Treatment of Autonomous Hyperparathyroidism in Post Renal Transplant Recipients

• Percent change in the bone mineral density at the femoral neck measured by dual X-ray absorptiometry (DXA) scan from baseline to Week 52 [ Time Frame: From baseline to Week 52 ] [ Designated as safety issue: No ]
• Absolute change in mean serum phosphorus from baseline to the EAP [ Time Frame: From baseline to the EAP ] [ Designated as safety issue: No ]

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.

• 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

• Drug: Cinacalcet

  Possible sequential doses of the investigational product for titration are 30, 60, 90, 120, and 180 mg.

  Subjects will be considered for dose adjustments of the investigational product and will be dispensed a new supply of investigational product at day 1, weeks 4, 8, 12, 16, 20, 22, 26, 34 and 42.

  Subjects will be eligible for a dose increase once every 4 weeks during the dose-titration phase and at study visits during the maintenance phase. Dose escalation is permitted during the EAP. Dose escalation will be based on corrected total serum calcium values, iPTH values, and subject safety information. Dose decreases will be permitted at any time during the study.

• Drug: Placebo

  Possible sequential doses of the investigational product for titration are 30, 60, 90, 120, and 180 mg.

  Subjects will be considered for dose adjustments of the investigational product and will be dispensed a new supply of investigational product at day 1, weeks 4, 8, 12, 16, 20, 22, 26, 34 and 42.

  Subjects will be eligible for a dose increase once every 4 weeks during the dose-titration phase and at study visits during the maintenance phase. Dose escalation is permitted during the EAP. Dose escalation will be based on corrected total serum calcium values, iPTH values, and subject safety information. Dose decreases will be permitted at any time during the study.

• Active Comparator: Cinacalcet
  Intervention: Drug: Cinacalcet
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo

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 (CKD 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.