20070360 Incident Dialysis

Randomized Trial to Evaluate the Efficacy and Safety of Cinacalcet Treatment in Combination With Low Dose Vitamin D for the Treatment of Subjects With Secondary Hyperparathyroidism (SHPT) Recently Initiating Hemodialysis

Randomized Trial to Evaluate the Efficacy and Safety of Cinacalcet Treatment in Combination with Low Dose Vitamin D for the Treatment of Subjects with Secondary Hyperparathyroidism (SHPT) Recently Initiating Hemodialysis

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Disease; Secondary Hyperparathyroidism
• Intervention / Treatment: Drug: Cinacalcet; Drug: Vitamin D

• Study Type: Interventional
• Enrollment (Actual): 313
• Phase: Phase 4

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:

• Adults greater than or equal to 18 years of age on hemodialysis for > 3 and less than or equal to 12 months prior to enrollment into the study
• Mean of 2 PTH determinations during the screening period (drawn at least 2 days apart) > 300 pg/mL (31.8 pmol/L); or biPTH > 160 pg/mL (17.0 pmol/L)
• Mean of 2 corrected serum calcium determinations drawn on the same day as the PTH determinations greater than or equal to 8.4 mg/dL (2.1 mmol/L)
• Subject will be able to complete the study, to the best of his/her knowledge
• Before any study-specific procedure, the appropriate written informed consent must be obtained

Exclusion Criteria:

• Mean of 2 PTH determinations during the screening period (drawn at least 2 days apart) > 800 pg/mL (84.9 pmol/L); or biPTH > 430 pg/mL (45.6 pmol/L) AND receiving vitamin D on entering screening
• Parathyroidectomy (partial or full) less than or equal to 6 months before entering screening
• Anticipated parathyroidectomy (partial or full) within 6 months after randomization
• Have a scheduled date for kidney transplant surgery
• Received cinacalcet since initiating hemodialysis
• Have received vitamin D therapy for less than 30 days before entering screening or required a change in prescribed vitamin D brand or dose within 30 days before entering screening. If subjects are not receiving vitamin D therapy, they must remain free of vitamin D therapy for the 30 days before entering screening
• Subject is pregnant (eg, positive HCG test) or is breast-feeding
• Refusal to use highly effective contraceptive measures (as determined by the investigator) throughout the study (screening and post enrollment)
• Current gastrointestinal disorder that may be associated with impaired absorption of orally administered medications or an inability to swallow tablets
• Known sensitivity, intolerance, or other adverse response to cinacalcet which would prevent on-study treatment compliance
• Have an unstable medical condition within 30 days before screening, or otherwise unstable in the judgment of the investigator
• Subject is currently enrolled in, or fewer than 30 days prior to entering screening have passed since subject received other investigational agent(s) (devices or drug).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cinacalcet Group; Cinacalcet plus low dose active Vitamin D (if prescribed)	Drug: Cinacalcet; Cinacalcet is a calcimimetic agent, which is synthesized as a hydrochloride salt.; Other Names: Sensipar/Mimpara
Active Comparator: Control Group; Flexible active vitamin D dosing	Drug: Vitamin D; Titration of active Vitamin D in accordance with treatment practice guidelines in order to treat Secondary Hyperparathyroidism.; Other Names: Active Vitamin D

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Achievement of a ≥ 30% Reduction in Mean PTH From Baseline to During the Efficacy Assessment Phase at Month 6 (Weeks 22 to 26)	All available measurements from the efficacy assessment phase (EAP) at month 6 were used in the calculation of the mean over the period. For participants with no measurements taken during the EAP, the mean of the last 2 measurements available after Day 1 were carried forward. If there was only 1 value available, this single value was carried forward to the EAP.	Weeks 22-26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Achievement of a Mean PTH <= 300 pg/mL During the Efficacy Assessment Phase at Month 6 (Weeks 22 to 26)	All available measurements from the efficacy assessment phase (EAP) at month 6 were used in the calculation of the mean over the period. For subjects with no measurements taken during the EAP, the mean of the last 2 measurements available after Day 1 were carried forward. If there was only 1 value available, this single value was carried forward to the EAP.	Weeks 22-26
Achievement of a ≥ 30% Reduction in Mean PTH From Baseline to During the Efficacy Assessment Phase at Month 12 (Weeks 48 to 52)	All available measurements from the efficacy assessment phase (EAP) at month 12 were used in the calculation of the mean over the period. For subjects with no measurements taken during the EAP, the mean of the last 2 measurements available after Day 1 were carried forward. If there was only 1 value available, this single value was carried forward to the EAP.	Weeks 48-52
Achievement of a Mean PTH <= 300 pg/mL During the Efficacy Assessment Phase at Month 12 (Weeks 48 to 52)	All available measurements from the efficacy assessment phase (EAP) at month 12 were used in the calculation of the mean over the period. For subjects with no measurements taken during the EAP, the mean of the last 2 measurements available after Day 1 were carried forward. If there was only 1 value available, this single value was carried forward to the EAP.	Weeks 48-52
Achievement of a Mean Corrected Serum Calcium < 10.2 mg/dL During the Efficacy Assessment Phase at Month 6 (Weeks 22 to 26)	All available measurements from the efficacy assessment phase (EAP) at month 6 were used in the calculation of the mean over the period. For subjects with no measurements taken during the EAP, the mean of the last 2 measurements available after Day 1 were carried forward. If there was only 1 value available, this single value was carried forward to the EAP.	Weeks 22-26
Achievement of a Mean Corrected Serum Calcium < 10.2 mg/dL During the Efficacy Assessment Phase at Month 12 (Weeks 48 to 52)	All available measurements from the efficacy assessment phase (EAP) at month 12 were used in the calculation of the mean over the period. For subjects with no measurements taken during the EAP, the mean of the last 2 measurements available after Day 1 were carried forward. If there was only 1 value available, this single value was carried forward to the EAP.	Weeks 48-52
Achievement of a Mean Serum Phosphorus < 5.5 mg/dL During the Efficacy Assessment Phase at Month 6 (Weeks 22 to 26)	All available measurements from the efficacy assessment phase (EAP) at month 6 were used in the calculation of the mean over the period. For subjects with no measurements taken during the EAP, the mean of the last 2 measurements available after Day 1 were carried forward. If there was only 1 value available, this single value was carried forward to the EAP.	Weeks 22-26
Achievement of a Mean Serum Phosphorus < 5.5 mg/dL During the Efficacy Assessment Phase at Month 12 (Weeks 48 to 52)	All available measurements from the efficacy assessment phase (EAP) at month 12 were used in the calculation of the mean over the period. For subjects with no measurements taken during the EAP, the mean of the last 2 measurements available after Day 1 were carried forward. If there was only 1 value available, this single value was carried forward to the EAP.	Weeks 48-52
Achievement of a >= 30% Reduction in Mean iPTH From Baseline to During Both Efficacy Assessment Phases at Month 6 (Weeks 22 to 26) and Month 12 (Weeks 48 to 52)	All available measurements from the efficacy assessment phases were used in the calculation of the mean over the period. For subjects with no measurements taken during an EAP, the mean of the last 2 measurements available after Day 1 were carried forward. If there was only 1 value available, this single value was carried forward to the EAP.	Weeks 22-26 and Weeks 48-52
Achievement of a Mean iPTH <=300 pg/mL During Both Efficacy Assessment Phases at Month 6 (Weeks 22 to 26) and Month 12 (Weeks 48 to 52)	All available measurements from the efficacy assessment phases were used in the calculation of the mean over the period. For subjects with no measurements taken during an EAP, the mean of the last 2 measurements available after Day 1 were carried forward. If there was only 1 value available, this single value was carried forward to the EAP.	Weeks 22-26 and Weeks 48-52
Achievement of a Mean Corrected Serum Calcium < 10.2 mg/dL During Both Efficacy Assessment Phases at Month 6 (Weeks 22 to 26) and Month 12 (Weeks 48 to 52)	All available measurements from the efficacy assessment phases were used in the calculation of the mean over the period. For subjects with no measurements taken during an EAP, the mean of the last 2 measurements available after Day 1 were carried forward. If there was only 1 value available, this single value was carried forward to the EAP.	Weeks 22-26 and Weeks 48-52
Achievement of a Mean Serum Phosphorus < 5.5 mg/dL During Both Efficacy Assessment Phases at Month 6 (Weeks 22 to 26) and Month 12 (Weeks 48 to 52)	All available measurements from the efficacy assessment phases were used in the calculation of the mean over the period. For subjects with no measurements taken during an EAP, the mean of the last 2 measurements available after Day 1 were carried forward. If there was only 1 value available, this single value was carried forward to the EAP.	Weeks 22-26 and Weeks 48-52
Summary of iPTH (pg/mL) at Month 6 Efficacy Assessment Phase	All available measurements from the efficacy assessment phases were used in the calculation of the mean over the period. For subjects with no measurements taken during an EAP, the mean of the last 2 measurements available after Day 1 were carried forward. If there was only 1 value available, this single value was carried forward to the EAP.	Weeks 22-26
Summary of Percent Change From Baseline in iPTH (pg/mL) at Month 6 Efficacy Assessment Phase	All available measurements from the efficacy assessment phases were used in the calculation of the mean over the period. For subjects with no measurements taken during an EAP, the mean of the last 2 measurements available after Day 1 were carried forward. If there was only 1 value available, this single value was carried forward to the EAP.	Weeks 22-26
Summary of iPTH (pg/mL) at Month 12 Efficacy Assessment Phase	All available measurements from the efficacy assessment phases were used in the calculation of the mean over the period. For subjects with no measurements taken during an EAP, the mean of the last 2 measurements available after Day 1 were carried forward. If there was only 1 value available, this single value was carried forward to the EAP.	Weeks 48-52
Summary of Percent Change From Baseline in iPTH (pg/mL) at Month 12 Efficacy Assessment Phase	All available measurements from the efficacy assessment phases were used in the calculation of the mean over the period. For subjects with no measurements taken during an EAP, the mean of the last 2 measurements available after Day 1 were carried forward. If there was only 1 value available, this single value was carried forward to the EAP.	Weeks 48-52
Summary of Corrected Serum Calcium (mg/dL) at Month 6 Efficacy Assessment Phase	All available measurements from the efficacy assessment phases were used in the calculation of the mean over the period. For subjects with no measurements taken during an EAP, the mean of the last 2 measurements available after Day 1 were carried forward. If there was only 1 value available, this single value was carried forward to the EAP.	Weeks 22-26
Summary of Percent Change From Baseline in Corrected Serum Calcium at Month 6 Efficacy Assessment Phase	All available measurements from the efficacy assessment phases were used in the calculation of the mean over the period. For subjects with no measurements taken during an EAP, the mean of the last 2 measurements available after Day 1 were carried forward. If there was only 1 value available, this single value was carried forward to the EAP.	Weeks 22-26
Summary of Corrected Serum Calcium (mg/dL) at Month 12 Efficacy Assessment Phase	All available measurements from the efficacy assessment phases were used in the calculation of the mean over the period. For subjects with no measurements taken during an EAP, the mean of the last 2 measurements available after Day 1 were carried forward. If there was only 1 value available, this single value was carried forward to the EAP.	Weeks 48-52
Summary of Percent Change From Baseline in Corrected Serum Calcium at Month 12 Efficacy Assessment Phase	All available measurements from the efficacy assessment phases were used in the calculation of the mean over the period. For subjects with no measurements taken during an EAP, the mean of the last 2 measurements available after Day 1 were carried forward. If there was only 1 value available, this single value was carried forward to the EAP.	Weeks 48-52
Summary of Serum Phosphorus (mg/dL) at Month 6 Efficacy Assessment Phase	All available measurements from the efficacy assessment phases were used in the calculation of the mean over the period. For subjects with no measurements taken during an EAP, the mean of the last 2 measurements available after Day 1 were carried forward. If there was only 1 value available, this single value was carried forward to the EAP.	Weeks 22-26
Summary of Percent Change From Baseline in Serum Phosphorus at Month 6 Efficacy Assessment Phase	All available measurements from the efficacy assessment phases were used in the calculation of the mean over the period. For subjects with no measurements taken during an EAP, the mean of the last 2 measurements available after Day 1 were carried forward. If there was only 1 value available, this single value was carried forward to the EAP.	Weeks 22-26
Summary of Serum Phosphorus (mg/dL) at Month 12 Efficacy Assessment Phase	All available measurements from the efficacy assessment phases were used in the calculation of the mean over the period. For subjects with no measurements taken during an EAP, the mean of the last 2 measurements available after Day 1 were carried forward. If there was only 1 value available, this single value was carried forward to the EAP.	Weeks 48-52
Summary of Percent Change From Baseline in Serum Phosphorus at Month 12 Efficacy Assessment Phase	All available measurements from the efficacy assessment phases were used in the calculation of the mean over the period. For subjects with no measurements taken during an EAP, the mean of the last 2 measurements available after Day 1 were carried forward. If there was only 1 value available, this single value was carried forward to the EAP.	Weeks 48-52
Subject Incidence of Hypercalcemia During the Efficacy Assessment Phase at Month 6	Hypercalcemia is defined as at least one corrected serum calcium value >= 10.2 mg/dL	Weeks 22-26
Subject Incidence of Hypercalcemia During the Maintenance Phase	Hypercalcemia is defined as at least one corrected serum calcium value >= 10.2 mg/dL	Weeks 26-48
Subject Incidence of Hypercalcemia During the Efficacy Assessment Phase at Month 12	Hypercalcemia is defined as at least one corrected serum calcium value >= 10.2 mg/dL	Weeks 48-52
Subject Incidence of Hyperphosphatemia During the Efficacy Assessment Phase at Month 6	Hyperphosphatemia is defined as at least one serum phosphorus value >= 5.5 mg/dL	Weeks 22-26
Subject Incidence of Hyperphosphatemia During the Maintenance Phase	Hyperphosphatemia is defined as at least one serum phosphorus value >= 5.5 mg/dL	Weeks 26-48
Subject Incidence of Hyperphosphatemia During the Efficacy Assessment Phase at Month 12	Hyperphosphatemia is defined as at least one serum phosphorus value >= 5.5 mg/dL	Weeks 48-52

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

General Publications

• Rodriguez M, Urena-Torres P, Petavy F, Cooper K, Farouk M, Goodman WG. Calcium-mediated parathyroid hormone suppression to assess progression of secondary hyperparathyroidism during treatment among incident dialysis patients. J Clin Endocrinol Metab. 2013 Feb;98(2):618-25. doi: 10.1210/jc.2012-3246. Epub 2013 Jan 30.
• Urena-Torres P, Bridges I, Christiano C, Cournoyer SH, Cooper K, Farouk M, Kopyt NP, Rodriguez M, Zehnder D, Covic A. Efficacy of cinacalcet with low-dose vitamin D in incident haemodialysis subjects with secondary hyperparathyroidism. Nephrol Dial Transplant. 2013 May;28(5):1241-54. doi: 10.1093/ndt/gfs568. Epub 2013 Jan 16.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2009
• Primary Completion (Actual): December 9, 2010
• Study Completion (Actual): July 5, 2011

Study Registration Dates

• First Submitted: November 26, 2008
• First Submitted That Met QC Criteria: December 4, 2008
• First Posted (Estimate): December 5, 2008

Study Record Updates

• Last Update Posted (Actual): October 17, 2018
• Last Update Submitted That Met QC Criteria: September 20, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Urologic Diseases; Endocrine System Diseases; Renal Insufficiency; Parathyroid Diseases; Neoplastic Processes; Kidney Diseases; Renal Insufficiency, Chronic; Hyperparathyroidism; Neoplasm Metastasis; Hyperparathyroidism, Secondary; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Micronutrients; Hormone Antagonists; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Calcimimetic Agents; Vitamin D; Cholecalciferol; Vitamins; Cinacalcet; Ergocalciferols
• Other Study ID Numbers: 20070360