Treatment of Autonomous Hyperparathyroidism in Post Renal Transplant Recipients

Phase 3

Completed

• Conditions: Chronic Kidney Disease; Chronic Allograft Nephropathy; Hyperparathyroidism; Kidney Disease; Post Renal Transplantation; Kidney Transplantation; Chronic Renal Failure; Hypophosphatemia; Disordered Mineral Metabolism; End Stage Renal Disease
• Interventions: Drug: Placebo; Drug: Cinacalcet

• Registration Number: NCT00975000
• Lead Sponsor: Amgen

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2009-09-10
• Study First Submitted QC: 2009-09-10
• Study First Posted: 2009-09-11
• Study Start: 2009-12-03
• Primary Completion: 2012-09-13
• Study Completion: 2013-04-16
• Disposition First Submitted: 2014-01-09
• Disposition First Submitted QC: 2014-01-09
• Disposition First Posted: 2014-02-07
• Results First Submitted: 2015-12-23
• Results First Submitted QC: 2015-12-23
• Results First Posted: 2016-01-29
• Status Verified: 2018-09
• Last Update Submitted: 2018-09-20
• Last Update Posted: 2018-10-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 114

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Participants received placebo orally once daily for 52 weeks.
Cinacalcet	Cinacalcet	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Percent Change From Baseline to Week 52 in Bone Mineral Density at the Femoral Neck	Baseline and Week 52	Bone mineral density (BMD) was measured using dual X-ray absorptiometry (DXA).
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	Baseline and Week 52	eGFR was calculated using the Modification of Diet in Renal Disease (MDRD) formula.
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

Trial Locations

Locations (1)

Research Site; 🇨🇭 Zurich, Switzerland