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Safety, Tolerability and Pharmacokinetics of Etelcalcetide in Healthy Male Volunteers

Sponsor
KAI Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT01134549
Collaborator
Nucleus Network Ltd (Other)
32
Enrollment
1
Location
2
Arms
1.7
Duration (Months)
18.7
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to characterize the safety and tolerability of etelcalcetide in healthy young males.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
32 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
A Double-Blind, Randomized, Placebo-Controlled, Rising Single Intravenous Dose Study to Assess the Safety, Tolerability and Pharmacokinetics of KAI-4169 in Healthy Male Volunteers
Study Start Date :
Jun 9, 2010
Actual Primary Completion Date :
Jul 31, 2010
Actual Study Completion Date :
Jul 31, 2010

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: Placebo

Participants received a single dose of placebo intravenous injection.

Drug: Placebo
Administered as a single intravenous (IV) injection
Experimental: Etelcalcetide

Participants received a single dose of etelcalcetide intravenous injection; the starting dose was 0.5 mg.

Drug: Etelcalcetide
Administered as a single intravenous (IV) injection
Other Names:
  • KAI-4169
  • AMG 416
  • Parsabiv™

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With Adverse Events [From the first dose of study drug through 7 days.]

    Secondary Outcome Measures

    1. Percent Change From Baseline in Serum Parathyroid Hormone [Baseline and 10 minutes, 30 minutes, 1 hour, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 36, 42 and 48 hours post-dose]

    2. Percent Change From Baseline in Plasma Ionized Calcium [Baseline and 10 minutes, 30 minutes, 1 hour, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 36, 42 and 48 hours post-dose]

    3. Change From Baseline in Serum Total Calcium [Baseline and 10 minutes, 30 minutes, 1 hour, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 36, 42 and 48 hours post-dose]

    4. Change From Baseline in Serum Corrected Calcium [Baseline and 10 minutes, 30 minutes, 1 hour, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 36, 42 and 48 hours post-dose]

    5. Change From Baseline in Serum Phosphate [Baseline and 10 minutes, 30 minutes, 1 hour, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 36, 42 and 48 hours post-dose]

    6. Percent Change From Baseline in Serum Calcitonin [Baseline and 10 minutes, 30 minutes, 3, 12, 24, and 48 hours post-dose]

    7. Percent Change From Baseline in Serum 1,25 (OH)2 Vitamin D [Baseline and 12, 24, and 48 hours post-dose]

    8. Maximum Observed Concentration (Cmax) for Etelcalcetide [Blood samples for PK assessment were drawn pre-dose, at 5, 10, 15, 20, and 30 minutes, post-dose, and at 1, 1.5, 2, 2.5, 3, 4, 6, 12, 24, 36, and 48 hours after drug administration.]

      Plasma samples were analyzed for levels of etelcalcetide for pharmacokinetic (PK) analysis using a validated liquid chromatography/mass spectrometry (LC/MS) method.

    9. Area Under the Concentration-time Curve Between the Time of Dose and the Last Time Point (AUCall) for Etelcalcetide [Blood samples for PK assessment were drawn pre-dose, at 5, 10, 15, 20, and 30 minutes, post-dose, and at 1, 1.5, 2, 2.5, 3, 4, 6, 12, 24, 36, and 48 hours after drug administration.]

    10. Observed Area Under the Concentration-time Curve Extrapolated to Infinity (AUCINFobs) for Etelcalcetide [Blood samples for PK assessment were drawn pre-dose, at 5, 10, 15, 20, and 30 minutes, post-dose, and at 1, 1.5, 2, 2.5, 3, 4, 6, 12, 24, 36, and 48 hours after drug administration.]

    11. Percent Observed Area Under the Concentration-time Curve Extrapolated to Infinity Resulting From Extrapolation to Concentration of 0 ng/mL (AUC%Extrapobs) [Blood samples for PK assessment were drawn pre-dose, at 5, 10, 15, 20, and 30 minutes, post-dose, and at 1, 1.5, 2, 2.5, 3, 4, 6, 12, 24, 36, and 48 hours after drug administration.]

    12. Terminal Elimination Rate Constant (λz) for Etelcalcetide [Blood samples for PK assessment were drawn pre-dose, at 5, 10, 15, 20, and 30 minutes, post-dose, and at 1, 1.5, 2, 2.5, 3, 4, 6, 12, 24, 36, and 48 hours after drug administration.]

    13. Half-life Associated With the Terminal (Log-linear) Elimination Phase (HLλz) for Etelcalcetide [Blood samples for PK assessment were drawn pre-dose, at 5, 10, 15, 20, and 30 minutes, post-dose, and at 1, 1.5, 2, 2.5, 3, 4, 6, 12, 24, 36, and 48 hours after drug administration.]

    14. Total Body Clearance (CL) for Etelcalcetide [Blood samples for PK assessment were drawn pre-dose, at 5, 10, 15, 20, and 30 minutes, post-dose, and at 1, 1.5, 2, 2.5, 3, 4, 6, 12, 24, 36, and 48 hours after drug administration.]

    15. Volume of Distribution at Steady State for Etelcalcetide [Blood samples for PK assessment were drawn pre-dose, at 5, 10, 15, 20, and 30 minutes, post-dose, and at 1, 1.5, 2, 2.5, 3, 4, 6, 12, 24, 36, and 48 hours after drug administration.]

    16. Number of Participants With Antibodies to Etelcalcetide [Samples for antibody analysis were collected pre-dose and between days 7-12 and days 21-28.]

      Serum samples were analyzed for antibodies against etelcalcetide using a validated enzyme-linked immunosorbent assay (ELISA).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 45 Years
    Sexes Eligible for Study:
    Male
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:

    • Male between 18 and 45 years of age who have provided written informed consent

    • Subject is judged to be in good health based on medical history, physical examination, and routine laboratory tests

    Exclusion Criteria:

    • History or presence of any significant acute or chronic illness (e.g., cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, or neurologic disease) according to the investigator

    • History of any ongoing medical condition requiring treatment with prescription medication

    • History of asthma, severe allergies including skin reactions or prior anaphylactic type reactions

    • Clinically significant abnormalities on screening clinical examination or laboratory safety tests

    • History of drug or alcohol abuse

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Melbourne Victoria Australia

    Sponsors and Collaborators

    • KAI Pharmaceuticals
    • Nucleus Network Ltd

    Investigators

    • Study Director: M D, Amgen

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    KAI Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT01134549
    Other Study ID Numbers:
    • KAI-4169-001
    • 20130107
    First Posted:
    Jun 2, 2010
    Last Update Posted:
    Apr 14, 2017
    Last Verified:
    Feb 1, 2017
    Additional relevant MeSH terms:
    Hyperparathyroidism
    Hyperparathyroidism, Secondary

    Study Results

    Participant Flow

    Recruitment Details This study was conducted at one clinical center in Australia.
    Pre-assignment Detail The study included 4 cohorts: 0.5 mg, 2 mg, 5 mg and 10 mg. Eight participants were enrolled into each cohort and were randomized 6:2 to receive etelcalcetide or placebo.
    Arm/Group Title Pooled Placebo Etelcalcetide 0.5 mg Etelcalcetide 2 mg Etelcalcetide 5 mg Etelcalcetide 10 mg
    Arm/Group Description Participants received a single dose of placebo administered by intravenous injection. Participants received a single dose of 0.5 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 2 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 5 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 10 mg etelcalcetide administered by intravenous injection.
    Period Title: Overall Study
    STARTED 8 6 6 6 6
    COMPLETED 8 6 6 6 6
    NOT COMPLETED 0 0 0 0 0

    Baseline Characteristics

    Arm/Group Title Pooled Placebo Etelcalcetide 0.5 mg Etelcalcetide 2 mg Etelcalcetide 5 mg Etelcalcetide 10 mg Total
    Arm/Group Description Participants received a single dose of placebo administered by intravenous injection. Participants received a single dose of 0.5 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 2 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 5 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 10 mg etelcalcetide administered by intravenous injection. Total of all reporting groups
    Overall Participants 8 6 6 6 6 32
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    22.4
    (3.5)
    27.8
    (8.9)
    26.8
    (4.9)
    24.2
    (4.4)
    26.0
    (6.2)
    25.3
    (5.7)
    Sex: Female, Male (Count of Participants)
    Female
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Male
    8
    100%
    6
    100%
    6
    100%
    6
    100%
    6
    100%
    32
    100%
    Race (Count of Participants)
    White
    6
    75%
    4
    66.7%
    6
    100%
    3
    50%
    4
    66.7%
    23
    71.9%
    Asian
    2
    25%
    2
    33.3%
    0
    0%
    2
    33.3%
    2
    33.3%
    8
    25%
    Other
    0
    0%
    0
    0%
    0
    0%
    1
    16.7%
    0
    0%
    1
    3.1%
    Ethnicity (Count of Participants)
    Hispanic or Latino
    0
    0%
    0
    0%
    1
    16.7%
    0
    0%
    0
    0%
    1
    3.1%
    Not Hispanic or Latino
    8
    100%
    6
    100%
    5
    83.3%
    6
    100%
    6
    100%
    31
    96.9%

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants With Adverse Events
    Description
    Time Frame From the first dose of study drug through 7 days.

    Outcome Measure Data

    Analysis Population Description
    The modified intent-to-treat (MITT) population consisted of all participants who were randomized and received study medication.
    Arm/Group Title Pooled Placebo Etelcalcetide 0.5 mg Etelcalcetide 2 mg Etelcalcetide 5 mg Etelcalcetide 10 mg
    Arm/Group Description Participants received a single dose of placebo administered by intravenous injection. Participants received a single dose of 0.5 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 2 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 5 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 10 mg etelcalcetide administered by intravenous injection.
    Measure Participants 8 6 6 6 6
    Any adverse event
    2
    25%
    0
    0%
    1
    16.7%
    2
    33.3%
    2
    33.3%
    Serious adverse events
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Withdrawals due to adverse events
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Treatment-related adverse events
    0
    0%
    0
    0%
    1
    16.7%
    1
    16.7%
    1
    16.7%
    Deaths
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2. Secondary Outcome
    Title Percent Change From Baseline in Serum Parathyroid Hormone
    Description
    Time Frame Baseline and 10 minutes, 30 minutes, 1 hour, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 36, 42 and 48 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    Modified intent-to-treat population
    Arm/Group Title Pooled Placebo Etelcalcetide 0.5 mg Etelcalcetide 2 mg Etelcalcetide 5 mg Etelcalcetide 10 mg
    Arm/Group Description Participants received a single dose of placebo administered by intravenous injection. Participants received a single dose of 0.5 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 2 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 5 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 10 mg etelcalcetide administered by intravenous injection.
    Measure Participants 8 6 6 6 6
    10 Minutes
    4.57
    (15.42)
    -20.58
    (4.25)
    -45.09
    (9.31)
    -59.38
    (8.89)
    -63.31
    (8.11)
    30 Minutes
    -3.52
    (16.29)
    -21.74
    (9.55)
    -55.42
    (4.31)
    -69.00
    (7.02)
    -72.56
    (6.33)
    1 Hour
    1.11
    (12.85)
    -18.71
    (11.68)
    -47.16
    (7.94)
    -67.72
    (10.84)
    -73.29
    (6.97)
    3 Hours
    1.76
    (26.67)
    -5.95
    (7.62)
    -39.87
    (10.87)
    -62.56
    (13.30)
    -69.70
    (7.62)
    6 Hours
    -2.57
    (30.28)
    7.01
    (10.64)
    -41.56
    (12.03)
    -60.87
    (13.41)
    -66.68
    (10.41)
    9 Hours
    19.87
    (25.16)
    46.50
    (27.97)
    12.54
    (40.52)
    -40.79
    (15.91)
    -54.43
    (12.97)
    12 Hours
    30.49
    (28.14)
    8.07
    (17.54)
    5.04
    (27.93)
    -24.05
    (13.94)
    -40.28
    (19.35)
    15 Hours
    31.97
    (25.22)
    4.17
    (19.38)
    20.06
    (39.27)
    -2.33
    (21.12)
    -24.31
    (17.06)
    18 Hours
    27.21
    (15.21)
    -6.22
    (11.89)
    25.91
    (28.39)
    2.19
    (20.72)
    -15.78
    (13.66)
    21 Hours
    9.65
    (16.08)
    -0.67
    (20.04)
    22.04
    (16.74)
    -2.10
    (25.36)
    -4.02
    (19.11)
    24 Hours
    -9.50
    (16.20)
    -1.72
    (22.40)
    -14.65
    (13.43)
    -19.25
    (17.66)
    -18.34
    (15.17)
    27 Hours
    -21.56
    (11.39)
    -27.97
    (10.32)
    -34.76
    (13.58)
    -49.48
    (12.23)
    -37.15
    (18.99)
    30 Hours
    10.58
    (15.51)
    -8.19
    (14.90)
    1.21
    (21.70)
    -11.15
    (23.59)
    -25.32
    (12.63)
    36 Hours
    25.24
    (20.51)
    18.19
    (25.35)
    20.63
    (34.27)
    17.61
    (37.53)
    1.08
    (27.77)
    42 Hours
    6.15
    (26.47)
    3.28
    (11.15)
    1.49
    (23.88)
    -19.21
    (20.33)
    -29.37
    (21.78)
    48 Hours
    -13.90
    (15.92)
    -10.39
    (12.66)
    -4.86
    (26.04)
    -24.02
    (15.00)
    -10.84
    (20.60)
    3. Secondary Outcome
    Title Percent Change From Baseline in Plasma Ionized Calcium
    Description
    Time Frame Baseline and 10 minutes, 30 minutes, 1 hour, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 36, 42 and 48 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    Modified intent-to-treat population
    Arm/Group Title Pooled Placebo Etelcalcetide 0.5 mg Etelcalcetide 2 mg Etelcalcetide 5 mg Etelcalcetide 10 mg
    Arm/Group Description Participants received a single dose of placebo administered by intravenous injection. Participants received a single dose of 0.5 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 2 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 5 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 10 mg etelcalcetide administered by intravenous injection.
    Measure Participants 8 6 6 6 6
    10 Minutes
    -1.48
    (3.55)
    0.98
    (2.79)
    -3.94
    (2.33)
    -5.30
    (2.13)
    -2.47
    (2.79)
    30 Minutes
    -1.27
    (3.67)
    -0.51
    (3.54)
    -2.46
    (3.20)
    -6.87
    (2.06)
    1.18
    (2.92)
    1 Hour
    -1.15
    (4.62)
    1.15
    (3.08)
    -4.50
    (2.65)
    -4.12
    (2.08)
    -3.27
    (1.52)
    3 Hours
    -1.72
    (4.85)
    0.73
    (1.40)
    -5.86
    (2.52)
    -6.65
    (2.31)
    -1.83
    (4.07)
    6 Hours
    -1.79
    (3.32)
    -1.36
    (2.66)
    -4.88
    (2.58)
    -9.95
    (1.91)
    -2.84
    (2.67)
    9 Hours
    -4.68
    (3.76)
    -3.39
    (5.00)
    -9.51
    (5.40)
    -16.45
    (2.55)
    -9.54
    (5.32)
    12 Hours
    -7.14
    (3.93)
    -2.83
    (3.22)
    -9.54
    (2.17)
    -15.27
    (1.49)
    -14.92
    (5.47)
    15 Hours
    -3.71
    (4.25)
    -2.53
    (2.98)
    -10.41
    (1.32)
    -15.38
    (3.05)
    -11.74
    (4.08)
    18 Hours
    -3.38
    (4.24)
    -1.62
    (5.07)
    -9.00
    (1.18)
    -14.33
    (2.31)
    -12.34
    (3.27)
    21 Hours
    -1.11
    (3.56)
    3.90
    (3.60)
    -6.38
    (1.74)
    -13.97
    (2.48)
    -11.77
    (1.85)
    24 Hours
    -0.70
    (4.64)
    3.77
    (1.93)
    -2.45
    (1.95)
    -11.83
    (4.46)
    -11.59
    (4.49)
    27 Hours
    -1.78
    (4.12)
    2.62
    (3.73)
    -6.26
    (2.74)
    -7.71
    (2.28)
    -7.89
    (1.46)
    30 Hours
    0.17
    (4.11)
    2.51
    (3.84)
    -5.82
    (2.06)
    -9.65
    (2.73)
    -11.78
    (5.66)
    36 Hours
    -5.02
    (5.40)
    -3.28
    (5.39)
    -7.68
    (3.35)
    -13.69
    (4.43)
    -9.45
    (3.11)
    42 Hours
    -1.38
    (3.56)
    0.55
    (3.44)
    0.14
    (1.32)
    -5.92
    (3.30)
    -3.40
    (3.07)
    48 Hours
    2.12
    (4.24)
    2.17
    (2.91)
    -0.42
    (1.83)
    -6.22
    (3.17)
    -0.39
    (2.85)
    4. Secondary Outcome
    Title Change From Baseline in Serum Total Calcium
    Description
    Time Frame Baseline and 10 minutes, 30 minutes, 1 hour, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 36, 42 and 48 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    Modified intent-to-treat population with available data at each time point
    Arm/Group Title Pooled Placebo Etelcalcetide 0.5 mg Etelcalcetide 2 mg Etelcalcetide 5 mg Etelcalcetide 10 mg
    Arm/Group Description Participants received a single dose of placebo administered by intravenous injection. Participants received a single dose of 0.5 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 2 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 5 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 10 mg etelcalcetide administered by intravenous injection.
    Measure Participants 8 6 6 6 6
    10 Minutes
    -0.019
    (0.047)
    -0.008
    (0.081)
    -0.022
    (0.063)
    -0.017
    (0.053)
    -0.030
    (0.049)
    30 Minutes
    -0.018
    (0.036)
    -0.008
    (0.079)
    -0.018
    (0.062)
    -0.023
    (0.041)
    -0.042
    (0.037)
    1 Hour
    -0.024
    (0.039)
    -0.033
    (0.073)
    -0.023
    (0.056)
    -0.017
    (0.058)
    -0.042
    (0.026)
    3 Hours
    -0.001
    (0.035)
    -0.018
    (0.074)
    -0.017
    (0.048)
    -0.025
    (0.066)
    -0.050
    (0.032)
    6 Hours
    -0.024
    (0.040)
    -0.065
    (0.090)
    0.008
    (0.066)
    -0.045
    (0.058)
    -0.138
    (0.061)
    9 Hours
    -0.010
    (0.041)
    -0.122
    (0.117)
    -0.120
    (0.218)
    -0.126
    (0.043)
    -0.170
    (0.065)
    12 Hours
    -0.055
    (0.038)
    -0.058
    (0.080)
    -0.067
    (0.024)
    -0.203
    (0.041)
    -0.285
    (0.079)
    15 Hours
    -0.176
    (0.324)
    -0.075
    (0.105)
    -0.107
    (0.039)
    -0.243
    (0.064)
    -0.312
    (0.056)
    18 Hours
    -0.090
    (0.074)
    -0.030
    (0.077)
    -0.100
    (0.027)
    -0.217
    (0.045)
    -0.328
    (0.075)
    21 Hours
    -0.058
    (0.038)
    -0.012
    (0.113)
    -0.090
    (0.041)
    -0.174
    (0.040)
    -0.285
    (0.039)
    24 Hours
    -0.025
    (0.030)
    -0.040
    (0.076)
    -0.038
    (0.061)
    -0.200
    (0.036)
    -0.270
    (0.072)
    27 Hours
    0.030
    (0.037)
    0.020
    (0.106)
    0.018
    (0.080)
    -0.070
    (0.057)
    -0.165
    (0.058)
    30 Hours
    -0.003
    (0.036)
    0.025
    (0.102)
    -0.013
    (0.063)
    -0.165
    (0.071)
    -0.182
    (0.057)
    36 Hours
    -0.035
    (0.035)
    -0.002
    (0.074)
    -0.058
    (0.084)
    -0.143
    (0.077)
    -0.210
    (0.040)
    42 Hours
    -0.009
    (0.055)
    -0.033
    (0.085)
    0.002
    (0.029)
    -0.100
    (0.021)
    -0.120
    (0.045)
    48 Hours
    0.013
    (0.042)
    -0.010
    (0.093)
    0.018
    (0.038)
    -0.085
    (0.036)
    -0.107
    (0.047)
    5. Secondary Outcome
    Title Change From Baseline in Serum Corrected Calcium
    Description
    Time Frame Baseline and 10 minutes, 30 minutes, 1 hour, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 36, 42 and 48 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    Modified intent-to-treat population with available data at each time point
    Arm/Group Title Pooled Placebo Etelcalcetide 0.5 mg Etelcalcetide 2 mg Etelcalcetide 5 mg Etelcalcetide 10 mg
    Arm/Group Description Participants received a single dose of placebo administered by intravenous injection. Participants received a single dose of 0.5 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 2 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 5 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 10 mg etelcalcetide administered by intravenous injection.
    Measure Participants 8 6 6 6 6
    10 Minutes
    -0.019
    (0.047)
    -0.008
    (0.081)
    -0.022
    (0.063)
    -0.017
    (0.053)
    -0.030
    (0.049)
    30 Minutes
    -0.018
    (0.036)
    -0.008
    (0.079)
    -0.018
    (0.062)
    -0.023
    (0.041)
    -0.042
    (0.037)
    1 Hour
    -0.024
    (0.039)
    -0.033
    (0.073)
    -0.023
    (0.056)
    -0.017
    (0.058)
    -0.042
    (0.026)
    3 Hours
    -0.001
    (0.035)
    -0.002
    (0.043)
    -0.017
    (0.048)
    -0.025
    (0.066)
    -0.043
    (0.028)
    6 Hours
    -0.024
    (0.040)
    -0.048
    (0.056)
    0.008
    (0.066)
    -0.045
    (0.058)
    -0.130
    (0.069)
    9 Hours
    -0.010
    (0.041)
    -0.102
    (0.079)
    -0.120
    (0.218)
    -0.126
    (0.043)
    -0.163
    (0.069)
    12 Hours
    -0.032
    (0.033)
    -0.035
    (0.048)
    -0.067
    (0.019)
    -0.173
    (0.026)
    -0.228
    (0.042)
    15 Hours
    -0.154
    (0.309)
    -0.052
    (0.072)
    -0.107
    (0.039)
    -0.213
    (0.064)
    -0.255
    (0.078)
    18 Hours
    -0.067
    (0.076)
    -0.007
    (0.063)
    -0.100
    (0.024)
    -0.187
    (0.058)
    -0.272
    (0.100)
    21 Hours
    -0.035
    (0.040)
    0.012
    (0.090)
    -0.090
    (0.023)
    -0.150
    (0.072)
    -0.228
    (0.056)
    24 Hours
    -0.015
    (0.026)
    -0.030
    (0.048)
    -0.018
    (0.036)
    -0.156
    (0.031)
    -0.214
    (0.063)
    27 Hours
    0.040
    (0.041)
    0.030
    (0.085)
    0.038
    (0.056)
    -0.027
    (0.050)
    -0.115
    (0.055)
    30 Hours
    0.008
    (0.035)
    0.035
    (0.078)
    0.007
    (0.046)
    -0.125
    (0.067)
    -0.138
    (0.064)
    36 Hours
    -0.025
    (0.037)
    0.008
    (0.046)
    -0.038
    (0.081)
    -0.103
    (0.068)
    -0.157
    (0.051)
    42 Hours
    0.001
    (0.060)
    -0.023
    (0.061)
    0.022
    (0.026)
    -0.056
    (0.021)
    -0.067
    (0.036)
    48 Hours
    0.020
    (0.033)
    -0.007
    (0.048)
    0.015
    (0.022)
    -0.048
    (0.034)
    -0.087
    (0.030)
    6. Secondary Outcome
    Title Change From Baseline in Serum Phosphate
    Description
    Time Frame Baseline and 10 minutes, 30 minutes, 1 hour, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 36, 42 and 48 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    Modified intent-to-treat population with available data at each time point
    Arm/Group Title Pooled Placebo Etelcalcetide 0.5 mg Etelcalcetide 2 mg Etelcalcetide 5 mg Etelcalcetide 10 mg
    Arm/Group Description Participants received a single dose of placebo administered by intravenous injection. Participants received a single dose of 0.5 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 2 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 5 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 10 mg etelcalcetide administered by intravenous injection.
    Measure Participants 8 6 6 6 6
    10 Minutes
    -0.033
    (0.035)
    0.007
    (0.094)
    -0.065
    (0.059)
    -0.010
    (0.031)
    0.022
    (0.042)
    30 Minutes
    -0.041
    (0.067)
    -0.055
    (0.085)
    -0.067
    (0.055)
    -0.017
    (0.042)
    0.012
    (0.056)
    1 Hour
    -0.055
    (0.079)
    -0.067
    (0.124)
    -0.058
    (0.039)
    -0.010
    (0.045)
    0.005
    (0.035)
    3 Hours
    0.000
    (0.093)
    -0.013
    (0.140)
    0.005
    (0.096)
    0.110
    (0.104)
    0.060
    (0.083)
    6 Hours
    0.008
    (0.153)
    -0.088
    (0.109)
    0.098
    (0.123)
    0.058
    (0.237)
    0.146
    (0.142)
    9 Hours
    0.130
    (0.174)
    0.128
    (0.122)
    0.100
    (0.118)
    0.162
    (0.135)
    0.275
    (0.126)
    12 Hours
    0.015
    (0.086)
    0.043
    (0.123)
    -0.090
    (0.165)
    -0.018
    (0.164)
    0.028
    (0.143)
    15 Hours
    0.228
    (0.251)
    0.258
    (0.132)
    0.188
    (0.180)
    0.220
    (0.139)
    0.355
    (0.141)
    18 Hours
    0.381
    (0.150)
    0.357
    (0.120)
    0.307
    (0.120)
    0.375
    (0.113)
    0.538
    (0.100)
    21 Hours
    0.278
    (0.164)
    0.315
    (0.132)
    0.312
    (0.065)
    0.296
    (0.129)
    0.518
    (0.120)
    24 Hours
    -0.003
    (0.079)
    0.093
    (0.099)
    0.053
    (0.079)
    0.158
    (0.126)
    0.116
    (0.096)
    27 Hours
    -0.085
    (0.156)
    -0.003
    (0.124)
    -0.127
    (0.044)
    -0.015
    (0.215)
    0.065
    (0.141)
    30 Hours
    0.060
    (0.210)
    0.085
    (0.137)
    0.130
    (0.157)
    0.148
    (0.242)
    0.388
    (0.087)
    36 Hours
    0.116
    (0.127)
    0.162
    (0.130)
    0.045
    (0.082)
    0.072
    (0.106)
    0.280
    (0.210)
    42 Hours
    0.335
    (0.155)
    0.343
    (0.123)
    0.342
    (0.076)
    0.398
    (0.222)
    0.480
    (0.235)
    48 Hours
    0.044
    (0.107)
    0.100
    (0.087)
    0.027
    (0.115)
    0.142
    (0.162)
    0.160
    (0.111)
    7. Secondary Outcome
    Title Percent Change From Baseline in Serum Calcitonin
    Description
    Time Frame Baseline and 10 minutes, 30 minutes, 3, 12, 24, and 48 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    Modified intent-to-treat population
    Arm/Group Title Pooled Placebo Etelcalcetide 0.5 mg Etelcalcetide 2 mg Etelcalcetide 5 mg Etelcalcetide 10 mg
    Arm/Group Description Participants received a single dose of placebo administered by intravenous injection. Participants received a single dose of 0.5 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 2 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 5 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 10 mg etelcalcetide administered by intravenous injection.
    Measure Participants 8 6 6 6 6
    10 Minutes
    15.92
    (50.25)
    9.18
    (14.47)
    -5.07
    (12.42)
    15.44
    (29.09)
    51.45
    (119.74)
    30 Minutes
    17.41
    (57.12)
    16.72
    (29.86)
    8.20
    (37.05)
    24.39
    (33.50)
    77.35
    (143.22)
    3 Hours
    11.48
    (25.51)
    3.33
    (8.16)
    -0.78
    (17.80)
    3.12
    (20.84)
    47.81
    (109.64)
    12 Hours
    12.14
    (52.58)
    10.56
    (25.86)
    -5.07
    (12.42)
    -10.89
    (17.56)
    9.71
    (28.64)
    24 Hours
    15.51
    (61.10)
    -1.11
    (2.72)
    -5.07
    (12.42)
    -13.45
    (20.84)
    -4.69
    (11.48)
    48 Hours
    26.42
    (74.89)
    5.00
    (12.25)
    -5.07
    (12.42)
    0.53
    (16.81)
    31.58
    (88.51)
    8. Secondary Outcome
    Title Percent Change From Baseline in Serum 1,25 (OH)2 Vitamin D
    Description
    Time Frame Baseline and 12, 24, and 48 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    Modified intent-to-treat population
    Arm/Group Title Pooled Placebo Etelcalcetide 0.5 mg Etelcalcetide 2 mg Etelcalcetide 5 mg Etelcalcetide 10 mg
    Arm/Group Description Participants received a single dose of placebo administered by intravenous injection. Participants received a single dose of 0.5 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 2 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 5 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 10 mg etelcalcetide administered by intravenous injection.
    Measure Participants 8 6 6 6 6
    12 Hours
    -14.46
    (5.49)
    -4.64
    (12.06)
    -6.12
    (19.16)
    -18.43
    (9.44)
    -25.60
    (7.90)
    24 Hours
    -0.61
    (13.13)
    3.16
    (16.23)
    4.16
    (17.23)
    -0.54
    (15.12)
    -14.51
    (7.11)
    48 Hours
    -4.32
    (11.22)
    0.09
    (19.03)
    5.99
    (18.81)
    0.61
    (11.49)
    -3.53
    (16.54)
    9. Secondary Outcome
    Title Maximum Observed Concentration (Cmax) for Etelcalcetide
    Description Plasma samples were analyzed for levels of etelcalcetide for pharmacokinetic (PK) analysis using a validated liquid chromatography/mass spectrometry (LC/MS) method.
    Time Frame Blood samples for PK assessment were drawn pre-dose, at 5, 10, 15, 20, and 30 minutes, post-dose, and at 1, 1.5, 2, 2.5, 3, 4, 6, 12, 24, 36, and 48 hours after drug administration.

    Outcome Measure Data

    Analysis Population Description
    Participants who received etelcalcetide
    Arm/Group Title Etelcalcetide 0.5 mg Etelcalcetide 2 mg Etelcalcetide 5 mg Etelcalcetide 10 mg
    Arm/Group Description Participants received a single dose of 0.5 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 2 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 5 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 10 mg etelcalcetide administered by intravenous injection.
    Measure Participants 6 6 6 6
    Mean (Standard Deviation) [μg/L]
    43.5
    (7.86)
    171
    (35.6)
    280
    (59.3)
    583
    (144)
    10. Secondary Outcome
    Title Area Under the Concentration-time Curve Between the Time of Dose and the Last Time Point (AUCall) for Etelcalcetide
    Description
    Time Frame Blood samples for PK assessment were drawn pre-dose, at 5, 10, 15, 20, and 30 minutes, post-dose, and at 1, 1.5, 2, 2.5, 3, 4, 6, 12, 24, 36, and 48 hours after drug administration.

    Outcome Measure Data

    Analysis Population Description
    Participants who received etelcalcetide
    Arm/Group Title Etelcalcetide 0.5 mg Etelcalcetide 2 mg Etelcalcetide 5 mg Etelcalcetide 10 mg
    Arm/Group Description Participants received a single dose of 0.5 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 2 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 5 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 10 mg etelcalcetide administered by intravenous injection.
    Measure Participants 6 6 6 6
    Mean (Standard Deviation) [hr*μg/L]
    81.1
    (11.7)
    256
    (32.5)
    544
    (57.7)
    1130
    (129)
    11. Secondary Outcome
    Title Observed Area Under the Concentration-time Curve Extrapolated to Infinity (AUCINFobs) for Etelcalcetide
    Description
    Time Frame Blood samples for PK assessment were drawn pre-dose, at 5, 10, 15, 20, and 30 minutes, post-dose, and at 1, 1.5, 2, 2.5, 3, 4, 6, 12, 24, 36, and 48 hours after drug administration.

    Outcome Measure Data

    Analysis Population Description
    Participants who received etelcalcetide
    Arm/Group Title Etelcalcetide 0.5 mg Etelcalcetide 2 mg Etelcalcetide 5 mg Etelcalcetide 10 mg
    Arm/Group Description Participants received a single dose of 0.5 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 2 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 5 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 10 mg etelcalcetide administered by intravenous injection.
    Measure Participants 6 6 6 6
    Mean (Standard Deviation) [hr*μg/L]
    94.3
    (12.5)
    294
    (34.1)
    623
    (71.5)
    1290
    (116)
    12. Secondary Outcome
    Title Percent Observed Area Under the Concentration-time Curve Extrapolated to Infinity Resulting From Extrapolation to Concentration of 0 ng/mL (AUC%Extrapobs)
    Description
    Time Frame Blood samples for PK assessment were drawn pre-dose, at 5, 10, 15, 20, and 30 minutes, post-dose, and at 1, 1.5, 2, 2.5, 3, 4, 6, 12, 24, 36, and 48 hours after drug administration.

    Outcome Measure Data

    Analysis Population Description
    Participants who received etelcalcetide
    Arm/Group Title Etelcalcetide 0.5 mg Etelcalcetide 2 mg Etelcalcetide 5 mg Etelcalcetide 10 mg
    Arm/Group Description Participants received a single dose of 0.5 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 2 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 5 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 10 mg etelcalcetide administered by intravenous injection.
    Measure Participants 6 6 6 6
    Mean (Standard Deviation) [percentage of AUCINFobs]
    14.0
    (1.33)
    13.2
    (2.57)
    12.6
    (2.43)
    12.0
    (2.79)
    13. Secondary Outcome
    Title Terminal Elimination Rate Constant (λz) for Etelcalcetide
    Description
    Time Frame Blood samples for PK assessment were drawn pre-dose, at 5, 10, 15, 20, and 30 minutes, post-dose, and at 1, 1.5, 2, 2.5, 3, 4, 6, 12, 24, 36, and 48 hours after drug administration.

    Outcome Measure Data

    Analysis Population Description
    Participants who received etelcalcetide
    Arm/Group Title Etelcalcetide 0.5 mg Etelcalcetide 2 mg Etelcalcetide 5 mg Etelcalcetide 10 mg
    Arm/Group Description Participants received a single dose of 0.5 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 2 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 5 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 10 mg etelcalcetide administered by intravenous injection.
    Measure Participants 6 6 6 6
    Mean (Standard Deviation) [1/hr]
    0.0357
    (0.00246)
    0.0349
    (0.00337)
    0.0378
    (0.00486)
    0.0382
    (0.00539)
    14. Secondary Outcome
    Title Half-life Associated With the Terminal (Log-linear) Elimination Phase (HLλz) for Etelcalcetide
    Description
    Time Frame Blood samples for PK assessment were drawn pre-dose, at 5, 10, 15, 20, and 30 minutes, post-dose, and at 1, 1.5, 2, 2.5, 3, 4, 6, 12, 24, 36, and 48 hours after drug administration.

    Outcome Measure Data

    Analysis Population Description
    Participants who received etelcalcetide
    Arm/Group Title Etelcalcetide 0.5 mg Etelcalcetide 2 mg Etelcalcetide 5 mg Etelcalcetide 10 mg
    Arm/Group Description Participants received a single dose of 0.5 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 2 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 5 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 10 mg etelcalcetide administered by intravenous injection.
    Measure Participants 6 6 6 6
    Mean (Standard Deviation) [hours]
    19.5
    (1.35)
    20.0
    (2.25)
    18.6
    (2.51)
    18.4
    (2.21)
    15. Secondary Outcome
    Title Total Body Clearance (CL) for Etelcalcetide
    Description
    Time Frame Blood samples for PK assessment were drawn pre-dose, at 5, 10, 15, 20, and 30 minutes, post-dose, and at 1, 1.5, 2, 2.5, 3, 4, 6, 12, 24, 36, and 48 hours after drug administration.

    Outcome Measure Data

    Analysis Population Description
    Participants who received etelcalcetide
    Arm/Group Title Etelcalcetide 0.5 mg Etelcalcetide 2 mg Etelcalcetide 5 mg Etelcalcetide 10 mg
    Arm/Group Description Participants received a single dose of 0.5 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 2 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 5 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 10 mg etelcalcetide administered by intravenous injection.
    Measure Participants 6 6 6 6
    Mean (Standard Deviation) [L/hr]
    5.38
    (0.675)
    6.87
    (0.750)
    8.11
    (0.928)
    7.83
    (0.755)
    16. Secondary Outcome
    Title Volume of Distribution at Steady State for Etelcalcetide
    Description
    Time Frame Blood samples for PK assessment were drawn pre-dose, at 5, 10, 15, 20, and 30 minutes, post-dose, and at 1, 1.5, 2, 2.5, 3, 4, 6, 12, 24, 36, and 48 hours after drug administration.

    Outcome Measure Data

    Analysis Population Description
    Participants who received etelcalcetide
    Arm/Group Title Etelcalcetide 0.5 mg Etelcalcetide 2 mg Etelcalcetide 5 mg Etelcalcetide 10 mg
    Arm/Group Description Participants received a single dose of 0.5 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 2 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 5 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 10 mg etelcalcetide administered by intravenous injection.
    Measure Participants 6 6 6 6
    Mean (Standard Deviation) [liters]
    113
    (19.6)
    138
    (26.0)
    160
    (21.0)
    152
    (30.0)
    17. Secondary Outcome
    Title Number of Participants With Antibodies to Etelcalcetide
    Description Serum samples were analyzed for antibodies against etelcalcetide using a validated enzyme-linked immunosorbent assay (ELISA).
    Time Frame Samples for antibody analysis were collected pre-dose and between days 7-12 and days 21-28.

    Outcome Measure Data

    Analysis Population Description
    Participants who received etelcalcetide
    Arm/Group Title Etelcalcetide 0.5 mg Etelcalcetide 2 mg Etelcalcetide 5 mg Etelcalcetide 10 mg
    Arm/Group Description Participants received a single dose of 0.5 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 2 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 5 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 10 mg etelcalcetide administered by intravenous injection.
    Measure Participants 6 6 6 6
    Count of Participants [Participants]
    0
    0%
    0
    0%
    0
    0%
    0
    0%

    Adverse Events

    Time Frame From the first dose of study drug through 7 days
    Adverse Event Reporting Description Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
    Arm/Group Title Pooled Placebo Etelcalcetide 0.5 mg Etelcalcetide 2 mg Etelcalcetide 5 mg Etelcalcetide 10 mg Etelcalcetide Pooled
    Arm/Group Description Participants received a single dose of placebo administered by intravenous injection. Participants received a single dose of 0.5 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 2 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 5 mg etelcalcetide administered by intravenous injection. Participants received a single dose of 10 mg etelcalcetide administered by intravenous injection. Participants received a single dose of etelcalcetide administered by intravenous injection.
    All Cause Mortality
    Pooled Placebo Etelcalcetide 0.5 mg Etelcalcetide 2 mg Etelcalcetide 5 mg Etelcalcetide 10 mg Etelcalcetide Pooled
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Pooled Placebo Etelcalcetide 0.5 mg Etelcalcetide 2 mg Etelcalcetide 5 mg Etelcalcetide 10 mg Etelcalcetide Pooled
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/8 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/24 (0%)
    Other (Not Including Serious) Adverse Events
    Pooled Placebo Etelcalcetide 0.5 mg Etelcalcetide 2 mg Etelcalcetide 5 mg Etelcalcetide 10 mg Etelcalcetide Pooled
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/8 (25%) 0/6 (0%) 1/6 (16.7%) 2/6 (33.3%) 2/6 (33.3%) 5/24 (20.8%)
    Gastrointestinal disorders
    ABDOMINAL DISCOMFORT 0/8 (0%) 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 1/24 (4.2%)
    ABDOMINAL PAIN 1/8 (12.5%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/24 (0%)
    DIARRHOEA 1/8 (12.5%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/24 (0%)
    General disorders
    FEELING HOT 0/8 (0%) 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 0/6 (0%) 1/24 (4.2%)
    Musculoskeletal and connective tissue disorders
    BACK PAIN 0/8 (0%) 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 0/6 (0%) 1/24 (4.2%)
    Nervous system disorders
    LETHARGY 1/8 (12.5%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 0/24 (0%)
    PARAESTHESIA 0/8 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 1/24 (4.2%)
    Respiratory, thoracic and mediastinal disorders
    EPISTAXIS 0/8 (0%) 0/6 (0%) 0/6 (0%) 0/6 (0%) 1/6 (16.7%) 1/24 (4.2%)

    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:
    KAI Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT01134549
    Other Study ID Numbers:
    • KAI-4169-001
    • 20130107
    First Posted:
    Jun 2, 2010
    Last Update Posted:
    Apr 14, 2017
    Last Verified:
    Feb 1, 2017