20070360 Incident Dialysis

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Chronic Kidney Disease, Secondary Hyperparathyroidism

Intervention / Treatment
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* Drug: Cinacalcet
* Drug: Vitamin D


Participation Criteria
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Eligibility Criteria
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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).

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: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 |