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Extension Study of Etelcalcetide in the Treatment of Secondary Hyperparathyroidism (SHPT) in Patients With Chronic Kidney Disease (CKD) on Hemodialysis

Sponsor
Amgen (Industry)
Overall Status
Completed
CT.gov ID
NCT01785875
Collaborator
(none)
891
Enrollment
209
Locations
1
Arm
23
Actual Duration (Months)
4.3
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is designed to describe the long-term safety and efficacy of etelcalcetide (AMG 416) for the treatment of SHPT in adults with CKD on hemodialysis.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
891 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Multicenter Single-arm Extension Study to Describe the Long-term Efficacy and Safety of AMG 416 in the Treatment of Secondary Hyperparathyroidism in Subjects With Chronic Kidney Disease on Hemodialysis
Actual Study Start Date :
Jul 31, 2013
Actual Primary Completion Date :
Jul 1, 2015
Actual Study Completion Date :
Jul 1, 2015

Arms and Interventions

Arm Intervention/Treatment
Experimental: Etelcalcetide

Participants received etelcalcetide at a starting dose of 5 mg three times a week (TIW) for up to 52 weeks. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL.

Drug: Etelcalcetide
Administered by bolus injection into the venous line of the dialysis circuit at the end of hemodialysis treatment, and prior to or during rinse-back with each hemodialysis session (ie, 3 times per week).
Other Names:
  • AMG 416

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With Adverse Events (AEs) [From first dose until 30 days after last dose; the treatment period was 52 weeks.]

      Treatment-related adverse events are those the investigator indicated as having a reasonable possibility of having been caused by etelcalcetide. A serious adverse event is defined as an adverse event that meets at least 1 of the following serious criteria: • fatal • life threatening • requires in-patient hospitalization or prolongation of existing hospitalization • results in persistent or significant disability/incapacity • congenital anomaly/birth defect • other medically important serious event.

    2. Number of Participants With Shift in Laboratory Values From Baseline Grade 0 or 1 to Post-baseline Grade 3 or 4 [52 weeks]

      Laboratory toxicity grading was based on Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, where Grade 0 represents values in the normal range and grade 4 represents values with life-threatening consequences and urgent intervention indicated.

    3. Number of Participants Who Developed Anti-etelcalcetide Antibodies [Baseline, Week 12, Week 24, Week 36, Week 53, the 30-day follow-up visit]

      A validated dual flow-cell biosensor immunoassay was used to detect antibodies capable of binding etelcalcetide. The number of participants with a negative or no result at baseline and positive binding antibodies at any time post-baseline is reported.

    4. Change From Baseline in Blood Pressure [Baseline and Weeks 24 and 48]

      Blood pressure (BP) values were taken post-hemodialysis assessments.

    Secondary Outcome Measures

    1. Percentage of Participants With > 30% Reduction From Baseline in PTH During the Efficacy Assessment Phase [Baseline and the efficacy assessment phase, defined as the last 6 weeks prior to ending treatment for participants who completed a minimum of 8 weeks of treatment (weeks 46-52 for participants who completed 52 weeks of treatment)]

      The efficacy assessment phase (EAP) is defined as the last 6 weeks before ending treatment, which was only for participants who completed a minimum of 8 weeks of treatment with etelcalcetide. If multiple assessments were available during the EAP, values were averaged.

    2. Percentage of Participants With > 30% Reduction From Baseline in PTH During the EAP12 [Baseline and the efficacy assessment phase at month 12 (weeks 46-53)]

      The efficacy assessment phase at 12 months (EAP12) was defined as the period from week 46 to 53 (inclusive). If multiple assessments were available during the EAP12, values were averaged.

    3. Percentage of Participants With PTH ≤ 300 pg/mL During the EAP [Baseline and the efficacy assessment phase]

    4. Percentage of Participants With PTH ≤ 300 pg/mL During the EAP12 [Week 46 to 53]

    5. Percent Change From Baseline in Mean PTH During the EAP [Baseline and the efficacy assessment phase]

    6. Percent Change From Baseline in Mean PTH During the EAP12 [Baseline and the efficacy assessment phase at month 12 (weeks 46-53)]

    7. Percent Change From Baseline in Mean Corrected Calcium During the EAP [Baseline and the efficacy assessment phase]

    8. Percent Change From Baseline in Mean Corrected Calcium During the EAP12 [Baseline and the efficacy assessment phase at month 12 (weeks 46-53)]

    9. Percent Change From Baseline in Mean Corrected Calcium Phosphorus Product During the EAP [Baseline and the efficacy assessment phase]

    10. Percent Change From Baseline in Mean Corrected Calcium Phosphorus Product During the EAP12 [Baseline and the efficacy assessment phase at month 12 (weeks 46-53)]

    11. Percent Change From Baseline in Mean Phosphorus During the EAP [Baseline and the efficacy assessment phase]

    12. Percent Change From Baseline in Mean Phosphorus During the EAP12 [Baseline and the efficacy assessment phase at month 12 (weeks 46-53)]

    Eligibility Criteria

    Criteria

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

    • Subject understands the study procedures and agrees to participate in the study by giving written informed consent.

    • Subject must complete the treatment and follow-up period, or have been discontinued for rising intact parathyroid hormone (iPTH), from an AMG 416 phase 3 parent study prior to the start of dosing in this study: 20120229 (NCT01785849), 20120230 (NCT01788046), or 20120359 (NCT01932970).

    • Subject agrees to not participate in another study of an investigational agent during the study.

    • Other Inclusion Criteria may apply

    Exclusion Criteria:

    • Currently receiving treatment in another investigational device or drug study.

    • Currently receiving other investigational procedures while participating in this study.

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

    • Subject has an unstable medical condition based on medical history, physical examination, and routine laboratory tests, or is otherwise unstable in the judgment of the Investigator.

    Other Exclusion Criteria may apply

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Research Site Birmingham Alabama United States 35211
    2 Research Site Pine Bluff Arkansas United States 71603
    3 Research Site Azusa California United States 91702
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    156 Research Site Miskolc Hungary 3526
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    159 Research Site Ashkelon Israel 78278
    160 Research Site Jerusalem Israel 91120
    161 Research Site Kfar-Saba Israel 44281
    162 Research Site Nahariya Israel 22100
    163 Research Site Tel Aviv Israel 64239
    164 Research Site Tel Hashomer Israel 52621
    165 Research Site Zerifin Israel 70300
    166 Research Site Ancona Italy 60131
    167 Research Site Lecco Italy 23900
    168 Research Site Milano Italy 20122
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    170 Research Site Pavia Italy 27100
    171 Research Site Verona Italy 37126
    172 Research Site Amsterdam Netherlands 1081 HV
    173 Research Site Enschede Netherlands 7511 JX
    174 Research Site Rotterdam Netherlands 3079 DZ
    175 Research Site Venlo Netherlands 5912 BL
    176 Research Site Bialystok Poland 15-540
    177 Research Site Gdansk Poland 80-952
    178 Research Site Golub-Dobrzyn Poland 87-400
    179 Research Site Krakow Poland 31-501
    180 Research Site Lodz Poland 90-153
    181 Research Site Rybnik Poland 44-200
    182 Research Site Warszawa Poland 02-006
    183 Research Site Warszawa Poland 02-097
    184 Research Site Warszawa Poland 04-749
    185 Research Site Zamosc Poland 87-100
    186 Research Site Moscow Russian Federation 123183
    187 Research Site Saint Petersburg Russian Federation 191104
    188 Research Site Saint Petersburg Russian Federation 196247
    189 Research Site Saint Petersburg Russian Federation 197110
    190 Research Site Saint Petersburg Russian Federation 198510
    191 Research Site Saint-Petersburg Russian Federation 195067
    192 Research Site Saint-Petersburg Russian Federation 195257
    193 Research Site Yaroslavl Russian Federation 150062
    194 Research Site Cordoba Andalucía Spain 14004
    195 Research Site Santander Cantabria Spain 39008
    196 Research Site Barcelona Cataluña Spain 08003
    197 Research Site Barcelona Cataluña Spain 08025
    198 Research Site Barcelona Cataluña Spain 08035
    199 Research Site Barcelona Cataluña Spain 08036
    200 Research Site Majadahonda Madrid Spain 28222
    201 Research Site Madrid Spain 28041
    202 Research Site Karlstad Sweden 651 85
    203 Research Site Stockholm Sweden 141 86
    204 Research Site Uppsala Sweden 751 85
    205 Research Site Cambridge United Kingdom CB2 2QQ
    206 Research Site Coventry United Kingdom CV2 2DX
    207 Research Site London United Kingdom NW3 2QG
    208 Research Site Nottingham United Kingdom NG5 1PB
    209 Research Site Sheffield United Kingdom S5 7AU

    Sponsors and Collaborators

    • Amgen

    Investigators

    • Study Director: MD, Amgen

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    Responsible Party:
    Amgen
    ClinicalTrials.gov Identifier:
    NCT01785875
    Other Study ID Numbers:
    • 20120231
    • KAI-4169-008
    • 2012-002808-41
    First Posted:
    Feb 7, 2013
    Last Update Posted:
    Apr 10, 2019
    Last Verified:
    Apr 1, 2019
    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
    Kidney Diseases
    Renal Insufficiency, Chronic
    Hyperparathyroidism
    Hyperparathyroidism, Secondary

    Study Results

    Participant Flow

    Recruitment Details This single-arm study was conducted at 205 centers in the US, Canada, Europe, Israel, Russian Federation and Australia. Participants were enrolled from 31 July 2013 to 9 June 2014. Participants who rolled over into another single-arm extension study 20130213 (NCT02102204) are reported as discontinuing the study due to protocol specified criteria.
    Pre-assignment Detail This extension study enrolled participants from 1 of 3 parent studies: 20120229 (NCT01785849), 20120230 (NCT01788046), or 20120359 (NCT01932970). In Studies 20120229 and 20120230, patients received either placebo or etelcalcetide 3 times a week (TIW) for up to 26 weeks; In Study 20120359, patients received 5 mg etelcalcetide TIW for 4 weeks.
    Arm/Group Title 20120229 / 20120230 Placebo 20120229 / 20120230 Etelcalcetide 20120359 Etelcalcetide
    Arm/Group Description Participants who received placebo in parent study 20120229 or 20120230 received etelcalcetide at a starting dose of 5 mg three times a week (TIW) for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL. Participants who received etelcalcetide in parent study 20120229 or 20120230 received etelcalcetide at a starting dose of 5 mg TIW for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL. Participants who received etelcalcetide in parent study 20120359 received etelcalcetide at a starting dose of 5 mg TIW for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL.
    Period Title: Overall Study
    STARTED 384 384 123
    Received Etelcalcetide 383 384 123
    COMPLETED 90 95 16
    NOT COMPLETED 294 289 107

    Baseline Characteristics

    Arm/Group Title Etelcalcetide
    Arm/Group Description All participants received etelcalcetide at a starting dose of 5 mg TIW for up to 52 weeks during the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL.
    Overall Participants 891
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    58.3
    (14.4)
    Age, Customized (participants) [Number]
    < 65 years
    577
    64.8%
    ≥ 65 years
    314
    35.2%
    Sex: Female, Male (Count of Participants)
    Female
    341
    38.3%
    Male
    550
    61.7%
    Race/Ethnicity, Customized (participants) [Number]
    American Indian or Alaska Native
    1
    0.1%
    Asian
    29
    3.3%
    Black (or African American)
    270
    30.3%
    Native Hawaiian or Other Pacific Islander
    12
    1.3%
    White
    567
    63.6%
    Other
    12
    1.3%
    Ethnicity (participants) [Number]
    Hispanic/Latino
    122
    13.7%
    Not Hispanic/Latino
    769
    86.3%
    Parathyroid Hormone (PTH) Level (participants) [Number]
    < 600 pg/mL
    405
    45.5%
    600 - ≤ 1000 pg/mL
    221
    24.8%
    > 1000 pg/mL
    228
    25.6%
    Missing
    37
    4.2%
    PTH Concentration (pg/mL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [pg/mL]
    769.5
    (574.4)
    Corrected Calcium (mg/dL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mg/dL]
    9.67
    (0.68)
    Phosphorus (mg/dL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mg/dL]
    5.63
    (1.75)
    Corrected Calcium Phosphorus Product (cCa x P) (mg²/dL²) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mg²/dL²]
    54.36
    (17.17)

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants With Adverse Events (AEs)
    Description Treatment-related adverse events are those the investigator indicated as having a reasonable possibility of having been caused by etelcalcetide. A serious adverse event is defined as an adverse event that meets at least 1 of the following serious criteria: • fatal • life threatening • requires in-patient hospitalization or prolongation of existing hospitalization • results in persistent or significant disability/incapacity • congenital anomaly/birth defect • other medically important serious event.
    Time Frame From first dose until 30 days after last dose; the treatment period was 52 weeks.

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least 1 dose of etelcalcetide.
    Arm/Group Title 20120229 / 20120230 Placebo 20120229 / 20120230 Etelcalcetide 20120359 Etelcalcetide Etelcalcetide Total
    Arm/Group Description Participants who received placebo in parent study 20120229 or 20120230 received etelcalcetide at a starting dose of 5 mg three times a week (TIW) for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL. Participants who received etelcalcetide in parent study 20120229 or 20120230 received etelcalcetide at a starting dose of 5 mg TIW for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL. Participants who received etelcalcetide in parent study 20120359 received etelcalcetide at a starting dose of 5 mg TIW for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL. Participants received etelcalcetide at a starting dose of 5 mg three times a week (TIW) for up to 52 weeks. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL.
    Measure Participants 383 384 123 890
    Any adverse event
    354
    39.7%
    337
    NaN
    108
    NaN
    799
    NaN
    Serious adverse events
    161
    18.1%
    142
    NaN
    53
    NaN
    356
    NaN
    Treatment-related adverse events
    215
    24.1%
    141
    NaN
    36
    NaN
    392
    NaN
    Treatment-related serious adverse events
    6
    0.7%
    5
    NaN
    2
    NaN
    13
    NaN
    AEs leading to discontinuation of etelcalcetide
    22
    2.5%
    11
    NaN
    8
    NaN
    41
    NaN
    Fatal adverse events
    27
    3%
    16
    NaN
    8
    NaN
    51
    NaN
    2. Primary Outcome
    Title Number of Participants With Shift in Laboratory Values From Baseline Grade 0 or 1 to Post-baseline Grade 3 or 4
    Description Laboratory toxicity grading was based on Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, where Grade 0 represents values in the normal range and grade 4 represents values with life-threatening consequences and urgent intervention indicated.
    Time Frame 52 weeks

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least 1 dose of etelcalcetide.
    Arm/Group Title Etelcalcetide Total
    Arm/Group Description Participants received etelcalcetide at a starting dose of 5 mg three times a week (TIW) for up to 52 weeks. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL.
    Measure Participants 890
    Alanine aminotransferase increase
    1
    0.1%
    Albumin decrease
    9
    1%
    Alkaline phosphatase increase
    2
    0.2%
    Aspartate aminotransferase increase
    3
    0.3%
    Bilirubin increase
    1
    0.1%
    Calcium (corrected) decrease
    51
    5.7%
    Calcium (corrected) increase
    8
    0.9%
    Phosphorus decrease
    77
    8.6%
    Potassium decrease
    9
    1%
    Potassium increase
    69
    7.7%
    Hemoglobin decrease
    4
    0.4%
    Hemoglobin increase
    1
    0.1%
    3. Primary Outcome
    Title Number of Participants Who Developed Anti-etelcalcetide Antibodies
    Description A validated dual flow-cell biosensor immunoassay was used to detect antibodies capable of binding etelcalcetide. The number of participants with a negative or no result at baseline and positive binding antibodies at any time post-baseline is reported.
    Time Frame Baseline, Week 12, Week 24, Week 36, Week 53, the 30-day follow-up visit

    Outcome Measure Data

    Analysis Population Description
    Participants who received at least 1 dose of etelcalcetide and with a post-baseline antibody result.
    Arm/Group Title 20120229 / 20120230 Placebo 20120229 / 20120230 Etelcalcetide 20120359 Etelcalcetide Etelcalcetide Total
    Arm/Group Description Participants who received placebo in parent study 20120229 or 20120230 received etelcalcetide at a starting dose of 5 mg three times a week (TIW) for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL. Participants who received etelcalcetide in parent study 20120229 or 20120230 received etelcalcetide at a starting dose of 5 mg TIW for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL. Participants who received etelcalcetide in parent study 20120359 received etelcalcetide at a starting dose of 5 mg TIW for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL. Participants received etelcalcetide at a starting dose of 5 mg three times a week (TIW) for up to 52 weeks. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL.
    Measure Participants 369 384 123 876
    Number [participants]
    10
    1.1%
    15
    NaN
    2
    NaN
    27
    NaN
    4. Secondary Outcome
    Title Percentage of Participants With > 30% Reduction From Baseline in PTH During the Efficacy Assessment Phase
    Description The efficacy assessment phase (EAP) is defined as the last 6 weeks before ending treatment, which was only for participants who completed a minimum of 8 weeks of treatment with etelcalcetide. If multiple assessments were available during the EAP, values were averaged.
    Time Frame Baseline and the efficacy assessment phase, defined as the last 6 weeks prior to ending treatment for participants who completed a minimum of 8 weeks of treatment (weeks 46-52 for participants who completed 52 weeks of treatment)

    Outcome Measure Data

    Analysis Population Description
    Participants with pre-dialysis PTH assessment at baseline and during the EAP who completed a minimum of 8 weeks of treatment with etelcalcetide.
    Arm/Group Title 20120229 / 20120230 Placebo 20120229 / 20120230 Etelcalcetide 20120359 Etelcalcetide Etelcalcetide Total
    Arm/Group Description Participants who received placebo in parent study 20120229 or 20120230 received etelcalcetide at a starting dose of 5 mg three times a week (TIW) for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL. Participants who received etelcalcetide in parent study 20120229 or 20120230 received etelcalcetide at a starting dose of 5 mg TIW for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL. Participants who received etelcalcetide in parent study 20120359 received etelcalcetide at a starting dose of 5 mg TIW for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL. Participants received etelcalcetide at a starting dose of 5 mg three times a week (TIW) for up to 52 weeks. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL.
    Measure Participants 341 332 106 779
    Number (95% Confidence Interval) [percentage of participants]
    81.2
    9.1%
    54.5
    NaN
    65.1
    NaN
    67.7
    NaN
    5. Secondary Outcome
    Title Percentage of Participants With > 30% Reduction From Baseline in PTH During the EAP12
    Description The efficacy assessment phase at 12 months (EAP12) was defined as the period from week 46 to 53 (inclusive). If multiple assessments were available during the EAP12, values were averaged.
    Time Frame Baseline and the efficacy assessment phase at month 12 (weeks 46-53)

    Outcome Measure Data

    Analysis Population Description
    Participants with pre-dialysis PTH assessment at baseline and during EAP12
    Arm/Group Title 20120229 / 20120230 Placebo 20120229 / 20120230 Etelcalcetide 20120359 Etelcalcetide Etelcalcetide Total
    Arm/Group Description Participants who received placebo in parent study 20120229 or 20120230 received etelcalcetide at a starting dose of 5 mg three times a week (TIW) for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL. Participants who received etelcalcetide in parent study 20120229 or 20120230 received etelcalcetide at a starting dose of 5 mg TIW for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL. Participants who received etelcalcetide in parent study 20120359 received etelcalcetide at a starting dose of 5 mg TIW for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL. Participants received etelcalcetide at a starting dose of 5 mg three times a week (TIW) for up to 52 weeks. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL.
    Measure Participants 302 300 74 676
    Number (95% Confidence Interval) [percentage of participants]
    82.5
    9.3%
    53.3
    NaN
    63.5
    NaN
    67.5
    NaN
    6. Secondary Outcome
    Title Percentage of Participants With PTH ≤ 300 pg/mL During the EAP
    Description
    Time Frame Baseline and the efficacy assessment phase

    Outcome Measure Data

    Analysis Population Description
    Participants with predialysis PTH assessment during the EAP who completed a minimum of 8 weeks of treatment with etelcalcetide
    Arm/Group Title 20120229 / 20120230 Placebo 20120229 / 20120230 Etelcalcetide 20120359 Etelcalcetide Etelcalcetide Total
    Arm/Group Description Participants who received placebo in parent study 20120229 or 20120230 received etelcalcetide at a starting dose of 5 mg three times a week (TIW) for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL. Participants who received etelcalcetide in parent study 20120229 or 20120230 received etelcalcetide at a starting dose of 5 mg TIW for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL. Participants who received etelcalcetide in parent study 20120359 received etelcalcetide at a starting dose of 5 mg TIW for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL. Participants received etelcalcetide at a starting dose of 5 mg three times a week (TIW) for up to 52 weeks. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL.
    Measure Participants 352 355 108 815
    Number (95% Confidence Interval) [percentage of participants]
    55.7
    6.3%
    59.7
    NaN
    54.6
    NaN
    57.3
    NaN
    7. Secondary Outcome
    Title Percentage of Participants With PTH ≤ 300 pg/mL During the EAP12
    Description
    Time Frame Week 46 to 53

    Outcome Measure Data

    Analysis Population Description
    Participants with predialysis PTH assessment during the EAP12
    Arm/Group Title 20120229 / 20120230 Placebo 20120229 / 20120230 Etelcalcetide 20120359 Etelcalcetide Etelcalcetide Total
    Arm/Group Description Participants who received placebo in parent study 20120229 or 20120230 received etelcalcetide at a starting dose of 5 mg three times a week (TIW) for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL. Participants who received etelcalcetide in parent study 20120229 or 20120230 received etelcalcetide at a starting dose of 5 mg TIW for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL. Participants who received etelcalcetide in parent study 20120359 received etelcalcetide at a starting dose of 5 mg TIW for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL. Participants received etelcalcetide at a starting dose of 5 mg three times a week (TIW) for up to 52 weeks. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL.
    Measure Participants 312 321 75 708
    Number (95% Confidence Interval) [percentage of participants]
    54.8
    6.2%
    61.1
    NaN
    42.7
    NaN
    56.4
    NaN
    8. Secondary Outcome
    Title Percent Change From Baseline in Mean PTH During the EAP
    Description
    Time Frame Baseline and the efficacy assessment phase

    Outcome Measure Data

    Analysis Population Description
    Participants with available data
    Arm/Group Title 20120229 / 20120230 Placebo 20120229 / 20120230 Etelcalcetide 20120359 Etelcalcetide Etelcalcetide Total
    Arm/Group Description Participants who received placebo in parent study 20120229 or 20120230 received etelcalcetide at a starting dose of 5 mg three times a week (TIW) for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL. Participants who received etelcalcetide in parent study 20120229 or 20120230 received etelcalcetide at a starting dose of 5 mg TIW for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL. Participants who received etelcalcetide in parent study 20120359 received etelcalcetide at a starting dose of 5 mg TIW for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL. Participants received etelcalcetide at a starting dose of 5 mg three times a week (TIW) for up to 52 weeks. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL.
    Measure Participants 341 332 106 779
    Mean (Standard Error) [percent change]
    -54.55
    (2.12)
    3.92
    (8.68)
    -28.40
    (6.96)
    -26.07
    (4.04)
    9. Secondary Outcome
    Title Percent Change From Baseline in Mean PTH During the EAP12
    Description
    Time Frame Baseline and the efficacy assessment phase at month 12 (weeks 46-53)

    Outcome Measure Data

    Analysis Population Description
    Participants with available data
    Arm/Group Title 20120229 / 20120230 Placebo 20120229 / 20120230 Etelcalcetide 20120359 Etelcalcetide Etelcalcetide Total
    Arm/Group Description Participants who received placebo in parent study 20120229 or 20120230 received etelcalcetide at a starting dose of 5 mg three times a week (TIW) for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL. Participants who received etelcalcetide in parent study 20120229 or 20120230 received etelcalcetide at a starting dose of 5 mg TIW for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL. Participants who received etelcalcetide in parent study 20120359 received etelcalcetide at a starting dose of 5 mg TIW for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL. Participants received etelcalcetide at a starting dose of 5 mg three times a week (TIW) for up to 52 weeks. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL.
    Measure Participants 302 300 74 676
    Mean (Standard Error) [percent change]
    -55.41
    (2.20)
    4.78
    (9.62)
    -27.05
    (7.57)
    -25.59
    (4.59)
    10. Secondary Outcome
    Title Percent Change From Baseline in Mean Corrected Calcium During the EAP
    Description
    Time Frame Baseline and the efficacy assessment phase

    Outcome Measure Data

    Analysis Population Description
    Participants with available data
    Arm/Group Title 20120229 / 20120230 Placebo 20120229 / 20120230 Etelcalcetide 20120359 Etelcalcetide Etelcalcetide Total
    Arm/Group Description Participants who received placebo in parent study 20120229 or 20120230 received etelcalcetide at a starting dose of 5 mg three times a week (TIW) for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL. Participants who received etelcalcetide in parent study 20120229 or 20120230 received etelcalcetide at a starting dose of 5 mg TIW for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL. Participants who received etelcalcetide in parent study 20120359 received etelcalcetide at a starting dose of 5 mg TIW for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL. Participants received etelcalcetide at a starting dose of 5 mg three times a week (TIW) for up to 52 weeks. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL.
    Measure Participants 352 352 103 807
    Mean (Standard Error) [percent change]
    -10.01
    (0.52)
    -6.74
    (0.47)
    -8.65
    (1.04)
    -8.41
    (0.34)
    11. Secondary Outcome
    Title Percent Change From Baseline in Mean Corrected Calcium During the EAP12
    Description
    Time Frame Baseline and the efficacy assessment phase at month 12 (weeks 46-53)

    Outcome Measure Data

    Analysis Population Description
    Participants with available data
    Arm/Group Title 20120229 / 20120230 Placebo 20120229 / 20120230 Etelcalcetide 20120359 Etelcalcetide Etelcalcetide Total
    Arm/Group Description Participants who received placebo in parent study 20120229 or 20120230 received etelcalcetide at a starting dose of 5 mg three times a week (TIW) for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL. Participants who received etelcalcetide in parent study 20120229 or 20120230 received etelcalcetide at a starting dose of 5 mg TIW for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL. Participants who received etelcalcetide in parent study 20120359 received etelcalcetide at a starting dose of 5 mg TIW for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL. Participants received etelcalcetide at a starting dose of 5 mg three times a week (TIW) for up to 52 weeks. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL.
    Measure Participants 310 319 75 704
    Mean (Standard Error) [percent change]
    -9.76
    (0.52)
    -6.43
    (0.45)
    -9.73
    (1.14)
    -8.25
    (0.34)
    12. Secondary Outcome
    Title Percent Change From Baseline in Mean Corrected Calcium Phosphorus Product During the EAP
    Description
    Time Frame Baseline and the efficacy assessment phase

    Outcome Measure Data

    Analysis Population Description
    Participants with available data
    Arm/Group Title 20120229 / 20120230 Placebo 20120229 / 20120230 Etelcalcetide 20120359 Etelcalcetide Etelcalcetide Total
    Arm/Group Description Participants who received placebo in parent study 20120229 or 20120230 received etelcalcetide at a starting dose of 5 mg three times a week (TIW) for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL. Participants who received etelcalcetide in parent study 20120229 or 20120230 received etelcalcetide at a starting dose of 5 mg TIW for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL. Participants who received etelcalcetide in parent study 20120359 received etelcalcetide at a starting dose of 5 mg TIW for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL. Participants received etelcalcetide at a starting dose of 5 mg three times a week (TIW) for up to 52 weeks. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL.
    Measure Participants 342 345 99 786
    Mean (Standard Error) [percent change]
    -15.26
    (1.58)
    -10.41
    (1.61)
    -6.58
    (4.28)
    -12.04
    (1.13)
    13. Secondary Outcome
    Title Percent Change From Baseline in Mean Corrected Calcium Phosphorus Product During the EAP12
    Description
    Time Frame Baseline and the efficacy assessment phase at month 12 (weeks 46-53)

    Outcome Measure Data

    Analysis Population Description
    Participants with available data
    Arm/Group Title 20120229 / 20120230 Placebo 20120229 / 20120230 Etelcalcetide 20120359 Etelcalcetide Etelcalcetide Total
    Arm/Group Description Participants who received placebo in parent study 20120229 or 20120230 received etelcalcetide at a starting dose of 5 mg three times a week (TIW) for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL. Participants who received etelcalcetide in parent study 20120229 or 20120230 received etelcalcetide at a starting dose of 5 mg TIW for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL. Participants who received etelcalcetide in parent study 20120359 received etelcalcetide at a starting dose of 5 mg TIW for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL. Participants received etelcalcetide at a starting dose of 5 mg three times a week (TIW) for up to 52 weeks. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL.
    Measure Participants 309 317 75 701
    Mean (Standard Error) [percent change]
    -15.30
    (1.53)
    -9.78
    (1.62)
    -7.29
    (4.82)
    -11.95
    (1.13)
    14. Secondary Outcome
    Title Percent Change From Baseline in Mean Phosphorus During the EAP
    Description
    Time Frame Baseline and the efficacy assessment phase

    Outcome Measure Data

    Analysis Population Description
    Participants with available data
    Arm/Group Title 20120229 / 20120230 Placebo 20120229 / 20120230 Etelcalcetide 20120359 Etelcalcetide Etelcalcetide Total
    Arm/Group Description Participants who received placebo in parent study 20120229 or 20120230 received etelcalcetide at a starting dose of 5 mg three times a week (TIW) for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL. Participants who received etelcalcetide in parent study 20120229 or 20120230 received etelcalcetide at a starting dose of 5 mg TIW for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL. Participants who received etelcalcetide in parent study 20120359 received etelcalcetide at a starting dose of 5 mg TIW for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL. Participants received etelcalcetide at a starting dose of 5 mg three times a week (TIW) for up to 52 weeks. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL.
    Measure Participants 343 348 105 796
    Mean (Standard Error) [percent change]
    -5.71
    (1.71)
    -3.50
    (1.68)
    2.82
    (4.56)
    -3.62
    (1.20)
    15. Secondary Outcome
    Title Percent Change From Baseline in Mean Phosphorus During the EAP12
    Description
    Time Frame Baseline and the efficacy assessment phase at month 12 (weeks 46-53)

    Outcome Measure Data

    Analysis Population Description
    Participants with available data
    Arm/Group Title 20120229 / 20120230 Placebo 20120229 / 20120230 Etelcalcetide 20120359 Etelcalcetide Etelcalcetide Total
    Arm/Group Description Participants who received placebo in parent study 20120229 or 20120230 received etelcalcetide at a starting dose of 5 mg three times a week (TIW) for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL. Participants who received etelcalcetide in parent study 20120229 or 20120230 received etelcalcetide at a starting dose of 5 mg TIW for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL. Participants who received etelcalcetide in parent study 20120359 received etelcalcetide at a starting dose of 5 mg TIW for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL. Participants received etelcalcetide at a starting dose of 5 mg three times a week (TIW) for up to 52 weeks. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL.
    Measure Participants 309 319 75 703
    Mean (Standard Error) [percent change]
    -5.87
    (1.65)
    -3.06
    (1.73)
    3.53
    (5.46)
    -3.59
    (1.22)
    16. Primary Outcome
    Title Change From Baseline in Blood Pressure
    Description Blood pressure (BP) values were taken post-hemodialysis assessments.
    Time Frame Baseline and Weeks 24 and 48

    Outcome Measure Data

    Analysis Population Description
    Participants who received at least 1 dose of etelcalcetide and with available data at each time point (indicated by n)
    Arm/Group Title 20120229 / 20120230 Placebo 20120229 / 20120230 Etelcalcetide 20120359 Etelcalcetide Etelcalcetide Total
    Arm/Group Description Participants who received placebo in parent study 20120229 or 20120230 received etelcalcetide at a starting dose of 5 mg three times a week (TIW) for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL. Participants who received etelcalcetide in parent study 20120229 or 20120230 received etelcalcetide at a starting dose of 5 mg TIW for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL. Participants who received etelcalcetide in parent study 20120359 received etelcalcetide at a starting dose of 5 mg TIW for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL. Participants received etelcalcetide at a starting dose of 5 mg three times a week (TIW) for up to 52 weeks. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL.
    Measure Participants 383 384 123 890
    Systolic BP Week 24 (n = 329, 342, 104, 775)
    4.0
    (1.5)
    4.5
    (1.4)
    -5.5
    (2.8)
    2.9
    (1.0)
    Systolic BP Week 48 (n = 305, 317, 74, 696)
    3.5
    (1.6)
    6.5
    (1.5)
    -6.8
    (3.0)
    3.8
    (1.0)
    Diastolic BP Week 24 (n = 329, 343, 104, 776)
    2.2
    (0.8)
    1.2
    (0.9)
    -5.1
    (1.5)
    0.8
    (0.6)
    Diastolic BP Week 48 (n = 305, 317, 74, 696)
    1.1
    (0.9)
    0.8
    (0.9)
    -2.6
    (1.7)
    0.6
    (0.6)

    Adverse Events

    Time Frame From first dose until 30 days after last dose; the treatment period was 52 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 20120229 / 20120230 Placebo 20120229 / 20120230 Etelcalcetide 20120359 Etelcalcetide Total
    Arm/Group Description Participants who received placebo in parent study 20120229 or 20120230 received etelcalcetide at a starting dose of 5 mg three times a week (TIW) for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL. Participants who received etelcalcetide in parent study 20120229 or 20120230 received etelcalcetide at a starting dose of 5 mg TIW for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL. Participants who received etelcalcetide in parent study 20120359 received etelcalcetide at a starting dose of 5 mg TIW for up to 52 weeks in the extension study. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL. Participants received etelcalcetide at a starting dose of 5 mg three times a week (TIW) for up to 52 weeks. Etelcalcetide dose could be increased at weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum parathyroid hormone levels ≤ 300 pg/mL.
    All Cause Mortality
    20120229 / 20120230 Placebo 20120229 / 20120230 Etelcalcetide 20120359 Etelcalcetide Total
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    20120229 / 20120230 Placebo 20120229 / 20120230 Etelcalcetide 20120359 Etelcalcetide Total
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 161/383 (42%) 142/384 (37%) 53/123 (43.1%) 356/890 (40%)
    Blood and lymphatic system disorders
    Anaemia 3/383 (0.8%) 1/384 (0.3%) 2/123 (1.6%) 6/890 (0.7%)
    Anaemia of chronic disease 0/383 (0%) 0/384 (0%) 1/123 (0.8%) 1/890 (0.1%)
    Haemorrhagic anaemia 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Leukocytosis 0/383 (0%) 0/384 (0%) 1/123 (0.8%) 1/890 (0.1%)
    Lymphadenopathy 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Nephrogenic anaemia 0/383 (0%) 0/384 (0%) 1/123 (0.8%) 1/890 (0.1%)
    Thrombocytopenia 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Cardiac disorders
    Acute coronary syndrome 3/383 (0.8%) 0/384 (0%) 1/123 (0.8%) 4/890 (0.4%)
    Acute myocardial infarction 5/383 (1.3%) 6/384 (1.6%) 0/123 (0%) 11/890 (1.2%)
    Angina pectoris 2/383 (0.5%) 3/384 (0.8%) 2/123 (1.6%) 7/890 (0.8%)
    Angina unstable 1/383 (0.3%) 1/384 (0.3%) 0/123 (0%) 2/890 (0.2%)
    Aortic valve disease 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Aortic valve incompetence 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Aortic valve stenosis 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Arrhythmia 0/383 (0%) 0/384 (0%) 1/123 (0.8%) 1/890 (0.1%)
    Atrial fibrillation 9/383 (2.3%) 4/384 (1%) 0/123 (0%) 13/890 (1.5%)
    Atrial flutter 1/383 (0.3%) 1/384 (0.3%) 0/123 (0%) 2/890 (0.2%)
    Atrioventricular block complete 1/383 (0.3%) 1/384 (0.3%) 1/123 (0.8%) 3/890 (0.3%)
    Bradycardia 2/383 (0.5%) 2/384 (0.5%) 1/123 (0.8%) 5/890 (0.6%)
    Cardiac arrest 6/383 (1.6%) 2/384 (0.5%) 4/123 (3.3%) 12/890 (1.3%)
    Cardiac disorder 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Cardiac failure 2/383 (0.5%) 3/384 (0.8%) 0/123 (0%) 5/890 (0.6%)
    Cardiac failure acute 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Cardiac failure chronic 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Cardiac failure congestive 8/383 (2.1%) 7/384 (1.8%) 3/123 (2.4%) 18/890 (2%)
    Cardiac valve disease 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Cardio-respiratory arrest 1/383 (0.3%) 3/384 (0.8%) 0/123 (0%) 4/890 (0.4%)
    Cardiogenic shock 1/383 (0.3%) 1/384 (0.3%) 0/123 (0%) 2/890 (0.2%)
    Cardiomyopathy 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Cardiovascular insufficiency 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Coronary artery disease 3/383 (0.8%) 6/384 (1.6%) 0/123 (0%) 9/890 (1%)
    Coronary artery stenosis 3/383 (0.8%) 0/384 (0%) 0/123 (0%) 3/890 (0.3%)
    Mitral valve incompetence 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Myocardial infarction 2/383 (0.5%) 4/384 (1%) 1/123 (0.8%) 7/890 (0.8%)
    Myocardial ischaemia 2/383 (0.5%) 0/384 (0%) 0/123 (0%) 2/890 (0.2%)
    Palpitations 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Pericardial effusion 0/383 (0%) 0/384 (0%) 1/123 (0.8%) 1/890 (0.1%)
    Sinus node dysfunction 0/383 (0%) 2/384 (0.5%) 0/123 (0%) 2/890 (0.2%)
    Supraventricular tachycardia 1/383 (0.3%) 2/384 (0.5%) 0/123 (0%) 3/890 (0.3%)
    Tachycardia 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Torsade de pointes 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Tricuspid valve incompetence 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Ventricular fibrillation 2/383 (0.5%) 2/384 (0.5%) 2/123 (1.6%) 6/890 (0.7%)
    Ear and labyrinth disorders
    Deafness neurosensory 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Vertigo 2/383 (0.5%) 1/384 (0.3%) 0/123 (0%) 3/890 (0.3%)
    Endocrine disorders
    Goitre 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Eye disorders
    Cataract 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Diplopia 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Lens dislocation 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Optic neuropathy 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Gastrointestinal disorders
    Abdominal adhesions 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Abdominal pain 3/383 (0.8%) 3/384 (0.8%) 1/123 (0.8%) 7/890 (0.8%)
    Abdominal pain lower 1/383 (0.3%) 1/384 (0.3%) 0/123 (0%) 2/890 (0.2%)
    Abdominal pain upper 0/383 (0%) 0/384 (0%) 1/123 (0.8%) 1/890 (0.1%)
    Abdominal wall haematoma 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Anorectal varices haemorrhage 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Ascites 0/383 (0%) 0/384 (0%) 1/123 (0.8%) 1/890 (0.1%)
    Colitis 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Colitis ischaemic 1/383 (0.3%) 0/384 (0%) 1/123 (0.8%) 2/890 (0.2%)
    Constipation 1/383 (0.3%) 1/384 (0.3%) 0/123 (0%) 2/890 (0.2%)
    Dental caries 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Diabetic gastroparesis 0/383 (0%) 0/384 (0%) 1/123 (0.8%) 1/890 (0.1%)
    Diarrhoea 2/383 (0.5%) 2/384 (0.5%) 0/123 (0%) 4/890 (0.4%)
    Diverticular perforation 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Diverticulum intestinal 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Duodenal ulcer 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Enteritis 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Enterocutaneous fistula 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Gastric antral vascular ectasia 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Gastric disorder 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Gastric haemorrhage 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Gastritis 2/383 (0.5%) 0/384 (0%) 0/123 (0%) 2/890 (0.2%)
    Gastritis erosive 1/383 (0.3%) 2/384 (0.5%) 0/123 (0%) 3/890 (0.3%)
    Gastritis haemorrhagic 1/383 (0.3%) 0/384 (0%) 2/123 (1.6%) 3/890 (0.3%)
    Gastrointestinal haemorrhage 2/383 (0.5%) 4/384 (1%) 4/123 (3.3%) 10/890 (1.1%)
    Gastrointestinal necrosis 0/383 (0%) 0/384 (0%) 1/123 (0.8%) 1/890 (0.1%)
    Gastrointestinal vascular malformation 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Gastrooesophageal reflux disease 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Haematemesis 0/383 (0%) 1/384 (0.3%) 1/123 (0.8%) 2/890 (0.2%)
    Haemorrhoidal haemorrhage 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Haemorrhoids 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Ileus 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Inguinal hernia 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Intestinal ischaemia 3/383 (0.8%) 0/384 (0%) 0/123 (0%) 3/890 (0.3%)
    Intestinal perforation 0/383 (0%) 0/384 (0%) 1/123 (0.8%) 1/890 (0.1%)
    Large intestine perforation 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Large intestine polyp 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Megacolon 0/383 (0%) 0/384 (0%) 1/123 (0.8%) 1/890 (0.1%)
    Nausea 1/383 (0.3%) 0/384 (0%) 1/123 (0.8%) 2/890 (0.2%)
    Oesophagitis 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Pancreatic duct obstruction 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Pancreatitis 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Pancreatitis acute 2/383 (0.5%) 1/384 (0.3%) 0/123 (0%) 3/890 (0.3%)
    Rectal haemorrhage 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Small intestinal obstruction 1/383 (0.3%) 2/384 (0.5%) 1/123 (0.8%) 4/890 (0.4%)
    Subileus 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Upper gastrointestinal haemorrhage 1/383 (0.3%) 0/384 (0%) 1/123 (0.8%) 2/890 (0.2%)
    Vomiting 3/383 (0.8%) 1/384 (0.3%) 1/123 (0.8%) 5/890 (0.6%)
    General disorders
    Adverse drug reaction 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Asthenia 2/383 (0.5%) 2/384 (0.5%) 1/123 (0.8%) 5/890 (0.6%)
    Chest pain 3/383 (0.8%) 7/384 (1.8%) 1/123 (0.8%) 11/890 (1.2%)
    Device occlusion 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Drug resistance 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Haemorrhagic cyst 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Hyperthermia 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Hyperthermia malignant 0/383 (0%) 0/384 (0%) 1/123 (0.8%) 1/890 (0.1%)
    Hypothermia 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Impaired healing 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Non-cardiac chest pain 6/383 (1.6%) 5/384 (1.3%) 1/123 (0.8%) 12/890 (1.3%)
    Pyrexia 2/383 (0.5%) 2/384 (0.5%) 3/123 (2.4%) 7/890 (0.8%)
    Sudden death 1/383 (0.3%) 1/384 (0.3%) 1/123 (0.8%) 3/890 (0.3%)
    Thrombosis in device 1/383 (0.3%) 0/384 (0%) 2/123 (1.6%) 3/890 (0.3%)
    Hepatobiliary disorders
    Bile duct stone 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Biliary colic 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Cholangitis acute 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Cholecystitis 2/383 (0.5%) 3/384 (0.8%) 0/123 (0%) 5/890 (0.6%)
    Cholelithiasis 1/383 (0.3%) 2/384 (0.5%) 0/123 (0%) 3/890 (0.3%)
    Hepatic cirrhosis 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Hepatitis acute 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Hepatotoxicity 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Immune system disorders
    Drug hypersensitivity 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Hypersensitivity 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Seasonal allergy 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Infections and infestations
    Abdominal wall abscess 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Abscess limb 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Acinetobacter bacteraemia 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Acinetobacter infection 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Appendicitis 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Arteriovenous graft site infection 1/383 (0.3%) 1/384 (0.3%) 2/123 (1.6%) 4/890 (0.4%)
    Bacteraemia 2/383 (0.5%) 2/384 (0.5%) 0/123 (0%) 4/890 (0.4%)
    Bacterial sepsis 0/383 (0%) 0/384 (0%) 1/123 (0.8%) 1/890 (0.1%)
    Bacterial tracheitis 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Bronchitis 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Bronchopneumonia 1/383 (0.3%) 1/384 (0.3%) 0/123 (0%) 2/890 (0.2%)
    Campylobacter gastroenteritis 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Cellulitis 8/383 (2.1%) 4/384 (1%) 1/123 (0.8%) 13/890 (1.5%)
    Clostridium difficile colitis 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Clostridium difficile infection 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Cystitis 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Device related infection 1/383 (0.3%) 0/384 (0%) 1/123 (0.8%) 2/890 (0.2%)
    Device related sepsis 1/383 (0.3%) 1/384 (0.3%) 1/123 (0.8%) 3/890 (0.3%)
    Diabetic gangrene 0/383 (0%) 1/384 (0.3%) 1/123 (0.8%) 2/890 (0.2%)
    Diverticulitis 1/383 (0.3%) 1/384 (0.3%) 0/123 (0%) 2/890 (0.2%)
    Endocarditis 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Enteritis infectious 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Erysipelas 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Escherichia bacteraemia 0/383 (0%) 0/384 (0%) 1/123 (0.8%) 1/890 (0.1%)
    Gangrene 0/383 (0%) 0/384 (0%) 2/123 (1.6%) 2/890 (0.2%)
    Gastroenteritis 6/383 (1.6%) 0/384 (0%) 0/123 (0%) 6/890 (0.7%)
    Gastroenteritis viral 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Genital abscess 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Graft infection 0/383 (0%) 0/384 (0%) 1/123 (0.8%) 1/890 (0.1%)
    Helicobacter gastritis 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Herpes zoster 2/383 (0.5%) 0/384 (0%) 0/123 (0%) 2/890 (0.2%)
    Infected skin ulcer 3/383 (0.8%) 1/384 (0.3%) 0/123 (0%) 4/890 (0.4%)
    Infectious mononucleosis 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Influenza 3/383 (0.8%) 1/384 (0.3%) 2/123 (1.6%) 6/890 (0.7%)
    Intervertebral discitis 2/383 (0.5%) 0/384 (0%) 0/123 (0%) 2/890 (0.2%)
    Localised infection 0/383 (0%) 1/384 (0.3%) 1/123 (0.8%) 2/890 (0.2%)
    Lower respiratory tract infection 2/383 (0.5%) 0/384 (0%) 0/123 (0%) 2/890 (0.2%)
    Osteomyelitis 4/383 (1%) 3/384 (0.8%) 1/123 (0.8%) 8/890 (0.9%)
    Osteomyelitis acute 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Perirectal abscess 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Peritonitis 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Pneumonia 7/383 (1.8%) 5/384 (1.3%) 3/123 (2.4%) 15/890 (1.7%)
    Pneumonia bacterial 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Postoperative wound infection 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Renal cyst infection 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Respiratory tract infection 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Sepsis 10/383 (2.6%) 2/384 (0.5%) 3/123 (2.4%) 15/890 (1.7%)
    Septic shock 3/383 (0.8%) 1/384 (0.3%) 2/123 (1.6%) 6/890 (0.7%)
    Shunt infection 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Skin infection 1/383 (0.3%) 1/384 (0.3%) 0/123 (0%) 2/890 (0.2%)
    Staphylococcal bacteraemia 1/383 (0.3%) 0/384 (0%) 1/123 (0.8%) 2/890 (0.2%)
    Staphylococcal sepsis 1/383 (0.3%) 1/384 (0.3%) 0/123 (0%) 2/890 (0.2%)
    Subcutaneous abscess 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Tracheitis 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Tracheobronchitis 2/383 (0.5%) 0/384 (0%) 0/123 (0%) 2/890 (0.2%)
    Upper respiratory tract infection 1/383 (0.3%) 1/384 (0.3%) 1/123 (0.8%) 3/890 (0.3%)
    Urinary tract infection 1/383 (0.3%) 2/384 (0.5%) 1/123 (0.8%) 4/890 (0.4%)
    Urosepsis 1/383 (0.3%) 2/384 (0.5%) 0/123 (0%) 3/890 (0.3%)
    Viral infection 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Viral upper respiratory tract infection 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Wound infection 2/383 (0.5%) 0/384 (0%) 0/123 (0%) 2/890 (0.2%)
    Wound sepsis 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Injury, poisoning and procedural complications
    Ankle fracture 0/383 (0%) 1/384 (0.3%) 1/123 (0.8%) 2/890 (0.2%)
    Arteriovenous fistula occlusion 0/383 (0%) 2/384 (0.5%) 0/123 (0%) 2/890 (0.2%)
    Arteriovenous fistula site complication 7/383 (1.8%) 6/384 (1.6%) 0/123 (0%) 13/890 (1.5%)
    Arteriovenous fistula site haemorrhage 3/383 (0.8%) 4/384 (1%) 1/123 (0.8%) 8/890 (0.9%)
    Arteriovenous fistula thrombosis 4/383 (1%) 6/384 (1.6%) 0/123 (0%) 10/890 (1.1%)
    Cervical vertebral fracture 0/383 (0%) 0/384 (0%) 1/123 (0.8%) 1/890 (0.1%)
    Clavicle fracture 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Complications of transplanted kidney 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Compression fracture 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Contusion 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Coronary bypass thrombosis 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Dialysis related complication 0/383 (0%) 0/384 (0%) 1/123 (0.8%) 1/890 (0.1%)
    Facial bones fracture 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Fall 0/383 (0%) 2/384 (0.5%) 1/123 (0.8%) 3/890 (0.3%)
    Femoral neck fracture 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Femur fracture 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Foot fracture 3/383 (0.8%) 0/384 (0%) 0/123 (0%) 3/890 (0.3%)
    Graft thrombosis 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Haemodialysis-induced symptom 0/383 (0%) 0/384 (0%) 1/123 (0.8%) 1/890 (0.1%)
    Hip fracture 1/383 (0.3%) 0/384 (0%) 1/123 (0.8%) 2/890 (0.2%)
    Humerus fracture 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Intentional overdose 0/383 (0%) 0/384 (0%) 1/123 (0.8%) 1/890 (0.1%)
    Jaw fracture 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Lower limb fracture 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Lumbar vertebral fracture 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Multiple fractures 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Patella fracture 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Peripheral arterial reocclusion 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Perirenal haematoma 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Post procedural complication 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Post procedural haematoma 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Postoperative respiratory failure 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Procedural hypotension 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Radius fracture 0/383 (0%) 2/384 (0.5%) 0/123 (0%) 2/890 (0.2%)
    Shunt stenosis 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Shunt thrombosis 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Soft tissue injury 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Splenic injury 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Stoma site pain 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Subdural haematoma 1/383 (0.3%) 1/384 (0.3%) 0/123 (0%) 2/890 (0.2%)
    Thermal burn 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Tibia fracture 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Toxicity to various agents 0/383 (0%) 0/384 (0%) 1/123 (0.8%) 1/890 (0.1%)
    Vascular access complication 0/383 (0%) 2/384 (0.5%) 0/123 (0%) 2/890 (0.2%)
    Vascular graft complication 0/383 (0%) 2/384 (0.5%) 2/123 (1.6%) 4/890 (0.4%)
    Vascular graft thrombosis 4/383 (1%) 2/384 (0.5%) 2/123 (1.6%) 8/890 (0.9%)
    Vascular pseudoaneurysm 1/383 (0.3%) 1/384 (0.3%) 0/123 (0%) 2/890 (0.2%)
    Wound 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Wound complication 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Wound dehiscence 0/383 (0%) 0/384 (0%) 1/123 (0.8%) 1/890 (0.1%)
    Wound haemorrhage 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Investigations
    Alanine aminotransferase increased 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Anticoagulation drug level below therapeutic 1/383 (0.3%) 0/384 (0%) 1/123 (0.8%) 2/890 (0.2%)
    Aspartate aminotransferase increased 2/383 (0.5%) 0/384 (0%) 0/123 (0%) 2/890 (0.2%)
    Bilirubin conjugated increased 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Blood alkaline phosphatase increased 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Blood bilirubin increased 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Blood calcium decreased 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Blood pressure increased 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Hepatitis C antibody positive 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    International normalised ratio increased 1/383 (0.3%) 1/384 (0.3%) 0/123 (0%) 2/890 (0.2%)
    Troponin increased 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Weight decreased 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Metabolism and nutrition disorders
    Dehydration 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Diabetes mellitus 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Diabetic ketoacidosis 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Failure to thrive 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Fluid overload 3/383 (0.8%) 8/384 (2.1%) 4/123 (3.3%) 15/890 (1.7%)
    Hyperkalaemia 14/383 (3.7%) 10/384 (2.6%) 5/123 (4.1%) 29/890 (3.3%)
    Hypervolaemia 1/383 (0.3%) 1/384 (0.3%) 0/123 (0%) 2/890 (0.2%)
    Hypocalcaemia 2/383 (0.5%) 0/384 (0%) 0/123 (0%) 2/890 (0.2%)
    Hypoglycaemia 5/383 (1.3%) 4/384 (1%) 1/123 (0.8%) 10/890 (1.1%)
    Hypophosphataemia 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Malnutrition 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Metabolic acidosis 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/383 (0%) 1/384 (0.3%) 1/123 (0.8%) 2/890 (0.2%)
    Arthritis 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Bone pain 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Bursitis 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Flank pain 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Joint swelling 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Musculoskeletal chest pain 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Musculoskeletal pain 0/383 (0%) 2/384 (0.5%) 0/123 (0%) 2/890 (0.2%)
    Neuropathic arthropathy 0/383 (0%) 0/384 (0%) 1/123 (0.8%) 1/890 (0.1%)
    Osteoarthritis 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Pain in extremity 1/383 (0.3%) 1/384 (0.3%) 0/123 (0%) 2/890 (0.2%)
    Rhabdomyolysis 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Rotator cuff syndrome 0/383 (0%) 0/384 (0%) 1/123 (0.8%) 1/890 (0.1%)
    Spinal osteoarthritis 2/383 (0.5%) 0/384 (0%) 0/123 (0%) 2/890 (0.2%)
    Spinal pain 2/383 (0.5%) 0/384 (0%) 0/123 (0%) 2/890 (0.2%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma of colon 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Bladder adenocarcinoma stage unspecified 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Breast cancer 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Clear cell renal cell carcinoma 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Colon cancer stage II 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Lung cancer metastatic 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Metastases to spine 2/383 (0.5%) 0/384 (0%) 0/123 (0%) 2/890 (0.2%)
    Neoplasm malignant 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Pancreatic carcinoma 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Prostate cancer 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Sarcoma 0/383 (0%) 0/384 (0%) 1/123 (0.8%) 1/890 (0.1%)
    Squamous cell carcinoma of skin 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Thyroid neoplasm 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Nervous system disorders
    Altered state of consciousness 0/383 (0%) 2/384 (0.5%) 0/123 (0%) 2/890 (0.2%)
    Ataxia 0/383 (0%) 0/384 (0%) 1/123 (0.8%) 1/890 (0.1%)
    Carotid artery stenosis 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Cerebral haemorrhage 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Cerebral infarction 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Cerebrovascular accident 3/383 (0.8%) 1/384 (0.3%) 0/123 (0%) 4/890 (0.4%)
    Dizziness 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Encephalopathy 0/383 (0%) 3/384 (0.8%) 1/123 (0.8%) 4/890 (0.4%)
    Generalised tonic-clonic seizure 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Haemorrhage intracranial 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Headache 2/383 (0.5%) 0/384 (0%) 0/123 (0%) 2/890 (0.2%)
    Hemiparesis 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Hypoaesthesia 0/383 (0%) 2/384 (0.5%) 0/123 (0%) 2/890 (0.2%)
    Hypoxic-ischaemic encephalopathy 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Loss of consciousness 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Meralgia paraesthetica 0/383 (0%) 0/384 (0%) 1/123 (0.8%) 1/890 (0.1%)
    Metabolic encephalopathy 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Migraine 0/383 (0%) 0/384 (0%) 1/123 (0.8%) 1/890 (0.1%)
    Presyncope 0/383 (0%) 2/384 (0.5%) 0/123 (0%) 2/890 (0.2%)
    Seizure 3/383 (0.8%) 1/384 (0.3%) 0/123 (0%) 4/890 (0.4%)
    Subarachnoid haemorrhage 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Syncope 6/383 (1.6%) 2/384 (0.5%) 3/123 (2.4%) 11/890 (1.2%)
    Transient ischaemic attack 1/383 (0.3%) 1/384 (0.3%) 0/123 (0%) 2/890 (0.2%)
    Tremor 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Psychiatric disorders
    Confusional state 2/383 (0.5%) 0/384 (0%) 0/123 (0%) 2/890 (0.2%)
    Delirium 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Depression 0/383 (0%) 2/384 (0.5%) 1/123 (0.8%) 3/890 (0.3%)
    Depression suicidal 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Hallucination, visual 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Mental status changes 6/383 (1.6%) 0/384 (0%) 2/123 (1.6%) 8/890 (0.9%)
    Renal and urinary disorders
    Azotaemia 2/383 (0.5%) 2/384 (0.5%) 0/123 (0%) 4/890 (0.4%)
    Chronic kidney disease 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Haematuria 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Nephrolithiasis 0/383 (0%) 1/384 (0.3%) 1/123 (0.8%) 2/890 (0.2%)
    Nephrosclerosis 0/383 (0%) 0/384 (0%) 1/123 (0.8%) 1/890 (0.1%)
    Renal colic 0/383 (0%) 0/384 (0%) 1/123 (0.8%) 1/890 (0.1%)
    Renal cyst haemorrhage 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Renal impairment 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Reproductive system and breast disorders
    Benign prostatic hyperplasia 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Menorrhagia 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Pelvic haemorrhage 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Postmenopausal haemorrhage 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema 1/383 (0.3%) 1/384 (0.3%) 0/123 (0%) 2/890 (0.2%)
    Acute respiratory failure 2/383 (0.5%) 1/384 (0.3%) 0/123 (0%) 3/890 (0.3%)
    Aspiration 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Asthma 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Bronchospasm 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Chronic obstructive pulmonary disease 1/383 (0.3%) 1/384 (0.3%) 0/123 (0%) 2/890 (0.2%)
    Cough 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Dyspnoea 0/383 (0%) 3/384 (0.8%) 1/123 (0.8%) 4/890 (0.4%)
    Dyspnoea exertional 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Epistaxis 1/383 (0.3%) 1/384 (0.3%) 1/123 (0.8%) 3/890 (0.3%)
    Hypoxia 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Pleural effusion 2/383 (0.5%) 2/384 (0.5%) 0/123 (0%) 4/890 (0.4%)
    Pneumonia aspiration 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Pulmonary cavitation 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Pulmonary congestion 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Pulmonary embolism 1/383 (0.3%) 2/384 (0.5%) 1/123 (0.8%) 4/890 (0.4%)
    Pulmonary infarction 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Pulmonary mass 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Pulmonary oedema 1/383 (0.3%) 3/384 (0.8%) 0/123 (0%) 4/890 (0.4%)
    Respiratory arrest 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Respiratory failure 3/383 (0.8%) 2/384 (0.5%) 0/123 (0%) 5/890 (0.6%)
    Stridor 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Throat tightness 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Skin and subcutaneous tissue disorders
    Angioedema 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Decubitus ulcer 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Diabetic foot 1/383 (0.3%) 2/384 (0.5%) 2/123 (1.6%) 5/890 (0.6%)
    Henoch-Schonlein purpura 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Purpura 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Skin ulcer 1/383 (0.3%) 5/384 (1.3%) 0/123 (0%) 6/890 (0.7%)
    Vasculitic rash 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Surgical and medical procedures
    Arteriovenous graft 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Therapy cessation 0/383 (0%) 0/384 (0%) 1/123 (0.8%) 1/890 (0.1%)
    Vascular disorders
    Aortic aneurysm 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Aortic stenosis 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Arterial occlusive disease 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Deep vein thrombosis 2/383 (0.5%) 0/384 (0%) 0/123 (0%) 2/890 (0.2%)
    Dry gangrene 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Extremity necrosis 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Haematoma 2/383 (0.5%) 0/384 (0%) 0/123 (0%) 2/890 (0.2%)
    Haemorrhage 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Hypertension 5/383 (1.3%) 4/384 (1%) 1/123 (0.8%) 10/890 (1.1%)
    Hypertensive crisis 0/383 (0%) 1/384 (0.3%) 1/123 (0.8%) 2/890 (0.2%)
    Hypertensive emergency 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Hypotension 5/383 (1.3%) 4/384 (1%) 2/123 (1.6%) 11/890 (1.2%)
    Jugular vein thrombosis 0/383 (0%) 0/384 (0%) 1/123 (0.8%) 1/890 (0.1%)
    Malignant hypertension 0/383 (0%) 2/384 (0.5%) 0/123 (0%) 2/890 (0.2%)
    Orthostatic hypotension 1/383 (0.3%) 0/384 (0%) 1/123 (0.8%) 2/890 (0.2%)
    Peripheral arterial occlusive disease 2/383 (0.5%) 1/384 (0.3%) 1/123 (0.8%) 4/890 (0.4%)
    Peripheral vascular disorder 2/383 (0.5%) 4/384 (1%) 0/123 (0%) 6/890 (0.7%)
    Shock haemorrhagic 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Steal syndrome 1/383 (0.3%) 0/384 (0%) 0/123 (0%) 1/890 (0.1%)
    Vasculitis 0/383 (0%) 1/384 (0.3%) 0/123 (0%) 1/890 (0.1%)
    Other (Not Including Serious) Adverse Events
    20120229 / 20120230 Placebo 20120229 / 20120230 Etelcalcetide 20120359 Etelcalcetide Total
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 289/383 (75.5%) 249/384 (64.8%) 75/123 (61%) 613/890 (68.9%)
    Gastrointestinal disorders
    Abdominal pain 22/383 (5.7%) 12/384 (3.1%) 3/123 (2.4%) 37/890 (4.2%)
    Diarrhoea 41/383 (10.7%) 46/384 (12%) 8/123 (6.5%) 95/890 (10.7%)
    Nausea 43/383 (11.2%) 27/384 (7%) 13/123 (10.6%) 83/890 (9.3%)
    Vomiting 40/383 (10.4%) 37/384 (9.6%) 11/123 (8.9%) 88/890 (9.9%)
    Infections and infestations
    Bronchitis 20/383 (5.2%) 6/384 (1.6%) 2/123 (1.6%) 28/890 (3.1%)
    Nasopharyngitis 19/383 (5%) 21/384 (5.5%) 3/123 (2.4%) 43/890 (4.8%)
    Upper respiratory tract infection 20/383 (5.2%) 14/384 (3.6%) 20/123 (16.3%) 54/890 (6.1%)
    Injury, poisoning and procedural complications
    Arteriovenous fistula site complication 22/383 (5.7%) 27/384 (7%) 8/123 (6.5%) 57/890 (6.4%)
    Fall 22/383 (5.7%) 14/384 (3.6%) 6/123 (4.9%) 42/890 (4.7%)
    Procedural hypotension 17/383 (4.4%) 8/384 (2.1%) 8/123 (6.5%) 33/890 (3.7%)
    Investigations
    Blood calcium decreased 226/383 (59%) 129/384 (33.6%) 30/123 (24.4%) 385/890 (43.3%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 19/383 (5%) 18/384 (4.7%) 10/123 (8.1%) 47/890 (5.3%)
    Back pain 26/383 (6.8%) 20/384 (5.2%) 4/123 (3.3%) 50/890 (5.6%)
    Muscle spasms 36/383 (9.4%) 33/384 (8.6%) 10/123 (8.1%) 79/890 (8.9%)
    Pain in extremity 16/383 (4.2%) 23/384 (6%) 6/123 (4.9%) 45/890 (5.1%)
    Nervous system disorders
    Headache 25/383 (6.5%) 25/384 (6.5%) 2/123 (1.6%) 52/890 (5.8%)
    Psychiatric disorders
    Anxiety 8/383 (2.1%) 10/384 (2.6%) 7/123 (5.7%) 25/890 (2.8%)
    Respiratory, thoracic and mediastinal disorders
    Cough 21/383 (5.5%) 20/384 (5.2%) 13/123 (10.6%) 54/890 (6.1%)
    Dyspnoea 24/383 (6.3%) 17/384 (4.4%) 5/123 (4.1%) 46/890 (5.2%)
    Vascular disorders
    Hypertension 30/383 (7.8%) 18/384 (4.7%) 10/123 (8.1%) 58/890 (6.5%)
    Hypotension 36/383 (9.4%) 25/384 (6.5%) 5/123 (4.1%) 66/890 (7.4%)

    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.

    Results Point of Contact

    Name/Title Study Director
    Organization Amgen Inc.
    Phone 866-572-6436
    Email
    Responsible Party:
    Amgen
    ClinicalTrials.gov Identifier:
    NCT01785875
    Other Study ID Numbers:
    • 20120231
    • KAI-4169-008
    • 2012-002808-41
    First Posted:
    Feb 7, 2013
    Last Update Posted:
    Apr 10, 2019
    Last Verified:
    Apr 1, 2019