E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Postmenopausal Osteoporosis |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10031285 |
E.1.2 | Term | Osteoporosis postmenopausal |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
|
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 assess the effect of treatment for up to five years with MK-0822 50 mg once weekly on the risk of morphometrically assessed vertebral fractures compared to placebo.
To assess the effect of treatment with MK-0822 on the risk of hip fractures compared to placebo.
To assess the effect of treatment with MK-0822 on the risk of clinical non-vertebral fractures compared to placebo. (Note: for the purposes of this study, non-vertebral fractures exclude fractures of the fingers, toes, face and skull).
|
|
E.2.2 | Secondary objectives of the trial |
To assess the effect of treatment with MK-0822 50 mg once weekly:
on the risk of clinical vertebral fractures compared to placebo.
on height compared to placebo.
on the lumbar spine, total hip, femoral neck, trochanter and distal forearm BMD compared to placebo.
on biochemical indices of bone resorption (serum C-Telopeptides of Type 1 collagen [s-CTx] and urine N-Telopeptides of Type 1 collagen [u-NTx]) compared to placebo.
on biochemical indices of bone formation (serum bone-specific alkaline phosphatase [BSAP] and serum-P1NP) compared to placebo.
on qualitative histomorphometry of transilial bone biopsy specimens compared to placebo.
on lumbar spine, total hip, femoral neck, and hip trochanter BMD compared to placebo, in patients who are bisphosphonate-intolerant (i.e. patients with a contraindication to or a history of intolerance or oral bisphosphonate use).
To assess the safety and tolerability of treatment with MK-0822 50 mg once weekly compared to placebo.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patient is a woman and is ≥ 65 years of age on the day of randomisation.
2. Patient meets one of the following:
a) Patient is a candidate for osteoporosis therapy (bisphosphonates, strontium, or PTH), has BMD T-score ≤-1.5 at either the total hip or femoral neck site, BMD T-score ≥-4.0 at both sites, and has one prior vertebral fracture (defined as anterior, mid or posterior height loss of >20%). – OR-
b) Patient is a candidate for osteoporosis therapy (bisphosphonates, strontium, or PTH), has BMD T-score ≤-2.5 at either the total hip or femoral neck site, BMD T-score ≥-4.0 at both sites, and does not have a prior vertebral fracture (defined as anterior, mid or posterior height loss of >20%). – OR -
c) Patient is not a suitable candidate for, or has declined osteoporosis therapy (bisphosphonates, strontium, or PTH), has BMD T-score ≤-1.5 at either the total hip or femoral neck site, and has at least one prior vertebral fracture (defined as anterior, mid or posterior height loss of >20%). – OR-
d) Patient is not a suitable candidate for, or has declined osteoporosis therapy (bisphosphonates, strontium, or PTH), and has a BMD T-score ≤-2.5 at either the total hip or femoral neck site and does not havea prior vertebral fracture (defined as anterior, mid or posterior height loss of >20%).
3. The patient has at least one hip that is evaluable by DXA (e.g., contains no hardware from orthopedic procedures).
4. Patient has been postmenopausal for at least 5 years, defined as no menses for at least 5 years OR at least 5 years status post bilateral oophorectomy
5. Patient completed the base study on blinded therapy PN018 (note that interruption up to 6 weeks at the end of the base study is acceptable
6. Patient understands the study procedures, alternative treatments available and risks involved with the study and voluntarily agrees to participate by providing informed consent
7. Patient/Subject is able to read, understand and complete questionnaires and diaries
|
|
E.4 | Principal exclusion criteria |
In addition to the exclusion criteria defined in the original submission:
1) Patient has a history or current evidence of any condition, therapy, lab abnormality or other circumstance that might confound the results of the study, or interfere with the patient’s participation for the full duration of the study, such that it is not in the best interest of the patient to participate.
2) Patient met excessive bone loss criteria as defined in the base study.
3) Patient met any of the discontinuation rules as defined in the base study PN018.
4) Patient is receiving treatment with:
a. Current use of osteoporosis therapy including: bisphosphonates, PTH, strontium, systemic estrogen + progestin, raloxifene or other SERM, RANK ligand inhibitor, or sub-cutaneous calcitonin. (Note: use of intranasal calcitonin is permitted.)
b. Current use of long-term therapy (6 months) with any strong CYP3A4 inducers (e.g. rifampicin, carbamazepine, phenytoin, St. John’s wort).
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Morphometric fractures, hip fractures, and clinical non-vertebral fractures. |
|
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 | Yes |
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 | Information not present in EudraCT |
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) | 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 | 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) | 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
| 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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 143 |
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
|
This Extension Study will continue as a Double blind trial until the patient has completed 5 years Blinded Treatment, after which the patient will be transfered to active, open label treatment until the last patient Worldwide has completed 5 Years Blinded Treatment |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 7 |