E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary Hyperparathyroidism. Patients included will have Osteopenia/Osteoporosis with a T-score between -1,0 and 3,5. |
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E.1.1.1 | Medical condition in easily understood language |
Patients included will be suffering from an overproduction of parathyroid hormone. They therefore have elevated calcium in blood and urine as well as osteoporosis.
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E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036693 |
E.1.2 | Term | Primary hyperparathyroidism |
E.1.2 | System Organ Class | 100000004860 |
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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 evaluate the effects of Denosumab alone, and in combination with Cinacalcet, as a medical treatment for patients suffering from primary hyperparathyroidism, with mild osteoporosis. Patients included do not meet the criteria for, or have no wish for a surgical procedure.
The main endpoints will be the effect of treatment on BMD and bone structure measured by DXA, VFA and QCT. Calcifications and the effect of treatment here on, in coronary arteries, the pancreas and kidneys will also be evaluated.
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E.2.2 | Secondary objectives of the trial |
Other objectives will be to investigate the effects of the treatment on,and general development in biochemical markers of bone turnover, levels of plasma- and urine -calcium and phosphorous.
The condition's impact on cortical and trabecular bonetissue will be evaluated at baseline, and compared with the development after one year.
Symptoms of disease and treatment, comorbidities, and the medical history of the included subjects are also points of interest.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Men and women of 18 years of age or older.
• T-score by DXA between -1,0 og -3,5.
• Patients from The North Jutland Region diagnosed with primary hyperparathyroidism at departments of endocinology in hospitals of the North Jutland Region.
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E.4 | Principal exclusion criteria |
• Medical history of diseases leading to hypercalcaemia other than Primary Hyperparathyroidism.
• Patients being treated with Denosumab or Cinacalcet prior to inclusion.
• Moderatly - Severely decreased liver function (ALAT >250u/l, GGT>150u/l, Bilirubin >30)
• AMI or apoplexia within 3 months before inclusion.
• Medical record of heartfailure.
• Risk factors of prolonged QTc-interval.
• Open lesions from oral surgery.
• Primary diseases of the bone other than osteoporosis.
• Patients suffering from kidney disease or renal failure.
• Patients under treatment with thiazide or lithium.
• Medical record of generalized seizures or epilepsia.
• Active malignant disease.
• Known allergies towards the specified IMP's.
• Pregnancy or breastfeeding.
• Fertile women who do not agree to the usage of effective anticonception.
• Other circumstances, evaluated by the responsible investigator, making the subject unsuitable for participation.
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E.5 End points |
E.5.1 | Primary end point(s) |
Change of Bone Mass Density in percentage after one year of treatment, for the subgroups as a whole from baseline, and in comparison between subgroups treated with IMP vs placebo.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
DXA, VFA and QCT will be performed at baseline and after one year of treatment (termination). Data will be evaluated mainly after termination of treatment. Results are expected evaluated by the beginning of spring 2019.
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E.5.2 | Secondary end point(s) |
-Change in vBMD, BMC, cortical and trabecular width and ratio between these.
-Changes in s-calcium and s-intact parathyroid hormone over time until after one year of treatment.
- Changes in markers of bone turnover in blood and urine.
- The prevalence of, and changes over time of coronary calcification by agatston-score.
- Development and prevalence of nephrolithiasis/nephrocalcinosis by computed tomography.
- Development and prevalence of pancreatic calcifications by computed tomography.
- Reset of the Ca-SR?: measured from effect on s-calcium and PTH 2 weeks after termination of IMP.- By Vertebral Fracture Assessment (VFA) development and prevalence of osteoporotic fractures of the column is assessed.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
CT, VFA and DXA will be performed at baseline and at the termination of the project. Markers of bone metabolism will be measured a total of 6 times throughout the year. Urine samples will be collectedat baseline, after 24 weeks, and at termination.
Other biochemical tests will be measured monthly through the whole project.
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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 | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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.8.2.4 | Number of treatment arms in the trial | 3 |
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 | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |