Treatment of Autonomous Hyperparathyroidism in Post Renal Transplant Recipients

Study Overview
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Brief Summary
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Hyperparathyroidism (HPT) is common in people with a kidney transplant. Patients with HPT often have high parathyroid hormone (PTH) levels and may have large parathyroid glands in the neck. Patients with HPT can develop bone disease (osteodystrophy). This bone disease can cause bone pain, fractures, and poor formation of red blood cells. Other problems from HPT may include increases in blood levels of calcium (hypercalcemia) and low blood levels of phosphorus (hypophosphatemia). The high calcium levels may cause calcium to deposit in body tissues. Calcium deposits can cause arthritis (joint pain and swelling), muscle inflammation, itching, gangrene (death of soft tissue), heart and lung problems or kidney transplant dysfunction (worsening of kidney transplant function). The purpose of this study is to evaluate the effects of cinacalcet (Sensipar/Mimpara) on high calcium levels in the blood in patients with HPT after a kidney transplant.

Official Title
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A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Using Cinacalcet to Correct Hypercalcemia in Renal Transplant Recipients With Autonomous Hyperparathyroidism

Conditions
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Chronic Allograft Nephropathy, Chronic Kidney Disease, Chronic Renal Failure, Disordered Mineral Metabolism, End Stage Renal Disease, Hyperparathyroidism, Hypophosphatemia, Kidney Disease, Kidney Transplantation, Post Renal Transplantation

Intervention / Treatment
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* Drug: Cinacalcet
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Received a kidney transplant ≥ 9 weeks at time of Screening and ≤ 24 months before first dose May be the first kidney transplant or a repeat kidney transplant. Subjects with a functional, stable kidney transplant, defined as MDRD estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m² (chromic kidney disease stage 3 or better) at Screening. Men or women ≥ 18 years at the start of Screening (ie, time of informed consent). Corrected total serum calcium > 10.5 mg/dL (2.63 mmol/L), defined as the mean of 2 values in Screening period. iPTH > 100 pg/mL (10.6 pmol/L), during the Screening period (obtained at either Screen 1 or Screen 2). Exclusion Criteria: Received cinacalcet therapy post-transplant for more than 14 days cumulatively post-transplant. If cinacalcet therapy was received for a total of 14 days or less post-transplant, there must be a 4-week washout before subject is eligible for screening (Note: This does not exclude pre-transplant use of cinacalcet). Anticipated parathyroidectomy within 6 to12 months after Randomization. Ongoing therapy with bisphosphonates or use within 6 months prior to Screening. Ongoing use of 1,25-dihydroxyvitamin D3 (including other active vitamin D metabolites or analogues) or use within 30 days prior to Screening. Ongoing use of calcium supplements or use within 30 days prior to Screening. Ongoing use of phosphate binders (calcium or non-calcium containing) or use within 30 days prior to Screening. Ongoing use of a thiazide diuretic. Subjects with a history of seizures who had a seizure within the 3 months prior to Randomization, which required adjustments to the seizure medication. Acute Kidney Injury (AKI) or renal biopsy within 6 weeks prior to Screening, unless it is an institutional protocol-driven biopsy.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cinacalcet<br>Participants received cinacalcet at a starting dose of 30 mg orally once daily for 52 weeks. Cinacalcet dose was titrated every 4 weeks during the dose-titration phase and during study visits in the maintenance phase based on intact parthyroid hormone (iPTH) values, corrected total serum calcium values, and safety assessments. | Drug: Cinacalcet<br>* Possible sequential doses are 30, 60, 90, 120, and 180 mg.<br>* Other names: Sensipar;|
| Placebo Comparator: Placebo<br>Participants received placebo orally once daily for 52 weeks. | Drug: Placebo<br>* Administered orally following the same dosing regimen as the experimental arm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a Mean Corrected Total Serum Calcium Value < 10.2 mg/dL (2.55 mmol/L) During the Efficacy Assessment Phase (EAP) |  | Weeks 21 to 26 (EAP) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline to Week 52 in Bone Mineral Density at the Femoral Neck | Bone mineral density (BMD) was measured using dual X-ray absorptiometry (DXA). | Baseline and Week 52 | 
| Change From Baseline to the EAP in Mean Serum Phosphorus |  | Baseline and the EAP (mean of Weeks 22, 24, and 26) | 
| Change From Baseline to Week 52 in eGFR | eGFR was calculated using the Modification of Diet in Renal Disease (MDRD) formula. | Baseline and Week 52 | 
| Change From Baseline to the EAP in Corrected Total Calcium |  | Baseline and the EAP (mean of Weeks 22, 24, and 26) | 
| Change From Baseline to the EAP in Intact Parathyroid Hormone (iPTH) |  | Baseline and the EAP (mean of Weeks 22, 24, and 26) | 
| Change From Baseline to the EAP in Urine Phosphorus |  | Baseline and the EAP (mean of Weeks 22, 24, and 26) | 
| Percentage of Participants With a Parathyroidectomy |  | 56 weeks | 
| Time to Parathyroidectomy |  | 56 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intervention, Cinacalcet, Sensipar, Mimpara, hyperparathyroidism, calcium, osteodystrophy, hypercalcemia, renal, transplant, acute rejection, kidney transplant failure, hypophosphatemia