Treatment of Autonomous Hyperparathyroidism in Post Renal Transplant Recipients

• Sponsor: Amgen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00975000
• Collaborator: (none)
• Enrollment: 114
• Locations: 51
• Arms: 2
• Actual Duration (Months): 40.4
• Patients Per Site: 2.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Hyperparathyroidism (HPT) is common in people with a kidney transplant. Patients with HPT often have high parathyroid hormone (PTH) levels and may have large parathyroid glands in the neck. Patients with HPT can develop bone disease (osteodystrophy). This bone disease can cause bone pain, fractures, and poor formation of red blood cells. Other problems from HPT may include increases in blood levels of calcium (hypercalcemia) and low blood levels of phosphorus (hypophosphatemia). The high calcium levels may cause calcium to deposit in body tissues. Calcium deposits can cause arthritis (joint pain and swelling), muscle inflammation, itching, gangrene (death of soft tissue), heart and lung problems or kidney transplant dysfunction (worsening of kidney transplant function). The purpose of this study is to evaluate the effects of cinacalcet (Sensipar/Mimpara) on high calcium levels in the blood in patients with HPT after a kidney transplant.

Condition or Disease	Intervention/Treatment	Phase
Chronic Allograft Nephropathy; Chronic Kidney Disease; Chronic Renal Failure; Disordered Mineral Metabolism; End Stage Renal Disease; Hyperparathyroidism; Hypophosphatemia; Kidney Disease; Kidney Transplantation; Post Renal Transplantation	Drug: Cinacalcet; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 114 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 Evaluate the Efficacy and Safety of Using Cinacalcet to Correct Hypercalcemia in Renal Transplant Recipients With Autonomous Hyperparathyroidism
• Actual Study Start Date: Dec 3, 2009
• Actual Primary Completion Date: Sep 13, 2012
• Actual Study Completion Date: Apr 16, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cinacalcet Participants received cinacalcet at a starting dose of 30 mg orally once daily for 52 weeks. Cinacalcet dose was titrated every 4 weeks during the dose-titration phase and during study visits in the maintenance phase based on intact parthyroid hormone (iPTH) values, corrected total serum calcium values, and safety assessments.	Drug: Cinacalcet; Possible sequential doses are 30, 60, 90, 120, and 180 mg.; Other Names: Mimpara Sensipar
Placebo Comparator: Placebo Participants received placebo orally once daily for 52 weeks.	Drug: Placebo; Administered orally following the same dosing regimen as the experimental arm.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With a Mean Corrected Total Serum Calcium Value < 10.2 mg/dL (2.55 mmol/L) During the Efficacy Assessment Phase (EAP) [Weeks 21 to 26 (EAP)]

Secondary Outcome Measures

1. Percent Change From Baseline to Week 52 in Bone Mineral Density at the Femoral Neck [Baseline and Week 52]

   Bone mineral density (BMD) was measured using dual X-ray absorptiometry (DXA).

2. Change From Baseline to the EAP in Mean Serum Phosphorus [Baseline and the EAP (mean of Weeks 22, 24, and 26)]

3. Change From Baseline to Week 52 in eGFR [Baseline and Week 52]

   eGFR was calculated using the Modification of Diet in Renal Disease (MDRD) formula.

4. Change From Baseline to the EAP in Corrected Total Calcium [Baseline and the EAP (mean of Weeks 22, 24, and 26)]

5. Change From Baseline to the EAP in Intact Parathyroid Hormone (iPTH) [Baseline and the EAP (mean of Weeks 22, 24, and 26)]

6. Change From Baseline to the EAP in Urine Phosphorus [Baseline and the EAP (mean of Weeks 22, 24, and 26)]

7. Percentage of Participants With a Parathyroidectomy [56 weeks]

8. Time to Parathyroidectomy [56 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Received a kidney transplant ≥ 9 weeks at time of Screening and ≤ 24 months before first dose

• May be the first kidney transplant or a repeat kidney transplant.

• Subjects with a functional, stable kidney transplant, defined as MDRD estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m² (chromic kidney disease stage 3 or better) at Screening.

• Men or women ≥ 18 years at the start of Screening (ie, time of informed consent).

• Corrected total serum calcium > 10.5 mg/dL (2.63 mmol/L), defined as the mean of 2 values in Screening period.

• iPTH > 100 pg/mL (10.6 pmol/L), during the Screening period (obtained at either Screen 1 or Screen 2).

Exclusion Criteria:

• Received cinacalcet therapy post-transplant for more than 14 days cumulatively post-transplant. If cinacalcet therapy was received for a total of 14 days or less post-transplant, there must be a 4-week washout before subject is eligible for screening (Note: This does not exclude pre-transplant use of cinacalcet).

• Anticipated parathyroidectomy within 6 to12 months after Randomization.

• Ongoing therapy with bisphosphonates or use within 6 months prior to Screening.

• Ongoing use of 1,25-dihydroxyvitamin D3 (including other active vitamin D metabolites or analogues) or use within 30 days prior to Screening.

• Ongoing use of calcium supplements or use within 30 days prior to Screening.

• Ongoing use of phosphate binders (calcium or non-calcium containing) or use within 30 days prior to Screening.

• Ongoing use of a thiazide diuretic.

• Subjects with a history of seizures who had a seizure within the 3 months prior to Randomization, which required adjustments to the seizure medication.

• Acute Kidney Injury (AKI) or renal biopsy within 6 weeks prior to Screening, unless it is an institutional protocol-driven biopsy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Phoenix	Arizona	United States	85012
2	Research Site	Tempe	Arizona	United States	85284
3	Research Site	San Francisco	California	United States	94143
4	Research Site	Aurora	Colorado	United States	80045
5	Research Site	Gainesville	Florida	United States	32610
6	Research Site	Atlanta	Georgia	United States	30322
7	Research Site	Chicago	Illinois	United States	60637
8	Research Site	Evanston	Illinois	United States	60201
9	Research Site	Springfield	Massachusetts	United States	01107
10	Research Site	Detroit	Michigan	United States	48202
11	Research Site	New York	New York	United States	10032
12	Research Site	Bethlehem	Pennsylvania	United States	18017
13	Research Site	Nashville	Tennessee	United States	37232
14	Research Site	Dallas	Texas	United States	75390
15	Research Site	Houston	Texas	United States	77030
16	Research Site	Camperdown	New South Wales	Australia	2050
17	Research Site	Westmead	New South Wales	Australia	2145
18	Research Site	Woodville South	South Australia	Australia	5011
19	Research Site	Parkville	Victoria	Australia	3050
20	Research Site	Wien		Austria	1090
21	Research Site	Brussels		Belgium	1200
22	Research Site	Gent		Belgium	9000
23	Research Site	Leuven		Belgium	3000
24	Research Site	Calgary	Alberta	Canada	T2N 2T9
25	Research Site	Vancouver	British Columbia	Canada	V6Z 1Y6
26	Research Site	London	Ontario	Canada	N6A 5A5
27	Research Site	Ottawa	Ontario	Canada	K1H 7W9
28	Research Site	Toronto	Ontario	Canada	M5C 2T2
29	Research Site	Bordeaux Cedex		France	33076
30	Research Site	Montpellier cedex 05		France	34295
31	Research Site	Nantes Cedex 1		France	44093
32	Research Site	Paris Cedex 15		France	75743
33	Research Site	Toulouse Cedex 09		France	31403
34	Research Site	Berlin		Germany	13353
35	Research Site	Kiel		Germany	24105
36	Research Site	Genova		Italy	16132
37	Research Site	Milano		Italy	20122
38	Research Site	Padova		Italy	35128
39	Research Site	Gdansk		Poland	80-952
40	Research Site	Katowice		Poland	40-027
41	Research Site	Lodz		Poland	90-153
42	Research Site	Poznan		Poland	60-539
43	Research Site	Szczecin		Poland	70-111
44	Research Site	Málaga	AndalucÃ-a	Spain	29010
45	Research Site	Barcelona	Cataluña	Spain	08025
46	Research Site	Barcelona	Cataluña	Spain	08036
47	Research Site	L'Hospitalet de Llobregat	Cataluña	Spain	08907
48	Research Site	Madrid		Spain	28041
49	Research Site	Bern		Switzerland	3010
50	Research Site	Geneva 14		Switzerland	1211
51	Research Site	Zurich		Switzerland	8091

Sponsors and Collaborators

• Amgen

Investigators

• Study Director: MD, Amgen

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• AmgenTrials clinical trials website

Publications

None provided.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT00975000
• Other Study ID Numbers: 20062007
• First Posted: Sep 11, 2009
• Last Update Posted: Oct 17, 2018
• Last Verified: Sep 1, 2018

• Keywords provided by Amgen: Intervention; Cinacalcet; Sensipar; Mimpara; hyperparathyroidism; calcium; osteodystrophy; hypercalcemia; renal; transplant; acute rejection; kidney transplant failure; hypophosphatemia
• Additional relevant MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Kidney Failure, Chronic; Hypophosphatemia; Hyperparathyroidism; Cinacalcet

Study Results

Participant Flow

Recruitment Details	This study was conducted at 33 centers in 11 countries (Australia, Austria, Belgium, Canada, France, Germany, Italy, Poland, Spain, Switzerland, and USA). First patient enrolled on 15 October 2009 and last patient enrolled on 07 March 2012.
Pre-assignment Detail	The study consisted of a 20-week titration phase, a 6-week efficacy assessment phase (EAP), a 26-week blinded maintenance phase and a 4-week follow-up phase. Randomization was stratified by corrected total serum calcium (Ca); enrollment into the low Ca stratum was limited to ≤70% of patients to ensure at least 30% enrollment in the high Ca stratum.

Arm/Group Title	Placebo	Cinacalcet
Arm/Group Description	Participants received placebo orally once daily for 52 weeks.	Participants received cinacalcet at a starting dose of 30 mg orally once daily for 52 weeks. Cinacalcet dose was titrated every 4 weeks during the dose-titration phase and during study visits in the maintenance phase based on intact parathyroid hormone (iPTH) values, corrected total serum calcium values, and safety assessments.
Period Title: Overall Study
STARTED	57	57
Completed Titration Phase	54	55
Completed Efficacy Assessment Phase	54	54
Completed Maintenance Phase	52	52
COMPLETED	52	52
NOT COMPLETED	5	5

Baseline Characteristics

Arm/Group Title	Placebo	Cinacalcet	Total
Arm/Group Description	Participants received placebo orally once daily for 52 weeks.	Participants received cinacalcet at a starting dose of 30 mg orally once daily for 52 weeks. Cinacalcet dose was titrated every 4 weeks during the dose-titration phase and during study visits in the maintenance phase based on the iPTH values, corrected total serum calcium values, and safety assessments.	Total of all reporting groups
Overall Participants	57	57	114
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.7 (9.9)	53.0 (10.7)	52.3 (10.3)
Sex: Female, Male (Count of Participants)
Female	25 43.9%	26 45.6%	51 44.7%
Male	32 56.1%	31 54.4%	63 55.3%
Race/Ethnicity, Customized (participants) [Number]
White or Caucasian	46 80.7%	47 82.5%	93 81.6%
Black or African American	4 7%	5 8.8%	9 7.9%
Hispanic or Latino	1 1.8%	2 3.5%	3 2.6%
Asian	3 5.3%	2 3.5%	5 4.4%
Native Hawaiian or Other Pacific Islander	2 3.5%	0 0%	2 1.8%
Other	1 1.8%	1 1.8%	2 1.8%
Stratification Factor: Albumin-corrected Calcium Level (participants) [Number]
Corrected calcium ≤ 11.2 mg/dL	22 38.6%	23 40.4%	45 39.5%
Corrected calcium > 11.2 mg/dL	35 61.4%	34 59.6%	69 60.5%
Corrected Total Serum Calcium (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	11.31 (0.50)	11.28 (0.41)	11.29 (0.45)
Intact Parathyroid Hormone (pg/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [pg/mL]	307.5 (180.5)	327.7 (262.6)	317.6 (224.5)
Serum Phosphorus (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	2.48 (0.52)	2.66 (0.54)	2.57 (0.54)
Estimated Glomerular Filtration Rate (eGFR) (mL/min/1.73 m²) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mL/min/1.73 m²]	54.68 (14.79)	57.00 (17.31)	55.84 (16.07)

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With a Mean Corrected Total Serum Calcium Value < 10.2 mg/dL (2.55 mmol/L) During the Efficacy Assessment Phase (EAP)
Time Frame	Weeks 21 to 26 (EAP)

Outcome Measure Data

Analysis Population Description

Full analysis set (all randomized participants excluding participants determined to have graft failure prior to week 26)

Arm/Group Title	Placebo	Cinacalcet
Arm/Group Description	Participants received placebo orally once daily for 52 weeks.	Participants received cinacalcet at a starting dose of 30 mg orally once daily for 52 weeks. Cinacalcet dose was titrated every 4 weeks during the dose-titration phase and during study visits in the maintenance phase based on the iPTH values, corrected total serum calcium values, and safety assessments.
Measure Participants	57	57
Number [percentage of participants]	3.5 6.1%	78.9 138.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Cinacalcet
	Comments	The primary endpoint was tested at a significance level of 0.05.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Cochran-Mantel-Haenszel (CMH) test stratified by baseline corrected total serum calcium level (≤ 11.2 mg/dL and > 11.2 mg/dL)
Method of Estimation	Estimation Parameter	Chi-Square test statistic
	Estimated Value	66.437
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Cinacalcet
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	91.41
	Confidence Interval	(2-Sided) 95%; 18.76 to 445.41
	Parameter Dispersion	Type: Value:
	Estimation Comments	Odds ratio of Cinacalcet/Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Cinacalcet
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	75.44
	Confidence Interval	(2-Sided) 95%; 63.83 to 87.05
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference = Cinacalcet-Placebo

2. Secondary Outcome

Title	Percent Change From Baseline to Week 52 in Bone Mineral Density at the Femoral Neck
Description	Bone mineral density (BMD) was measured using dual X-ray absorptiometry (DXA).
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

Full analysis set with available data

Arm/Group Title	Placebo	Cinacalcet
Arm/Group Description	Participants received placebo orally once daily for 52 weeks.	Participants received cinacalcet at a starting dose of 30 mg orally once daily for 52 weeks. Cinacalcet dose was titrated every 4 weeks during the dose-titration phase and during study visits in the maintenance phase based on the iPTH values, corrected total serum calcium values, and safety assessments.
Measure Participants	49	52
Median (Inter-Quartile Range) [percent change]	1.05	1.24

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Cinacalcet
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.266
	Comments
	Method	ANCOVA
	Comments	Analysis of covariance (ANCOVA) with Baseline corrected total serum calcium group as a covariate.
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	1.41
	Confidence Interval	(2-Sided) 95%; -1.10 to 3.93
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least square estimate for the difference in the percent change in BMD between the 2 treatment groups (cinacalcet - placebo)

3. Secondary Outcome

Title	Change From Baseline to the EAP in Mean Serum Phosphorus
Time Frame	Baseline and the EAP (mean of Weeks 22, 24, and 26)

Outcome Measure Data

Analysis Population Description

Full analysis set with available data

Arm/Group Title	Placebo	Cinacalcet
Arm/Group Description	Participants received placebo orally once daily for 52 weeks.	Participants received cinacalcet at a starting dose of 30 mg orally once daily for 52 weeks. Cinacalcet dose was titrated every 4 weeks during the dose-titration phase and during study visits in the maintenance phase based on the iPTH values, corrected total serum calcium values, and safety assessments.
Measure Participants	56	56
Mean (Standard Deviation) [mg/dL]	0.07 (0.48)	0.52 (0.54)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Cinacalcet
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments	Analysis of covariance (ANCOVA) with Baseline corrected total serum calcium group as a covariate.
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	0.45
	Confidence Interval	(2-Sided) 95%; 0.26 to 0.64
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least square estimate for the difference in the absolute change in mean serum phosphorus between the 2 treatment groups (cinacalcet - placebo)

4. Secondary Outcome

Title	Change From Baseline to Week 52 in eGFR
Description	eGFR was calculated using the Modification of Diet in Renal Disease (MDRD) formula.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

Full analysis set with available data

Arm/Group Title	Placebo	Cinacalcet
Arm/Group Description	Participants received placebo orally once daily for 52 weeks.	Participants received cinacalcet at a starting dose of 30 mg orally once daily for 52 weeks. Cinacalcet dose was titrated every 4 weeks during the dose-titration phase and during study visits in the maintenance phase based on the iPTH values, corrected total serum calcium values, and safety assessments.
Measure Participants	52	51
Mean (Standard Deviation) [mL/min/1.73 m²]	0.06 (8.70)	-0.37 (11.69)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Cinacalcet
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.842
	Comments
	Method	ANCOVA
	Comments	ANCOVA with Baseline corrected total serum calcium group as a covariate.
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-0.40
	Confidence Interval	(2-Sided) 95%; -4.37 to 3.57
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least square estimate for the difference in the absolute change in mean eGFR between the 2 treatment groups (cinacalcet - placebo)

5. Secondary Outcome

Title	Change From Baseline to the EAP in Corrected Total Calcium
Time Frame	Baseline and the EAP (mean of Weeks 22, 24, and 26)

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Placebo	Cinacalcet
Arm/Group Description	Participants received placebo orally once daily for 52 weeks.	Participants received cinacalcet at a starting dose of 30 mg orally once daily for 52 weeks. Cinacalcet dose was titrated every 4 weeks during the dose-titration phase and during study visits in the maintenance phase based on the iPTH values, corrected total serum calcium values, and safety assessments.
Measure Participants	57	57
Mean (Standard Deviation) [mg/dL]	-0.14 (0.51)	-1.53 (0.74)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Cinacalcet
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments	ANCOVA with Baseline corrected total serum calcium group as a covariate.
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-1.39
	Confidence Interval	(2-Sided) 95%; -1.62 to -1.16
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least square estimate for the difference in the absolute change in corrected total calcium between the 2 treatment groups (cinacalcet - placebo)

6. Secondary Outcome

Title	Change From Baseline to the EAP in Intact Parathyroid Hormone (iPTH)
Time Frame	Baseline and the EAP (mean of Weeks 22, 24, and 26)

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Placebo	Cinacalcet
Arm/Group Description	Participants received placebo orally once daily for 52 weeks.	Participants received cinacalcet at a starting dose of 30 mg orally once daily for 52 weeks. Cinacalcet dose was titrated every 4 weeks during the dose-titration phase and during study visits in the maintenance phase based on the iPTH values, corrected total serum calcium values, and safety assessments.
Measure Participants	57	57
Mean (Standard Deviation) [pg/mL]	-10.6 (106.4)	-127.9 (254.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Cinacalcet
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	ANCOVA
	Comments	ANCOVA with Baseline corrected total serum calcium group as a covariate.
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-117.21
	Confidence Interval	(2-Sided) 95%; -189.88 to -44.55
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least square estimate for the difference in the absolute change in iPTH between the 2 treatment groups (cinacalcet - placebo)

7. Secondary Outcome

Title	Change From Baseline to the EAP in Urine Phosphorus
Time Frame	Baseline and the EAP (mean of Weeks 22, 24, and 26)

Outcome Measure Data

Analysis Population Description

Full analysis set with available data

Arm/Group Title	Placebo	Cinacalcet
Arm/Group Description	Participants received placebo orally once daily for 52 weeks.	Participants received cinacalcet at a starting dose of 30 mg orally once daily for 52 weeks. Cinacalcet dose was titrated every 4 weeks during the dose-titration phase and during study visits in the maintenance phase based on the iPTH values, corrected total serum calcium values, and safety assessments.
Measure Participants	56	53
Mean (Standard Deviation) [mg/dL]	-1.47 (31.51)	-2.62 (43.93)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Cinacalcet
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.846
	Comments
	Method	ANCOVA
	Comments	ANCOVA with Baseline corrected total serum calcium group as a covariate.
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-1.42
	Confidence Interval	(2-Sided) 95%; -15.91 to 13.06
	Parameter Dispersion	Type: Value:
	Estimation Comments	Least square estimate for the difference in the absolute change in urine phosphorus between the 2 treatment groups (cinacalcet - placebo)

8. Secondary Outcome

Title	Percentage of Participants With a Parathyroidectomy
Time Frame	56 weeks

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Placebo	Cinacalcet
Arm/Group Description	Participants received placebo orally once daily for 52 weeks.	Participants received cinacalcet at a starting dose of 30 mg orally once daily for 52 weeks. Cinacalcet dose was titrated every 4 weeks during the dose-titration phase and during study visits in the maintenance phase based on the iPTH values, corrected total serum calcium values, and safety assessments.
Measure Participants	57	57
Number [percentage of participants]	0.0 0%	0.0 0%

9. Secondary Outcome

Title	Time to Parathyroidectomy
Time Frame	56 weeks

Outcome Measure Data

Analysis Population Description

Full analysis set who underwent a parathyroidectomy

Arm/Group Title	Placebo	Cinacalcet
Arm/Group Description	Participants received placebo orally once daily for 52 weeks.	Participants received cinacalcet at a starting dose of 30 mg orally once daily for 52 weeks. Cinacalcet dose was titrated every 4 weeks during the dose-titration phase and during study visits in the maintenance phase based on the iPTH values, corrected total serum calcium values, and safety assessments.
Measure Participants	0	0

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	Placebo		Cinacalcet
Arm/Group Description	Participants received placebo orally once daily for 52 weeks.		Participants received cinacalcet at a starting dose of 30 mg orally once daily for 52 weeks. Cinacalcet dose was titrated every 4 weeks during the dose-titration phase and during study visits in the maintenance phase based on the iPTH values, corrected total serum calcium values, and safety assessments.
All Cause Mortality
	Placebo		Cinacalcet
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Cinacalcet
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/57 (33.3%)		15/57 (26.3%)
Blood and lymphatic system disorders
Anaemia	0/57 (0%)		1/57 (1.8%)
Neutropenia	1/57 (1.8%)		0/57 (0%)
Cardiac disorders
Bradycardia	1/57 (1.8%)		0/57 (0%)
Eye disorders
Glaucoma	0/57 (0%)		1/57 (1.8%)
Gastrointestinal disorders
Abdominal hernia	0/57 (0%)		1/57 (1.8%)
Abdominal pain upper	0/57 (0%)		1/57 (1.8%)
Colitis	1/57 (1.8%)		0/57 (0%)
Diarrhoea	0/57 (0%)		1/57 (1.8%)
Gastrooesophageal reflux disease	1/57 (1.8%)		0/57 (0%)
Haematochezia	1/57 (1.8%)		0/57 (0%)
Inguinal hernia	0/57 (0%)		1/57 (1.8%)
Intestinal obstruction	1/57 (1.8%)		0/57 (0%)
Pancreatitis acute	0/57 (0%)		1/57 (1.8%)
General disorders
Influenza like illness	0/57 (0%)		1/57 (1.8%)
Pyrexia	1/57 (1.8%)		1/57 (1.8%)
Hepatobiliary disorders
Cholecystitis	1/57 (1.8%)		0/57 (0%)
Immune system disorders
Kidney transplant rejection	0/57 (0%)		1/57 (1.8%)
Transplant rejection	1/57 (1.8%)		0/57 (0%)
Infections and infestations
Cystitis	0/57 (0%)		1/57 (1.8%)
Cytomegalovirus infection	1/57 (1.8%)		2/57 (3.5%)
Escherichia sepsis	1/57 (1.8%)		0/57 (0%)
Escherichia urinary tract infection	1/57 (1.8%)		0/57 (0%)
Gastroenteritis	1/57 (1.8%)		1/57 (1.8%)
Gastroenteritis viral	0/57 (0%)		1/57 (1.8%)
Lung infection	0/57 (0%)		1/57 (1.8%)
Muscle abscess	1/57 (1.8%)		0/57 (0%)
Osteomyelitis	1/57 (1.8%)		0/57 (0%)
Pneumonia	0/57 (0%)		1/57 (1.8%)
Pyelonephritis	1/57 (1.8%)		1/57 (1.8%)
Upper respiratory tract infection	1/57 (1.8%)		0/57 (0%)
Urinary tract infection	1/57 (1.8%)		1/57 (1.8%)
Injury, poisoning and procedural complications
Complications of transplanted kidney	1/57 (1.8%)		0/57 (0%)
Femoral neck fracture	1/57 (1.8%)		0/57 (0%)
Foot fracture	0/57 (0%)		1/57 (1.8%)
Urostomy complication	1/57 (1.8%)		0/57 (0%)
Metabolism and nutrition disorders
Diabetes mellitus	1/57 (1.8%)		0/57 (0%)
Hyperglycaemia	1/57 (1.8%)		0/57 (0%)
Musculoskeletal and connective tissue disorders
Osteoporotic fracture	1/57 (1.8%)		0/57 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Clear cell renal cell carcinoma	1/57 (1.8%)		0/57 (0%)
Lung adenocarcinoma metastatic	0/57 (0%)		1/57 (1.8%)
Nervous system disorders
Cerebrovascular accident	0/57 (0%)		1/57 (1.8%)
Transient ischaemic attack	1/57 (1.8%)		0/57 (0%)
Renal and urinary disorders
Proteinuria	1/57 (1.8%)		0/57 (0%)
Renal impairment	0/57 (0%)		1/57 (1.8%)
Ureteric stenosis	1/57 (1.8%)		0/57 (0%)
Respiratory, thoracic and mediastinal disorders
Lung infiltration	0/57 (0%)		1/57 (1.8%)
Skin and subcutaneous tissue disorders
Diabetic foot	1/57 (1.8%)		0/57 (0%)
Vascular disorders
Intermittent claudication	1/57 (1.8%)		0/57 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Cinacalcet
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	45/57 (78.9%)		45/57 (78.9%)
Blood and lymphatic system disorders
Anaemia	3/57 (5.3%)		1/57 (1.8%)
Gastrointestinal disorders
Abdominal discomfort	2/57 (3.5%)		3/57 (5.3%)
Abdominal pain	5/57 (8.8%)		2/57 (3.5%)
Diarrhoea	3/57 (5.3%)		8/57 (14%)
Nausea	6/57 (10.5%)		7/57 (12.3%)
Vomiting	4/57 (7%)		3/57 (5.3%)
General disorders
Fatigue	7/57 (12.3%)		6/57 (10.5%)
Influenza like illness	3/57 (5.3%)		0/57 (0%)
Malaise	0/57 (0%)		4/57 (7%)
Oedema peripheral	8/57 (14%)		6/57 (10.5%)
Infections and infestations
Nasopharyngitis	8/57 (14%)		7/57 (12.3%)
Upper respiratory tract infection	2/57 (3.5%)		5/57 (8.8%)
Urinary tract infection	6/57 (10.5%)		8/57 (14%)
Metabolism and nutrition disorders
Decreased appetite	3/57 (5.3%)		2/57 (3.5%)
Gout	0/57 (0%)		3/57 (5.3%)
Hypercholesterolaemia	2/57 (3.5%)		4/57 (7%)
Hyperlipidaemia	2/57 (3.5%)		3/57 (5.3%)
Hypokalaemia	0/57 (0%)		4/57 (7%)
Hypomagnesaemia	1/57 (1.8%)		5/57 (8.8%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/57 (3.5%)		3/57 (5.3%)
Back pain	3/57 (5.3%)		5/57 (8.8%)
Musculoskeletal pain	3/57 (5.3%)		1/57 (1.8%)
Osteoporosis	3/57 (5.3%)		1/57 (1.8%)
Nervous system disorders
Headache	3/57 (5.3%)		5/57 (8.8%)
Psychiatric disorders
Insomnia	1/57 (1.8%)		3/57 (5.3%)
Respiratory, thoracic and mediastinal disorders
Cough	3/57 (5.3%)		8/57 (14%)
Dyspnoea	4/57 (7%)		3/57 (5.3%)
Oropharyngeal pain	0/57 (0%)		3/57 (5.3%)
Skin and subcutaneous tissue disorders
Alopecia	3/57 (5.3%)		1/57 (1.8%)
Rash	3/57 (5.3%)		0/57 (0%)
Vascular disorders
Hypertension	2/57 (3.5%)		5/57 (8.8%)

Limitations/Caveats

[Not Specified]

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.