End Stage Renal Disease
Conditions
Keywords
Secondary HyperParaThyroidism (SHPT), Dialysis, End Stage Renal Disease (ESRD), KDOQI, Cinacalcet, Clinical Trial, Amgen
Brief summary
The purpose of this study is to evaluate the ability of a treatment strategy, that includes cinacalcet for the management of secondary hyperparathyroidism, to control parathyroid hormone (PTH) compared with the standard of care.
Interventions
DRUGcinacalcet
Treatment with cinacalcet will be initiated at a dose of 30 mg/day. Possible daily doses of cinacalcet are 30, 60, 90, 120, and 180 mg.
OTHERStandard of care
Subjects randomised to the standard care arm are to receive appropriate therapy in accordance with the investigator's practice in an attempt to achieve the K/DOQI PTH, serum calcium, phosphorus, and Ca x P treatment targets.
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* ESRD patients requiring maintenance dialysis (haemodialysis, haemodiafiltration, haemofiltration, or peritoneal dialysis) for at least 1 month * The mean of 2 iPTH determinations within 21 days before randomization and drawn at least 2 days apart must be greater than or equal to 300 pg/mL (31.8 pmol/L) and less than 800 pg/mL (84.8 pmol/L). If biPTH is determined, the mean levels must be greater than or equal to 150 pg/mL (15.9 pmol/L) and less than 410 pg/mL (43.5 pmol/L) * The mean of 2 serum calcium determinations (corrected for albumin) drawn on the same day as the PTH determinations must be greater than or equal to 8.4 mg/dL (2.1 mmol/L)
Exclusion criteria
* Have an unstable medical condition, defined as having been hospitalised, other than for dialysis vascular access revision, within 30 days before day 1, or otherwise unstable in the judgment of the investigator * Have had a parathyroidectomy in the 6 months before day 1 * Have received vitamin D therapy for less than 21 days before day 1 or required a change in prescribed vitamin D brand or dose within 21 days before day 1. If subjects are not prescribed vitamin D therapy, they must remain free of vitamin D therapy for the 21 days before day 1. * Received, within 21 days before day 1 of the dose titration phase, therapy with medications that are predominantly metabolized by the enzyme CYP2D6 and have a narrow therapeutic index (e.g., flecainide, vinblastine, thioridazine, and most tricyclic antidepressants). The tricyclic antidepressant amitriptyline is permitted. - Experienced a myocardial infarction within 3 months prior to day 1 * Are currently enrolled in, or have not yet completed at least 30 days before day 1, other invasive investigational device or investigational drug trials, or are receiving other investigational agents (experimental dialysis machines are acceptable) * Have a gastrointestinal disorder that may be associated with impaired absorption or orally administered medications or an inability to swallow tablets
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Mean PTH ≤ 300 pg/mL | Efficacy Assessment Phase (weeks 17 to 23) | Number of participants with mean parathyroid hormone (PTH) ≤ 300 pg/mL during the efficacy assessment phase |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Mean Ca x P < 55 mg^2/dL^2 and iPTH ≤ 300 pg/mL | Efficacy Assesment Phase (weeks 17-23) | Number of participants with mean calcium x phosphorus (Ca x P) \< 55 mg\^2/dL\^2 and intact parathyroid hormone (iPTH) ≤ 300 pg/mL during the efficacy assessment phase |
| Number of Participants With Mean Ca x P < 55 mg^2/dL^2 | Efficacy Assessment Phase (weeks 17 to 23) | Number of participants with mean calcium x phosphorus (Ca x P) \< 55 mg\^2/dL\^2 during the efficacy assessment phase |
| Number of Participants With Mean Serum Ca < 9.5 mg/dL | Efficacy Assessment Phase (weeks 17-23) | Number of participants with mean serum calcium (Ca) \< 9.5 mg/dL during the efficacy assessment phase |
| Number of Participants With Mean Serum P < 5.5 mg/dL | Efficacy Assessment Phase (weeks 17 to 23) | Number of participants with mean serum phosphorus (P) \< 5.5 mg/dL during the efficacy assessment phase |
Participant flow
Recruitment details
Participants were enrolled from 28 May 2004 through 12 November 2004
Participants by arm
| Arm | Count |
|---|---|
| Cinacalcet Treatment with cinacalcet will be initiated at a dose of 30 mg/day. Possible daily doses of cinacalcet are 30, 60, 90, 120, and 180 mg. Dose escalation of cinacalcet may occur based on intact parathyroid hormone (iPTH) values. | 368 |
| Standard of Care Subjects randomised to the standard care arm are to receive appropriate therapy in accordance with the investigator's practice in an attempt to achieve the Kidney Disease Outcomes Quality Initiative (K/DOQI) parathyroid hormone (PTH), serum calcium, phosphorus, and Ca x P treatment targets. | 184 |
| Total | 552 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 30 | 7 |
| Overall Study | Death | 16 | 9 |
| Overall Study | Did not enter follow-up phase | 10 | 4 |
| Overall Study | Disease progression | 0 | 1 |
| Overall Study | Ineligibility determined | 3 | 0 |
| Overall Study | Invest. Product Commercially Available | 217 | 110 |
| Overall Study | Kidney Transplant | 16 | 12 |
| Overall Study | Lost to Follow-up | 3 | 1 |
| Overall Study | Noncompliance | 10 | 0 |
| Overall Study | Other | 34 | 23 |
| Overall Study | Parathyroidectomy | 0 | 1 |
| Overall Study | Physician Decision | 4 | 5 |
| Overall Study | Protocol Deviation | 1 | 0 |
| Overall Study | Requirement for alternative therapy | 0 | 1 |
| Overall Study | Withdrawal by Subject | 17 | 5 |
Baseline characteristics
| Characteristic | Standard of Care | Total | Cinacalcet |
|---|---|---|---|
| Age Continuous | 58.3 Years STANDARD_DEVIATION 14.5 | 58.4 Years STANDARD_DEVIATION 14.5 | 58.5 Years STANDARD_DEVIATION 14.5 |
| Baseline Strata Vitamin D not prescribed and Ca x P ≤ 55 mg^2/dL^2 | 34 Participants | 103 Participants | 69 Participants |
| Baseline Strata Vitamin D not prescribed and Ca x P > 55 mg^2/dL^2 | 24 Participants | 71 Participants | 47 Participants |
| Baseline Strata Vitamin D prescribed and Ca x P ≤ 55 mg^2/dL^2 | 79 Participants | 237 Participants | 158 Participants |
| Baseline Strata Vitamin D prescribed and Ca x P > 55 mg^2/dL^2 | 47 Participants | 141 Participants | 94 Participants |
| Race/Ethnicity, Customized Black | 7 Participants | 16 Participants | 9 Participants |
| Race/Ethnicity, Customized Other | 5 Participants | 10 Participants | 5 Participants |
| Race/Ethnicity, Customized Unknown | 0 Participants | 5 Participants | 5 Participants |
| Race/Ethnicity, Customized White | 172 Participants | 521 Participants | 349 Participants |
| Sex: Female, Male Female | 67 Participants | 211 Participants | 144 Participants |
| Sex: Female, Male Male | 117 Participants | 341 Participants | 224 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 31 / 182 | 173 / 365 |
| serious Total, serious adverse events | 31 / 182 | 83 / 365 |
Outcome results
Primary
Number of Participants With Mean PTH ≤ 300 pg/mL
Number of participants with mean parathyroid hormone (PTH) ≤ 300 pg/mL during the efficacy assessment phase
Time frame: Efficacy Assessment Phase (weeks 17 to 23)
Population: Full Analysis Set, composed of all randomized participants with imputation using modified last value carried forward (mLVCF)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cinacalcet | Number of Participants With Mean PTH ≤ 300 pg/mL | 262 Participants |
| Standard of Care | Number of Participants With Mean PTH ≤ 300 pg/mL | 41 Participants |
p-value: <0.00195% CI: [5.72, 13.36]Cochran-Mantel-Haenszel
Secondary
Number of Participants With Mean Ca x P < 55 mg^2/dL^2
Number of participants with mean calcium x phosphorus (Ca x P) \< 55 mg\^2/dL\^2 during the efficacy assessment phase
Time frame: Efficacy Assessment Phase (weeks 17 to 23)
Population: Full Analysis Set, composed of all randomized participants with imputation using modified last value carried forward (mLVCF)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cinacalcet | Number of Participants With Mean Ca x P < 55 mg^2/dL^2 | 282 Participants |
| Standard of Care | Number of Participants With Mean Ca x P < 55 mg^2/dL^2 | 106 Participants |
p-value: <0.00195% CI: [2, 4.84]Cochran-Mantel-Haenszel
Secondary
Number of Participants With Mean Ca x P < 55 mg^2/dL^2 and iPTH ≤ 300 pg/mL
Number of participants with mean calcium x phosphorus (Ca x P) \< 55 mg\^2/dL\^2 and intact parathyroid hormone (iPTH) ≤ 300 pg/mL during the efficacy assessment phase
Time frame: Efficacy Assesment Phase (weeks 17-23)
Population: Full Analysis Set, composed of all randomized participants with imputation using modified last value carried forward (mLVCF)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cinacalcet | Number of Participants With Mean Ca x P < 55 mg^2/dL^2 and iPTH ≤ 300 pg/mL | 217 Participants |
| Standard of Care | Number of Participants With Mean Ca x P < 55 mg^2/dL^2 and iPTH ≤ 300 pg/mL | 29 Participants |
p-value: <0.00195% CI: [5.38, 14.19]Cochran-Mantel-Haenszel
Secondary
Number of Participants With Mean Serum Ca < 9.5 mg/dL
Number of participants with mean serum calcium (Ca) \< 9.5 mg/dL during the efficacy assessment phase
Time frame: Efficacy Assessment Phase (weeks 17-23)
Population: Full Analysis Set, composed of all randomized participants with imputation using modified last value carried forward (mLVCF)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cinacalcet | Number of Participants With Mean Serum Ca < 9.5 mg/dL | 281 Participants |
| Standard of Care | Number of Participants With Mean Serum Ca < 9.5 mg/dL | 61 Participants |
p-value: <0.00195% CI: [4.65, 10.34]Cochran-Mantel-Haenszel
Secondary
Number of Participants With Mean Serum P < 5.5 mg/dL
Number of participants with mean serum phosphorus (P) \< 5.5 mg/dL during the efficacy assessment phase
Time frame: Efficacy Assessment Phase (weeks 17 to 23)
Population: Full Analysis Set, composed of all randomized participants with imputation using modified last value carried forward (mLVCF)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cinacalcet | Number of Participants With Mean Serum P < 5.5 mg/dL | 231 Participants |
| Standard of Care | Number of Participants With Mean Serum P < 5.5 mg/dL | 92 Participants |
p-value: 0.00295% CI: [1.26, 2.81]Cochran-Mantel-Haenszel