Trial Outcomes & Findings for A Phase 1 Study to Evaluate PK, Safety and Tolerability of AMG 416 (NCT NCT03283098)
NCT ID: NCT03283098
Last Updated: 2020-02-10
Results Overview
Tmax is the time to maximum drug concentration of plasma etelcalcetide after dosing on Days 1 and 27.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
33 participants
Primary outcome timeframe
Days 1 and 27; PK blood sampling predialysis, and at 10, 30, 60, 90 min postdose, as well as on Day 2 and 28 between 18 and 30 hours after study drug administration
Results posted on
2020-02-10
Participant Flow
This study was conducted at 5 centers in China.
Of the 37 subjects screened, 33 participants were randomized in a 3:1 ratio to either etelcalcetide or placebo in a double-blind manner prior to the Day 1 activities.
Participant milestones
| Measure |
Placebo
Intravenous (IV) administration of placebo three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27) . Participants were followed for an additional 4 weeks.
|
Etelcalcetide
5 mg intravenous (IV) dose of etelcalcetide three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27). Participants were followed for an additional 4 weeks.
|
|---|---|---|
|
Overall Study
STARTED
|
8
|
25
|
|
Overall Study
COMPLETED
|
8
|
24
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
Reasons for withdrawal
| Measure |
Placebo
Intravenous (IV) administration of placebo three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27) . Participants were followed for an additional 4 weeks.
|
Etelcalcetide
5 mg intravenous (IV) dose of etelcalcetide three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27). Participants were followed for an additional 4 weeks.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
Baseline Characteristics
A Phase 1 Study to Evaluate PK, Safety and Tolerability of AMG 416
Baseline characteristics by cohort
| Measure |
Placebo
n=8 Participants
Intravenous (IV) administration of placebo three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27) . Participants were followed for an additional 4 weeks.
|
Etelcalcetide
n=25 Participants
5 mg intravenous (IV) dose of etelcalcetide three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27). Participants were followed for an additional 4 weeks.
|
Total
n=33 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
49.8 years
STANDARD_DEVIATION 12.5 • n=99 Participants
|
50.2 years
STANDARD_DEVIATION 11.4 • n=107 Participants
|
50.1 years
STANDARD_DEVIATION 11.5 • n=206 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=99 Participants
|
10 Participants
n=107 Participants
|
13 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=99 Participants
|
15 Participants
n=107 Participants
|
20 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
8 Participants
n=99 Participants
|
25 Participants
n=107 Participants
|
33 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Height
|
167.54 cm
STANDARD_DEVIATION 8.17 • n=99 Participants
|
164.48 cm
STANDARD_DEVIATION 7.68 • n=107 Participants
|
165.22 cm
STANDARD_DEVIATION 7.79 • n=206 Participants
|
|
Weight
|
65.74 kg
STANDARD_DEVIATION 8.45 • n=99 Participants
|
67.71 kg
STANDARD_DEVIATION 13.53 • n=107 Participants
|
67.24 kg
STANDARD_DEVIATION 12.40 • n=206 Participants
|
|
Body Mass Index (BMI)
|
23.64 kg/m^2
STANDARD_DEVIATION 3.03 • n=99 Participants
|
24.98 kg/m^2
STANDARD_DEVIATION 4.03 • n=107 Participants
|
24.65 kg/m^2
STANDARD_DEVIATION 3.81 • n=206 Participants
|
|
Systolic Blood Pressure
|
139.25 mmHg
STANDARD_DEVIATION 27.37 • n=99 Participants
|
141.24 mmHg
STANDARD_DEVIATION 19.39 • n=107 Participants
|
140.76 mmHg
STANDARD_DEVIATION 21.13 • n=206 Participants
|
|
Diastolic Blood Pressure
|
80.38 mmHg
STANDARD_DEVIATION 13.54 • n=99 Participants
|
81.68 mmHg
STANDARD_DEVIATION 13.00 • n=107 Participants
|
81.36 mmHg
STANDARD_DEVIATION 12.93 • n=206 Participants
|
|
Intact Parathyroid Hormone (iPTH)
|
74.10 pmol/L
STANDARD_DEVIATION 35.08 • n=99 Participants
|
63.03 pmol/L
STANDARD_DEVIATION 20.10 • n=107 Participants
|
65.72 pmol/L
STANDARD_DEVIATION 24.40 • n=206 Participants
|
|
Corrected Calcium
|
2.57 mmol/L
STANDARD_DEVIATION 0.12 • n=99 Participants
|
2.46 mmol/L
STANDARD_DEVIATION 0.20 • n=107 Participants
|
2.49 mmol/L
STANDARD_DEVIATION 0.19 • n=206 Participants
|
|
Calcium
|
2.57 mmol/L
STANDARD_DEVIATION 0.14 • n=99 Participants
|
2.44 mmol/L
STANDARD_DEVIATION 0.22 • n=107 Participants
|
2.47 mmol/L
STANDARD_DEVIATION 0.21 • n=206 Participants
|
|
Phosphorus
|
2.17 mmol/L
STANDARD_DEVIATION 0.49 • n=99 Participants
|
2.11 mmol/L
STANDARD_DEVIATION 0.58 • n=107 Participants
|
2.13 mmol/L
STANDARD_DEVIATION 0.55 • n=206 Participants
|
|
Potassium
|
4.67 mmol/L
STANDARD_DEVIATION 0.48 • n=99 Participants
|
4.74 mmol/L
STANDARD_DEVIATION 0.80 • n=107 Participants
|
4.72 mmol/L
STANDARD_DEVIATION 0.73 • n=206 Participants
|
PRIMARY outcome
Timeframe: Days 1 and 27; PK blood sampling predialysis, and at 10, 30, 60, 90 min postdose, as well as on Day 2 and 28 between 18 and 30 hours after study drug administrationPopulation: Pharmacokinetic Concentration Analysis Set: all participants who received at least 1 dose of etelcalcetide and had at least 1 pharmacokinetic sample collected.
Tmax is the time to maximum drug concentration of plasma etelcalcetide after dosing on Days 1 and 27.
Outcome measures
| Measure |
Placebo
Intravenous (IV) administration of placebo three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27) . Participants were followed for an additional 4 weeks.
|
Etelcalcetide
n=25 Participants
5 mg intravenous (IV) dose of etelcalcetide three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27). Participants were followed for an additional 4 weeks.
|
|---|---|---|
|
Pharmacokinetic (PK) Parameter: Time to Maximum Drug Concentration (Tmax) of Plasma Etelcalcetide on Days 1 and 27
Day 1
|
—
|
0.22 hour
Interval 0.17 to 0.27
|
|
Pharmacokinetic (PK) Parameter: Time to Maximum Drug Concentration (Tmax) of Plasma Etelcalcetide on Days 1 and 27
Day 27
|
—
|
0.22 hour
Interval 0.17 to 0.25
|
PRIMARY outcome
Timeframe: Days 1 and 27; PK blood sampling predialysis, and at 10, 30, 60, 90 min postdose, as well as on Day 2 and 28 between 18 and 30 hours after study drug administrationPopulation: Pharmacokinetic concentration analysis set
Cmax was defined as the maximum observed plasma drug concentration measured between the time of drug administration to the beginning of the next dialysis session.
Outcome measures
| Measure |
Placebo
Intravenous (IV) administration of placebo three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27) . Participants were followed for an additional 4 weeks.
|
Etelcalcetide
n=25 Participants
5 mg intravenous (IV) dose of etelcalcetide three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27). Participants were followed for an additional 4 weeks.
|
|---|---|---|
|
PK: Maximum Observed Drug Concentration (Cmax) of Plasma Etelcalcetide on Days 1 and 27
Day 27
|
—
|
236 ng/mL
Standard Deviation 53.7
|
|
PK: Maximum Observed Drug Concentration (Cmax) of Plasma Etelcalcetide on Days 1 and 27
Day 1
|
—
|
216 ng/mL
Standard Deviation 157
|
PRIMARY outcome
Timeframe: Days 1 and 27; PK blood sampling predialysis, and up to 44-50 hour postdose.at 10, 30, 60, 90 min postdose: Day 2 and 28 between 18 and 30 hours after study drug administration; Day 3 (predialysis) + Day 29Population: Pharmacokinetic concentration analysis set
AUClast was specifically defined in this study as the area under the concentration time curve measured from the time of drug administration to the beginning of the next dialysis session, following the first and last dose.
Outcome measures
| Measure |
Placebo
Intravenous (IV) administration of placebo three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27) . Participants were followed for an additional 4 weeks.
|
Etelcalcetide
n=25 Participants
5 mg intravenous (IV) dose of etelcalcetide three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27). Participants were followed for an additional 4 weeks.
|
|---|---|---|
|
Pharmacokinetic (PK) Parameter: Area Under the Curve From Time Zero to the Beginning of the Subsequent Hemodialysis Treatment (AUClast) of Plasma Etelcalcetide on Days 1 and 27
Day 1
|
—
|
1110 hour*ng/mL
Standard Deviation 311
|
|
Pharmacokinetic (PK) Parameter: Area Under the Curve From Time Zero to the Beginning of the Subsequent Hemodialysis Treatment (AUClast) of Plasma Etelcalcetide on Days 1 and 27
Day 27
|
—
|
3310 hour*ng/mL
Standard Deviation 893
|
PRIMARY outcome
Timeframe: Days 1 and 27; PK blood sampling predialysis, and up to 44-50 hour postdose.at 10, 30, 60, 90 min postdose: Day 2 and 28 between 18 and 30 hours after study drug administration; Day 3 (predialysis) + Day 29Population: Pharmacokinetic concentration analysis set
Accumulation ratio, calculated as AUClast day 27/AUClast day 1.
Outcome measures
| Measure |
Placebo
Intravenous (IV) administration of placebo three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27) . Participants were followed for an additional 4 weeks.
|
Etelcalcetide
n=25 Participants
5 mg intravenous (IV) dose of etelcalcetide three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27). Participants were followed for an additional 4 weeks.
|
|---|---|---|
|
Pharmacokinetic (PK) Parameter: Accumulation Ratio Comparing Days 1 and 27
|
—
|
3.02 ratio
Standard Deviation 0.607
|
SECONDARY outcome
Timeframe: Day 1 up to Day 55 (end of study)Population: Safety Analysis set containing all participants who received at least 1 dose of investigational product (IP)
The severity of each adverse event was assessed using the NCI-CTCAE Version 4.0 according to the following: * Grade 1 - Mild: Asymptomatic or mild symptoms; intervention not indicated * Grade 2 - Moderate: Minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL) * Grade 3 - Severe: Medically significant but not life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL * Grade 4 - Life-threatening * Grade 5 - Fatal. A serious AE is an AE that met one or more of the following criteria: * Death * Life-threatening * Required inpatient hospitalization or prolongation of an existing hospitalization * Resulted in persistent or significant disability/incapacity * A congenital anomaly/birth defect * Important medical events that required medical or surgical intervention to prevent one of the outcomes above.
Outcome measures
| Measure |
Placebo
n=8 Participants
Intravenous (IV) administration of placebo three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27) . Participants were followed for an additional 4 weeks.
|
Etelcalcetide
n=25 Participants
5 mg intravenous (IV) dose of etelcalcetide three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27). Participants were followed for an additional 4 weeks.
|
|---|---|---|
|
Participants With Treatment-Emergent Adverse Events (TEAEs)
All TEAEs
|
7 Participants
|
25 Participants
|
|
Participants With Treatment-Emergent Adverse Events (TEAEs)
TEAEs Grade >= 3
|
0 Participants
|
5 Participants
|
|
Participants With Treatment-Emergent Adverse Events (TEAEs)
TEAEs Grade >= 4
|
0 Participants
|
1 Participants
|
|
Participants With Treatment-Emergent Adverse Events (TEAEs)
Serious TEAEs
|
0 Participants
|
3 Participants
|
|
Participants With Treatment-Emergent Adverse Events (TEAEs)
TEAEs leading to study treatment discontinuation
|
0 Participants
|
0 Participants
|
|
Participants With Treatment-Emergent Adverse Events (TEAEs)
Fatal TEAEs
|
0 Participants
|
0 Participants
|
|
Participants With Treatment-Emergent Adverse Events (TEAEs)
Treatment-related TEAEs
|
1 Participants
|
18 Participants
|
|
Participants With Treatment-Emergent Adverse Events (TEAEs)
Treatment-related TEAEs Grade >= 3
|
0 Participants
|
1 Participants
|
|
Participants With Treatment-Emergent Adverse Events (TEAEs)
Treatment-related TEAEs Grade >= 4
|
0 Participants
|
0 Participants
|
|
Participants With Treatment-Emergent Adverse Events (TEAEs)
Treatment-related serious TEAEs
|
0 Participants
|
1 Participants
|
|
Participants With Treatment-Emergent Adverse Events (TEAEs)
Trt-related TEAEs leading to study trt discon
|
0 Participants
|
0 Participants
|
|
Participants With Treatment-Emergent Adverse Events (TEAEs)
Treatment-related Fatal TEAEs
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Day 1 up to Day 55 (end of study)Population: Safety Analysis Set
Terms were coded with Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. Narrow search criteria used for both standardized MedDRA queries (SMQ) and events of interest (EOI). One preferred term (PT) could match multiple EOIs. Infusion Reaction EOI counts included only those events which had onset day coinciding with study medication infusion and resolved on the same day or the day after onset.
Outcome measures
| Measure |
Placebo
n=8 Participants
Intravenous (IV) administration of placebo three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27) . Participants were followed for an additional 4 weeks.
|
Etelcalcetide
n=25 Participants
5 mg intravenous (IV) dose of etelcalcetide three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27). Participants were followed for an additional 4 weeks.
|
|---|---|---|
|
Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest
Adynamic bone (EOI)
|
0 Participants
|
0 Participants
|
|
Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest
Cardiac Failure (EOI)
|
0 Participants
|
0 Participants
|
|
Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest
Convulsions (SMQ)
|
0 Participants
|
0 Participants
|
|
Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest
Fractures (EOI)
|
0 Participants
|
0 Participants
|
|
Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest
Hypersensitivity (SMQ)
|
0 Participants
|
5 Participants
|
|
Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest
Dermatitis allergic (PT)
|
0 Participants
|
2 Participants
|
|
Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest
Rash (PT)
|
0 Participants
|
2 Participants
|
|
Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest
Dermatitis (PT)
|
0 Participants
|
1 Participants
|
|
Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest
Hypocalcemia (EOI)
|
0 Participants
|
11 Participants
|
|
Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest
Blood calcium decreased (PT)
|
0 Participants
|
10 Participants
|
|
Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest
Hypocalcaemia (PT)
|
0 Participants
|
2 Participants
|
|
Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest
Hypophosphatemia (EOI)
|
0 Participants
|
0 Participants
|
|
Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest
Infusion reaction (EOI)
|
0 Participants
|
1 Participants
|
|
Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest
Hypotension (PT)
|
0 Participants
|
1 Participants
|
|
Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest
Torsade de pointes-QT prolongation (SMQ)
|
0 Participants
|
0 Participants
|
|
Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest
Ventricular tachyarrhythmias (SMQ)
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline is Day -2; End of Study is Day 55Population: Safety Analysis set of participants with both a baseline and end of study ECG.
Count of participants who exhibited a clinically significant change in the results of their 12-lead electrocardiograms (ECG) when comparing baseline to end of study ECGs.
Outcome measures
| Measure |
Placebo
n=8 Participants
Intravenous (IV) administration of placebo three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27) . Participants were followed for an additional 4 weeks.
|
Etelcalcetide
n=24 Participants
5 mg intravenous (IV) dose of etelcalcetide three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27). Participants were followed for an additional 4 weeks.
|
|---|---|---|
|
Participants With Clinically-Significant Changes in Electrocardiograms (ECGs) From Baseline to End of Study
Normal Baseline / Abnormal End of Study
|
0 Participants
|
2 Participants
|
|
Participants With Clinically-Significant Changes in Electrocardiograms (ECGs) From Baseline to End of Study
Abnormal Baseline / Normal End of Study
|
0 Participants
|
1 Participants
|
|
Participants With Clinically-Significant Changes in Electrocardiograms (ECGs) From Baseline to End of Study
No Change in Baseline to End of Study
|
8 Participants
|
21 Participants
|
SECONDARY outcome
Timeframe: Day 1 up to Day 55Population: Safety Analysis set
Change from baseline in weight measured at visit.
Outcome measures
| Measure |
Placebo
n=8 Participants
Intravenous (IV) administration of placebo three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27) . Participants were followed for an additional 4 weeks.
|
Etelcalcetide
n=25 Participants
5 mg intravenous (IV) dose of etelcalcetide three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27). Participants were followed for an additional 4 weeks.
|
|---|---|---|
|
Change From Baseline to End of Study in Weight
|
1.32 kg
Standard Deviation 0.79
|
0.76 kg
Standard Deviation 1.39
|
SECONDARY outcome
Timeframe: Baseline Day 1 prior to dialysis; End of Study is Day 55Population: Safety Analysis set
Participants remained seated for at least 10 minutes prior to measurement of predialysis heart rate and blood pressure.
Outcome measures
| Measure |
Placebo
n=8 Participants
Intravenous (IV) administration of placebo three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27) . Participants were followed for an additional 4 weeks.
|
Etelcalcetide
n=25 Participants
5 mg intravenous (IV) dose of etelcalcetide three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27). Participants were followed for an additional 4 weeks.
|
|---|---|---|
|
Change From Baseline to End of Study in Systolic and Diastolic Blood Pressures
Systolic Blood Pressure
|
1.1 mmHg
Standard Deviation 15.5
|
6.1 mmHg
Standard Deviation 18.6
|
|
Change From Baseline to End of Study in Systolic and Diastolic Blood Pressures
Diastolic Blood Pressure
|
4.4 mmHg
Standard Deviation 9.2
|
1.5 mmHg
Standard Deviation 11.9
|
SECONDARY outcome
Timeframe: Baseline Day 1 prior to dialysis; End of Study is Day 55Population: Safety Analysis set
Participants remained seated for at least 10 minutes prior to measurement of predialysis heart rate and blood pressure.
Outcome measures
| Measure |
Placebo
n=8 Participants
Intravenous (IV) administration of placebo three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27) . Participants were followed for an additional 4 weeks.
|
Etelcalcetide
n=25 Participants
5 mg intravenous (IV) dose of etelcalcetide three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27). Participants were followed for an additional 4 weeks.
|
|---|---|---|
|
Baseline and Change From Baseline to End of Study in Heart Rate
Baseline
|
79.5 beats/minute
Standard Deviation 8.3
|
82.8 beats/minute
Standard Deviation 13.8
|
|
Baseline and Change From Baseline to End of Study in Heart Rate
Change from Baseline to End of Study
|
-2.9 beats/minute
Standard Deviation 6.5
|
-1.4 beats/minute
Standard Deviation 8.9
|
SECONDARY outcome
Timeframe: Baseline is Day 1 prior to dialysis; End of Study is Day 55Population: Safety Analysis set
Calcium was tested at a central laboratory.
Outcome measures
| Measure |
Placebo
n=8 Participants
Intravenous (IV) administration of placebo three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27) . Participants were followed for an additional 4 weeks.
|
Etelcalcetide
n=25 Participants
5 mg intravenous (IV) dose of etelcalcetide three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27). Participants were followed for an additional 4 weeks.
|
|---|---|---|
|
Change From Baseline to End of Study in Calcium
|
-0.10 mmol/L
Standard Deviation 0.11
|
-0.07 mmol/L
Standard Deviation 0.12
|
SECONDARY outcome
Timeframe: Baseline is the average of Day -2 and Day 1 prior to dialysis; End of Study is Day 55Population: Safety Analysis set
Total serum calcium was corrected if the serum albumin was \< 4 g/dL or 40 g/L, otherwise cCa equals total serum calcium. The correction formula was: Corrected calcium (mg/dL) = Total calcium (mg/dL) + (4 - albumin \[g/dL\]) \* 0.8
Outcome measures
| Measure |
Placebo
n=8 Participants
Intravenous (IV) administration of placebo three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27) . Participants were followed for an additional 4 weeks.
|
Etelcalcetide
n=25 Participants
5 mg intravenous (IV) dose of etelcalcetide three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27). Participants were followed for an additional 4 weeks.
|
|---|---|---|
|
Change From Baseline to End of Study in Corrected Calcium (cCa)
|
-0.08 mmol/L
Standard Deviation 0.10
|
-0.05 mmol/L
Standard Deviation 0.10
|
SECONDARY outcome
Timeframe: Timeframes: Days 8, 15, 22, 27, 29, 34, 41, 55Population: Safety Analysis set
The lowest cCA value for each participant is reported. Total serum calcium was corrected if the serum albumin was \< 4 g/dL or 40 g/L, otherwise cCa equals total serum calcium. The correction formula was: Corrected calcium (mg/dL) = Total calcium (mg/dL) + (4 - albumin \[g/dL\]) \* 0.8
Outcome measures
| Measure |
Placebo
n=8 Participants
Intravenous (IV) administration of placebo three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27) . Participants were followed for an additional 4 weeks.
|
Etelcalcetide
n=25 Participants
5 mg intravenous (IV) dose of etelcalcetide three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27). Participants were followed for an additional 4 weeks.
|
|---|---|---|
|
Participants With Low Corrected Calcium (cCA) By Category
Participants with cCA < 1.75 mmol/L
|
0 Participants
|
0 Participants
|
|
Participants With Low Corrected Calcium (cCA) By Category
Participants with cCA 1.75 to < 1.87 mmol/L
|
0 Participants
|
1 Participants
|
|
Participants With Low Corrected Calcium (cCA) By Category
Participants with cCA 1.87 to < 2.07 mmol/L
|
0 Participants
|
12 Participants
|
SECONDARY outcome
Timeframe: Baseline is the average of Day -2 and Day 1 prior to dialysis; End of Study is Day 55Population: Safety Analysis set
Serum albumin was tested at a central laboratory.
Outcome measures
| Measure |
Placebo
n=8 Participants
Intravenous (IV) administration of placebo three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27) . Participants were followed for an additional 4 weeks.
|
Etelcalcetide
n=25 Participants
5 mg intravenous (IV) dose of etelcalcetide three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27). Participants were followed for an additional 4 weeks.
|
|---|---|---|
|
Baseline and Change From Baseline to End of Study in Serum Albumin
Baseline
|
41.20 g/dL
Standard Deviation 2.37
|
39.37 g/dL
Standard Deviation 2.79
|
|
Baseline and Change From Baseline to End of Study in Serum Albumin
Change from Baseline to End of Study
|
-1.06 g/dL
Standard Deviation 1.81
|
-0.59 g/dL
Standard Deviation 2.13
|
SECONDARY outcome
Timeframe: Baseline is Day 1 prior to dialysis; End of Study is Day 55Population: Safety Analysis set
Serum phosphorus was tested at a central laboratory.
Outcome measures
| Measure |
Placebo
n=8 Participants
Intravenous (IV) administration of placebo three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27) . Participants were followed for an additional 4 weeks.
|
Etelcalcetide
n=25 Participants
5 mg intravenous (IV) dose of etelcalcetide three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27). Participants were followed for an additional 4 weeks.
|
|---|---|---|
|
Change From Baseline to End of Study in Serum Phosphorus
|
-0.03 mmol/L
Standard Deviation 0.53
|
-0.06 mmol/L
Standard Deviation 0.56
|
SECONDARY outcome
Timeframe: Baseline: Day 1 prior to dialysis. Postbaseline: Days 29 and 55 prior to dialysisPopulation: Safety Analysis set
Participants with positive titers for antibodies to etelcalcetide could be asked to return to the clinical research unit to provide additional serum samples.
Outcome measures
| Measure |
Placebo
Intravenous (IV) administration of placebo three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27) . Participants were followed for an additional 4 weeks.
|
Etelcalcetide
n=25 Participants
5 mg intravenous (IV) dose of etelcalcetide three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27). Participants were followed for an additional 4 weeks.
|
|---|---|---|
|
Participants With Anti-etelcalcetide Antibody at Baseline and Postbaseline
Binding antibody positive at or before baseline
|
—
|
1 Participants
|
|
Participants With Anti-etelcalcetide Antibody at Baseline and Postbaseline
Positive postbaseline/negative baseline
|
—
|
0 Participants
|
|
Participants With Anti-etelcalcetide Antibody at Baseline and Postbaseline
Transient, i.e. negative at last timepoint tested
|
—
|
0 Participants
|
Adverse Events
Placebo
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Etelcalcetide
Serious events: 3 serious events
Other events: 22 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=8 participants at risk
Intravenous (IV) administration of placebo three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27) . Participants were followed for an additional 4 weeks.
|
Etelcalcetide
n=25 participants at risk
5 mg intravenous (IV) dose of etelcalcetide three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27). Participants were followed for an additional 4 weeks.
|
|---|---|---|
|
Infections and infestations
Pneumonia
|
0.00%
0/8 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
4.0%
1/25 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
0.00%
0/8 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
4.0%
1/25 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.00%
0/8 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
4.0%
1/25 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
Other adverse events
| Measure |
Placebo
n=8 participants at risk
Intravenous (IV) administration of placebo three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27) . Participants were followed for an additional 4 weeks.
|
Etelcalcetide
n=25 participants at risk
5 mg intravenous (IV) dose of etelcalcetide three times a week (TIW) administered at the end of dialysis for 4 weeks for a total of 12 doses (on Study Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27). Participants were followed for an additional 4 weeks.
|
|---|---|---|
|
Cardiac disorders
Arrhythmia
|
12.5%
1/8 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
0.00%
0/25 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
|
Cardiac disorders
Atrioventricular block first degree
|
0.00%
0/8 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
8.0%
2/25 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
|
Eye disorders
Eye disorder
|
12.5%
1/8 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
0.00%
0/25 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
|
Gastrointestinal disorders
Constipation
|
12.5%
1/8 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
4.0%
1/25 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/8 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
8.0%
2/25 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
|
Injury, poisoning and procedural complications
Contusion
|
12.5%
1/8 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
0.00%
0/25 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
|
Injury, poisoning and procedural complications
Limb injury
|
12.5%
1/8 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
0.00%
0/25 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
|
Investigations
Blood alkaline phosphatase increased
|
12.5%
1/8 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
0.00%
0/25 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
|
Investigations
Blood calcium decreased
|
0.00%
0/8 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
40.0%
10/25 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
|
Metabolism and nutrition disorders
Hyperphosphataemia
|
0.00%
0/8 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
8.0%
2/25 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
|
Metabolism and nutrition disorders
Hypertriglyceridaemia
|
12.5%
1/8 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
0.00%
0/25 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
25.0%
2/8 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
0.00%
0/25 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
|
Metabolism and nutrition disorders
Hypoproteinaemia
|
0.00%
0/8 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
8.0%
2/25 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/8 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
16.0%
4/25 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
12.5%
1/8 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
0.00%
0/25 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
|
Nervous system disorders
Muscle spasticity
|
12.5%
1/8 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
0.00%
0/25 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
|
Nervous system disorders
Somnolence
|
12.5%
1/8 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
4.0%
1/25 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
12.5%
1/8 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
0.00%
0/25 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
|
Skin and subcutaneous tissue disorders
Dermatitis allergic
|
0.00%
0/8 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
8.0%
2/25 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
12.5%
1/8 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
16.0%
4/25 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/8 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
8.0%
2/25 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
|
Vascular disorders
Blood pressure inadequately controlled
|
12.5%
1/8 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
0.00%
0/25 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
|
Vascular disorders
Hypertension
|
0.00%
0/8 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
8.0%
2/25 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
|
Vascular disorders
Hypotension
|
0.00%
0/8 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
16.0%
4/25 • Day 1 up to Day 55 (end of study)
Treatment-emergent adverse events - any adverse events started on or after the first dose of investigational product (IP) up to the end of study date (Day 55).
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER