Study to Assess the Impact on Calcium Levels When Hemodialysis Patients With Secondary Hyperparathyroidism (SHPT) Switch From Cinacalcet to Etelcalcetide

• Sponsor: Amgen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01932970
• Collaborator: (none)
• Enrollment: 158
• Locations: 40
• Arm: 1
• Actual Duration (Months): 42.1
• Patients Per Site: 4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a multicenter, multiple-dose, single-arm, open-label study to assess the impact on serum corrected calcium levels when switching patients from cinacalcet to etelcalcetide (AMG 416).

Condition or Disease	Intervention/Treatment	Phase
Hyperparathyroidism, Secondary	Drug: Etelcalcetide	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 158 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Multiple-dose, Single-arm Study to Switch Hemodialysis Subjects With Secondary Hyperparathyroidism From Oral Cinacalcet HCl to Intravenous AMG 416
• Actual Study Start Date: Aug 12, 2013
• Actual Primary Completion Date: Jan 14, 2014
• Actual Study Completion Date: Feb 14, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Etelcalcetide Participants were treated with 5 mg etelcalcetide administered by intravenous bolus injection at the end of each hemodialysis session three times per week (TIW) for 4 weeks.	Drug: Etelcalcetide; Etelcalcetide is provided as a sterile lyophilized powder to be reconstituted with sterile water for injection.; Other Names: KAI 4169 AMG 416 Parsabiv™

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Serum Corrected Calcium < 7.5 mg/dL During the 4-week Treatment Period [4 weeks]

Secondary Outcome Measures

1. Percent Change From Baseline in Parathyroid Hormone During the Treatment Period [Baseline and weeks 2, 3 and 4]

2. Percentage of Participants With Serum Corrected Calcium < 8.3 mg/dL During the 4-week Treatment Period [4 weeks]

Other Outcome Measures

1. Number of Participants With Adverse Events [From the first dose of study drug up to 30 days after the last dose; 8 weeks]

2. Percentage of Participants With Symptomatic Hypocalcemia During the 4-week Treatment Period [From the first dose of study drug up to 30 days after the last dose; 8 weeks]

   Hpocalcemia was used for events of decreased calcium accompanied by clinical signs and symptoms of hypocalcemia.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 100 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria

• Subject is 18 years of age or older at the time of informed consent.

• Subject must be receiving maintenance hemodialysis 3 times weekly for at least 8 weeks.

• Subject must have SHPT as defined by having a mean of 3 consecutive central laboratory screening predialysis serum parathyroid hormone (PTH) values ≥ 200 pg/mL, with measurements obtained from 3 different calendar weeks in the 4-week screening period while receiving cinacalcet.

• Subject must have a mean of 3 consecutive central laboratory screening predialysis serum corrected calcium (cCa) values ≥ 7.5 mg/dL, with measurements obtained from 3 different calendar weeks in the 4-week screening period while receiving cinacalcet.

• Subject must be on a stable dose of cinacalcet before screening (defined as no dose change within the 4 weeks prior to screening).

• Other Inclusion Criteria may apply.

Exclusion Criteria

• Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(s).

• Subject has received AMG 416 in a prior clinical trial of AMG 416 (also known as KAI-4169).

• Subject has known sensitivity to any of the products or components of AMG 416 to be administered during dosing.

• Subject is unwilling to use effective contraception during the study, and for women, up to a period of up to 3 months after the last dose of AMG 416.

• Subject is pregnant or nursing.

• Anticipated or scheduled parathyroidectomy during the study period.

• Subject has received a parathyroidectomy within 6 months prior to dosing.

• Other Exclusion Criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Alhambra	California	United States	91801
2	Research Site	Azusa	California	United States	91702
3	Research Site	Bakersfield	California	United States	93308
4	Research Site	Chula Vista	California	United States	91910
5	Research Site	La Mesa	California	United States	91942
6	Research Site	Los Angeles	California	United States	90022
7	Research Site	Lynwood	California	United States	90262
8	Research Site	Riverside	California	United States	92505
9	Research Site	Whittier	California	United States	90603
10	Research Site	Arvada	Colorado	United States	80002
11	Research Site	North Haven	Connecticut	United States	06473
12	Research Site	Coral Springs	Florida	United States	33071
13	Research Site	Hollywood	Florida	United States	33021
14	Research Site	Miami	Florida	United States	33150
15	Research Site	Pembroke Pines	Florida	United States	33028
16	Research Site	Pinecrest	Florida	United States	33156
17	Research Site	Tampa	Florida	United States	33614
18	Research Site	Augusta	Georgia	United States	30909
19	Research Site	Evergreen Park	Illinois	United States	60805
20	Research Site	Michigan City	Indiana	United States	46360
21	Research Site	Baton Rouge	Louisiana	United States	70808
22	Research Site	Lafayette	Louisiana	United States	70506
23	Research Site	Columbus	Mississippi	United States	39705
24	Research Site	Gulfport	Mississippi	United States	39501
25	Research Site	Farmington	Missouri	United States	63640
26	Research Site	Kansas City	Missouri	United States	64111
27	Research Site	Saint Louis	Missouri	United States	63136
28	Research Site	Portsmouth	New Hampshire	United States	03801
29	Research Site	Eatontown	New Jersey	United States	07724
30	Research Site	College Point	New York	United States	11356
31	Research Site	Oklahoma City	Oklahoma	United States	73116
32	Research Site	Philadelphia	Pennsylvania	United States	19106
33	Research Site	Orangeburg	South Carolina	United States	29118
34	Research Site	Arlington	Texas	United States	76015
35	Research Site	Greenville	Texas	United States	75402
36	Research Site	Houston	Texas	United States	77004
37	Research Site	McAllen	Texas	United States	78503
38	Research Site	San Antonio	Texas	United States	78229
39	Research Site	Fairfax	Virginia	United States	22033
40	Research Site	Hampton	Virginia	United States	23666

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: NCT01932970
• Other Study ID Numbers: 20120359; 2013-000964-28; KAI-4169
• First Posted: Aug 30, 2013
• Last Update Posted: Oct 17, 2018
• Last Verified: Sep 1, 2018

• Keywords provided by Amgen: Secondary Hyperparathyroidism (SHPT), chronic kidney disease (CKD), hemodialysis, parathyroid hormone (PTH), hypocalcemia, bone and mineral metabolism
• Additional relevant MeSH terms: Neoplasm Metastasis; Hyperparathyroidism; Hyperparathyroidism, Secondary

Study Results

Participant Flow

Recruitment Details	This study was conducted at 33 centers in the United States. Participants were enrolled from 1 September 2013 to 9 December 2013. Participants were required to be on a stable dose of daily oral cinacalcet for a minimum of 4 weeks before screening, and during the 4 weeks of screening.
Pre-assignment Detail	Upon enrollment, participants underwent a washout period of a minimum of 7 days, wherein no cinacalcet use was allowed. Participants who had a serum corrected calcium ≥ 8.3 mg/dL during the washout period entered the treatment phase and were categorized based on their pre-washout, screening cinacalcet daily dose level (30 mg, 60 mg or ≥ 90 mg).

Arm/Group Title	Etelcalcetide
Arm/Group Description	Participants were treated with 5 mg etelcalcetide administered by intravenous bolus injection at the end of each hemodialysis session three times per week (TIW) for 4 weeks.
Period Title: Overall Study
STARTED	158
Received Treatment	148
COMPLETED	140
NOT COMPLETED	18

Baseline Characteristics

Arm/Group Title	Etelcalcetide
Arm/Group Description	Participants were treated with 5 mg etelcalcetide administered by intravenous bolus injection at the end of each hemodialysis session three times per week (TIW) for 4 weeks.
Overall Participants	147
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.5 (14.0)
Age, Customized (participants) [Number]
< 65 years	106 72.1%
≥ 65 years	41 27.9%
Sex: Female, Male (Count of Participants)
Female	55 37.4%
Male	92 62.6%
Race (participants) [Number]
American Indian or Alaska Native	1 0.7%
Asian	12 8.2%
Black (or African American)	68 46.3%
Native Hawaiian or Other Pacific Islander	2 1.4%
White	64 43.5%
Ethnicity (participants) [Number]
Hispanic/Latino	39 26.5%
Not Hispanic/Latino	108 73.5%
Corrected Calcium (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	9.81 (0.75)
Parathyroid Hormone (pg/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [pg/mL]	786.3 (467.8)
Phosphorus (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	5.88 (1.71)

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Serum Corrected Calcium < 7.5 mg/dL During the 4-week Treatment Period
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Etelcalcetide
Arm/Group Description	Participants were treated with 5 mg etelcalcetide administered by intravenous bolus injection at the end of each hemodialysis session three times per week (TIW) for 4 weeks.
Measure Participants	147
Number (95% Confidence Interval) [percentage of participants]	0.7 0.5%

2. Secondary Outcome

Title	Percent Change From Baseline in Parathyroid Hormone During the Treatment Period
Time Frame	Baseline and weeks 2, 3 and 4

Outcome Measure Data

Analysis Population Description

Full analysis set with available data at each time point

Arm/Group Title	Etelcalcetide
Arm/Group Description	Participants were treated with 5 mg etelcalcetide administered by intravenous bolus injection at the end of each hemodialysis session three times per week (TIW) for 4 weeks.
Measure Participants	140
Week 2 (n = 125)	-3.9 (2.6)
Week 3 (n = 131)	-7.8 (3.1)
Week 4 (n = 123)	-10.9 (2.9)

3. Secondary Outcome

Title	Percentage of Participants With Serum Corrected Calcium < 8.3 mg/dL During the 4-week Treatment Period
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Etelcalcetide
Arm/Group Description	Participants were treated with 5 mg etelcalcetide administered by intravenous bolus injection at the end of each hemodialysis session three times per week (TIW) for 4 weeks.
Measure Participants	147
Number (95% Confidence Interval) [percentage of participants]	15.6 10.6%

4. Other Pre-specified Outcome

Title	Number of Participants With Adverse Events
Time Frame	From the first dose of study drug up to 30 days after the last dose; 8 weeks

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug

Arm/Group Title	Etelcalcetide
Arm/Group Description	Participants were treated with 5 mg etelcalcetide administered by intravenous bolus injection at the end of each hemodialysis session three times per week (TIW) for 4 weeks.
Measure Participants	148
Any adverse event (AE)	72 49%
Serious adverse event (SAE)	17 11.6%
AE leading to discontinuation of etelcalcetide	2 1.4%
Fatal adverse event	1 0.7%
Treatment-related adverse event	11 7.5%

5. Other Pre-specified Outcome

Title	Percentage of Participants With Symptomatic Hypocalcemia During the 4-week Treatment Period
Description	Hpocalcemia was used for events of decreased calcium accompanied by clinical signs and symptoms of hypocalcemia.
Time Frame	From the first dose of study drug up to 30 days after the last dose; 8 weeks

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of study drug

Arm/Group Title	Etelcalcetide
Arm/Group Description	Participants were treated with 5 mg etelcalcetide administered by intravenous bolus injection at the end of each hemodialysis session three times per week (TIW) for 4 weeks.
Measure Participants	148
Number (95% Confidence Interval) [percentage of participants]	0.0 0%

Adverse Events

Time Frame	From the first dose of study drug up to 30 days after the last dose; up to 8 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	Etelcalcetide
Arm/Group Description	Participants were treated with 5 mg etelcalcetide administered by intravenous bolus injection at the end of each hemodialysis session three times per week (TIW) for 4 weeks.
All Cause Mortality
	Etelcalcetide
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Etelcalcetide
	Affected / at Risk (%)	# Events
Total	17/148 (11.5%)
Cardiac disorders
Acute myocardial infarction	1/148 (0.7%)
Cardiac arrest	1/148 (0.7%)
General disorders
Asthenia	1/148 (0.7%)
Chest pain	1/148 (0.7%)
Hepatobiliary disorders
Bile duct obstruction	1/148 (0.7%)
Infections and infestations
Arteriovenous graft site infection	1/148 (0.7%)
Biliary sepsis	1/148 (0.7%)
Osteomyelitis	1/148 (0.7%)
Pneumonia	2/148 (1.4%)
Staphylococcal bacteraemia	1/148 (0.7%)
Injury, poisoning and procedural complications
Hip fracture	1/148 (0.7%)
Procedural hypotension	1/148 (0.7%)
Investigations
Blood glucose increased	1/148 (0.7%)
Metabolism and nutrition disorders
Fluid overload	1/148 (0.7%)
Hyperkalaemia	1/148 (0.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/148 (0.7%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Non-small cell lung cancer	1/148 (0.7%)
Nervous system disorders
Cerebrovascular accident	1/148 (0.7%)
Psychiatric disorders
Mental status changes	1/148 (0.7%)
Respiratory, thoracic and mediastinal disorders
Pneumothorax	1/148 (0.7%)
Pulmonary oedema	1/148 (0.7%)
Other (Not Including Serious) Adverse Events
	Etelcalcetide
	Affected / at Risk (%)	# Events
Total	0/148 (0%)

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.