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 | 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 |
To demonstrate the non-inferiority of oral rsCT tablets compared with calcitonin nasal spray in postmenopausal osteoporotic women using bone mineral density measurements (DXA) in L1-L4 axial lumbar spine over 1 year of treatment. |
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E.2.2 | Secondary objectives of the trial |
To demonstrate the superiority of oral rsCT tablets to placebo in postmenopausal osteoporotic women using bone mineral density measurements (DXA) in L1-L4 lumbar spine over 1 year of treatment.
To evaluate the safety and tolerability of rsCT tablets and calcitonin nasal spray following administration of 200 µg and 200 IU per day, respectively, over 1 year of treatment.
To evaluate the biologic response to rsCT tablets compared with baseline values (time zero) and to the placebo tablet group and calcitonin nasal spray group in postmenopausal osteoporotic women using Beta-CrossLaps, NTx, and total P1NP as markers for bone turnover over 1 year of treatment. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Female and age 45 or over.
Must have undergone the onset of spontaneous or surgical menopause. Spontaneous menopause is defined as 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels >40 mIU/mL or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy.
Diagnosis of osteoporosis on the basis of an axial lumbar spine, femoral neck or total hip BMD which is below the mean for premenopausal women by a magnitude of at least 2.5 SD or 2.0 SD, if there is a documented history of a vertebral fragility fracture.
Must have at least three contiguous lumbar vertebrae (L1-L4) that are evaluable by DXA for BMD that is, without fracture or significant degenerative disease, as determined by Bio-Imaging Technologies, Inc.
A body mass index (BMI) of not greater than 39 (BMI = weight [kg]/height[m]2).
No clinically significant abnormal findings in the medical history, physical exam or nasal exam.
No clinically significant abnormal laboratory values at the screening assessment.
Patients must give written informed consent after reading the Patient Information and Consent Form and having had the opportunity to discuss the study with the Investigator. |
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E.4 | Principal exclusion criteria |
History of severe allergic disease.
History of metabolic and other bone diseases, including osteogenesis imperfecta, osteomalacia, and Paget's disease.
Vitamin D insufficiency defined as a 25 hydroxyvitamin D level <20 ng/mL.
Use of any intravenous bisphosphonate in the past 24 months, or >2 doses of intravenous bisphosphonate ever.
Use of oral bisphosphonate before randomization, including investigational bisphosphonates, unless: less than 6 months of treatment and off for 6 months, or 6 to 12 months of treatment and off for 2 years, or More than 12 months of treatment and off for 5 years
Use of denosumab, fluoride, or strontium, ever.
Use of parathyroid hormone analogs or other bone metabolic agents within 1 year preceding randomization.
Any condition or disease that may interfere with the ability to have a DXA scan or to evaluate a DXA scan, for example, severe osteoarthritis of the spine, spinal fusion, pedicle screws, history of vertebroplasty, or degenerative disease that results in insufficient number of evaluable lumbar vertebrae, or more than 1 lumbar vertebral fracture in L1 through L4. More than 4 vertebral fractures in T4 through L4 Bilateral hip replacements
Use of anabolic steroids or androgens within 6 months preceding randomization.
Use of Vitamin D metabolites and analogs, (e.g., calcitriol) within 3 months preceding randomization. Note: Vitamin D supplementation is not exclusionary.
Use of estrogen or estrogen-related drugs, for example, tamoxifen, tibolone, or raloxifene within 3 months preceding randomization.
Use of calcineurin inhibitors [e.g., cyclosporine, tacrolimus], methotrexate, aromatase inhibitors andantiepileptic medications.
Use of coumadin within 4 weeks preceding randomization or heparin within 1 week preceding randomization.”
Chronic systemic treatment with glucocorticoids, hormone replacement therapy, calcitonin or any other medication within the previous three months which, in the opinion of the Investigator, would interfere with the study.
Clinically relevant abnormal history, physical findings or laboratory values at the pre-study screening assessment that could interfere with the objectives of the study or the safety of the patient.
Presence of acute or chronic illness or history of chronic illness which, in the judgment of the Investigator, makes participation in the study medically inappropriate.
Uncontrolled hypertension, significant gastrointestinal abnormalities, uncontrolled diabetes mellitus, significant coronary heart disease, any psychotic mental illness, chronic allergic rhinitis, asthma, uncorrected endocrine dysfunction, or significantly impaired hepatic, respiratory or renal function.
Participation in any other clinical study within the previous 1 month.
History of drug or alcohol abuse, or intake of more than 30 units of alcohol weekly.
Possibility that the patient will not cooperate with the requirements of the protocol.
Any nasal abnormality, such as nasal polyps, that, in the opinion of the Investigator, could interfere with absorption of intranasally administered test drug.
Known sensitivity to sCT or excipients.
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E.5 End points |
E.5.1 | Primary end point(s) |
Bone Mineral Density, Bone Resorption Markers, Bone Formation Marker |
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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 | No |
E.6.7 | Pharmacodynamic | Yes |
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 |
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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 | 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 | 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.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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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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 | 15 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 15 |