Efficacy and Safety Study of Cinacalcet for the Treatment of Hypercalcemia in Patients With Primary Hyperparathyroidism Unable to Undergo Parathyroidectomy

• Sponsor: Amgen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00975221
• Collaborator: (none)
• Enrollment: 67
• Locations: 47
• Arms: 2
• Actual Duration (Months): 33.4
• Patients Per Site: 1.4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This study is designed to demonstrate the efficacy and to assess the safety of cinacalcet for the reduction of hypercalcemia in patients with primary hyperparathyroidism for whom parathyroidectomy is indicated on the basis of an elevated corrected total serum calcium, but who are unable to undergo parathyroidectomy.

Condition or Disease	Intervention/Treatment	Phase
Hyperparathyroidism, Primary; Hypercalcemia	Drug: Cinacalcet; Drug: Placebo	Phase 3

Detailed Description

The study will consist of a 30-day screening phase, a 12-week placebo-controlled dose-titration phase, and a 16-week placebo-controlled efficacy assessment phase (EAP). Participants who complete 28 weeks on study will continue into an open-label safety extension phase for 24 weeks of investigational cinacalcet treatment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 67 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 Cinacalcet for the Treatment of Hypercalcemia in Subjects With Primary Hyperparathyroidism Unable to Undergo Parathyroidectomy
• Actual Study Start Date: Mar 10, 2010
• Actual Primary Completion Date: Jul 12, 2012
• Actual Study Completion Date: Dec 21, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cinacalcet Participants received cinacalcet at a starting dose of 30 mg orally BID and were eligible for a dose titration once every 3 weeks during the 12-week dose-titration phase based on corrected total serum calcium concentration and safety assessments. Participants continued to receive cinacalcet for another 16 weeks during the efficacy assessment phase and then continued into the open-label extension phase and received cinacalcet at a starting dose of 30 mg BID for 24 weeks. The dose of cinacalcet could have been increased or decreased as needed to maintain a corrected total serum calcium concentration within the normal range through Week 52.	Drug: Cinacalcet; Administered orally at a starting dose of 30 mg twice a day (BID). Participants will be eligible for a dose titration once every 3 weeks during the placebo-controlled dose titration phase based on corrected total serum calcium concentration and safety assessments obtained the previous week. Doses may be sequentially increased to 60 mg BID, 90 mg BID, and 90 mg 3 times a day (TID).; Other Names: Sensipar Mimpara
Placebo Comparator: Placebo Participants received placebo orally twice a day (BID) for 12 weeks during the dose titration phase and for another 16 weeks during the efficacy assessment phase. Participants then continued into the open-label extension phase and received cinacalcet at a starting dose of 30 mg BID for 24 weeks. The dose of cinacalcet could have been increased or decreased as needed to maintain a corrected total serum calcium concentration within the normal range through Week 52.	Drug: Cinacalcet; Administered orally at a starting dose of 30 mg twice a day (BID). Participants will be eligible for a dose titration once every 3 weeks during the placebo-controlled dose titration phase based on corrected total serum calcium concentration and safety assessments obtained the previous week. Doses may be sequentially increased to 60 mg BID, 90 mg BID, and 90 mg 3 times a day (TID).; Other Names: Sensipar Mimpara ; Drug: Placebo; Administered orally following the same tiitration regimen as the experimental arm.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Mean Corrected Total Serum Calcium Concentration ≤ 10.3 mg/dL (2.57 mmol/L) During the EAP [Efficacy assessment phase (study visits at Weeks 16, 20, 24, and 28)]

Secondary Outcome Measures

1. Percentage of Participants With a ≥ 1 mg/dL (0.25 mmol/L) Decrease From Baseline in Mean Corrected Total Serum Calcium Concentration During the EAP [Baseline and the EAP (mean of Weeks 16, 20, 24, and 28)]

2. Percent Change From Baseline in Corrected Total Serum Calcium Concentration During the EAP [Baseline and the EAP (mean of Weeks 16, 20, 24, and 28)]

3. Percent Change From Baseline in Plasma Parathyroid Hormone Level During the EAP [Baseline and the EAP (mean of Weeks 16, 20, 24, and 28)]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• age ≥ 18 years

• diagnosis of primary hyperparathyroidism (HPT)

• subjects must have the following laboratory values:

1. local/historical laboratory result showing a corrected total serum calcium > 1 mg/dL (0.25 mmol/L) above the upper limit of normal and

≤ 12.5 mg/dL (3.12 mmol/L) within the past 12 months, and

• local/historical laboratory result showing a plasma parathyroid horone (PTH)

75% of upper limit of normal within the past 12 months, and

• one central laboratory draw at the screen visit showing a corrected total serum calcium > 11.3 mg/dL (2.82 mmol/L) and ≤ 12.5 mg/dL (3.12 mmol/L), and

• one central laboratory draw at the screen visit showing a plasma PTH > 55 pg/mL (5.8 pmol/L) OR

1. two central laboratory draws performed during the screening period at least 7 days apart, showing a

• corrected total serum calcium > 11.3 mg/dL (2.82 mmol/L) and ≤ 12.5 mg/dL (3.12 mmol/L), and

• plasma PTH > 55 pg/mL (5.8 pmol/L)

• not able to undergo parathyroidectomy for ≥ 1 of the following reasons:

• failed parathyroidectomy

• comorbid conditions contraindicating parathyroidectomy

• parathyroidectomy not considered appropriate or is not feasible by primary physician and subject

• before any study-specific procedure is performed, the appropriate written informed consent must be obtained

Exclusion Criteria:

• symptoms attributable to hypercalcemia, requiring immediate medical intervention, as judged by the investigator (including acute kidney stone, nausea and vomiting requiring intravenous hydration, confusion, lethargy, stupor, or coma)

• unstable medical condition, defined as having been hospitalized within 30 days before the date of informed consent, or otherwise unstable in the judgment of the investigator

• administration of drugs that increase serum calcium concentration, including but not limited to thiazide diuretics or lithium

• initiated bisphosphonate therapy or changed bisphosphonate dose within 12 weeks before the date of informed consent

• current administration of drugs for ventricular arrhythmia

• unable to provide informed consent, or is at risk for poor compliance with study procedures

• currently enrolled in another investigational device or drug study(s), or completed such study within 30 days before the date of informed consent

• known hypersensitivity to or unable to tolerate cinacalcet

• received treatment with cinacalcet within 60 days before the date of informed consent

• history of seizures or an adjustment of anti-seizure medication within 12 weeks before the date of informed consent

• family history or diagnosis a genetic syndrome, such as familial benign hypocalciuric hypercalcemia (FBHH) or multiple endocrine neoplasia type 1 (MEN1) and type 2 (MEN2), where primary HPT is one of the clinical manifestations of familial benign hypocalciuric hypercalcemia (FBHH)

• refused to use highly effective contraceptive measures (as determined by the investigator) throughout the study

• pregnant or breastfeeding

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Lake Forest	California	United States	92630
2	Research Site	Lancaster	California	United States	93534
3	Research Site	Los Gatos	California	United States	95032
4	Research Site	Mission Viejo	California	United States	92691
5	Research Site	Orange	California	United States	92869
6	Research Site	San Diego	California	United States	92124
7	Research Site	Aurora	Colorado	United States	80045
8	Research Site	Washington	District of Columbia	United States	20010
9	Research Site	Aventura	Florida	United States	33180
10	Research Site	Clearwater	Florida	United States	33756
11	Research Site	Jacksonville	Florida	United States	32204
12	Research Site	Miami	Florida	United States	33145
13	Research Site	Pembroke Pines	Florida	United States	33028
14	Research Site	Weston	Florida	United States	33331
15	Research Site	Atlanta	Georgia	United States	30322
16	Research Site	Indianapolis	Indiana	United States	46202
17	Research Site	Kenner	Louisiana	United States	70065
18	Research Site	New Orleans	Louisiana	United States	70121
19	Research Site	Detroit	Michigan	United States	48236
20	Research Site	New York	New York	United States	10032
21	Research Site	Morehead City	North Carolina	United States	28557
22	Research Site	Columbus	Ohio	United States	43210-1296
23	Research Site	Randwick	New South Wales	Australia	2031
24	Research Site	St Leonards	New South Wales	Australia	2065
25	Research Site	Footscray	Victoria	Australia	3011
26	Research Site	Geelong	Victoria	Australia	3220
27	Research Site	Nedlands	Western Australia	Australia	6009
28	Research Site	Calgary	Alberta	Canada	T2N 4Z6
29	Research Site	London	Ontario	Canada	N6A 4V2
30	Research Site	Oakville	Ontario	Canada	L6J 1X8
31	Research Site	Toronto	Ontario	Canada	M5C 2T2
32	Research Site	Budapest		Hungary	1083
33	Research Site	Budapest		Hungary	1088
34	Research Site	Budapest		Hungary	1113
35	Research Site	Szeged		Hungary	6720
36	Research Site	Warszawa		Poland	01-809
37	Research Site	Warszawa		Poland	02-097
38	Research Site	Warszawa		Poland	02-507
39	Research Site	Coimbra		Portugal	3000-075
40	Research Site	Lisboa		Portugal	1350-179
41	Research Site	Lisboa		Portugal	1649-035
42	Research Site	Moscow		Russian Federation	117036
43	Research Site	Moscow		Russian Federation	119034
44	Research Site	Moscow		Russian Federation	129110
45	Research Site	Rostov-na-Dony		Russian Federation	344022
46	Research Site	Saint Petersburg		Russian Federation	197341
47	Research Site	Yaroslavl		Russian Federation	150003

Sponsors and Collaborators

• Amgen

Investigators

• Study Director: MD, Amgen

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• AmgenTrials clinical trials website

Publications

• Khan A, Bilezikian J, Bone H, Gurevich A, Lakatos P, Misiorowski W, Rozhinskaya L, Trotman ML, Tóth M. Cinacalcet normalizes serum calcium in a double-blind randomized, placebo-controlled study in patients with primary hyperparathyroidism with contraindications to surgery. Eur J Endocrinol. 2015 May;172(5):527-35. doi: 10.1530/EJE-14-0877. Epub 2015 Jan 30.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT00975221
• Other Study ID Numbers: 20070277
• First Posted: Sep 11, 2009
• Last Update Posted: Oct 17, 2018
• Last Verified: Sep 1, 2018

• Keywords provided by Amgen: Primary hyperparathyroidism; Parathyroidectomy; Hypercalcemia
• Additional relevant MeSH terms: Hypercalcemia; Hyperparathyroidism; Hyperparathyroidism, Primary; Cinacalcet

Study Results

Participant Flow

Recruitment Details	The study was conducted at 29 centers in United States, Australia, Canada, Hungary, Poland, Portugal, and Russian Federation. The first participant enrolled on 10 March 2010 and the last participant enrolled on 28 December 2011.
Pre-assignment Detail	This study consisted of a 12-week placebo-controlled dose-titration phase, a 16-week placebo-controlled efficacy assessment phase (EAP), and an open-label safety extension phase for 24 weeks of cinacalcet treatment. Participants were randomized in a 1:1 ratio to cinacalcet or placebo stratified by bisphosphonate use.

Arm/Group Title	Placebo	Cinacalcet
Arm/Group Description	Participants received placebo orally twice a day (BID) for 12 weeks during the dose titration phase and for another 16 weeks during the efficacy assessment phase. Participants then continued into the open-label extension phase and received cinacalcet at a starting dose of 30 mg BID for 24 weeks. The dose of cinacalcet could have been increased or decreased as needed to maintain a corrected total serum calcium concentration within the normal range through Week 52.	Participants received cinacalcet at a starting dose of 30 mg orally BID and were eligible for a dose titration once every 3 weeks during the 12-week dose-titration phase based on corrected total serum calcium concentration and safety assessments. Participants continued to receive cinacalcet for another 16 weeks during the efficacy assessment phase and then continued into the open-label extension phase and received cinacalcet at a starting dose of 30 mg BID for 24 weeks. The dose of cinacalcet could have been increased or decreased as needed to maintain a corrected total serum calcium concentration within the normal range through Week 52.
Period Title: Titration Phase (Weeks 1-12)
STARTED	34	33
Received Study Drug	34	33
COMPLETED	31	29
NOT COMPLETED	3	4
Period Title: Titration Phase (Weeks 1-12)
STARTED	30	29
COMPLETED	30	28
NOT COMPLETED	0	1
Period Title: Titration Phase (Weeks 1-12)
STARTED	29	28
COMPLETED	27	27
NOT COMPLETED	2	1

Baseline Characteristics

Arm/Group Title	Placebo	Cinacalcet	Total
Arm/Group Description	Participants received placebo orally twice a day (BID) for 12 weeks during the dose titration phase and for another 16 weeks during the efficacy assessment phase. Participants then continued into the open-label extension phase and received cinacalcet at a starting dose of 30 mg BID for 24 weeks. The dose of cinacalcet could have been increased or decreased as needed to maintain a corrected total serum calcium concentration within the normal range through Week 52.	Participants received cinacalcet at a starting dose of 30 mg orally BID and were eligible for a dose titration once every 3 weeks during the 12-week dose-titration phase based on corrected total serum calcium concentration and safety assessments. Participants continued to receive cinacalcet for another 16 weeks during the efficacy assessment phase and then continued into the open-label extension phase and received cinacalcet at a starting dose of 30 mg BID for 24 weeks. The dose of cinacalcet could have been increased or decreased as needed to maintain a corrected total serum calcium concentration within the normal range through Week 52.	Total of all reporting groups
Overall Participants	34	33	67
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	75.0 (8.9)	69.5 (13.0)	72.3 (11.4)
Sex: Female, Male (Count of Participants)
Female	27 79.4%	25 75.8%	52 77.6%
Male	7 20.6%	8 24.2%	15 22.4%
Race/Ethnicity, Customized (participants) [Number]
Black or African American	1 2.9%	4 12.1%	5 7.5%
Hispanic or Latino	0 0%	1 3%	1 1.5%
White or Caucasian	33 97.1%	28 84.8%	61 91%
Albumin-corrected Calcium (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	11.80 (0.48)	11.73 (0.45)	11.77 (0.46)
Intact Parathyroid Hormone (iPTH) (pg/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [pg/mL]	238.6 (212.2)	179.0 (98.0)	209.7 (168.4)
Bisphosphonate Use (participants) [Number]
Yes	10 29.4%	9 27.3%	19 28.4%
No	24 70.6%	24 72.7%	48 71.6%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Mean Corrected Total Serum Calcium Concentration ≤ 10.3 mg/dL (2.57 mmol/L) During the EAP
Time Frame	Efficacy assessment phase (study visits at Weeks 16, 20, 24, and 28)

Outcome Measure Data

Analysis Population Description

Full analysis set (all participants randomized to treatment). For participants with no data for the EAP, the last post-baseline value from the titration phase was used to impute the missing EAP values (last value carried forward (LVCF) imputation). Participants with only baseline information were counted as non-responders.

Arm/Group Title	Placebo	Cinacalcet
Arm/Group Description	Participants received placebo orally twice a day (BID) for 12 weeks during the dose titration phase and for another 16 weeks during the efficacy assessment phase. Participants then continued into the open-label extension phase and received cinacalcet at a starting dose of 30 mg BID for 24 weeks. The dose of cinacalcet could have been increased or decreased as needed to maintain a corrected total serum calcium concentration within the normal range through Week 52.	Participants received cinacalcet at a starting dose of 30 mg orally BID and were eligible for a dose titration once every 3 weeks during the 12-week dose-titration phase based on corrected total serum calcium concentration and safety assessments. Participants continued to receive cinacalcet for another 16 weeks during the efficacy assessment phase and then continued into the open-label extension phase and received cinacalcet at a starting dose of 30 mg BID for 24 weeks. The dose of cinacalcet could have been increased or decreased as needed to maintain a corrected total serum calcium concentration within the normal range through Week 52.
Measure Participants	34	33
Number [percentage of participants]	0.0 0%	75.8 229.7%

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	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Cochran-Mantel-Haenszel (CMH) statistic
	Estimated Value	39.866
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Participants With a ≥ 1 mg/dL (0.25 mmol/L) Decrease From Baseline in Mean Corrected Total Serum Calcium Concentration During the EAP
Time Frame	Baseline and the EAP (mean of Weeks 16, 20, 24, and 28)

Outcome Measure Data

Analysis Population Description

Full analysis set (all participants randomized to treatment). For participants with no data for the EAP, the last post-baseline value from the titration phase was used to impute the missing EAP values (last value carried forward (LVCF) imputation). Participants with only baseline information were counted as non-responders.

Arm/Group Title	Placebo	Cinacalcet
Arm/Group Description	Participants received placebo orally twice a day (BID) for 12 weeks during the dose titration phase and for another 16 weeks during the efficacy assessment phase. Participants then continued into the open-label extension phase and received cinacalcet at a starting dose of 30 mg BID for 24 weeks. The dose of cinacalcet could have been increased or decreased as needed to maintain a corrected total serum calcium concentration within the normal range through Week 52.	Participants received cinacalcet at a starting dose of 30 mg orally BID and were eligible for a dose titration once every 3 weeks during the 12-week dose-titration phase based on corrected total serum calcium concentration and safety assessments. Participants continued to receive cinacalcet for another 16 weeks during the efficacy assessment phase and then continued into the open-label extension phase and received cinacalcet at a starting dose of 30 mg BID for 24 weeks. The dose of cinacalcet could have been increased or decreased as needed to maintain a corrected total serum calcium concentration within the normal range through Week 52.
Measure Participants	34	33
Number [percentage of participants]	5.9 17.4%	84.8 257%

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	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	CMH statistic
	Estimated Value	40.953
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percent Change From Baseline in Corrected Total Serum Calcium Concentration During the EAP
Time Frame	Baseline and the EAP (mean of Weeks 16, 20, 24, and 28)

Outcome Measure Data

Analysis Population Description

Full analysis set with at least 1 post-baseline measurement; for participants with no data for the EAP, the last post-baseline value from the titration phase was used to impute the missing EAP values (LVCF imputation).

Arm/Group Title	Placebo	Cinacalcet
Arm/Group Description	Participants received placebo orally twice a day (BID) for 12 weeks during the dose titration phase and for another 16 weeks during the efficacy assessment phase. Participants then continued into the open-label extension phase and received cinacalcet at a starting dose of 30 mg BID for 24 weeks. The dose of cinacalcet could have been increased or decreased as needed to maintain a corrected total serum calcium concentration within the normal range through Week 52.	Participants received cinacalcet at a starting dose of 30 mg orally BID and were eligible for a dose titration once every 3 weeks during the 12-week dose-titration phase based on corrected total serum calcium concentration and safety assessments. Participants continued to receive cinacalcet for another 16 weeks during the efficacy assessment phase and then continued into the open-label extension phase and received cinacalcet at a starting dose of 30 mg BID for 24 weeks. The dose of cinacalcet could have been increased or decreased as needed to maintain a corrected total serum calcium concentration within the normal range through Week 52.
Measure Participants	33	33
Least Squares Mean (Standard Error) [percent change]	-1.66 (0.99)	-15.21 (1.00)

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 serum calcium and baseline bisphosphonate included as covariates.
Method of Estimation	Estimation Parameter	LS Mean Treatment Difference
	Estimated Value	-13.55
	Confidence Interval	(2-Sided) 95%; -16.23 to -10.88
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.34
	Estimation Comments	Treatment difference: cinacalcet-placebo

4. Secondary Outcome

Title	Percent Change From Baseline in Plasma Parathyroid Hormone Level During the EAP
Time Frame	Baseline and the EAP (mean of Weeks 16, 20, 24, and 28)

Outcome Measure Data

Analysis Population Description

Full analysis set with at least 1 post-baseline measurement; for participants with no data for the EAP, the last post-baseline value from the titration phase was used to impute the missing EAP values (LVCF imputation).

Arm/Group Title	Placebo	Cinacalcet
Arm/Group Description	Participants received placebo orally twice a day (BID) for 12 weeks during the dose titration phase and for another 16 weeks during the efficacy assessment phase. Participants then continued into the open-label extension phase and received cinacalcet at a starting dose of 30 mg BID for 24 weeks. The dose of cinacalcet could have been increased or decreased as needed to maintain a corrected total serum calcium concentration within the normal range through Week 52.	Participants received cinacalcet at a starting dose of 30 mg orally BID and were eligible for a dose titration once every 3 weeks during the 12-week dose-titration phase based on corrected total serum calcium concentration and safety assessments. Participants continued to receive cinacalcet for another 16 weeks during the efficacy assessment phase and then continued into the open-label extension phase and received cinacalcet at a starting dose of 30 mg BID for 24 weeks. The dose of cinacalcet could have been increased or decreased as needed to maintain a corrected total serum calcium concentration within the normal range through Week 52.
Measure Participants	33	31
Least Squares Mean (Standard Error) [percent change]	-1.01 (4.05)	-23.80 (4.18)

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 serum calcium and baseline bisphosphonate included as covariates.
Method of Estimation	Estimation Parameter	LS Mean Treatment Difference
	Estimated Value	-22.79
	Confidence Interval	(2-Sided) 95%; -34.01 to -11.57
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.61
	Estimation Comments	Treatment difference: 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	Participants received placebo orally twice a day (BID) for 12 weeks during the dose titration phase and for another 16 weeks during the efficacy assessment phase.		Participants received cinacalcet at a starting dose of 30 mg orally BID and were eligible for a dose titration once every 3 weeks during the 12-week double-blind dose-titration phase based on corrected total serum calcium concentration and safety assessments. Participants continued to receive cinacalcet for another 16 weeks during the double-blind efficacy assessment phase.		Participants who received placebo during the double-blind phase (Weeks 1-28) then received cinacalcet at a starting dose of 30 mg BID for 24 weeks in the open-label extension phase. The dose of cinacalcet could have been increased or decreased as needed to maintain a corrected total serum calcium concentration within the normal range through Week 52.		Participants who received cinacalcet during the double-blind phase continued to receive cinacalcet at a starting dose of 30 mg BID for 24 weeks in the open-label extension phase. The dose of cinacalcet could have been increased or decreased as needed to maintain a corrected total serum calcium concentration within the normal range through Week 52.
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	4/34 (11.8%)		3/33 (9.1%)		7/29 (24.1%)		1/28 (3.6%)
Cardiac disorders
Coronary artery occlusion	1/34 (2.9%)		0/33 (0%)		0/29 (0%)		0/28 (0%)
Endocrine disorders
Hyperparathyroidism primary	1/34 (2.9%)		0/33 (0%)		1/29 (3.4%)		0/28 (0%)
Gastrointestinal disorders
Abdominal pain	0/34 (0%)		0/33 (0%)		1/29 (3.4%)		0/28 (0%)
Nausea	0/34 (0%)		1/33 (3%)		0/29 (0%)		0/28 (0%)
Vomiting	0/34 (0%)		1/33 (3%)		0/29 (0%)		0/28 (0%)
Hepatobiliary disorders
Cholelithiasis	0/34 (0%)		0/33 (0%)		1/29 (3.4%)		0/28 (0%)
Infections and infestations
Infective exacerbation of chronic obstructive airways disease	0/34 (0%)		0/33 (0%)		1/29 (3.4%)		0/28 (0%)
Urinary tract infection	0/34 (0%)		0/33 (0%)		1/29 (3.4%)		0/28 (0%)
Injury, poisoning and procedural complications
Foot fracture	0/34 (0%)		1/33 (3%)		0/29 (0%)		0/28 (0%)
Hip fracture	1/34 (2.9%)		0/33 (0%)		0/29 (0%)		0/28 (0%)
Rib fracture	1/34 (2.9%)		0/33 (0%)		0/29 (0%)		0/28 (0%)
Metabolism and nutrition disorders
Decreased appetite	0/34 (0%)		1/33 (3%)		0/29 (0%)		0/28 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/34 (0%)		1/33 (3%)		0/29 (0%)		0/28 (0%)
Nervous system disorders
Neuropathy peripheral	0/34 (0%)		0/33 (0%)		0/29 (0%)		1/28 (3.6%)
Vertebrobasilar insufficiency	0/34 (0%)		0/33 (0%)		1/29 (3.4%)		0/28 (0%)
Psychiatric disorders
Anxiety	0/34 (0%)		0/33 (0%)		1/29 (3.4%)		0/28 (0%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	0/34 (0%)		0/33 (0%)		1/29 (3.4%)		0/28 (0%)
Vascular disorders
Aortic aneurysm	1/34 (2.9%)		0/33 (0%)		1/29 (3.4%)		0/28 (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	15/34 (44.1%)		25/33 (75.8%)		15/29 (51.7%)		10/28 (35.7%)
Ear and labyrinth disorders
Vertigo	3/34 (8.8%)		1/33 (3%)		0/29 (0%)		0/28 (0%)
Gastrointestinal disorders
Abdominal distension	0/34 (0%)		2/33 (6.1%)		0/29 (0%)		0/28 (0%)
Abdominal pain upper	2/34 (5.9%)		2/33 (6.1%)		3/29 (10.3%)		1/28 (3.6%)
Constipation	3/34 (8.8%)		0/33 (0%)		0/29 (0%)		1/28 (3.6%)
Diarrhoea	4/34 (11.8%)		4/33 (12.1%)		1/29 (3.4%)		1/28 (3.6%)
Nausea	6/34 (17.6%)		9/33 (27.3%)		6/29 (20.7%)		1/28 (3.6%)
Vomiting	2/34 (5.9%)		2/33 (6.1%)		0/29 (0%)		2/28 (7.1%)
General disorders
Asthenia	1/34 (2.9%)		0/33 (0%)		0/29 (0%)		2/28 (7.1%)
Oedema peripheral	0/34 (0%)		2/33 (6.1%)		3/29 (10.3%)		1/28 (3.6%)
Hepatobiliary disorders
Cholelithiasis	3/34 (8.8%)		0/33 (0%)		0/29 (0%)		0/28 (0%)
Infections and infestations
Nasopharyngitis	1/34 (2.9%)		2/33 (6.1%)		1/29 (3.4%)		0/28 (0%)
Sinusitis	0/34 (0%)		0/33 (0%)		2/29 (6.9%)		0/28 (0%)
Upper respiratory tract infection	3/34 (8.8%)		1/33 (3%)		1/29 (3.4%)		1/28 (3.6%)
Urinary tract infection	1/34 (2.9%)		3/33 (9.1%)		0/29 (0%)		1/28 (3.6%)
Injury, poisoning and procedural complications
Fall	0/34 (0%)		2/33 (6.1%)		0/29 (0%)		0/28 (0%)
Metabolism and nutrition disorders
Hypocalcaemia	0/34 (0%)		0/33 (0%)		2/29 (6.9%)		0/28 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/34 (0%)		3/33 (9.1%)		0/29 (0%)		0/28 (0%)
Back pain	2/34 (5.9%)		3/33 (9.1%)		2/29 (6.9%)		0/28 (0%)
Bone pain	2/34 (5.9%)		1/33 (3%)		0/29 (0%)		0/28 (0%)
Muscle spasms	0/34 (0%)		6/33 (18.2%)		4/29 (13.8%)		2/28 (7.1%)
Muscle twitching	0/34 (0%)		2/33 (6.1%)		0/29 (0%)		0/28 (0%)
Musculoskeletal pain	2/34 (5.9%)		0/33 (0%)		0/29 (0%)		0/28 (0%)
Pain in extremity	2/34 (5.9%)		3/33 (9.1%)		0/29 (0%)		1/28 (3.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	0/34 (0%)		2/33 (6.1%)		1/29 (3.4%)		0/28 (0%)
Nervous system disorders
Dizziness	2/34 (5.9%)		3/33 (9.1%)		0/29 (0%)		1/28 (3.6%)
Headache	2/34 (5.9%)		4/33 (12.1%)		2/29 (6.9%)		2/28 (7.1%)
Hypoaesthesia	0/34 (0%)		0/33 (0%)		1/29 (3.4%)		2/28 (7.1%)
Tremor	2/34 (5.9%)		0/33 (0%)		0/29 (0%)		0/28 (0%)
Renal and urinary disorders
Renal pain	0/34 (0%)		2/33 (6.1%)		0/29 (0%)		0/28 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	1/34 (2.9%)		2/33 (6.1%)		0/29 (0%)		0/28 (0%)
Dyspnoea	2/34 (5.9%)		1/33 (3%)		0/29 (0%)		1/28 (3.6%)
Skin and subcutaneous tissue disorders
Hyperhidrosis	0/34 (0%)		2/33 (6.1%)		0/29 (0%)		0/28 (0%)
Vascular disorders
Hypertension	1/34 (2.9%)		1/33 (3%)		2/29 (6.9%)		0/28 (0%)

Limitations/Caveats

[Not Specified]

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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.