Hyperparathyroidism, Secondary
Conditions
Keywords
Secondary Hyperthyroidism, Hemodialysis, Parathyroid, PARADIGM
Brief summary
The purpose of this study is to determine the efficacy of treatment with cinacalcet to manage plasma parathyroid levels as to compared traditional vitamin D therapy, whether given orally or intravenously, among hemodialysis subjects with secondary hyperparathyroidism when the doses are adjusted appropriately to maintain serum calcium and phosphorous levels with currently recommended ranges.
Interventions
DRUGTraditional Vitamin D Therapy
Traditional vitamin D therapy (eg, calcitriol, paricalcitol, alfacalcidol, doxercalciferol), to manage secondary hyperparathyroidism (SHPT) in this study will be administered according to strategies that have been used in clinical practice and that conform to current therapeutic recommendations and available clinical practice guidelines and product labeling.
DRUGCinacalcet
Subjects randomized to treatment with cinacalcet will receive an initial oral dose of 30 mg once daily. Doses will be titrated incrementally to 60, 90,120, and 180 mg per day based upon periodic measurements of serum calcium and plasma PTH levels. Cinacalcet is formulated as light green tablets in 30, 60, and 90 mg free-based equivalents. Tablets will be 30, 60, and 90 mg, graduated in size, smallest to largest. Combinations of these 3 fixed dosage formulations will be used to achieve the 120 and 180 mg daily doses.
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
* Age ≥ 18 years at screening * Treated with maintenance hemodialysis 3 times a week for ≥ 3 months prior to screening * Informed consent provided by the study candidate * For subjects NOT receiving cinacalcet and/or vitamin D therapy for SHPT within 60 days prior to enrollment: Plasma PTH levels ≥ 450 pg/mL (50 pmol/L) during screening, as obtained from the central laboratory and, Serum corrected total calcium ≥ 8.4 mg/dL (2.1 mmol/L) and \< 10.2 mg/dL (2.55 mmol/L) during screening, as obtained from the central laboratory
Exclusion criteria
* Parathyroidectomy in the 12 weeks before the date of informed consent * History of seizure within 12 weeks prior to randomization * Scheduled for kidney transplant * Parathyroidectomy anticipated within the next 6 months * Liver function tests \> than 2 x the Upper Limit of Normal * Prior use of bisphosphonates, or expected to receive bisphosphonates during the trial * Subject has previously enrolled in this study * General * Other investigational procedures are excluded * Currently enrolled in another investigational device or drug study, or less than 30 days since ending another investigational device or drug study(s), or receiving other investigational agent(s) * Subject (male or female) is not willing to use highly effective contraception during treatment and for at least one month (women) and 3 months (men) after the end of treatment * Subject is pregnant or breast feeding, or planning to become pregnant during study or within 1 month after the end of treatment Male subject with a pregnant partner who is not willing to use a condom during treatment and for at least 1 month after the end of treatment * Subject has known sensitivity or intolerance to any of the protocol required therapies * Subject will not be available for protocol-required study visits, to the best of the subject and investigator's knowledge * Subject has any kind of disorder that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent and/or to comply with all required study procedures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Mean PTH During Efficacy Assessment Phase (EAP) | Baseline to week 40-52 | Mean PTH during EAP is defined as the mean of values at study weeks 40, 44, 48 and 52 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Comparison of >=30% Reduction From Baseline in Mean PTH During the Efficacy Assessment Phase (EAP) | Baseline to week 40-52 | Number of participants achieving a \>=30% Reduction From Baseline in Mean PTH During Efficacy Assessment Phase (EAP) |
| Treatment Comparison of Plasma PTH < 300 pg/mL During Efficacy Assessment Phase (EAP) | week 40-52 | Number of participants achieving Plasma PTH \< 300 pg/mL During Efficacy Assessment Phase (EAP) |
Participant flow
Recruitment details
Participants were enrolled from 08 September 2010 through 14 August 2012 Two participants in each arm did not receive Investigational Product (IP) and Traditional Vitamin D.
Participants by arm
| Arm | Count |
|---|---|
| Traditional Vitamin D Vitamin D sterol, intravenous (IV) or oral | 157 |
| Cinacalcet Cinacalcet Hydrochloride (Sensipar) | 155 |
| Total | 312 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Death | 9 | 12 |
| Overall Study | Ineligibility determined | 1 | 2 |
| Overall Study | Noncompliance | 2 | 2 |
| Overall Study | Other | 17 | 12 |
| Overall Study | Partial consent by subject withdrawn | 0 | 1 |
| Overall Study | Physician Decision | 3 | 1 |
| Overall Study | Pregnancy | 0 | 1 |
| Overall Study | Protocol Specified Criteria | 15 | 8 |
| Overall Study | Protocol Violation | 6 | 6 |
| Overall Study | Withdrawal by Subject | 8 | 7 |
Baseline characteristics
| Characteristic | Cinacalcet | Total | Traditional Vitamin D |
|---|---|---|---|
| Age, Continuous | 53.5 years STANDARD_DEVIATION 14.5 | 53.9 years STANDARD_DEVIATION 14.2 | 54.3 years STANDARD_DEVIATION 13.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 32 Participants | 79 Participants | 47 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 123 Participants | 233 Participants | 110 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Asian | 8 participants | 12 participants | 4 participants |
| Race/Ethnicity, Customized Black or African American | 76 participants | 136 participants | 60 participants |
| Race/Ethnicity, Customized More than one race | 5 participants | 9 participants | 4 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized White | 66 participants | 152 participants | 86 participants |
| Sex: Female, Male Female | 62 Participants | 124 Participants | 62 Participants |
| Sex: Female, Male Male | 93 Participants | 188 Participants | 95 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 83 / 155 | 98 / 153 |
| serious Total, serious adverse events | 68 / 155 | 60 / 153 |
Outcome results
Primary
Percent Change From Baseline in Mean PTH During Efficacy Assessment Phase (EAP)
Mean PTH during EAP is defined as the mean of values at study weeks 40, 44, 48 and 52
Time frame: Baseline to week 40-52
Population: All subjects randomized by treatment arm.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Traditional Vitamin D | Percent Change From Baseline in Mean PTH During Efficacy Assessment Phase (EAP) | -7 Percent change | Standard Error 4 |
| Cinacalcet | Percent Change From Baseline in Mean PTH During Efficacy Assessment Phase (EAP) | -12.1 Percent change | Standard Error 4 |
Comparison: Null hypothesis: no difference in % change from baseline in PTH comparing the two treatment arms.p-value: 0.34695% CI: [-15.4, 5.4]Mixed Models Analysis
Secondary
Treatment Comparison of >=30% Reduction From Baseline in Mean PTH During the Efficacy Assessment Phase (EAP)
Number of participants achieving a \>=30% Reduction From Baseline in Mean PTH During Efficacy Assessment Phase (EAP)
Time frame: Baseline to week 40-52
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Traditional Vitamin D | Treatment Comparison of >=30% Reduction From Baseline in Mean PTH During the Efficacy Assessment Phase (EAP) | Yes | 53 Participants |
| Traditional Vitamin D | Treatment Comparison of >=30% Reduction From Baseline in Mean PTH During the Efficacy Assessment Phase (EAP) | No | 104 Participants |
| Cinacalcet | Treatment Comparison of >=30% Reduction From Baseline in Mean PTH During the Efficacy Assessment Phase (EAP) | Yes | 66 Participants |
| Cinacalcet | Treatment Comparison of >=30% Reduction From Baseline in Mean PTH During the Efficacy Assessment Phase (EAP) | No | 89 Participants |
p-value: 0.1195% CI: [0.92, 2.29]Cochran-Mantel-Haenszel
Secondary
Treatment Comparison of Plasma PTH < 300 pg/mL During Efficacy Assessment Phase (EAP)
Number of participants achieving Plasma PTH \< 300 pg/mL During Efficacy Assessment Phase (EAP)
Time frame: week 40-52
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Traditional Vitamin D | Treatment Comparison of Plasma PTH < 300 pg/mL During Efficacy Assessment Phase (EAP) | Yes | 24 Participants |
| Traditional Vitamin D | Treatment Comparison of Plasma PTH < 300 pg/mL During Efficacy Assessment Phase (EAP) | No | 133 Participants |
| Cinacalcet | Treatment Comparison of Plasma PTH < 300 pg/mL During Efficacy Assessment Phase (EAP) | Yes | 30 Participants |
| Cinacalcet | Treatment Comparison of Plasma PTH < 300 pg/mL During Efficacy Assessment Phase (EAP) | No | 125 Participants |
p-value: 0.34695% CI: [0.74, 2.39]Cochran-Mantel-Haenszel