Cinacalcet in Management of Secondary Hyperparathyroidism in Haemodialysis Patients

An Open-label Study of Combination of Cinacalcet and Active Vitamin D Analogue in the Management of Severe Secondary Hyperparathyroidism in Haemodialysis Patients

This is a single arm, open-labelled study to determine the effectiveness of combination Cinacalcet with Vitamin D analogue in the treatment of severe hyperparathyroidism in patients with ESRF on haemodialysis. Patients will be started on PO Cinacalcet 25mg OD + PO/IV active Vitamin D analogues adjusted by increments/decrements in steps of 1 mcg 3x per week every 1-4 weeks until the corrected calcium level is within 2.4-2.54 mmol/L. After iPTH has reached 2-9x ULN, patient enters maintenance phase. If serum calcium falls below 2.1mmol/L, active Vit D dose will be increased and if it is above 2.54 mmol/L, the dose will be decreased.

Percentage reduction of iPTH levels from baseline at 6,12 and 24 months treatment and Percentage of patients achieving iPTH levels within the target range of 2-9x upper limit normal at 6, 12 and 24 months will be determined

Study Overview

• Status: Unknown
• Conditions: Secondary Hyperparathyroidism
• Intervention / Treatment: Drug: Combination Cinacalcet with Vitamin D analogue

Detailed Description

Many patients on haemodialysis will develop secondary hyperparathyroidism. Vitamin D analogues such as alphacalcidol are needed to bring their iPTH levels down to normal. However, these analogues can cause hypercalcaemia, thus its doses are limited by this effect. Cinacalcet, which is currently not widely available to patients in hospitals, is a calcimimetic that can reduce both iPTH and serum calcium levels. No studies have yet to be carried out investigating the outcome of using low doses of Cinacalcet as a means of optimizing doses of vitamin D analogues by keeping calcium levels from going over the upper limit. So a single arm, open-labelled study has been designed to determine the effectiveness of combination Cinacalcet with Vitamin D analogue in the treatment of severe hyperparathyroidism in patients with ESRF on haemodialysis. No formal sample size calculation was done as this is a proof of concept study. Power calculation will be done at the end based on the primary outcome of the study.

Methodology: Patients will be started on PO Cinacalcet 25mg OD + PO/IV active Vitamin D analogues adjusted by increments/decrements in steps of 1 mcg 3x per week every 1-4 weeks until the corrected calcium level is within 2.4-2.54 mmol/L. After iPTH has reached 2-9x ULN, patient enters maintenance phase. If serum calcium falls below 2.1mmol/L, active Vit D dose will be increased and if it is above 2.54 mmol/L, the dose will be decreased.

Percentage reduction of iPTH levels from baseline at 6,12 and 24 months treatment and Percentage of patients achieving iPTH levels within the target range of 2-9x upper limit normal at 6, 12 and 24 months will be determined.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Ong Loke Meng, FRCS; Phone Number: 767 00 604 2225333; Email: onglm@crc.gov.my

Study Locations

• Malaysia
  • Penang
    • George Town, Penang, Malaysia, 10990
      • Penang Hospital
      • Contact: Ong Loke Meng, FRCS; Phone Number: 767 00 604 2225333; Email: onglm@crc.gov.my
    • George Town, Penang, Malaysia, 10990
      • Clinical Research Centre, Penang Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:1. End Stage Renal Failure (ESRF) patients on haemodialysis with iPTH levels more than 9x upper limit normal 2. Patients who has history of active Vitamin D analogue doses limited by hypercalcaemia (>2.54 mmol/L)

Exclusion Criteria:

1. Pregnant or breastfeeding or planning to become pregnant
2. Life expectancy of 6 months or less
3. History of decompensated liver disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Cinacalcet with Vitamin D arm; Depending on the iPTH level and the serum calcium level they will be started on Cinacalcet 25mg OD and active Vitamin D will be adjusted. If Serum Cal <2.4 mmol/L - Start Cinacalcet 25mg OD & Increase active Vit D by 1 mcg/dose 3x/week Increase active Vit D by 1 mcg/dose 3x/week or Serum Ca 2.4-2.54 mmol/L- Start Cinacalcet 25mg OD and Maintain active Vit D dose OR if >2.54 mmol/L - Start Cinacalcet 25mg OD & Maintain active Vit D dose. Then they will go to maintenance phase.

Drug: Combination Cinacalcet with Vitamin D analogue; Depending on the iPTH level and the serum calcium level they will be started on Cinacalcet 25mg OD and active Vitamin D will be adjusted. If Serum Cal <2.4 mmol/L - Start Cinacalcet 25mg OD & Increase active Vit D by 1 mcg/dose 3x/week Increase active Vit D by 1 mcg/dose 3x/week or Serum Ca 2.4-2.54 mmol/L- Start Cinacalcet 25mg OD and Maintain active Vit D dose OR if >2.54 mmol/L - Start Cinacalcet 25mg OD & Maintain active Vit D dose. Then they will go to maintenance phase.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage reduction of iPTH levels from baseline at 6 months treatment	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage of patients achieving iPTH levels within the target range of 2-9x upper limit normal at 6, 12 and 24 months	24 months
The maximum iPTH reduction from baseline	24 months

Collaborators and Investigators

• Sponsor: Penang Hospital, Malaysia
• Collaborators: Ministry of Health, Malaysia
• Investigators: Principal Investigator: Ong Loke Meng, FRCS, Clinical Research Centre, Penang Hospital, Malaysia

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Anticipated): January 1, 2017
• Study Completion (Anticipated): January 1, 2017

Study Registration Dates

• First Submitted: January 11, 2015
• First Submitted That Met QC Criteria: January 13, 2015
• First Posted (Estimate): January 14, 2015

Study Record Updates

• Last Update Posted (Estimate): January 14, 2015
• Last Update Submitted That Met QC Criteria: January 13, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Endocrine System Diseases; Parathyroid Diseases; Neoplastic Processes; Hyperparathyroidism; Neoplasm Metastasis; Hyperparathyroidism, Secondary; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Micronutrients; Hormone Antagonists; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Calcimimetic Agents; Vitamin D; Cinacalcet
• Other Study ID Numbers: CT14-HPP-004