Pediatric Chronic Kidney Disease Safety and Efficacy
Sponsor
Amgen (Industry)
Overall Status
Terminated
CT.gov ID
NCT01277510
Collaborator
(none)
43
51
2
0.8
Study Details
Study Description
Brief Summary
The purpose of this study is to assess the safety and efficacy of adding cinacalcet to the current treatment of secondary hyperparathyroidism in children currently receiving dialysis compared to a treatment regimen that does not include cinacalcet.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
Secondary hyperparathyroidism (SHPT) is a condition that can develop early in patients with chronic kidney disease (CKD), usually gets worse over time, and is known to cause problems for patients on dialysis. Children on dialysis can have a wide range of bone and growth issues, and common treatments have a chance of making these things worse by increasing serum calcium and serum phosphorus. Cinacalcet has been shown to be effective in controlling parathyroid hormone (PTH), calcium and phosphorus in adults. The purpose of this study is to show that including cinacalcet in the treatment of SHPT will lower the levels of intact parathyroid hormone (iPTH) in a larger number of pediatric patients with CKD who are receiving dialysis, compared to a treatment regimen that does not include cinacalcet.
Study Design
Study Type:
Interventional
Actual Enrollment
:
43 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-blind, Placebo Controlled Study to Assess the Efficacy and Safety of Cinacalcet HCl in Pediatric Subjects With Chronic Kidney Disease and Secondary Hyperparathyroidism Receiving Dialysis
Actual Study Start Date
:
Jun 28, 2011
Actual Primary Completion Date
:
Apr 30, 2014
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Placebo Participants received standard of care and placebo once daily for 30 weeks during the double-blind phase. During the open-label phase, participants received cinacalcet with standard of care for an additional 30 weeks. The starting dose of cinacalcet was ≤ 0.20 mg/kg based on dry weight, and could be titrated up according to plasma iPTH and serum calcium levels every 4 weeks up to Week 54 to a maximum dose of 4.2 mg/kg. |
Drug: placebo
Placebo tablets and capsules for sprinkling identical to active treatment.
Drug: Standard of Care
All participants, regardless of treatment assignment, will receive standard of care with vitamin D sterols (calcitriol and its analogs), as prescribed by the treating physician.
|
| Experimental: Cinacalcet Participants received standard of care and cinacalcet once daily for 30 weeks during the double-blind phase. The starting dose of cinacalcet was ≤ 0.20 mg/kg based on dry weight, and could be titrated up according to plasma iPTH and serum calcium levels every 4 weeks until Week 24 to a maximum dose of 4.2 mg/kg. During the open-label phase participants continued to receive cinacalcet with standard of care for an additional 30 weeks. |
Drug: cinacalcet capsule
Cinacalcet was prepared for oral administration as both capsules for sprinkling and film coated tablets for swallowing.
Other Names:
Drug: Standard of Care
All participants, regardless of treatment assignment, will receive standard of care with vitamin D sterols (calcitriol and its analogs), as prescribed by the treating physician.
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants Achieving ≥ 30% Reduction in Mean iPTH From Baseline to the Efficacy Assessment Phase [From Baseline to the Efficacy Assessment Phase, Weeks 25-30]
The efficacy assessment value is based on the scheduled assessment(s) taken during the efficacy assessment phase (EAP; Weeks 25 - 30). When multiple assessments were available, the average of those was used. If an efficacy measurement during the EAP was missing, the mean of the last 2 available post-baseline values in the dose-titration phase was used. If only one post-baseline value was available, this single value was used.
Secondary Outcome Measures
- Percentage of Participants Achieving Mean iPTH ≤ 300 pg/mL (31.8 Pmol/L) During the Efficacy Assessment Phase [From Baseline to the Efficacy Assessment Phase (EAP), Weeks 25-30]
The efficacy assessment value is based on the scheduled assessment(s) taken during the efficacy assessment phase. When multiple assessments were available, the average of those was used. If an efficacy measurement during the EAP was missing, the mean of the last 2 available postbaseline values in the dose-titration phase was used. If only one post-baseline value was available, this single value was used.
- Percent Change From Baseline in Mean Corrected Total Serum Calcium During the Efficacy Assessment Period [From Baseline to the Efficacy Assessment Phase, Weeks 25-30.]
Serum calcium was reported as a corrected value by the central laboratory based on calcium and albumin concentrations: Corrected total calcium (mg/dL) = measured total serum calcium (mg/dL) + 0.8 (4.0 - Serum albumin (g/dL)). The efficacy assessment value is based on the scheduled assessment(s) taken during the efficacy assessment phase. When multiple assessments were available, the average of those was used. If an efficacy measurement during the EAP was missing, the mean of the last 2 available postbaseline values in the dose-titration phase was used. If only one post-baseline value was available, this single value was used."
- Percent Change From Baseline in Mean Serum Phosphorus During the Efficacy Assessment Phase [From Baseline to the Efficacy Assessment Phase, Weeks 25-30.]
The efficacy assessment value is based on the scheduled assessment(s) taken during the efficacy assessment phase. When multiple assessments were available, the average of those was used. If an efficacy measurement during the EAP was missing, the mean of the last 2 available postbaseline values in the dose-titration phase was used. If only one post-baseline value was available, this single value was used.
- Percent Change From Baseline in Mean Phosphorous Product (Ca x P) During the Efficacy Assessment Phase [From Baseline to end of Efficacy Assessment Period, assessed up to 30 weeks]
The efficacy assessment value is based on the scheduled assessment(s) taken during the efficacy assessment phase. When multiple assessments were available, the average of those was used. If an efficacy measurement during the EAP was missing, the mean of the last 2 available postbaseline values in the dose-titration phase was used. If only one post-baseline value was available, this single value was used.
- Growth Velocity From Baseline to End of Double-blind Phase [From Baseline to end of Efficacy Assessment at Week 30]
Linear growth velocity (cm/year) = 52 x change in height (cm) / number of weeks between the two assessments. End of double-blind phase visit was at Week 30 by design but the last assessment in the double-blind phase was used due to the early termination of the study.
- Growth Velocity From End of Double-blind Phase to End of Open-label Phase [End of double-blind phase (Week 30) until end of the open-label phase (Week 60)]
Linear growth velocity (cm/year) = 52 x change in height (cm) / number of weeks between the two assessments. End of open-label phase visit was at Week 60 by design but the last assessment in the open-label phase was used due to the early termination of the study.
- Percent Change From Baseline in Mean Ionized Calcium During the Efficacy Assessment Phase [From Baseline to the Efficacy Assessment Phase, Weeks 25-30.]
The efficacy assessment value is based on the scheduled assessment(s) taken during the efficacy assessment phase. When multiple assessments were available, the average of those was used. If an efficacy measurement during the EAP was missing, the mean of the last 2 available postbaseline values in the dose-titration phase was used. If only one post-baseline value was available, this single value was used.
Eligibility Criteria
Criteria
Ages Eligible for Study:
6 Years
to 17 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Age 6 to less than 18 years at screening
-
Diagnosed with CKD and SHPT receiving hemodialysis or peritoneal dialysis for ≥ 2 months before randomization
-
Dry weight ≥ 12.5 kg at screening
-
iPTH obtained from the central laboratory must be > 300 pg/mL (31.8 pmol/L)
-
Serum calcium (corrected) obtained from the central laboratory must be ≥ 8.8 mg/dL (2.2 mmol/L)
-
Serum phosphorus obtained from the central laboratory ≥ 4.0 mg/dL (1.3 mmol/L) for children 6 to less than 12 years old, or ≥ 3.5 mg/dL (1.1 mmol/L) for children 12 to less than 18 years old
-
Subjects already receiving vitamin D sterols (either calcitriol or a synthetic analog), a stable dose within the last 2 months prior to randomization
-
Subjects taking growth hormone, a stable dose defined as no change > than 20% in the last 2 months prior to randomization
-
Subjects on anti-convulsant medication must be on a stable dose for 3 months, and have a therapeutic blood level of the anti-convulsant at the time of randomization
-
Subjects must be on a dialysate calcium concentration of ≥ 2.5 mEq/L (1.25 mmol/L) for at least 2 months prior to randomization
Exclusion Criteria:
-
Underwent parathyroidectomy in the last 6 months
-
Anticipated parathyroidectomy within 6 months after randomization
-
Received therapy with cinacalcet (sensipar/mimpara) within the last month
-
A new onset of seizure or worsening of a pre-existing seizure disorder within the last 3 months
-
Scheduled date for kidney transplant from a known living donor that makes completion of the study unlikely
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Research Site | Birmingham | Alabama | United States | 35233 |
| 2 | Research Site | Los Angeles | California | United States | 90095 |
| 3 | Research Site | San Francisco | California | United States | 94143 |
| 4 | Research Site | Gainesville | Florida | United States | 32610 |
| 5 | Research Site | Baltimore | Maryland | United States | 21287 |
| 6 | Research Site | Boston | Massachusetts | United States | 02115 |
| 7 | Research Site | Kansas City | Missouri | United States | 64108 |
| 8 | Research Site | Saint Louis | Missouri | United States | 63104 |
| 9 | Research Site | Saint Louis | Missouri | United States | 63110 |
| 10 | Research Site | Livingston | New Jersey | United States | 07039 |
| 11 | Research Site | Bronx | New York | United States | 10467 |
| 12 | Research Site | Greenville | North Carolina | United States | 27834 |
| 13 | Research Site | Cincinnati | Ohio | United States | 45229 |
| 14 | Research Site | Portland | Oregon | United States | 97227 |
| 15 | Research Site | Philadelphia | Pennsylvania | United States | 19104 |
| 16 | Research Site | Houston | Texas | United States | 77030 |
| 17 | Research Site | San Antonio | Texas | United States | 78229 |
| 18 | Research Site | Charlottesville | Virginia | United States | 22908 |
| 19 | Research Site | Randwick | New South Wales | Australia | 2031 |
| 20 | Research Site | Westmead | New South Wales | Australia | 2145 |
| 21 | Research Site | Herston | Queensland | Australia | 4029 |
| 22 | Research Site | Parkville | Victoria | Australia | 3052 |
| 23 | Research Site | Bruxelles | Belgium | 1020 | |
| 24 | Research Site | Edegem | Belgium | 2650 | |
| 25 | Research Site | Gent | Belgium | 9000 | |
| 26 | Research Site | Leuven | Belgium | 3000 | |
| 27 | Research Site | Heidelberg | Germany | 69120 | |
| 28 | Research Site | Marburg | Germany | 35043 | |
| 29 | Research Site | Budapest | Hungary | 1083 | |
| 30 | Research Site | Debrecen | Hungary | 4032 | |
| 31 | Research Site | Pecs | Hungary | 7623 | |
| 32 | Research Site | Szeged | Hungary | 6720 | |
| 33 | Research Site | Mexico | Distrito Federal | Mexico | 04530 |
| 34 | Research Site | Aguascalientes | Mexico | 20219 | |
| 35 | Research Site | Gdansk | Poland | 80-952 | |
| 36 | Research Site | Gorzow Wielkopolski | Poland | 66-400 | |
| 37 | Research Site | Lodz | Poland | 93-338 | |
| 38 | Research Site | Warszawa | Poland | 00-576 | |
| 39 | Research Site | Warszawa | Poland | 04-730 | |
| 40 | Research Site | Moscow | Russian Federation | 107014 | |
| 41 | Research Site | Saint Petersburg | Russian Federation | 198205 | |
| 42 | Research Site | Samara | Russian Federation | 443095 | |
| 43 | Research Site | Banska Bystrica | Slovakia | 974 09 | |
| 44 | Research Site | Bratislava | Slovakia | 833 40 | |
| 45 | Research Site | Kosice | Slovakia | 040 11 | |
| 46 | Research Site | Barcelona | Cataluña | Spain | 08035 |
| 47 | Research Site | Barcelona | Cataluña | Spain | 08035 |
| 48 | Research Site | Valencia | Comunidad Valenciana | Spain | 46026 |
| 49 | Research Site | Baracaldo | PaÃ-s Vasco | Spain | 48903 |
| 50 | Research Site | Baracaldo | País Vasco | Spain | 48903 |
| 51 | Research Site | Madrid | Spain | 28046 |
Sponsors and Collaborators
- Amgen
Investigators
- Study Director: MD, Amgen
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- Warady BA, Iles JN, Ariceta G, Dehmel B, Hidalgo G, Jiang X, Laskin B, Shahinfar S, Vande Walle J, Schaefer F. A randomized, double-blind, placebo-controlled study to assess the efficacy and safety of cinacalcet in pediatric patients with chronic kidney disease and secondary hyperparathyroidism receiving dialysis. Pediatr Nephrol. 2019 Mar;34(3):475-486. doi: 10.1007/s00467-018-4116-y. Epub 2018 Nov 30.
- Warady BA, Ng E, Bloss L, Mo M, Schaefer F, Bacchetta J. Cinacalcet studies in pediatric subjects with secondary hyperparathyroidism receiving dialysis. Pediatr Nephrol. 2020 Sep;35(9):1679-1697. doi: 10.1007/s00467-020-04516-4. Epub 2020 May 4. Review.
Responsible Party:
Amgen
ClinicalTrials.gov Identifier:
NCT01277510
Other Study ID Numbers:
- 20070208
First Posted:
Jan 17, 2011
Last Update Posted:
Jun 29, 2020
Last Verified:
Jun 1, 2020
Keywords provided by Amgen
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | The first patient was enrolled on 28 June 2011 and the last patient enrolled was on 15 January 2013. Eligible participants were between the ages of 6 to less than 18 years old who had chronic kidney (CKD) and secondary hyperparathyroidism treated with either hemodialysis or peritoneal dialysis for ≥ 2 months. |
|---|---|
| Pre-assignment Detail | This study consisted of a 30-week randomized, double-blind phase followed by a 30-week open-label phase. Participants were randomized 1:1 to receive either cinacalcet or placebo in the double-blind phase. All participants received cinacalcet in the open-label phase. |
| Arm/Group Title | Placebo | Cinacalcet |
|---|---|---|
| Arm/Group Description | Participants received standard of care and placebo once daily for 30 weeks during the double-blind phase. During the open-label phase, participants received cinacalcet with standard of care for an additional 30 weeks. The starting dose of cinacalcet was ≤ 0.20 mg/kg based on dry weight, and could be titrated up according to plasma iPTH and serum calcium levels every 4 weeks up to Week 54 to a maximum dose of 4.2 mg/kg. | Participants received standard of care and cinacalcet once daily for 30 weeks during the double-blind phase. The starting dose of cinacalcet was ≤ 0.20 mg/kg based on dry weight, and could be titrated up according to plasma iPTH and serum calcium levels every 4 weeks until Week 24 to a maximum dose of 4.2 mg/kg. During the open-label phase participants continued to receive cinacalcet with standard of care for an additional 30 weeks. Regardless of the titration level reached at the last dose of IP in the double-blind phase, all participants started titration at ≤ 0.20 mg/kg based on dry weight. |
| Period Title: Double-blind Phase | ||
| STARTED | 21 | 22 |
| Received Investigational Product | 21 | 22 |
| COMPLETED | 8 | 4 |
| NOT COMPLETED | 13 | 18 |
| Period Title: Double-blind Phase | ||
| STARTED | 8 | 4 |
| Received Investigational Product | 6 | 4 |
| COMPLETED | 1 | 1 |
| NOT COMPLETED | 7 | 3 |
Baseline Characteristics
| Arm/Group Title | Placebo | Cinacalcet | Total |
|---|---|---|---|
| Arm/Group Description | Participants received standard of care and placebo once daily for 30 weeks during the double-blind phase. During the open-label phase, participants received cinacalcet with standard of care for an additional 30 weeks. The starting dose of cinacalcet was ≤ 0.20 mg/kg based on dry weight, and could be titrated up according to plasma iPTH and serum calcium levels every 4 weeks up to Week 54 to a maximum dose of 4.2 mg/kg. | Participants received standard of care and cinacalcet once daily for 30 weeks during the double-blind phase. The starting dose of cinacalcet was ≤ 0.20 mg/kg based on dry weight, and could be titrated up according to plasma iPTH and serum calcium levels every 4 weeks until Week 24 to a maximum dose of 4.2 mg/kg. During the open-label phase participants continued to receive cinacalcet with standard of care for an additional 30 weeks. Regardless of the titration level reached at the last dose of IP in the double-blind phase, all participants started titration at ≤ 0.20 mg/kg based on dry weight. | Total of all reporting groups |
| Overall Participants | 21 | 22 | 43 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
13.2
(2.9)
|
13.3
(3.6)
|
13.2
(3.3)
|
| Age, Customized (participants) [Number] | |||
| 6 to < 12 years |
5
23.8%
|
6
27.3%
|
11
25.6%
|
| 12 to < 18 years |
16
76.2%
|
16
72.7%
|
32
74.4%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
10
47.6%
|
12
54.5%
|
22
51.2%
|
| Male |
11
52.4%
|
10
45.5%
|
21
48.8%
|
| Race/Ethnicity, Customized (participants) [Number] | |||
| White |
15
71.4%
|
16
72.7%
|
31
72.1%
|
| Black or African American |
6
28.6%
|
5
22.7%
|
11
25.6%
|
| Other |
0
0%
|
1
4.5%
|
1
2.3%
|
| Race/Ethnicity, Customized (participants) [Number] | |||
| Hispanic or Latino |
5
23.8%
|
3
13.6%
|
8
18.6%
|
| Not Hispanic or Latino |
16
76.2%
|
19
86.4%
|
35
81.4%
|
| Intact Parathyroid Hormone (iPTH) (pg/mL) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [pg/mL] |
795.8
(537.9)
|
757.1
(440.1)
|
776.0
(484.8)
|
| Corrected Total Serum Calcium (mg/dL) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [mg/dL] |
9.88
(0.62)
|
9.91
(0.54)
|
9.90
(0.58)
|
| Serum Phosphorous (mg/dL) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [mg/dL] |
6.37
(1.48)
|
6.68
(1.78)
|
6.53
(1.63)
|
Outcome Measures
| Title | Percentage of Participants Achieving ≥ 30% Reduction in Mean iPTH From Baseline to the Efficacy Assessment Phase |
|---|---|
| Description | The efficacy assessment value is based on the scheduled assessment(s) taken during the efficacy assessment phase (EAP; Weeks 25 - 30). When multiple assessments were available, the average of those was used. If an efficacy measurement during the EAP was missing, the mean of the last 2 available post-baseline values in the dose-titration phase was used. If only one post-baseline value was available, this single value was used. |
| Time Frame | From Baseline to the Efficacy Assessment Phase, Weeks 25-30 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set, which includes all randomized participants with at least 1 post-baseline assessment. |
| Arm/Group Title | Placebo | Cinacalcet |
|---|---|---|
| Arm/Group Description | Participants received standard of care and placebo once daily for 30 weeks during the double-blind phase. During the open-label phase, participants received cinacalcet with standard of care for an additional 30 weeks. The starting dose of cinacalcet was ≤ 0.20 mg/kg based on dry weight, and could be titrated up according to plasma iPTH and serum calcium levels every 4 weeks up to Week 54 to a maximum dose of 4.2 mg/kg. | Participants received standard of care and cinacalcet once daily for 30 weeks during the double-blind phase. The starting dose of cinacalcet was ≤ 0.20 mg/kg based on dry weight, and could be titrated up according to plasma iPTH and serum calcium levels every 4 weeks until Week 24 to a maximum dose of 4.2 mg/kg. During the open-label phase participants continued to receive cinacalcet with standard of care for an additional 30 weeks. Regardless of the titration level reached at the last dose of IP in the double-blind phase, all participants started titration at ≤ 0.20 mg/kg based on dry weight. |
| Measure Participants | 21 | 22 |
| Number [percentage of participants] |
19.0
90.5%
|
54.5
247.7%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Cinacalcet |
|---|---|---|
| Comments | A hierarchical testing procedure was used to test the primary and biochemical secondary endpoints (Outcome Measures 1-5). The primary endpoint was tested at a significance level of 0.05. The four biochemical secondary endpoints were to be tested using Holm's method at 0.05 should the primary endpoint achieve a significant result. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.017 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran- Mantel-Haenszel (CMH) test stratified by baseline age group (6 -<12 years old or 12 - <18 years old). | |
| Method of Estimation | Estimation Parameter | Difference (Cinacalcet - Placebo) |
| Estimated Value | 35.50 | |
| Confidence Interval |
(2-Sided) 95% 8.76 to 62.24 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants Achieving Mean iPTH ≤ 300 pg/mL (31.8 Pmol/L) During the Efficacy Assessment Phase |
|---|---|
| Description | The efficacy assessment value is based on the scheduled assessment(s) taken during the efficacy assessment phase. When multiple assessments were available, the average of those was used. If an efficacy measurement during the EAP was missing, the mean of the last 2 available postbaseline values in the dose-titration phase was used. If only one post-baseline value was available, this single value was used. |
| Time Frame | From Baseline to the Efficacy Assessment Phase (EAP), Weeks 25-30 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set |
| Arm/Group Title | Placebo | Cinacalcet |
|---|---|---|
| Arm/Group Description | Participants received standard of care and placebo once daily for 30 weeks during the double-blind phase. During the open-label phase, participants received cinacalcet with standard of care for an additional 30 weeks. The starting dose of cinacalcet was ≤ 0.20 mg/kg based on dry weight, and could be titrated up according to plasma iPTH and serum calcium levels every 4 weeks up to Week 54 to a maximum dose of 4.2 mg/kg. | Participants received standard of care and cinacalcet once daily for 30 weeks during the double-blind phase. The starting dose of cinacalcet was ≤ 0.20 mg/kg based on dry weight, and could be titrated up according to plasma iPTH and serum calcium levels every 4 weeks until Week 24 to a maximum dose of 4.2 mg/kg. During the open-label phase participants continued to receive cinacalcet with standard of care for an additional 30 weeks. Regardless of the titration level reached at the last dose of IP in the double-blind phase, all participants started titration at ≤ 0.20 mg/kg based on dry weight. |
| Measure Participants | 21 | 22 |
| Number [pecentage of participants] |
23.8
113.3%
|
27.3
124.1%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Cinacalcet |
|---|---|---|
| Comments | The secondary endpoint with the smallest p-value was first compared at a significance level of 0.0125. If the p-value was > 0.0125, all 4 secondary endpoints were non-significant; if ≤ 0.0125, the null hypothesis for that endpoint was rejected. Next, the 2nd smallest p-value was compared at a level of 0.0167; if > 0.0167, the remaining 3 endpoints were not significant, or, the null hypothesis of that endpoint was rejected. The other 2 endpoints were analyzed similarly, at 0.025 and 0.05. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.826 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran- Mantel-Haenszel (CMH) test stratified by baseline age group (6 -<12 years old or 12 - <18 years old). | |
| Method of Estimation | Estimation Parameter | Difference (Cinacalcet - Placebo) |
| Estimated Value | 3.46 | |
| Confidence Interval |
(2-Sided) 95% -22.58 to 29.51 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percent Change From Baseline in Mean Corrected Total Serum Calcium During the Efficacy Assessment Period |
|---|---|
| Description | Serum calcium was reported as a corrected value by the central laboratory based on calcium and albumin concentrations: Corrected total calcium (mg/dL) = measured total serum calcium (mg/dL) + 0.8 (4.0 - Serum albumin (g/dL)). The efficacy assessment value is based on the scheduled assessment(s) taken during the efficacy assessment phase. When multiple assessments were available, the average of those was used. If an efficacy measurement during the EAP was missing, the mean of the last 2 available postbaseline values in the dose-titration phase was used. If only one post-baseline value was available, this single value was used." |
| Time Frame | From Baseline to the Efficacy Assessment Phase, Weeks 25-30. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set |
| Arm/Group Title | Placebo | Cinacalcet |
|---|---|---|
| Arm/Group Description | Participants received standard of care and placebo once daily for 30 weeks during the double-blind phase. During the open-label phase, participants received cinacalcet with standard of care for an additional 30 weeks. The starting dose of cinacalcet was ≤ 0.20 mg/kg based on dry weight, and could be titrated up according to plasma iPTH and serum calcium levels every 4 weeks up to Week 54 to a maximum dose of 4.2 mg/kg. | Participants received standard of care and cinacalcet once daily for 30 weeks during the double-blind phase. The starting dose of cinacalcet was ≤ 0.20 mg/kg based on dry weight, and could be titrated up according to plasma iPTH and serum calcium levels every 4 weeks until Week 24 to a maximum dose of 4.2 mg/kg. During the open-label phase participants continued to receive cinacalcet with standard of care for an additional 30 weeks. Regardless of the titration level reached at the last dose of IP in the double-blind phase, all participants started titration at ≤ 0.20 mg/kg based on dry weight. |
| Measure Participants | 21 | 22 |
| Least Squares Mean (95% Confidence Interval) [percent change] |
-1.0
(1.91)
|
-4.6
(1.84)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Cinacalcet |
|---|---|---|
| Comments | The secondary endpoint with the smallest p-value was first compared at a significance level of 0.0125. If the p-value was > 0.0125, all 4 secondary endpoints were non-significant; if ≤ 0.0125, the null hypothesis for that endpoint was rejected. Next, the 2nd smallest p-value was compared at a level of 0.0167; if > 0.0167, the remaining 3 endpoints were not significant, or, the null hypothesis of that endpoint was rejected. The other 2 endpoints were analyzed similarly, at 0.025 and 0.05. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.147 |
| Comments | ||
| Method | ANCOVA | |
| Comments | Baseline age group was used as covariate. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -3.7 | |
| Confidence Interval |
(2-Sided) 95% -8.6 to 1.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Cinacalcet-Placebo | |
| Title | Percent Change From Baseline in Mean Serum Phosphorus During the Efficacy Assessment Phase |
|---|---|
| Description | The efficacy assessment value is based on the scheduled assessment(s) taken during the efficacy assessment phase. When multiple assessments were available, the average of those was used. If an efficacy measurement during the EAP was missing, the mean of the last 2 available postbaseline values in the dose-titration phase was used. If only one post-baseline value was available, this single value was used. |
| Time Frame | From Baseline to the Efficacy Assessment Phase, Weeks 25-30. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set; data for one participant in the Placebo group were not available. |
| Arm/Group Title | Placebo | Cinacalcet |
|---|---|---|
| Arm/Group Description | Participants received standard of care and placebo once daily for 30 weeks during the double-blind phase. During the open-label phase, participants received cinacalcet with standard of care for an additional 30 weeks. The starting dose of cinacalcet was ≤ 0.20 mg/kg based on dry weight, and could be titrated up according to plasma iPTH and serum calcium levels every 4 weeks up to Week 54 to a maximum dose of 4.2 mg/kg. | Participants received standard of care and cinacalcet once daily for 30 weeks during the double-blind phase. The starting dose of cinacalcet was ≤ 0.20 mg/kg based on dry weight, and could be titrated up according to plasma iPTH and serum calcium levels every 4 weeks until Week 24 to a maximum dose of 4.2 mg/kg. During the open-label phase participants continued to receive cinacalcet with standard of care for an additional 30 weeks. Regardless of the titration level reached at the last dose of IP in the double-blind phase, all participants started titration at ≤ 0.20 mg/kg based on dry weight. |
| Measure Participants | 20 | 22 |
| Least Squares Mean (95% Confidence Interval) [percent change] |
10.2
|
4.9
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Cinacalcet |
|---|---|---|
| Comments | The secondary endpoint with the smallest p-value was first compared at a significance level of 0.0125. If the p-value was > 0.0125, all 4 secondary endpoints were non-significant; if ≤ 0.0125, the null hypothesis for that endpoint was rejected. Next, the 2nd smallest p-value was compared at a level of 0.0167; if > 0.0167, the remaining 3 endpoints were not significant, or, the null hypothesis of that endpoint was rejected. The other 2 endpoints were analyzed similarly, at 0.025 and 0.05. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.454 |
| Comments | ||
| Method | ANCOVA | |
| Comments | Baseline age group was used as covariate | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -5.3 | |
| Confidence Interval |
(2-Sided) 95% -19.4 to 8.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Cinacalcet-Placebo | |
| Title | Percent Change From Baseline in Mean Phosphorous Product (Ca x P) During the Efficacy Assessment Phase |
|---|---|
| Description | The efficacy assessment value is based on the scheduled assessment(s) taken during the efficacy assessment phase. When multiple assessments were available, the average of those was used. If an efficacy measurement during the EAP was missing, the mean of the last 2 available postbaseline values in the dose-titration phase was used. If only one post-baseline value was available, this single value was used. |
| Time Frame | From Baseline to end of Efficacy Assessment Period, assessed up to 30 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set |
| Arm/Group Title | Placebo | Cinacalcet |
|---|---|---|
| Arm/Group Description | Participants received standard of care and placebo once daily for 30 weeks during the double-blind phase. During the open-label phase, participants received cinacalcet with standard of care for an additional 30 weeks. The starting dose of cinacalcet was ≤ 0.20 mg/kg based on dry weight, and could be titrated up according to plasma iPTH and serum calcium levels every 4 weeks up to Week 54 to a maximum dose of 4.2 mg/kg. | Participants received standard of care and cinacalcet once daily for 30 weeks during the double-blind phase. The starting dose of cinacalcet was ≤ 0.20 mg/kg based on dry weight, and could be titrated up according to plasma iPTH and serum calcium levels every 4 weeks until Week 24 to a maximum dose of 4.2 mg/kg. During the open-label phase participants continued to receive cinacalcet with standard of care for an additional 30 weeks. Regardless of the titration level reached at the last dose of IP in the double-blind phase, all participants started titration at ≤ 0.20 mg/kg based on dry weight. |
| Measure Participants | 21 | 22 |
| Least Squares Mean (95% Confidence Interval) [percent change] |
8.0
|
-2.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Cinacalcet |
|---|---|---|
| Comments | The secondary endpoint with the smallest p-value was first compared at a significance level of 0.0125. If the p-value was > 0.0125, all 4 secondary endpoints were non-significant; if ≤ 0.0125, the null hypothesis for that endpoint was rejected. Next, the 2nd smallest p-value was compared at a level of 0.0167; if > 0.0167, the remaining 3 endpoints were not significant, or, the null hypothesis of that endpoint was rejected. The other 2 endpoints were analyzed similarly, at 0.025 and 0.05. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.117 |
| Comments | ||
| Method | ANCOVA | |
| Comments | Baseline age group was used as covariate. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -10.0 | |
| Confidence Interval |
(2-Sided) 95% -22.5 to 2.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Cinacalcet-Placebo | |
| Title | Growth Velocity From Baseline to End of Double-blind Phase |
|---|---|
| Description | Linear growth velocity (cm/year) = 52 x change in height (cm) / number of weeks between the two assessments. End of double-blind phase visit was at Week 30 by design but the last assessment in the double-blind phase was used due to the early termination of the study. |
| Time Frame | From Baseline to end of Efficacy Assessment at Week 30 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set; the last assessment in the double-blind phase was used due to the early termination of the study. Only participants with available data are included in the analysis. |
| Arm/Group Title | Placebo | Cinacalcet |
|---|---|---|
| Arm/Group Description | Participants received standard of care and placebo once daily for 30 weeks during the double-blind phase. During the open-label phase, participants received cinacalcet with standard of care for an additional 30 weeks. The starting dose of cinacalcet was ≤ 0.20 mg/kg based on dry weight, and could be titrated up according to plasma iPTH and serum calcium levels every 4 weeks up to Week 54 to a maximum dose of 4.2 mg/kg. | Participants received standard of care and cinacalcet once daily for 30 weeks during the double-blind phase. The starting dose of cinacalcet was ≤ 0.20 mg/kg based on dry weight, and could be titrated up according to plasma iPTH and serum calcium levels every 4 weeks until Week 24 to a maximum dose of 4.2 mg/kg. During the open-label phase participants continued to receive cinacalcet with standard of care for an additional 30 weeks. Regardless of the titration level reached at the last dose of IP in the double-blind phase, all participants started titration at ≤ 0.20 mg/kg based on dry weight. |
| Measure Participants | 19 | 17 |
| Least Squares Mean (95% Confidence Interval) [cm/year] |
3.1
|
3.3
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Cinacalcet |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.896 |
| Comments | No adjustments for multiplicity were made. | |
| Method | ANCOVA | |
| Comments | Baseline age group was used as covariate. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 0.2 | |
| Confidence Interval |
(2-Sided) 95% -3.1 to 3.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Cinacalcet-Placebo | |
| Title | Growth Velocity From End of Double-blind Phase to End of Open-label Phase |
|---|---|
| Description | Linear growth velocity (cm/year) = 52 x change in height (cm) / number of weeks between the two assessments. End of open-label phase visit was at Week 60 by design but the last assessment in the open-label phase was used due to the early termination of the study. |
| Time Frame | End of double-blind phase (Week 30) until end of the open-label phase (Week 60) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set. Only participants with available data were included in the anaysis. |
| Arm/Group Title | Placebo | Cinacalcet |
|---|---|---|
| Arm/Group Description | Participants received standard of care and placebo once daily for 30 weeks during the double-blind phase. During the open-label phase, participants received cinacalcet with standard of care for an additional 30 weeks. The starting dose of cinacalcet was ≤ 0.20 mg/kg based on dry weight, and could be titrated up according to plasma iPTH and serum calcium levels every 4 weeks up to Week 54 to a maximum dose of 4.2 mg/kg. | Participants received standard of care and cinacalcet once daily for 30 weeks during the double-blind phase. The starting dose of cinacalcet was ≤ 0.20 mg/kg based on dry weight, and could be titrated up according to plasma iPTH and serum calcium levels every 4 weeks until Week 24 to a maximum dose of 4.2 mg/kg. During the open-label phase participants continued to receive cinacalcet with standard of care for an additional 30 weeks. Regardless of the titration level reached at the last dose of IP in the double-blind phase, all participants started titration at ≤ 0.20 mg/kg based on dry weight. |
| Measure Participants | 7 | 3 |
| Mean (Standard Deviation) [cm/year] |
2.75
(3.23)
|
1.21
(1.31)
|
| Title | Percent Change From Baseline in Mean Ionized Calcium During the Efficacy Assessment Phase |
|---|---|
| Description | The efficacy assessment value is based on the scheduled assessment(s) taken during the efficacy assessment phase. When multiple assessments were available, the average of those was used. If an efficacy measurement during the EAP was missing, the mean of the last 2 available postbaseline values in the dose-titration phase was used. If only one post-baseline value was available, this single value was used. |
| Time Frame | From Baseline to the Efficacy Assessment Phase, Weeks 25-30. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set; only participants with available data were included in the analysis. |
| Arm/Group Title | Placebo | Cinacalcet |
|---|---|---|
| Arm/Group Description | Participants received standard of care and placebo once daily for 30 weeks during the double-blind phase. During the open-label phase, participants received cinacalcet with standard of care for an additional 30 weeks. The starting dose of cinacalcet was ≤ 0.20 mg/kg based on dry weight, and could be titrated up according to plasma iPTH and serum calcium levels every 4 weeks up to Week 54 to a maximum dose of 4.2 mg/kg. | Participants received standard of care and cinacalcet once daily for 30 weeks during the double-blind phase. The starting dose of cinacalcet was ≤ 0.20 mg/kg based on dry weight, and could be titrated up according to plasma iPTH and serum calcium levels every 4 weeks until Week 24 to a maximum dose of 4.2 mg/kg. During the open-label phase participants continued to receive cinacalcet with standard of care for an additional 30 weeks. Regardless of the titration level reached at the last dose of IP in the double-blind phase, all participants started titration at ≤ 0.20 mg/kg based on dry weight. |
| Measure Participants | 12 | 18 |
| Least Squares Mean (95% Confidence Interval) [percent change] |
-1.5
|
-2.3
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Cinacalcet |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.854 |
| Comments | ||
| Method | ANCOVA | |
| Comments | Baseline age group was used as covariate. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.8 | |
| Confidence Interval |
(2-Sided) 95% -9.4 to 7.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Cinacalcet-Placebo | |
Adverse Events
| Time Frame | 60 Weeks | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. | |||||||
| Arm/Group Title | Double-blind Phase: Placebo | Double-blind Phase: Cinacalcet | Open-label Phase: Previous Placebo | Open-label Phase: Previous Cinacalcet | ||||
| Arm/Group Description | ||||||||
All Cause Mortality |
||||||||
| Double-blind Phase: Placebo | Double-blind Phase: Cinacalcet | Open-label Phase: Previous Placebo | Open-label Phase: Previous Cinacalcet | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| Double-blind Phase: Placebo | Double-blind Phase: Cinacalcet | Open-label Phase: Previous Placebo | Open-label Phase: Previous Cinacalcet | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 9/21 (42.9%) | 9/22 (40.9%) | 3/6 (50%) | 1/4 (25%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 0/21 (0%) | 1/22 (4.5%) | 0/6 (0%) | 0/4 (0%) | ||||
| Febrile neutropenia | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Neutropenia | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Cardiac disorders | ||||||||
| Cardiopulmonary failure | 0/21 (0%) | 1/22 (4.5%) | 0/6 (0%) | 0/4 (0%) | ||||
| Eye disorders | ||||||||
| Papilloedema | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal pain | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Diarrhoea | 2/21 (9.5%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Gastric ulcer | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Gastritis | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Nausea | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Varices oesophageal | 0/21 (0%) | 0/22 (0%) | 1/6 (16.7%) | 0/4 (0%) | ||||
| General disorders | ||||||||
| Medical device complication | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Pain | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Pyrexia | 2/21 (9.5%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Thirst | 0/21 (0%) | 1/22 (4.5%) | 0/6 (0%) | 0/4 (0%) | ||||
| Thrombosis in device | 0/21 (0%) | 1/22 (4.5%) | 0/6 (0%) | 0/4 (0%) | ||||
| Immune system disorders | ||||||||
| Rubber sensitivity | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Transplant rejection | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Infections and infestations | ||||||||
| Catheter site cellulitis | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Device related infection | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Gastroenteritis | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Measles | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Peritonitis | 0/21 (0%) | 1/22 (4.5%) | 0/6 (0%) | 1/4 (25%) | ||||
| Pneumonia | 0/21 (0%) | 0/22 (0%) | 0/6 (0%) | 1/4 (25%) | ||||
| Pyelonephritis | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Sepsis | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Urinary tract infection | 1/21 (4.8%) | 0/22 (0%) | 1/6 (16.7%) | 0/4 (0%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Arteriovenous fistula site complication | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Graft complication | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Overdose | 0/21 (0%) | 1/22 (4.5%) | 0/6 (0%) | 0/4 (0%) | ||||
| Vascular graft complication | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Investigations | ||||||||
| Blood creatinine increased | 0/21 (0%) | 1/22 (4.5%) | 0/6 (0%) | 0/4 (0%) | ||||
| Blood pressure increased | 0/21 (0%) | 1/22 (4.5%) | 0/6 (0%) | 0/4 (0%) | ||||
| Haemoglobin increased | 0/21 (0%) | 0/22 (0%) | 1/6 (16.7%) | 0/4 (0%) | ||||
| Weight decreased | 0/21 (0%) | 1/22 (4.5%) | 0/6 (0%) | 0/4 (0%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Acidosis | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Dehydration | 2/21 (9.5%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Fluid overload | 1/21 (4.8%) | 1/22 (4.5%) | 0/6 (0%) | 0/4 (0%) | ||||
| Food intolerance | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Hyperglycaemia | 0/21 (0%) | 1/22 (4.5%) | 0/6 (0%) | 0/4 (0%) | ||||
| Hyperkalaemia | 0/21 (0%) | 1/22 (4.5%) | 0/6 (0%) | 0/4 (0%) | ||||
| Hyperphosphataemia | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Hypocalcaemia | 0/21 (0%) | 1/22 (4.5%) | 1/6 (16.7%) | 0/4 (0%) | ||||
| Nervous system disorders | ||||||||
| Hypertensive encephalopathy | 1/21 (4.8%) | 0/22 (0%) | 1/6 (16.7%) | 0/4 (0%) | ||||
| Migraine | 0/21 (0%) | 1/22 (4.5%) | 0/6 (0%) | 0/4 (0%) | ||||
| Renal and urinary disorders | ||||||||
| Glycosuria | 0/21 (0%) | 1/22 (4.5%) | 0/6 (0%) | 0/4 (0%) | ||||
| Vascular disorders | ||||||||
| Hypertension | 1/21 (4.8%) | 2/22 (9.1%) | 1/6 (16.7%) | 0/4 (0%) | ||||
| Hypertensive crisis | 0/21 (0%) | 1/22 (4.5%) | 0/6 (0%) | 0/4 (0%) | ||||
| Hypotension | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Thrombosis | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Double-blind Phase: Placebo | Double-blind Phase: Cinacalcet | Open-label Phase: Previous Placebo | Open-label Phase: Previous Cinacalcet | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 17/21 (81%) | 16/22 (72.7%) | 6/6 (100%) | 3/4 (75%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Neutropenia | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Cardiac disorders | ||||||||
| Mitral valve stenosis | 0/21 (0%) | 1/22 (4.5%) | 0/6 (0%) | 0/4 (0%) | ||||
| Palpitations | 1/21 (4.8%) | 0/22 (0%) | 1/6 (16.7%) | 0/4 (0%) | ||||
| Tachycardia | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Endocrine disorders | ||||||||
| Hyperparathyroidism | 0/21 (0%) | 1/22 (4.5%) | 0/6 (0%) | 0/4 (0%) | ||||
| Eye disorders | ||||||||
| Keratitis | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Ocular hyperaemia | 0/21 (0%) | 1/22 (4.5%) | 0/6 (0%) | 0/4 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal distension | 0/21 (0%) | 0/22 (0%) | 1/6 (16.7%) | 0/4 (0%) | ||||
| Abdominal pain | 2/21 (9.5%) | 3/22 (13.6%) | 2/6 (33.3%) | 0/4 (0%) | ||||
| Abdominal pain upper | 0/21 (0%) | 1/22 (4.5%) | 0/6 (0%) | 0/4 (0%) | ||||
| Constipation | 3/21 (14.3%) | 1/22 (4.5%) | 0/6 (0%) | 0/4 (0%) | ||||
| Diarrhoea | 2/21 (9.5%) | 2/22 (9.1%) | 0/6 (0%) | 0/4 (0%) | ||||
| Dry mouth | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Dyspepsia | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Gastrooesophageal reflux disease | 0/21 (0%) | 1/22 (4.5%) | 0/6 (0%) | 0/4 (0%) | ||||
| Hypoaesthesia oral | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Nausea | 2/21 (9.5%) | 4/22 (18.2%) | 2/6 (33.3%) | 1/4 (25%) | ||||
| Stomatitis | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Vomiting | 5/21 (23.8%) | 7/22 (31.8%) | 1/6 (16.7%) | 0/4 (0%) | ||||
| General disorders | ||||||||
| Catheter site pain | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Catheter site pruritus | 0/21 (0%) | 1/22 (4.5%) | 0/6 (0%) | 0/4 (0%) | ||||
| Catheter site related reaction | 0/21 (0%) | 0/22 (0%) | 0/6 (0%) | 1/4 (25%) | ||||
| Chest pain | 0/21 (0%) | 0/22 (0%) | 0/6 (0%) | 1/4 (25%) | ||||
| Chills | 2/21 (9.5%) | 1/22 (4.5%) | 1/6 (16.7%) | 0/4 (0%) | ||||
| Device breakage | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Device leakage | 0/21 (0%) | 0/22 (0%) | 1/6 (16.7%) | 0/4 (0%) | ||||
| Face oedema | 0/21 (0%) | 0/22 (0%) | 0/6 (0%) | 1/4 (25%) | ||||
| Fatigue | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Feeling cold | 0/21 (0%) | 1/22 (4.5%) | 0/6 (0%) | 0/4 (0%) | ||||
| Local swelling | 2/21 (9.5%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Oedema peripheral | 0/21 (0%) | 1/22 (4.5%) | 0/6 (0%) | 0/4 (0%) | ||||
| Pain | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 1/4 (25%) | ||||
| Pyrexia | 2/21 (9.5%) | 1/22 (4.5%) | 2/6 (33.3%) | 0/4 (0%) | ||||
| Immune system disorders | ||||||||
| Drug hypersensitivity | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Infections and infestations | ||||||||
| Acute sinusitis | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Catheter site infection | 0/21 (0%) | 2/22 (9.1%) | 0/6 (0%) | 0/4 (0%) | ||||
| Cellulitis | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Device related infection | 1/21 (4.8%) | 2/22 (9.1%) | 0/6 (0%) | 0/4 (0%) | ||||
| Infection | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Influenza | 1/21 (4.8%) | 3/22 (13.6%) | 1/6 (16.7%) | 0/4 (0%) | ||||
| Nasopharyngitis | 1/21 (4.8%) | 2/22 (9.1%) | 0/6 (0%) | 1/4 (25%) | ||||
| Oral herpes | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Otitis media acute | 0/21 (0%) | 1/22 (4.5%) | 0/6 (0%) | 0/4 (0%) | ||||
| Peritonitis | 0/21 (0%) | 0/22 (0%) | 0/6 (0%) | 1/4 (25%) | ||||
| Pharyngitis streptococcal | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Respiratory tract infection | 1/21 (4.8%) | 1/22 (4.5%) | 0/6 (0%) | 0/4 (0%) | ||||
| Upper respiratory tract infection | 4/21 (19%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Viral infection | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Arteriovenous fistula site complication | 2/21 (9.5%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Arthropod bite | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Dialysis related complication | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Femur fracture | 0/21 (0%) | 0/22 (0%) | 1/6 (16.7%) | 0/4 (0%) | ||||
| Overdose | 0/21 (0%) | 0/22 (0%) | 0/6 (0%) | 1/4 (25%) | ||||
| Procedural hypotension | 0/21 (0%) | 1/22 (4.5%) | 0/6 (0%) | 0/4 (0%) | ||||
| Procedural nausea | 0/21 (0%) | 1/22 (4.5%) | 0/6 (0%) | 0/4 (0%) | ||||
| Vascular graft complication | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Investigations | ||||||||
| Blood calcium abnormal | 0/21 (0%) | 1/22 (4.5%) | 0/6 (0%) | 0/4 (0%) | ||||
| Blood phosphorus increased | 0/21 (0%) | 1/22 (4.5%) | 0/6 (0%) | 1/4 (25%) | ||||
| Electrocardiogram T wave abnormal | 0/21 (0%) | 1/22 (4.5%) | 0/6 (0%) | 0/4 (0%) | ||||
| Haematocrit decreased | 0/21 (0%) | 1/22 (4.5%) | 0/6 (0%) | 0/4 (0%) | ||||
| Haemoglobin decreased | 0/21 (0%) | 1/22 (4.5%) | 0/6 (0%) | 0/4 (0%) | ||||
| Haemoglobin increased | 0/21 (0%) | 1/22 (4.5%) | 0/6 (0%) | 0/4 (0%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Acidosis | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Fluid overload | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Hypercholesterolaemia | 1/21 (4.8%) | 1/22 (4.5%) | 0/6 (0%) | 0/4 (0%) | ||||
| Hyperkalaemia | 3/21 (14.3%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Hyperuricaemia | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Hypoalbuminaemia | 0/21 (0%) | 1/22 (4.5%) | 0/6 (0%) | 0/4 (0%) | ||||
| Hypocalcaemia | 4/21 (19%) | 5/22 (22.7%) | 2/6 (33.3%) | 1/4 (25%) | ||||
| Hypokalaemia | 0/21 (0%) | 1/22 (4.5%) | 0/6 (0%) | 1/4 (25%) | ||||
| Hypomagnesaemia | 1/21 (4.8%) | 1/22 (4.5%) | 0/6 (0%) | 0/4 (0%) | ||||
| Hyponatraemia | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Vitamin D deficiency | 2/21 (9.5%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Back pain | 2/21 (9.5%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Knee deformity | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Muscle spasms | 1/21 (4.8%) | 3/22 (13.6%) | 0/6 (0%) | 0/4 (0%) | ||||
| Musculoskeletal pain | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Musculoskeletal stiffness | 0/21 (0%) | 2/22 (9.1%) | 0/6 (0%) | 0/4 (0%) | ||||
| Myalgia | 1/21 (4.8%) | 3/22 (13.6%) | 0/6 (0%) | 0/4 (0%) | ||||
| Pain in extremity | 0/21 (0%) | 1/22 (4.5%) | 1/6 (16.7%) | 0/4 (0%) | ||||
| Nervous system disorders | ||||||||
| Convulsion | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Dizziness | 0/21 (0%) | 2/22 (9.1%) | 0/6 (0%) | 0/4 (0%) | ||||
| Epilepsy | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Headache | 2/21 (9.5%) | 3/22 (13.6%) | 1/6 (16.7%) | 1/4 (25%) | ||||
| Hypoaesthesia | 1/21 (4.8%) | 1/22 (4.5%) | 0/6 (0%) | 0/4 (0%) | ||||
| Paraesthesia | 1/21 (4.8%) | 1/22 (4.5%) | 1/6 (16.7%) | 1/4 (25%) | ||||
| Syncope | 0/21 (0%) | 1/22 (4.5%) | 0/6 (0%) | 0/4 (0%) | ||||
| Tremor | 0/21 (0%) | 3/22 (13.6%) | 0/6 (0%) | 0/4 (0%) | ||||
| Psychiatric disorders | ||||||||
| Adjustment disorder | 0/21 (0%) | 0/22 (0%) | 0/6 (0%) | 1/4 (25%) | ||||
| Anxiety | 0/21 (0%) | 2/22 (9.1%) | 0/6 (0%) | 0/4 (0%) | ||||
| Daydreaming | 0/21 (0%) | 1/22 (4.5%) | 0/6 (0%) | 0/4 (0%) | ||||
| Staring | 0/21 (0%) | 1/22 (4.5%) | 0/6 (0%) | 0/4 (0%) | ||||
| Renal and urinary disorders | ||||||||
| Hydronephrosis | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Leukocyturia | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Cough | 3/21 (14.3%) | 1/22 (4.5%) | 1/6 (16.7%) | 0/4 (0%) | ||||
| Dyspnoea | 0/21 (0%) | 0/22 (0%) | 1/6 (16.7%) | 0/4 (0%) | ||||
| Nasal congestion | 3/21 (14.3%) | 0/22 (0%) | 1/6 (16.7%) | 0/4 (0%) | ||||
| Oropharyngeal pain | 2/21 (9.5%) | 0/22 (0%) | 1/6 (16.7%) | 0/4 (0%) | ||||
| Rhinorrhoea | 0/21 (0%) | 0/22 (0%) | 1/6 (16.7%) | 0/4 (0%) | ||||
| Wheezing | 1/21 (4.8%) | 1/22 (4.5%) | 0/6 (0%) | 0/4 (0%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Acne | 0/21 (0%) | 0/22 (0%) | 1/6 (16.7%) | 0/4 (0%) | ||||
| Alopecia | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Dandruff | 0/21 (0%) | 0/22 (0%) | 1/6 (16.7%) | 0/4 (0%) | ||||
| Dermatitis contact | 0/21 (0%) | 1/22 (4.5%) | 0/6 (0%) | 0/4 (0%) | ||||
| Hirsutism | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Pruritus | 1/21 (4.8%) | 1/22 (4.5%) | 0/6 (0%) | 0/4 (0%) | ||||
| Rash | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Skin irritation | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Swelling face | 0/21 (0%) | 1/22 (4.5%) | 0/6 (0%) | 0/4 (0%) | ||||
| Urticaria | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Vascular disorders | ||||||||
| Haematoma | 1/21 (4.8%) | 0/22 (0%) | 0/6 (0%) | 0/4 (0%) | ||||
| Hypertension | 4/21 (19%) | 1/22 (4.5%) | 0/6 (0%) | 1/4 (25%) | ||||
| Hypotension | 0/21 (0%) | 2/22 (9.1%) | 0/6 (0%) | 1/4 (25%) | ||||
Limitations/Caveats
The study was terminated early with a smaller sample size. However, the study was still sufficiently powered for the double-blind phase. The data collected in the open-label phase is very sparse.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Amgen Inc. |
| Phone | 866-572-6436 |
Responsible Party:
Amgen
ClinicalTrials.gov Identifier:
NCT01277510
Other Study ID Numbers:
- 20070208
First Posted:
Jan 17, 2011
Last Update Posted:
Jun 29, 2020
Last Verified:
Jun 1, 2020