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Efficacy and Safety of Etelcalcetide (AMG 416) in the Treatment of Secondary Hyperparathyroidism (SHPT) in Patients With Chronic Kidney Disease on Hemodialysis

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ClinicalTrials.gov Identifier: NCT01785849
Recruitment Status : Completed
First Posted : February 7, 2013
Results First Posted : March 27, 2017
Last Update Posted : September 3, 2018
Sponsor:
Information provided by (Responsible Party):
Amgen

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Hyperparathyroidism, Secondary
Interventions Drug: Etelcalcetide
Drug: Placebo
Enrollment 508
Recruitment Details This study was conducted at 111 centers in the US, Canada, Europe, Israel, Russian Federation, and Australia. The first participant was enrolled on 12 March 2013 and the last participant enrolled on 08 November 2013.
Pre-assignment Details Eligible participants were randomized in a 1:1 ratio to etelcalcetide or placebo. Randomization was stratified by mean screening parathyroid hormone (PTH) (< 600 pg/mL, 600 to ≤ 1000 pg/mL, and > 1000 pg/mL), prior cinacalcet use and region (North America or non-North America).
Arm/Group Title Placebo Etelcalcetide
Hide Arm/Group Description Participants received placebo administered by intravenous bolus injection at the end of each hemodialysis session, three times per week (TIW) for 26 weeks. Participants received etelcalcetide administered by intravenous bolus injection at the end of each hemodialysis session, TIW, for 26 weeks. The starting dose was 5 mg and may have been increased at weeks 5, 9, 13 and 17 to achieve a predialysis PTH ≤ 300 pg/mL.
Period Title: Overall Study
Started 254 254
Received Treatment 254 251
Completed 193 220
Not Completed 61 34
Reason Not Completed
Death             7             9
Protocol Specified Criteria             29             1
Withdrawal by Subject             15             12
Sponsor Decision             0             1
Lost to Follow-up             10             11
Arm/Group Title Placebo Etelcalcetide Total
Hide Arm/Group Description Participants received placebo administered by intravenous bolus injection at the end of each hemodialysis session, three times per week (TIW) for 26 weeks. Participants received etelcalcetide administered by intravenous bolus injection at the end of each hemodialysis session, TIW, for 26 weeks. The starting dose was 5 mg and may have been increased at weeks 5, 9, 13 and 17 to achieve a predialysis PTH ≤ 300 pg/mL. Total of all reporting groups
Overall Number of Baseline Participants 254 254 508
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 254 participants 254 participants 508 participants
57.1  (14.5) 58.4  (14.6) 57.7  (14.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 254 participants 254 participants 508 participants
Female
114
  44.9%
103
  40.6%
217
  42.7%
Male
140
  55.1%
151
  59.4%
291
  57.3%
Race  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 254 participants 254 participants 508 participants
American Indian or Alaska Native 0 0 0
Asian 3 5 8
Black (or African American) 69 72 141
Native Hawaiian or Other Pacific Islander 2 0 2
White 175 173 348
Other 4 4 8
Missing 1 0 1
Stratification Factor: Mean Screening Serum Parathyroid Hormone (PTH)   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 254 participants 254 participants 508 participants
< 600 pg/mL 84 87 171
≥ 600 to ≤ 1000 pg/mL 114 115 229
> 1000 pg/mL 56 52 108
[1]
Measure Description: Mean screening parathyroid hormone (PTH) obtained within 2 weeks prior to randomization.
Stratification Factor: Cinacalcet Use Within 8 Weeks of Randomization  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 254 participants 254 participants 508 participants
Yes 34 33 67
No 220 221 441
Stratification Factor: Region  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 254 participants 254 participants 508 participants
North America 129 132 261
Non-North America 125 122 247
Parathyroid Hormone (PTH)  
Mean (Standard Deviation)
Unit of measure:  pg/mL
Number Analyzed 254 participants 254 participants 508 participants
819.7  (386.0) 848.7  (520.4) 834.2  (457.9)
Phosphorus   [1] 
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 254 participants 254 participants 508 participants
5.78  (1.60) 5.95  (1.59) 5.87  (1.59)
[1]
Measure Description: Data were available for 250 subjects in each treatment group.
Corrected Calcium  
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 254 participants 254 participants 508 participants
9.61  (0.60) 9.65  (0.66) 9.63  (0.63)
Corrected Calcium Phosphorus Product (cCa x P)   [1] 
Mean (Standard Deviation)
Unit of measure:  mg²/dL²
Number Analyzed 254 participants 254 participants 508 participants
55.54  (15.81) 57.37  (15.51) 56.46  (15.67)
[1]
Measure Description: Data were available for 249 and 250 subjects in each treatment group respectively.
1.Primary Outcome
Title Percentage of Participants With a > 30% Decrease From Baseline in Mean PTH During the Efficacy Assessment Phase
Hide Description Participants who did not have any scheduled assessments during the EAP were considered non-responders.
Time Frame Baseline and the efficacy assessment phase (EAP; defined as Weeks 20 to 27, inclusive).
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The full analysis set, consisting of all randomized participants
Arm/Group Title Placebo Etelcalcetide
Hide Arm/Group Description:
Participants received placebo administered by intravenous bolus injection at the end of each hemodialysis session, three times per week (TIW) for 26 weeks.
Participants received etelcalcetide administered by intravenous bolus injection at the end of each hemodialysis session, TIW, for 26 weeks. The starting dose was 5 mg and may have been increased at weeks 5, 9, 13 and 17 to achieve a predialysis PTH ≤ 300 pg/mL.
Overall Number of Participants Analyzed 254 254
Measure Type: Number
Unit of Measure: percentage of participants
8.3 74.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Etelcalcetide
Comments A Cochran-Mantel-Haenszel test stratified by screening PTH category (< 600, ≥ 600 to ≤ 1000, and > 1000 pg/mL), recent cinacalcet use within 8 weeks before randomization (yes and no), and region (North America and non-North America) was used to compare the primary endpoint of proportion of participants with > 30% reduction from baseline in PTH during the EAP between etelcalcetide and placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 32.46
Confidence Interval (2-Sided) 95%
18.71 to 56.31
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Participants With Mean Predialysis Parathyroid Hormone ≤ 300 pg/mL During the Efficacy Assessment Phase
Hide Description Participants who had no scheduled assessments during the EAP were considered non-responders.
Time Frame Baseline and the efficacy assessment phase (Week 20 to Week 27)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Etelcalcetide
Hide Arm/Group Description:
Participants received placebo administered by intravenous bolus injection at the end of each hemodialysis session, three times per week (TIW) for 26 weeks.
Participants received etelcalcetide administered by intravenous bolus injection at the end of each hemodialysis session, TIW, for 26 weeks. The starting dose was 5 mg and may have been increased at weeks 5, 9, 13 and 17 to achieve a predialysis PTH ≤ 300 pg/mL.
Overall Number of Participants Analyzed 254 254
Measure Type: Number
Unit of Measure: percentage of participants
5.1 49.6
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Etelcalcetide
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test stratified by screening PTH category, recent cinacalcet use within 8 weeks before randomization, and region.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 22.08
Confidence Interval (2-Sided) 95%
11.47 to 42.48
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percent Change From Baseline in Predialysis PTH During the Efficacy Assessment Phase
Hide Description [Not Specified]
Time Frame Baseline and the Efficacy Assessment Phase (Week 20 to Week 27)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set participants with observed data
Arm/Group Title Placebo Etelcalcetide
Hide Arm/Group Description:
Participants received placebo administered by intravenous bolus injection at the end of each hemodialysis session, three times per week (TIW) for 26 weeks.
Participants received etelcalcetide administered by intravenous bolus injection at the end of each hemodialysis session, TIW, for 26 weeks. The starting dose was 5 mg and may have been increased at weeks 5, 9, 13 and 17 to achieve a predialysis PTH ≤ 300 pg/mL.
Overall Number of Participants Analyzed 219 229
Mean (Standard Error)
Unit of Measure: percent change
13.00  (2.81) -55.11  (1.94)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Etelcalcetide
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Repeated Measures Mixed Effects Model
Comments Repeated measures mixed-effects model included treatment, stratification factors, visit, and treatment by visit interaction as covariates.
Method of Estimation Estimation Parameter Mean Difference
Estimated Value -71.11
Confidence Interval (2-Sided) 95%
-77.77 to -64.46
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.39
Estimation Comments Etelcalcetide - Placebo
4.Secondary Outcome
Title Percent Change From Baseline in Predialysis Corrected Calcium During the Efficacy Assessment Phase
Hide Description [Not Specified]
Time Frame Baseline and the efficacy assessment phase (Week 20 to Week 27)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set participants with observed data
Arm/Group Title Placebo Etelcalcetide
Hide Arm/Group Description:
Participants received placebo administered by intravenous bolus injection at the end of each hemodialysis session, three times per week (TIW) for 26 weeks.
Participants received etelcalcetide administered by intravenous bolus injection at the end of each hemodialysis session, TIW, for 26 weeks. The starting dose was 5 mg and may have been increased at weeks 5, 9, 13 and 17 to achieve a predialysis PTH ≤ 300 pg/mL.
Overall Number of Participants Analyzed 219 229
Mean (Standard Error)
Unit of Measure: percent change
1.18  (0.29) -7.29  (0.53)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Etelcalcetide
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Repeated Measures Mixed Effects Model
Comments Repeated measures mixed-effects model included treatment, stratification factors, visit, and treatment by visit interaction as covariates.
Method of Estimation Estimation Parameter Mean Difference
Estimated Value -8.38
Confidence Interval (2-Sided) 95%
-9.52 to -7.23
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.58
Estimation Comments Etelcalcetide - Placebo
5.Secondary Outcome
Title Percent Change From Baseline in Predialysis Corrected Calcium Phosphorus Product During the Efficacy Assessment Phase
Hide Description [Not Specified]
Time Frame Baseline and the efficacy assessment phase (Week 20 to Week 27)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set participants with observed data
Arm/Group Title Placebo Etelcalcetide
Hide Arm/Group Description:
Participants received placebo administered by intravenous bolus injection at the end of each hemodialysis session, three times per week (TIW) for 26 weeks.
Participants received etelcalcetide administered by intravenous bolus injection at the end of each hemodialysis session, TIW, for 26 weeks. The starting dose was 5 mg and may have been increased at weeks 5, 9, 13 and 17 to achieve a predialysis PTH ≤ 300 pg/mL.
Overall Number of Participants Analyzed 213 227
Mean (Standard Error)
Unit of Measure: percent change
-0.19  (1.44) -14.34  (2.06)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Etelcalcetide
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Repeated Measures Mixed Effects Model
Comments Repeated measures mixed-effects model included treatment, stratification factors, visit, and treatment by visit interaction as covariates.
Method of Estimation Estimation Parameter Mean Difference
Estimated Value -14.99
Confidence Interval (2-Sided) 95%
-19.73 to -10.25
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.41
Estimation Comments Etelcalcetide - Placebo
6.Secondary Outcome
Title Percent Change From Baseline in Predialysis Phosphorus During the Efficacy Assessment Phase
Hide Description [Not Specified]
Time Frame Baseline and the efficacy assessment phase (Week 20 to Week 27)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set participants with observed data
Arm/Group Title Placebo Etelcalcetide
Hide Arm/Group Description:
Participants received placebo administered by intravenous bolus injection at the end of each hemodialysis session, three times per week (TIW) for 26 weeks.
Participants received etelcalcetide administered by intravenous bolus injection at the end of each hemodialysis session, TIW, for 26 weeks. The starting dose was 5 mg and may have been increased at weeks 5, 9, 13 and 17 to achieve a predialysis PTH ≤ 300 pg/mL.
Overall Number of Participants Analyzed 214 227
Mean (Standard Deviation)
Unit of Measure: percent change
-1.31  (1.42) -7.71  (2.16)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Etelcalcetide
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments [Not Specified]
Method Repeated Measures Mixed Effects Model
Comments Repeated measures mixed-effects model included treatment, stratification factors, visit, and treatment by visit interaction as covariates.
Method of Estimation Estimation Parameter Mean Difference
Estimated Value -7.45
Confidence Interval (2-Sided) 95%
-12.31 to -2.59
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.47
Estimation Comments Etelcalcetide - Placebo
Time Frame From Day 1 until 30 days after the last dose; the treatment period was 26 weeks.
Adverse Event Reporting Description Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
 
Arm/Group Title Placebo Etelcalcetide
Hide Arm/Group Description Participants received placebo administered by intravenous bolus injection at the end of each hemodialysis session, three times per week (TIW) for 26 weeks. Participants received etelcalcetide administered by intravenous bolus injection at the end of each hemodialysis session, TIW, for 26 weeks. The starting dose was 5 mg and may have been increased at weeks 5, 9, 13 and 17 to achieve a predialysis PTH ≤ 300 pg/mL.
All-Cause Mortality
Placebo Etelcalcetide
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Etelcalcetide
Affected / at Risk (%) Affected / at Risk (%)
Total   78/254 (30.71%)   68/251 (27.09%) 
Blood and lymphatic system disorders     
Anaemia  1  4/254 (1.57%)  0/251 (0.00%) 
Bone marrow failure  1  1/254 (0.39%)  0/251 (0.00%) 
Nephrogenic anaemia  1  1/254 (0.39%)  0/251 (0.00%) 
Cardiac disorders     
Angina pectoris  1  1/254 (0.39%)  6/251 (2.39%) 
Angina unstable  1  1/254 (0.39%)  0/251 (0.00%) 
Aortic valve stenosis  1  0/254 (0.00%)  2/251 (0.80%) 
Atrial fibrillation  1  4/254 (1.57%)  3/251 (1.20%) 
Atrial flutter  1  1/254 (0.39%)  1/251 (0.40%) 
Atrioventricular block first degree  1  1/254 (0.39%)  0/251 (0.00%) 
Bradyarrhythmia  1  1/254 (0.39%)  0/251 (0.00%) 
Cardiac arrest  1  1/254 (0.39%)  1/251 (0.40%) 
Cardiac failure  1  1/254 (0.39%)  2/251 (0.80%) 
Cardiac failure congestive  1  1/254 (0.39%)  3/251 (1.20%) 
Cardiogenic shock  1  0/254 (0.00%)  1/251 (0.40%) 
Cardiomyopathy  1  1/254 (0.39%)  0/251 (0.00%) 
Coronary artery disease  1  2/254 (0.79%)  2/251 (0.80%) 
Coronary artery occlusion  1  0/254 (0.00%)  1/251 (0.40%) 
Myocardial infarction  1  1/254 (0.39%)  2/251 (0.80%) 
Myocardial ischaemia  1  1/254 (0.39%)  1/251 (0.40%) 
Supraventricular tachycardia  1  0/254 (0.00%)  1/251 (0.40%) 
Ventricular fibrillation  1  1/254 (0.39%)  0/251 (0.00%) 
Ventricular tachycardia  1  0/254 (0.00%)  1/251 (0.40%) 
Congenital, familial and genetic disorders     
Sickle cell anaemia with crisis  1  1/254 (0.39%)  0/251 (0.00%) 
Eye disorders     
Conjunctivitis allergic  1  1/254 (0.39%)  0/251 (0.00%) 
Gastrointestinal disorders     
Abdominal discomfort  1  0/254 (0.00%)  1/251 (0.40%) 
Abdominal pain  1  2/254 (0.79%)  0/251 (0.00%) 
Abdominal pain upper  1  1/254 (0.39%)  1/251 (0.40%) 
Constipation  1  0/254 (0.00%)  1/251 (0.40%) 
Diarrhoea  1  1/254 (0.39%)  0/251 (0.00%) 
Gastric ulcer  1  0/254 (0.00%)  1/251 (0.40%) 
Gastritis  1  1/254 (0.39%)  0/251 (0.00%) 
Gastrointestinal haemorrhage  1  2/254 (0.79%)  0/251 (0.00%) 
Gastrointestinal telangiectasia  1  1/254 (0.39%)  0/251 (0.00%) 
Gastrooesophageal reflux disease  1  1/254 (0.39%)  0/251 (0.00%) 
Haematochezia  1  1/254 (0.39%)  0/251 (0.00%) 
Impaired gastric emptying  1  0/254 (0.00%)  1/251 (0.40%) 
Large intestine polyp  1  0/254 (0.00%)  1/251 (0.40%) 
Oesophageal ulcer haemorrhage  1  0/254 (0.00%)  1/251 (0.40%) 
Pancreatitis  1  1/254 (0.39%)  1/251 (0.40%) 
Small intestinal obstruction  1  1/254 (0.39%)  0/251 (0.00%) 
Tooth impacted  1  1/254 (0.39%)  0/251 (0.00%) 
Upper gastrointestinal haemorrhage  1  1/254 (0.39%)  0/251 (0.00%) 
Vomiting  1  0/254 (0.00%)  1/251 (0.40%) 
General disorders     
Brain death  1  1/254 (0.39%)  0/251 (0.00%) 
Chills  1  2/254 (0.79%)  0/251 (0.00%) 
Death  1  0/254 (0.00%)  1/251 (0.40%) 
Device issue  1  0/254 (0.00%)  1/251 (0.40%) 
Impaired healing  1  1/254 (0.39%)  0/251 (0.00%) 
Malaise  1  2/254 (0.79%)  0/251 (0.00%) 
Medical device complication  1  0/254 (0.00%)  2/251 (0.80%) 
Non-cardiac chest pain  1  2/254 (0.79%)  3/251 (1.20%) 
Pyrexia  1  3/254 (1.18%)  0/251 (0.00%) 
Thrombosis in device  1  1/254 (0.39%)  0/251 (0.00%) 
Hepatobiliary disorders     
Acute hepatic failure  1  0/254 (0.00%)  1/251 (0.40%) 
Bile duct stone  1  1/254 (0.39%)  1/251 (0.40%) 
Cholangitis  1  0/254 (0.00%)  1/251 (0.40%) 
Cholecystitis  1  1/254 (0.39%)  1/251 (0.40%) 
Cholelithiasis  1  1/254 (0.39%)  0/251 (0.00%) 
Hyperbilirubinaemia  1  0/254 (0.00%)  1/251 (0.40%) 
Ischaemic hepatitis  1  1/254 (0.39%)  0/251 (0.00%) 
Immune system disorders     
Kidney transplant rejection  1  1/254 (0.39%)  0/251 (0.00%) 
Infections and infestations     
Abdominal wall abscess  1  1/254 (0.39%)  0/251 (0.00%) 
Abscess limb  1  1/254 (0.39%)  0/251 (0.00%) 
Arteriovenous graft site infection  1  1/254 (0.39%)  0/251 (0.00%) 
Arthritis bacterial  1  0/254 (0.00%)  1/251 (0.40%) 
Bacteraemia  1  1/254 (0.39%)  0/251 (0.00%) 
Bronchitis  1  0/254 (0.00%)  1/251 (0.40%) 
Cellulitis  1  1/254 (0.39%)  1/251 (0.40%) 
Clostridium difficile infection  1  1/254 (0.39%)  0/251 (0.00%) 
Device related infection  1  0/254 (0.00%)  1/251 (0.40%) 
Diabetic foot infection  1  1/254 (0.39%)  0/251 (0.00%) 
Endocarditis bacterial  1  1/254 (0.39%)  0/251 (0.00%) 
Gangrene  1  1/254 (0.39%)  1/251 (0.40%) 
Gastroenteritis  1  0/254 (0.00%)  2/251 (0.80%) 
H1N1 influenza  1  0/254 (0.00%)  1/251 (0.40%) 
Lobar pneumonia  1  0/254 (0.00%)  1/251 (0.40%) 
Osteomyelitis  1  1/254 (0.39%)  2/251 (0.80%) 
Osteomyelitis acute  1  1/254 (0.39%)  0/251 (0.00%) 
Pneumonia  1  4/254 (1.57%)  6/251 (2.39%) 
Sepsis  1  3/254 (1.18%)  2/251 (0.80%) 
Septic embolus  1  0/254 (0.00%)  1/251 (0.40%) 
Septic shock  1  1/254 (0.39%)  1/251 (0.40%) 
Staphylococcal sepsis  1  1/254 (0.39%)  0/251 (0.00%) 
Subacute endocarditis  1  1/254 (0.39%)  0/251 (0.00%) 
Upper respiratory tract infection  1  0/254 (0.00%)  1/251 (0.40%) 
Urinary tract infection  1  2/254 (0.79%)  1/251 (0.40%) 
Viral upper respiratory tract infection  1  0/254 (0.00%)  1/251 (0.40%) 
Wound infection  1  0/254 (0.00%)  1/251 (0.40%) 
Injury, poisoning and procedural complications     
Ankle fracture  1  1/254 (0.39%)  0/251 (0.00%) 
Arteriovenous fistula site complication  1  0/254 (0.00%)  2/251 (0.80%) 
Arteriovenous fistula thrombosis  1  3/254 (1.18%)  0/251 (0.00%) 
Clavicle fracture  1  1/254 (0.39%)  0/251 (0.00%) 
Concussion  1  1/254 (0.39%)  0/251 (0.00%) 
Femur fracture  1  2/254 (0.79%)  1/251 (0.40%) 
Foot fracture  1  1/254 (0.39%)  0/251 (0.00%) 
Graft haemorrhage  1  0/254 (0.00%)  1/251 (0.40%) 
Hip fracture  1  0/254 (0.00%)  1/251 (0.40%) 
Limb injury  1  1/254 (0.39%)  0/251 (0.00%) 
Pelvic fracture  1  1/254 (0.39%)  0/251 (0.00%) 
Peripheral artery restenosis  1  1/254 (0.39%)  0/251 (0.00%) 
Perirenal haematoma  1  1/254 (0.39%)  0/251 (0.00%) 
Postoperative respiratory distress  1  0/254 (0.00%)  1/251 (0.40%) 
Rib fracture  1  1/254 (0.39%)  0/251 (0.00%) 
Road traffic accident  1  0/254 (0.00%)  1/251 (0.40%) 
Scapula fracture  1  0/254 (0.00%)  1/251 (0.40%) 
Shunt thrombosis  1  0/254 (0.00%)  1/251 (0.40%) 
Subdural haematoma  1  0/254 (0.00%)  1/251 (0.40%) 
Vascular graft complication  1  0/254 (0.00%)  1/251 (0.40%) 
Vascular graft thrombosis  1  1/254 (0.39%)  1/251 (0.40%) 
Wound  1  1/254 (0.39%)  0/251 (0.00%) 
Wound secretion  1  1/254 (0.39%)  0/251 (0.00%) 
Investigations     
Anticoagulation drug level above therapeutic  1  1/254 (0.39%)  0/251 (0.00%) 
Metabolism and nutrition disorders     
Diabetes mellitus inadequate control  1  0/254 (0.00%)  1/251 (0.40%) 
Diabetic ketoacidosis  1  1/254 (0.39%)  0/251 (0.00%) 
Fluid overload  1  5/254 (1.97%)  4/251 (1.59%) 
Hyperglycaemia  1  1/254 (0.39%)  2/251 (0.80%) 
Hyperkalaemia  1  1/254 (0.39%)  4/251 (1.59%) 
Hypervolaemia  1  0/254 (0.00%)  1/251 (0.40%) 
Hypoglycaemia  1  2/254 (0.79%)  2/251 (0.80%) 
Metabolic acidosis  1  0/254 (0.00%)  1/251 (0.40%) 
Musculoskeletal and connective tissue disorders     
Arthritis  1  1/254 (0.39%)  0/251 (0.00%) 
Back pain  1  1/254 (0.39%)  0/251 (0.00%) 
Haemarthrosis  1  1/254 (0.39%)  0/251 (0.00%) 
Lumbar spinal stenosis  1  1/254 (0.39%)  0/251 (0.00%) 
Osteoarthritis  1  1/254 (0.39%)  0/251 (0.00%) 
Spinal pain  1  1/254 (0.39%)  0/251 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Biliary cancer metastatic  1  0/254 (0.00%)  1/251 (0.40%) 
Bone giant cell tumour benign  1  1/254 (0.39%)  0/251 (0.00%) 
Lung neoplasm  1  0/254 (0.00%)  1/251 (0.40%) 
Malignant melanoma  1  0/254 (0.00%)  1/251 (0.40%) 
Nervous system disorders     
Cerebrovascular accident  1  0/254 (0.00%)  1/251 (0.40%) 
Convulsion  1  2/254 (0.79%)  1/251 (0.40%) 
Haemorrhagic cerebral infarction  1  1/254 (0.39%)  0/251 (0.00%) 
Hepatic encephalopathy  1  1/254 (0.39%)  0/251 (0.00%) 
Hypoxic-ischaemic encephalopathy  1  1/254 (0.39%)  0/251 (0.00%) 
Neuropathy peripheral  1  1/254 (0.39%)  0/251 (0.00%) 
Syncope  1  0/254 (0.00%)  1/251 (0.40%) 
Psychiatric disorders     
Anxiety  1  0/254 (0.00%)  1/251 (0.40%) 
Confusional state  1  1/254 (0.39%)  0/251 (0.00%) 
Delirium  1  0/254 (0.00%)  1/251 (0.40%) 
Mental status changes  1  0/254 (0.00%)  1/251 (0.40%) 
Renal and urinary disorders     
Urinary retention  1  0/254 (0.00%)  1/251 (0.40%) 
Reproductive system and breast disorders     
Ovarian cyst  1  2/254 (0.79%)  0/251 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Acute pulmonary oedema  1  1/254 (0.39%)  2/251 (0.80%) 
Acute respiratory distress syndrome  1  0/254 (0.00%)  1/251 (0.40%) 
Asthma  1  0/254 (0.00%)  1/251 (0.40%) 
Chronic obstructive pulmonary disease  1  1/254 (0.39%)  1/251 (0.40%) 
Dyspnoea  1  1/254 (0.39%)  2/251 (0.80%) 
Dyspnoea exertional  1  1/254 (0.39%)  0/251 (0.00%) 
Pleural effusion  1  1/254 (0.39%)  0/251 (0.00%) 
Pulmonary oedema  1  1/254 (0.39%)  1/251 (0.40%) 
Respiratory failure  1  1/254 (0.39%)  0/251 (0.00%) 
Skin and subcutaneous tissue disorders     
Diabetic foot  1  1/254 (0.39%)  0/251 (0.00%) 
Skin ulcer  1  1/254 (0.39%)  1/251 (0.40%) 
Vascular disorders     
Accelerated hypertension  1  1/254 (0.39%)  0/251 (0.00%) 
Aortic stenosis  1  0/254 (0.00%)  1/251 (0.40%) 
Blood pressure fluctuation  1  1/254 (0.39%)  0/251 (0.00%) 
Deep vein thrombosis  1  1/254 (0.39%)  0/251 (0.00%) 
Granulomatosis with polyangiitis  1  0/254 (0.00%)  1/251 (0.40%) 
Haematoma  1  1/254 (0.39%)  0/251 (0.00%) 
Hypertension  1  2/254 (0.79%)  0/251 (0.00%) 
Hypertensive emergency  1  0/254 (0.00%)  1/251 (0.40%) 
Hypotension  1  1/254 (0.39%)  2/251 (0.80%) 
Peripheral arterial occlusive disease  1  2/254 (0.79%)  1/251 (0.40%) 
Peripheral artery stenosis  1  1/254 (0.39%)  0/251 (0.00%) 
Peripheral vascular disorder  1  1/254 (0.39%)  1/251 (0.40%) 
Shock  1  0/254 (0.00%)  1/251 (0.40%) 
Shock haemorrhagic  1  0/254 (0.00%)  1/251 (0.40%) 
Vascular rupture  1  1/254 (0.39%)  0/251 (0.00%) 
Vascular stenosis  1  1/254 (0.39%)  0/251 (0.00%) 
Venous stenosis  1  0/254 (0.00%)  1/251 (0.40%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Etelcalcetide
Affected / at Risk (%) Affected / at Risk (%)
Total   110/254 (43.31%)   194/251 (77.29%) 
Gastrointestinal disorders     
Diarrhoea  1  17/254 (6.69%)  18/251 (7.17%) 
Nausea  1  13/254 (5.12%)  31/251 (12.35%) 
Vomiting  1  18/254 (7.09%)  25/251 (9.96%) 
Infections and infestations     
Nasopharyngitis  1  13/254 (5.12%)  11/251 (4.38%) 
Injury, poisoning and procedural complications     
Arteriovenous fistula site complication  1  14/254 (5.51%)  11/251 (4.38%) 
Investigations     
Blood calcium decreased  1  21/254 (8.27%)  153/251 (60.96%) 
Metabolism and nutrition disorders     
Hypocalcaemia  1  1/254 (0.39%)  18/251 (7.17%) 
Musculoskeletal and connective tissue disorders     
Muscle spasms  1  18/254 (7.09%)  30/251 (11.95%) 
Pain in extremity  1  11/254 (4.33%)  17/251 (6.77%) 
Nervous system disorders     
Headache  1  20/254 (7.87%)  18/251 (7.17%) 
Paraesthesia  1  3/254 (1.18%)  13/251 (5.18%) 
Vascular disorders     
Hypertension  1  16/254 (6.30%)  12/251 (4.78%) 
Hypotension  1  10/254 (3.94%)  14/251 (5.58%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Results Point of Contact
Name/Title: Study Director
Organization: Amgen Inc.
Phone: 866-572-6436
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01785849     History of Changes
Other Study ID Numbers: 20120229
KAI-4169-006 ( Other Identifier: KAI Pharmaceuticals, Inc (wholly owned subsidiary of Amgen Inc.) )
2012-002805-23 ( EudraCT Number )
First Submitted: February 5, 2013
First Posted: February 7, 2013
Results First Submitted: February 7, 2017
Results First Posted: March 27, 2017
Last Update Posted: September 3, 2018