Secondary Hyperparathyroidism
Conditions
Keywords
Cinacalcet HCl, Cinacalcet, Amgen (AMG) 073, Sensipar, Mimpara, Calcimimetic
Brief summary
The purpose of this study is to evaluate the effects of cinacalcet on markers of bone turnover in patients with kidney disease who are receiving dialysis.
Detailed description
Secondary hyperparathyroidism (HPT) is common in people with end stage renal disease (kidney disease). Patients with secondary HPT often have enlarged parathyroid glands in the neck and as a result often have elevated parathyroid hormone (PTH) levels . Patients with secondary HPT may have bone disease (osteodystrophy). Cinacalcet has been used to decrease PTH levels in patients with secondary HPT. Patients with secondary HPT may have bone disease (osteodystrophy). This bone disease may cause bone pain, fractures, and poor formation of red blood cells. The purpose of this study is to evaluate effects of cinacalcet on markers of bone turnover in patients with kidney disease who are receiving dialysis.
Interventions
DRUGSensipar (Cinacalcet HCl)
All enrolled subjects receive study medication at a starting dose of 30 mg cinacalcet once daily beginning on day 1. Possible sequential doses are 30 mg, 60mg, 90mg, 120mg, 180 mg taken once daily. During the study, dose adjustment (dose increase/decrease/withholding) is based upon iPTH, serum calcium, and subject safety information. Subjects swallowed tablets whole without biting or chewing. Subjects were dispensed investigational product every 4 weeks starting from Day 1 through to Week 48.
Sponsors
Amgen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Subjects will be eligible for the study if they meet all of the following criteria: * One Intact Parathyroid Hormone (iPTH) determination obtained from the central laboratory must be \>/= 300 pg/mL. * One serum calcium determination obtained from the central laboratory must be \>/= 8.4 mg/dL (2.1 mmol/L). * One Bone Alkaline Phosphatase (BALP) determination obtained from the central laboratory must be \>/= 20.9 ng/mL. * Positive histologic confirmation of high bone turnover disease as assessed by the central bone histology center. * Treated with dialysis \>/= 1 month before the date of informed consent.
Exclusion criteria
Subjects will be ineligible for the study if they: * Have an unstable medical condition in the judgment of the investigator. * Are pregnant or nursing women. * Had a parathyroidectomy in the 3 months before the date of informed consent. * For subjects prescribed vitamin D, have received vitamin D therapy for less than 30 days before day 1 or required a change in vitamin D brand or dose level within 30 days before day 1. * Ever received therapy with Sensipar®/Mimpara®
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change From Baseline to End of Study in Bone Formation Rate (BFR) | Baseline to week 52 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Serum Calcium During the Efficacy Assessment Phase (EAP) | Baseline to weeks 40-52 | — |
| Percent Change From Baseline in Serum Phosphorus During the Efficacy Assessment Phase (EAP) | Baseline to weeks 40-52 | — |
| Percent Change From Baseline in Ca x P During the Efficacy Assessment Phase (EAP) | Baseline to weeks 40-52 | — |
| Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BALP) at Week 52 | Baseline to week 52 | — |
| Percent Change From Baseline in N - Telopeptide (NTx) at Week 52 | Baseline to week 52 | — |
| Percent Change From Baseline in Tartrate Resistant Acid Phosphatase(TRAP) at Week 52 | Baseline to week 52 | — |
| Change From Baseline to End of Study in Osteoblast Perimeter (Osteoblast Perimeter/Osteoid Perimeter) | Baseline to week 52 | Osteoblast Perimeter was calculated as Osteoblast Perimeter/Osteoid Perimeter \* 100 |
| Change From Baseline to End of Study in Osteoclast Perimeter (Osteoclast Perimeter/Eroded Perimeter) | Baseline to week 52 | Osteoclast Perimeter was calculated as Osteoclast Perimeter/Eroded Perimeter \* 100 |
| Change in Categorization From Baseline to End of Study in Fibrosis Area/Tissue Area | Baseline to week 52 | Categorisation at each timepoint was based on fibrosis area as a percentage of tissue area (Fibrosis Area/Tissue Area \* 100) |
| Change From Baseline to End of Study in Eroded Perimeter/Bone Perimeter | Baseline to week 52 | Eroded Perimeter/Bone Perimeter was calculated as Eroded Perimeter/Bone Perimeter \* 100 |
| Percent Change From Baseline in Osteocalcin (OC) at Week 52 | Baseline to week 52 | — |
| Percent Change From Baseline in Parathyroid Hormone (PTH) During the Efficacy Assessment Phase (EAP) | Baseline to weeks 40-52 | — |
Countries
Belgium, Czechia, Hungary, Italy, North Macedonia, Poland, Portugal, Spain, Switzerland, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
May 22 2006 is study initiation date and 13 May 2011 is study completion date.
Participants by arm
| Arm | Count |
|---|---|
| Cinacalcet cinacalcet hydrochloride. Participants received a starting dose of 30 mg cinacalcet daily (QD). Dose adjustments were based upon repeated measurements of intact parathyroid hormone, calcium serum concentrations, and participant safety information. | 110 |
| Total | 110 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 6 |
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Other | 1 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Protocol specified Criteria | 11 |
| Overall Study | Withdrawal by Subject | 5 |
Baseline characteristics
| Characteristic | Cinacalcet |
|---|---|
| Age, Continuous | 55.2 years STANDARD_DEVIATION 14.2 |
| Race/Ethnicity, Customized Black | 10 Participants |
| Race/Ethnicity, Customized Other | 9 Participants |
| Race/Ethnicity, Customized White | 91 Participants |
| Sex: Female, Male Female | 40 Participants |
| Sex: Female, Male Male | 70 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 84 / 110 |
| serious Total, serious adverse events | 45 / 110 |
Outcome results
Primary
Change From Baseline to End of Study in Bone Formation Rate (BFR)
Time frame: Baseline to week 52
Population: Enrolled subjects with bone biopsy at week 52
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cinacalcet | Change From Baseline to End of Study in Bone Formation Rate (BFR) | -488 μm^2/mm^2/day | Standard Error 73 |
Secondary
Change From Baseline to End of Study in Eroded Perimeter/Bone Perimeter
Eroded Perimeter/Bone Perimeter was calculated as Eroded Perimeter/Bone Perimeter \* 100
Time frame: Baseline to week 52
Population: Enrolled subjects with eroded perimeter/bone perimeter at week 52
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cinacalcet | Change From Baseline to End of Study in Eroded Perimeter/Bone Perimeter | -3.4 percentage of bone perimeter | Standard Error 0.6 |
Secondary
Change From Baseline to End of Study in Osteoblast Perimeter (Osteoblast Perimeter/Osteoid Perimeter)
Osteoblast Perimeter was calculated as Osteoblast Perimeter/Osteoid Perimeter \* 100
Time frame: Baseline to week 52
Population: Enrolled subjects with Osteoblast Perimeter at week 52
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cinacalcet | Change From Baseline to End of Study in Osteoblast Perimeter (Osteoblast Perimeter/Osteoid Perimeter) | -4.3 percentage of osteoid perimeter | Standard Error 1.4 |
Secondary
Change From Baseline to End of Study in Osteoclast Perimeter (Osteoclast Perimeter/Eroded Perimeter)
Osteoclast Perimeter was calculated as Osteoclast Perimeter/Eroded Perimeter \* 100
Time frame: Baseline to week 52
Population: Enrolled subjects with Osteoclast Perimeter at week 52
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cinacalcet | Change From Baseline to End of Study in Osteoclast Perimeter (Osteoclast Perimeter/Eroded Perimeter) | -2.7 percentage of eroded perimeter | Standard Error 1.5 |
Secondary
Change in Categorization From Baseline to End of Study in Fibrosis Area/Tissue Area
Categorisation at each timepoint was based on fibrosis area as a percentage of tissue area (Fibrosis Area/Tissue Area \* 100)
Time frame: Baseline to week 52
Population: Enrolled subjects with Fibrosis Area/Tissue Area at week 52
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cinacalcet | Change in Categorization From Baseline to End of Study in Fibrosis Area/Tissue Area | Baseline ≥ 26% End of Study 6-10% | 1 participants |
| Cinacalcet | Change in Categorization From Baseline to End of Study in Fibrosis Area/Tissue Area | Baseline 0% End of Study 0% | 3 participants |
| Cinacalcet | Change in Categorization From Baseline to End of Study in Fibrosis Area/Tissue Area | Baseline 0% End of Study 1-5% | 3 participants |
| Cinacalcet | Change in Categorization From Baseline to End of Study in Fibrosis Area/Tissue Area | Baseline 0% End of Study 6-10% | 0 participants |
| Cinacalcet | Change in Categorization From Baseline to End of Study in Fibrosis Area/Tissue Area | Baseline 0% End of Study 11-25% | 0 participants |
| Cinacalcet | Change in Categorization From Baseline to End of Study in Fibrosis Area/Tissue Area | Baseline 0% End of Study ≥ 26% | 0 participants |
| Cinacalcet | Change in Categorization From Baseline to End of Study in Fibrosis Area/Tissue Area | Baseline 1-5% End of Study 0% | 17 participants |
| Cinacalcet | Change in Categorization From Baseline to End of Study in Fibrosis Area/Tissue Area | Baseline 1-5% End of Study 1-5% | 31 participants |
| Cinacalcet | Change in Categorization From Baseline to End of Study in Fibrosis Area/Tissue Area | Baseline 1-5% End of Study 6-10% | 2 participants |
| Cinacalcet | Change in Categorization From Baseline to End of Study in Fibrosis Area/Tissue Area | Baseline 1-5% End of Study 11-25% | 0 participants |
| Cinacalcet | Change in Categorization From Baseline to End of Study in Fibrosis Area/Tissue Area | Baseline 1-5% End of Study ≥ 26% | 0 participants |
| Cinacalcet | Change in Categorization From Baseline to End of Study in Fibrosis Area/Tissue Area | Baseline 6-10% End of Study 0% | 4 participants |
| Cinacalcet | Change in Categorization From Baseline to End of Study in Fibrosis Area/Tissue Area | Baseline 6-10% End of Study 1-5% | 7 participants |
| Cinacalcet | Change in Categorization From Baseline to End of Study in Fibrosis Area/Tissue Area | Baseline 6-10%% End of Study 6-10% | 5 participants |
| Cinacalcet | Change in Categorization From Baseline to End of Study in Fibrosis Area/Tissue Area | Baseline 6-10% End of Study 11-25% | 2 participants |
| Cinacalcet | Change in Categorization From Baseline to End of Study in Fibrosis Area/Tissue Area | Baseline 6-10% End of Study ≥ 26% | 0 participants |
| Cinacalcet | Change in Categorization From Baseline to End of Study in Fibrosis Area/Tissue Area | Baseline 11-25% End of Study 0% | 0 participants |
| Cinacalcet | Change in Categorization From Baseline to End of Study in Fibrosis Area/Tissue Area | Baseline 11-25% End of Study 1-5% | 0 participants |
| Cinacalcet | Change in Categorization From Baseline to End of Study in Fibrosis Area/Tissue Area | Baseline 11-25% End of Study 6-10% | 1 participants |
| Cinacalcet | Change in Categorization From Baseline to End of Study in Fibrosis Area/Tissue Area | Baseline 11-25% End of Study 11-25% | 0 participants |
| Cinacalcet | Change in Categorization From Baseline to End of Study in Fibrosis Area/Tissue Area | Baseline 11-25% End of Study ≥ 26% | 0 participants |
| Cinacalcet | Change in Categorization From Baseline to End of Study in Fibrosis Area/Tissue Area | Baseline ≥ 26% End of Study 0% | 0 participants |
| Cinacalcet | Change in Categorization From Baseline to End of Study in Fibrosis Area/Tissue Area | Baseline ≥ 26% End of Study 1-5% | 1 participants |
| Cinacalcet | Change in Categorization From Baseline to End of Study in Fibrosis Area/Tissue Area | Baseline ≥ 26% End of Study 11-25% | 0 participants |
| Cinacalcet | Change in Categorization From Baseline to End of Study in Fibrosis Area/Tissue Area | Baseline ≥ 26% End of Study ≥ 26% | 0 participants |
Secondary
Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BALP) at Week 52
Time frame: Baseline to week 52
Population: Enrolled subjects with BALP at week 52
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cinacalcet | Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BALP) at Week 52 | 6.6 percent change | Standard Error 12.7 |
Secondary
Percent Change From Baseline in Ca x P During the Efficacy Assessment Phase (EAP)
Time frame: Baseline to weeks 40-52
Population: Enrolled subjects with Ca x P during the Efficacy Assessment Phase (EAP)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cinacalcet | Percent Change From Baseline in Ca x P During the Efficacy Assessment Phase (EAP) | -6.9 percent change | Standard Error 3.1 |
Secondary
Percent Change From Baseline in N - Telopeptide (NTx) at Week 52
Time frame: Baseline to week 52
Population: Enrolled subjects with NTx at week 52
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cinacalcet | Percent Change From Baseline in N - Telopeptide (NTx) at Week 52 | -14.0 percent change | Standard Error 14.7 |
Secondary
Percent Change From Baseline in Osteocalcin (OC) at Week 52
Time frame: Baseline to week 52
Population: Enrolled subjects with osteocalcin (OC) at week 52
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cinacalcet | Percent Change From Baseline in Osteocalcin (OC) at Week 52 | -21.8 Percent change | Standard Error 6.2 |
Secondary
Percent Change From Baseline in Parathyroid Hormone (PTH) During the Efficacy Assessment Phase (EAP)
Time frame: Baseline to weeks 40-52
Population: Enrolled subjects with PTH during the Efficacy Assessment Phase (EAP)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cinacalcet | Percent Change From Baseline in Parathyroid Hormone (PTH) During the Efficacy Assessment Phase (EAP) | -41.6 percent change | Standard Error 4.4 |
Secondary
Percent Change From Baseline in Serum Calcium During the Efficacy Assessment Phase (EAP)
Time frame: Baseline to weeks 40-52
Population: Enrolled subjects with serum calcium during the Efficacy Assessment Phase (EAP)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cinacalcet | Percent Change From Baseline in Serum Calcium During the Efficacy Assessment Phase (EAP) | -6.5 percent change | Standard Error 1.1 |
Secondary
Percent Change From Baseline in Serum Phosphorus During the Efficacy Assessment Phase (EAP)
Time frame: Baseline to weeks 40-52
Population: Enrolled subjects with serum phosphorus during the Efficacy Assessment Phase (EAP)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cinacalcet | Percent Change From Baseline in Serum Phosphorus During the Efficacy Assessment Phase (EAP) | -1.1 percent change | Standard Error 2.9 |
Secondary
Percent Change From Baseline in Tartrate Resistant Acid Phosphatase(TRAP) at Week 52
Time frame: Baseline to week 52
Population: Enrolled subjects with TRAP at week 52
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cinacalcet | Percent Change From Baseline in Tartrate Resistant Acid Phosphatase(TRAP) at Week 52 | -3.8 percent change | Standard Error 9.2 |