E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Postmenopausal Osteoporosis |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
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 |
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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 |
First Extension
To assess the effect of treatment up to 5 years with odanacatib on the risk of morphometrically assessed vertebral fractures compared to placebo. To assess the effect of treatment up to 5 years with odanacatib on the risk of clinical hip fractures compared to placebo. To assess the effect of treatment up to 5 years with odanacatib on the risk of non-vertebral clinical fractures compared to placebo. To assess safety and tolerability of treatment up to 5 years with odanacatib 50 mg once weekly compared to placebo.
Second extension:
To assess long-term changes from baseline in total hip BMD during 10 years of treatment with odanacatib 50 mg once-weekly in postmenopausal osteoporotic women
previously treated with once-weekly odanacatib for at least 5 years (cumulative of base study and 1st extension study, i.e randomized to odanacatib during the base study
To assess safety and tolerability of long-term treatment with odanacatib 50 mg once-weekly. |
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E.2.2 | Secondary objectives of the trial |
First Extension
To assess the effect of treatment up to 5 years with odanacatib 50 mg once weekly on the lumbar spine, total hip, femoral neck, and trochanter BMD compared to placebo.
To assess the effect of treatment up to 5 years with odanacatib on the risk of all clinical (both non-vertebral and vertebral) fractures compared to placebo.
Second extension
To assess long-term changes from baseline in BMD of lumbar spine, femoral neck, and trochanter during 10 years of treatment with odanacatib 50 mg once-weekly.
To determine the incidence of morphometrically assessed vertebral fractures during 10 years of treatment with odanacatib 50 mg once-weekly.
To determine the incidence of all clinical (both non-vertebral and vertebral) fractures during 10 years of treatment with odanacatib 50 mg once-weekly.
To assess changes from baseline in BMD of lumbar spine, total hip, femoral neck, and trochanter during 5 years of treatment with odanacatib 50 mg onceweekly.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
First Extension
Note that patients inappropriately randomized into the trial (i.e., those who do not meet entry criteria) may be discontinued from the study at the discretion of the SPONSOR.
1) Patient completed the base study on blinded study therapy PN018 (Note that an interruption up to 6 weeks at end of the base study is acceptable).
2) Patient has at least one hip (e.g. contains no hardware from orthopedic procedures) and suitable spinal anatomy that is evaluable by DXA.
3) Patient understands the study procedures, alternative treatments available, and risks involved with the study, and voluntarily agrees to participate by providing informed consent.
4) Patient/subject is able to read, understand and complete questionnaires and diaries. Note: If a patient who understands the purpose and use of the diary cards and study questionnaires is unable to complete these without assistance (e.g. due to visual
problems, difficulty writing due to arthritis, inability to read, etc.), a family member or care-giver may assist or may complete the diary card on her behalf.
Second Extension
NOTE: Subjects inappropriately randomized into the trial (i.e., those who do not meet entry
criteria) may be discontinued from the study at the discretion of the SPONSOR.
1. Have met all initial inclusion criteria and have not met any of the exclusion or discontinuation criteria of either the base or 1st extension studies.
2. Be an active participant and have successfully completed the 1st extension study on study medication. (Note that an interruption about 12 weeks at end of the extension study is acceptable).
3. Have demonstrated compliance in following the procedures required during the base and/or 1st extension studies.
4. Have at least one hip (e.g. contains no hardware from orthopedic procedures) AND suitable spinal anatomy that is evaluable by DXA.
5. Understand the study procedures, alternative treatments available, risks involved with the study, and voluntarily agrees to participate by providing informed consent.
6. Be able to read, understand and complete questionnaires and diaries.
7. Subject is in generally good health, based on medical history, physical examination, and laboratory evaluation. |
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E.4 | Principal exclusion criteria |
Base study
1) Patient has chosen treatment with oral bisphosphonates or other agents demonstrated to reduce the risk of hip fracture.
2) Patient has had a prior hip fracture.
3) Patient experienced a clinical fragility fracture (including a clinical vertebral fracture) within 24 months. (Note: Finger, toe, and skull fractures should not be considered with regard to this exclusion criterion.)
4) Patient has had more than 1 prior vertebral fracture, as defined in Inclusion Criterion 1 above, and she is a suitable candidate for osteoporosis therapy (i.e., bisphosphonates, strontium, or PTH).
5) Patient has or has had evidence of a metabolic bone disorder other than osteoporosis.
First Extension
Note that patients inappropriately randomized into the trial (i.e., those who do not meet entry criteria) may be discontinued from the study at the discretion of the SPONSOR.
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 ranelate, 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. rifampin, carbamazepine, phenytoin, St. John’s wort).
Second extension
The subject must be excluded from participating in the trial if the subject:
1. 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 subject’s participation for the full duration of the study, such that it is not in the best interest of the subject to participate.
2. Is receiving treatment with:
1) 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.)
2) Subject is planning to initiate or is currently using long-term therapy (6 weeks or longer) with any strong CYP3A4 inducers (see Appendix 12.5 for examples).
3. Is, in the opinion of the investigator, mentally or legally incapacitated such that informed consent cannot be obtained or the subject cannot read or comprehend the written material.
4. Has participated in an investigational drug study other than the base study or 1st extension study within the past 30 days.
5. Is currently a user of recreational or illicit drugs or has had a recent history of drug or alcohol abuse or dependence. |
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E.5 End points |
E.5.1 | Primary end point(s) |
First Extension
The primary focus of this study will be on morphometic vertebral fractures. Lateral thoracic and lumbar spine radiographs will be obtained for each patient at baseline of the core study, Month 6, Month 12, and yearly thereafter until the end of the 5-year doubleblind extension study. The primary endpoint will be the first morphometrically assessed vertebral fracture per patient determined from these radiographs, analyzed as intervalcensored
survival data. All available x-ray data will be included in the analyses and time windows will be defined in a separate document to define timing, extending those of the core study.
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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 | 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 | Yes |
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 | 20 |
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 |
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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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This is an event-driven trial, which will end when the required number of fractures to test the hypotheses have occurred |
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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 | 13 |
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 | 13 |
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 |