence of any of the following:
- Untreated hyper- or hypothyroidism (TSH out of normal range as determined by the central laboratory).
- Current hyper- or hypoparathyroidism (PTH outside the normal range as determined by the central lab).
- Elevated transaminases as determined by the central laboratory.
a) Serum aspartate aminotransferase (AST; serum glutamate-oxaloacetic transaminase [SGOT]) > or = 2.0 x upper limits of normal.
b) Serum alanine aminotransferase (ALT; serum glutamate-pyruvate transaminase [SGPT]) > or = 2.0 x upper limits of normal.
- Significantly impaired renal function as determined by a derived creatinine clearance of less than or equal 30 mL/min using the Modification of Diet in Renal Disease equation, calculated by the central laboratory.
- Current hyper- or hypocalcemia as determined by the central laboratory analysis of albumin adjusted serum calcium.
- History of spinal stenosis.
- History of facial nerve paralysis.
- Known to have tested positive for human immunodeficiency virus, hepatitis C virus, or hepatitis B surface antigen.
- Malignancy (except fully resected cutaneous basal cell or squamous cell carcinoma, cervical or breast ductal carcinoma in situ) within the last 5 years.
- History of solid organ or bone marrow transplants.
- Use of the following agents affecting bone metabolism:
- Intravenous bisphosphonates at any time in the past.
- Fluoride (for osteoporosis) within the past 24 months.
- Denosumab at any time in the past.
- Bisphosphonates, parathyroid hormone or strontium within the past 12 months.
- Calcitonin, selective estrogen receptor modulators, systemic oral or transdermal estrogen (except vaginal preparations and estrogen creams which are acceptable) or tibolone within the past 3 months.
- Systemic glucocorticosteroids (> or = 5 mg prednisone equivalent per day for more than 10 days) within the past 3 months.
- Contraindicated or intolerant of ALN therapy; contraindications and potential signs of intolerance for ALN therapy include:
- Abnormalities of the esophagus and other factors which delay esophageal emptying such as stricture or achalasia.
- Inability to stand or sit upright for at least 30 minutes.
- Hypersensitivity to ALN or any component of the ALN product.
- Active gastric or duodenal ulcer; history of significant gastrointestinal bleed requiring hospitalization or transfusion, or dyspepsia or gastroesophageal reflux disease that is uncontrolled by medication.
- Contraindicated or intolerant of TPTD therapy; contraindications for TPTD therapy include:
- Hypersensitivity to teriparatide or to any of its excipients.
- Unexplained elevations of alkaline phosphatase.
- Prior external beam or implant radiation therapy involving the skeleton.
- Bone metastases or a history of skeletal malignancies.
- Known sensitivity to mammalian cell derived drug products.
- Known intolerance to calcium supplements.
- Previous enrollment in an AMG 785 clinical study.
- Currently enrolled in or has not yet completed at least 1 month since ending other investigational device or drug trial(s).
- Any condition which in the opinion of the investigator.
- Compromises the ability of the subject to give written informed consent.
- Prevents the subject from complying with study procedures.
- Prevents the subject from completing the study.
- Interferes with the interpretation of study results. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint is the percent change from baseline at month 12 in BMD at the lumbar spine for the individual AMG 785 groups and pooled placebo arms. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| The study is placebo-controlled with open label active comparators |
|
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 19 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The end of study (EOS) will be the date on which the final subject completes the final
study procedure. However, subjects with neutralizing antibodies present at EOS will
return to the clinic approximately every 12 weeks for blood sampling to test for presence of neutralizing antibodies. Subjects will be followed for a period of one year or until the neutralizing antibodies are no longer detectable, whichever comes first. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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