E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The trial is Phase III. The population will be osteoporotic post-menopausal women who are between 55 and 85 years of age |
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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 |
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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 |
The primary objective is to demonstrate the superiority of 0.8 mg of SMC021 relative to placebo on the proportion of study subjects with new vertebral fractures. The primary safety objective is to characterize the safety and tolerability profile of SMC021 in this population based on the adverse event incidence and changes in laboratory profiles. Exploratory objectives include investigating new bone or cartilage markers that may become available. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective is to demonstrate the superiority of 0.8 mg of SMC021 relative to placebo on the proportion of study subjects with non-vertebral fractures.
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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 |
BMD substudy according to Protocol Version 1.4 dated 17 January 2007.
1. The BMD substudy (equal number of study subjects from group A and B).
In total, six hundred randomly selected subjects will have their DXA BMD analyzed centrally:
o The changes in BMD measured at the proximal femur (total hip, femoral neck) for all patients. o The changes in BMD measured at the lumbar spine (L1 – L4) for all patients.
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E.3 | Principal inclusion criteria |
· Postmenopausal, ambulatory women, between 55 and 85 years old
· A: BMD T-score <=–2.5 at one or more of the following regions: the lumbar spine, femoral neck or total hip, and no more than 2 prevalent mild or moderate vertebral fractures according to the definition of Genant et al (15). No severe fracture is permitted. The inclusion will be defined by the absolute BMD values (g/cm2).
OR
· B: BMD T-score <= –1.5 at one or more of the following regions: the lumbar spine, femoral neck or total hip together with one or two osteoporotic fracture(s) located at the spine according to the definition of Genant et al (15). The inclusion will be defined by the absolute BMD values (g/cm2).
· Ethical criteria - before any study-specific procedure is performed, the appropriate written informed consent must be obtained.
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E.4 | Principal exclusion criteria |
· Any participant will be excluded from the study, if they have a bone mineral density (BMD) T-score below –4.0 (based on absolute values g/cm2 as given in the protocol) at one or more of the measured sites.
· Any participant will be excluded from the study, if they have more than 2 prevalent vertebral fractures (Genant et al, 15).
· If BMD is lower than -2.5 T-score at one or more of the measured sites, the participants will be excluded from the study, if they have a severe vertebral fracture (Genant et al, 15).
· Participants will be excluded from the study, if they have evidence of any clinical osteoporotic fracture and/or if they have a history of a clinical osteoporotic fracture (excluding wrist fractures). A clinical vertebral fracture is defined as vertebral fracture associated with pain or functional disability.
· BMD T-score > -1.5 in all of the following regions: Lumbar spine, femoral neck or total hip.
· Evidence of any of the following from medical history, laboratory results, DXA, or X-ray review:
o History of renal stone o Current hyper- or hypothyroidism. Patients on stable thyroid treatment will be allowed o Current hyper- or hypoparathyroidism o Rheumatoid arthritis o Paget’s disease o Malignancy (except basal cell carcinoma, cervical or breast ductal carcinoma in situ) within the last 5 years o Any bone disease, e.g. osteomalacia or osteogenesis imperfecta, which may interfere with the interpretation of the findings o Untreated or symptomatic malabsorption syndrome o Height, weight and girth which may preclude accurate DXA measurements o Advanced scoliosis or extensive lumbar fusion which would preclude vertebral fracture assessment o Less than 2 lumbar vertebrae (L1-L4) evaluable for DXA (for the BMD substudy population). Subjects that fulfil the BMD inclusion criteria at the hip, and are not enrolled in the BMD substudy, may be enrolled even if there are not 2 evaluable lumbar vertebrae. o Screening 25 (OH) vitamin D level less than 24 ng/mL (=60 nmol/l). The patient may be treated with 25 (OH) vitamin D3 and serum vitamin D may then be retested. o Serum levels of intact PTH above 68 pg/ml o Current hypocalcaemia (albumin adjusted serum calcium below 2.13 mmol/L [8.5 mg/dL])
· Any organic or psychiatric disorder, or laboratory abnormality which, in the opinion of the Investigator, will prevent the subject from completing the study or interfere with the interpretation of the study results.
· Evidence of alcohol or substance abuse that the Investigator believes would interfere with understanding or completing the study.
· Subjects with any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures.
· The subject is currently enrolled in a clinical study or at least 30 days have not elapsed since ending other investigational device or drug trial(s).
· The subject has evidence of any heart conduction disorders (this criterion is applicable to Lithuania only by Amendment 3).
· Participants will be excluded from the trial if they have evidence of any new heart conduction disorders (this criterion is applicable to Lithuania only by Amendment 3).
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint to be assessed is the number of patients with new vertebral fracture.
Safety endpoints include adverse events, changes in safety laboratory analyses (serum chemistry, hematology), and number of subjects with antibodies (Yes/No) |
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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 | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | No |
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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 11 |
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 |
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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
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The last visit of the last patient defines the end of the trial |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
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 | 4 |
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 |