Phase 3
N=46
Treatment of Primary Hyperparathyroidism With Denosumab and Cinacalcet.
Primary Hyperparathyroidism · Parathyroid Adenoma · Parathyroid Hyperplasia
Bottom Line
View on ClinicalTrials.gov: NCT03027557 ↗Enrolled (actual)
46
Serious AEs
13.0%
Results posted
May 2021
Primary outcome: Primary: Change in Lumbar Spine Bone Mineral Density — 0.030; 0.042; -0.016 g/cm^2 — p=< 0.00001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Cinacalcet 30 mg Tablet (Drug); Denosumab Inj 60 mg/ml (Drug); Placebo tablets (Other); Saline Injection (Placebo) (Other)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Peter Vestergaard
- Primary completion
- Apr 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change in Lumbar Spine Bone Mineral Density |
0.030; 0.042; -0.016 | < 0.00001 sig |
| PRIMARY Change in Total Hip Bone Mineral Density |
0.027; 0.021; -0.013 | < 0.00001 sig |
| PRIMARY Change in Femoral Neck Bone Mineral Density |
0.023; 0.020; -0.007 | = 0.0019 sig |
| PRIMARY Change in 1/3 Forearm Bone Mineral Density |
0.005; 0.005; -0.005 | = 0.096 |
| PRIMARY Percentage Change in Lumbar Spine Bone Mineral Density |
3.6; 5.1; -1.8 | = 0.0001 sig |
| PRIMARY Percentage Change in Total Hip Bone Mineral Density |
3.45; 2.64; -1.50 | < 0.00001 sig |
| PRIMARY Percentage Change in Femoral Neck Bone Mineral Density |
3.70; 3.03; -0.78 | = 0.0027 sig |
| PRIMARY Percentage Change in 1/3 Forearm Bone Mineral Density |
0.94; 0.88; -0.91 | = 0.081 |
| SECONDARY Change in Volumetric BMD for the Lumbar Spine. |
4.93; 5.35; -2.56 | = 0.0071 sig |
| SECONDARY Mean P-calcium During Treatment. |
1.28; 1.38; 1.40 | = 0.0001 sig |
| SECONDARY Percent Change From Baseline in P-carboxy-terminal Collagen Crosslinks (CTX) |
-48.7; -58.2; 11.8 | = 0.0001 sig |
| SECONDARY Median Agatstons Score Final |
5.0; 24.3; 117.8 | = 0.38 |
| SECONDARY Patients With Nephrolithiasis Final Scan. |
0; 3; 1 | — |
| SECONDARY Patients With Pancreas-calcifications Final Scan. |
0; 1; 2 | — |
| SECONDARY Reset of the Calcium Sensing Receptor? |
— | — |
| SECONDARY Vertebral Fracture Assessment - Final Scan |
1; 3; 2 | — |
| SECONDARY Change MDI-score |
0.0; -0.5; 0.0 | = 0.83 |
| SECONDARY Adverse Reactions. |
— | — |
| SECONDARY Bone Mineral Content |
— | — |
| SECONDARY Change in Cortical Width. |
-0.04; 0.02; 0.04 | >0.05 |
| SECONDARY Change in Volumetric BMD for the Distal Forearm. |
1.0; 9.6; -1.1 | = 0.0077 sig |
| SECONDARY Percentage Change in Volumetric BMD for the Lumbar Spine. |
6.18; 5.66; -2.94 | = 0.011 sig |
| SECONDARY Percentage Change in Volumetric BMD for the Distal Forearm. |
0.53; 5.2; -0.74 | = 0.011 sig |
| SECONDARY Mean p-PTH During Treatment. |
12.0; 13.4; 9.9 | = 0.0001 sig |
| SECONDARY Mean p-Phosphate During Treatment. |
0.83; 0.76; 0.083 | < 0.00001 sig |
| SECONDARY Percent Change From Baseline in p-N-terminal Propeptide of Type I Procollagen (p-P1NP). |
-63.1; -66.1; 17.8 | = 0.0001 sig |
| SECONDARY Percent Change From Baseline in P-osteocalcin. |
-60.0; -58.9; 7.0 | = 0.0001 sig |
| SECONDARY Percent Change From Baseline in S-bone-specific Alkaline Phosphatase (BAP). |
-40.0; -46.3; 9.7 | = 0.0001 sig |
| SECONDARY Percent Change From Baseline in p-Tartrate-resistant Acid Phosphatase 5b (Trap5b). |
-27.8; -36.7; 2.3 | — |
| SECONDARY Percent Change From Baseline in p-Sclerostin. |
10.0; 6.5; 4.8 | = 0.5 |
| SECONDARY Percent Change From Baseline in P-fibroblast Growth Factor 23 (FGF23). |
35.8; 20.4; 28.0 | = 0.85 |
| SECONDARY Changes in p-25-vitamin D |
22.1; 16.0; 21.2 | = 0.22 |
| SECONDARY Changes in s-1,25-vitamin D |
7.5; 4.5; 26.0 | = 0.18 |
| SECONDARY Patients With Nephrocalcinosis, Final Scan. |
2; 1; 3 | — |
Summary
The only known cure for primary hyperparathyroidism is surgical removal of one or more parathyroid glands. Some patients however, do not fulfill criteria for surgery or do not want to undergo a procedure due to fear of the associated risks. Therefore a medical alternative is warranted.
This study aims 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. To the best of our knowledge no previously reported randomized controlled trial has investigated the use of denosumab in primary hyperparathyroidism.
60 patients will be enrolled in three different treatment-groups: 20 receiving both Denosumab and Cinacalcet, 20 Denosumab and placebo and 20 placebo and placebo. Patients included do not meet the criteria for, or have no wish for a surgical procedure.
By combining the two drugs, this study could possibly contribute to the discovery of a realistic medical alternative to surgery. It is expected that the therapy will be able to both control s-calcium and s-intact parathyroid hormone (iPTH), and simultaneously enhance bone-structure. The therapy thus has the potential of preventing fractures and possibly other long-term effects of primary hyperparathyroidism such as formation of kidney stones, and coronary calcification. Another objective of this project is to investigate whether the combined therapy can facilitate an actual reset of the Calcium-sensing receptor, and thereby de facto cure the disease.
Eligibility Criteria
Inclusion Criteria
- Men and women of 18 years of age or older.
- T-score by Dual X-ray Absorptiometry (DXA) between -1,0 og -3,5
- Patients from The North Jutland Region diagnosed with primary hyperparathyroidism at the Department of Endocrinology, Aalborg University Hospital. (Hypercalcaemia measured at two different time-points and simultaneous elevated/inappropriately high PTH, and exclusion of differential diagnosis.)
Exclusion Criteria
- Medical history of diseases leading to hypercalcaemia other than Primary Hyperparathyroidism.
- Patients being treated with Denosumab or Cinacalcet prior to inclusion or previously treated with Denosumab or Cinacalcet.
- Moderately - Severely decreased liver function (alanine aminotransferase >250u/l, gamma-glutamyl transferase>150u/l, Bilirubin >30)
- Acute myocardial infarction or apoplexia in the 3 months before inclusion.
- Medical record of heart failure
- Risk factors of prolonged corrected QT interval (QTc).
- 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 epilepsy.
- Active malignant disease.
- Known allergies towards the specified medicinal products (IMPs).
- Pregnancy or breastfeeding.
- Fertile women who do not agree to the usage of effective contraception.
- Other circumstances, evaluated by the responsible investigator, making the subject unsuitable for participation.
Data sourced from ClinicalTrials.gov (NCT03027557). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.