Study to Evaluate the Safety and Efficacy of IV Infusion Treatment With Omecamtiv Mecarbil in Subjects With Left Ventricular Systolic Dysfunction Hospitalized for Acute Heart Failure (ATOMIC-AHF)

Sponsor
Cytokinetics (Industry)
Overall Status
Completed
CT.gov ID
NCT01300013
Collaborator
(none)
614
150
2
29
4.1
0.1

Study Details

Study Description

Brief Summary

The primary objective of the study is to evaluate the effect of 48 hours of intravenous (IV) omecamtiv mecarbil compared with placebo on dyspnea in subjects with left ventricular systolic dysfunction hospitalized for acute heart failure. This is a multicenter, randomized, double-blind, placebo-controlled study with 3 dose cohorts enrolled sequentially in order of ascending dose strength of omecamtiv mecarbil. In each cohort, subjects are randomized 1:1 to omecamtiv mecarbil or placebo.

Condition or Disease Intervention/Treatment Phase
  • Drug: Placebo
  • Drug: Omecamtiv mecarbil
Phase 2

Detailed Description

This study was conducted by Amgen as the IND holder, with Cytokinetics as a collaborator. Due to the termination of the collaboration agreement between Amgen and Cytokinetics in May 2021 and subsequent transfer of the omecamtiv mecarbil IND from Amgen to Cytokinetics, Cytokinetics is now listed as the sponsor.

Study Design

Study Type:
Interventional
Actual Enrollment :
614 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate the Safety and Efficacy of IV Infusion Treatment With Omecamtiv Mecarbil in Subjects With Left Ventricular Systolic Dysfunction Hospitalized for Acute Heart Failure
Study Start Date :
Apr 1, 2011
Actual Primary Completion Date :
Apr 1, 2013
Actual Study Completion Date :
Sep 1, 2013

Arms and Interventions

Arm Intervention/Treatment
Experimental: Omecamtiv mecarbil

Drug: Omecamtiv mecarbil
48-hour infusion of omecamtiv mecarbil; dose strength will depend on cohort assignment.
Other Names:
  • CK-1827452
  • AMG 423
  • Placebo Comparator: Placebo

    Drug: Placebo
    48-hour infusion of placebo

    Outcome Measures

    Primary Outcome Measures

    1. The primary objective of the study is to evaluate the effect of 48 hours of intravenous (IV) omecamtiv mecarbil compared with placebo on dyspnea in subjects with left ventricular systolic dysfunction hospitalized for acute heart failure. [48 hours]

    Secondary Outcome Measures

    1. To characterize pharmacokinetics of omecamtiv mecarbil including metabolites following IV infusion and to evaluate the relationship between omecamtiv mecarbil plasma concentration and echocardiographic parameters in subjects with AHF [48 hours]

    2. To assess the safety and tolerability of 3 dose levels of IV omecamtiv mecarbil compared with placebo in subjects with left ventricular systolic dysfunction hospitalized for acute heart failure [48 hours]

    3. To evaluate the effects of 48 hours treatment with IV omecamtiv mecarbil on additional measures of dyspnea, patient global assessment (PGA), change in NT-proBNP, incidence of worsening heart failure, and short term clinical outcomes [48 hours]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 85 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Male or female 18 - 85 years

    • Hospitalized for worsening heart failure, within 24 hours of initiating IV loop diuretic

    • Dyspnea due to heart failure, at rest or with minimal exertion

    • History of left ventricular ejection fraction (LVEF) ≤ 40%

    • Elevated brain natriuretic peptide (BNP) or N-terminal fragment BNP (NT-proBNP)

    Exclusion Criteria:
    • Receiving IV vasopressor (excluding low dopamine), inotropic or mechanical support

    • Acute coronary syndrome (ACS)

    • Within 30 days prior to enrollment: cardiac resynchronization therapy (CRT) or implantable cardioverter defibrillator (ICD) implantation, ACS, coronary revascularization, transient ischemic attack (TIA) or stroke, sustained ventricular arrhythmia, or major surgery

    • Severe valvular stenosis, hypertrophic obstructive cardiomyopathy, active myocarditis, constrictive pericarditis, or clinically significant congenital heart disease

    • Estimated glomerular filtration rate (eGFR) < 20 mL/min/1.73m2

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Research Site Mobile Alabama United States 36608
    2 Research Site Inglewood California United States 90301
    3 Research Site La Jolla California United States 92037
    4 Research Site San Francisco California United States 94121
    5 Research Site Danbury Connecticut United States 06810
    6 Research Site Newark Delaware United States 19718
    7 Research Site Atlantis Florida United States 33462
    8 Research Site Clearwater Florida United States 33756
    9 Research Site Fort Lauderdale Florida United States 33308
    10 Research Site Miami Florida United States 33133
    11 Research Site Orlando Florida United States 32803
    12 Research Site Atlanta Georgia United States 30322
    13 Research Site Chicago Illinois United States 60611
    14 Research Site Peoria Illinois United States 61636
    15 Research Site Baltimore Maryland United States 21201
    16 Research Site Detroit Michigan United States 48201
    17 Research Site Detroit Michigan United States 48202
    18 Research Site Novi Michigan United States 48374
    19 Research Site Minneapolis Minnesota United States 55417
    20 Research Site Saint Louis Missouri United States 63110
    21 Research Site Lincoln Nebraska United States 68506
    22 Research Site Newark New Jersey United States 07103
    23 Research Site Bronx New York United States 10467
    24 Research Site Cortlandt Manor New York United States 10567
    25 Research Site Roslyn New York United States 11576
    26 Research Site Chapel Hill North Carolina United States 27599
    27 Research Site Charlotte North Carolina United States 28204
    28 Research Site Durham North Carolina United States 27705
    29 Research Site Winston-Salem North Carolina United States 27103
    30 Research Site Cincinnati Ohio United States 45219
    31 Research Site Cincinnati Ohio United States 45220
    32 Research Site Cincinnati Ohio United States 45267
    33 Research Site Cleveland Ohio United States 44109
    34 Research Site Columbus Ohio United States 43210
    35 Research Site Fairfield Ohio United States 45014
    36 Research Site Oklahoma City Oklahoma United States 73120
    37 Research Site Portland Oregon United States 97239
    38 Research Site Charleston South Carolina United States 29425
    39 Research Site Greenville South Carolina United States 29605
    40 Research Site Memphis Tennessee United States 38120
    41 Research Site Nashville Tennessee United States 37203
    42 Research Site Nashville Tennessee United States 37232-8802
    43 Research Site Tullahoma Tennessee United States 37388
    44 Research Site Houston Texas United States 77030
    45 Research Site Murray Utah United States 84107
    46 Research Site Darlinghurst New South Wales Australia 2010
    47 Research Site Woolloongabba Queensland Australia 4102
    48 Research Site Bedford Park South Australia Australia 5042
    49 Research Site Prahran Victoria Australia 3181
    50 Research Site Richmond Victoria Australia 3121
    51 Research Site Aalst Belgium 9300
    52 Research Site Bonheiden Belgium 2820
    53 Research Site Gent Belgium 9000
    54 Research Site Roeselare Belgium 8800
    55 Research Site Blagoevgrad Bulgaria 2700
    56 Research Site Kazanlak Bulgaria 6100
    57 Research Site Pazardzhik Bulgaria 4700
    58 Research Site Plovdiv Bulgaria 4002
    59 Research Site Sandanski Bulgaria 2800
    60 Research Site Smolyan Bulgaria 4400
    61 Research Site Sofia Bulgaria 1309
    62 Research Site Sofia Bulgaria 1431
    63 Research Site Sofia Bulgaria 1527
    64 Research Site Calgary Alberta Canada T2N 4Z6
    65 Research Site Edmonton Alberta Canada T6G 2B7
    66 Research Site Edmonton Alberta Canada T6L 5X8
    67 Research Site Halifax Nova Scotia Canada B3H 3A7
    68 Research Site Ottawa Ontario Canada K1Y 4W7
    69 Research Site Toronto Ontario Canada M5B 1W8
    70 Research Site Toronto Ontario Canada M5G 1X5
    71 Research Site Montreal Quebec Canada H3G 1A4
    72 Research Site Québec Quebec Canada G1V 4G5
    73 Research Site Sherbrooke Quebec Canada J1H 5N4
    74 Research Site Brno Czechia 625 00
    75 Research Site Brno Czechia 656 91
    76 Research Site Praha 2 Czechia 128 08
    77 Research Site Praha 5 Czechia 150 06
    78 Research Site Usti nad Labem Czechia 401 13
    79 Research Site Helsinki Finland 00029
    80 Research Site Turku Finland 20521
    81 Research Site Caen Cedex 9 France 14033
    82 Research Site Lille Cedex France 59037
    83 Research Site Montpellier cedex 05 France 34295
    84 Research Site Paris Cedex 13 France 75651
    85 Research Site Paris France 75010
    86 Research Site Strasbourg France 67091
    87 Research Site Toulouse Cedex 09 France 31403
    88 Research Site Bad Nauheim Germany 61231
    89 Research Site Dortmund Germany 44137
    90 Research Site Dresden Germany 01307
    91 Research Site Frankfurt Germany 60488
    92 Research Site Frankfurt Germany 60590
    93 Research Site Greifswald Germany 17475
    94 Research Site Halle/Saale Germany 06097
    95 Research Site Hamburg Germany 20246
    96 Research Site Homburg Germany 66421
    97 Research Site Langen Germany 63225
    98 Research Site Regensburg Germany 93053
    99 Research Site Stuttgart Germany 70376
    100 Research Site Würzburg Germany 97080
    101 Research Site Athens Greece 11528
    102 Research Site Athens Greece 16673
    103 Research Site Haidari Greece 12462
    104 Research Site Heraklion Greece 71110
    105 Research Site Patra Greece 26500
    106 Research Site Budapest Hungary 1023
    107 Research Site Budapest Hungary 1122
    108 Research Site Budapest Hungary 1125
    109 Research Site Budapest Hungary 1134
    110 Research Site Pecs Hungary 7624
    111 Research Site Szolnok Hungary 5004
    112 Research Site Brescia Italy 25125
    113 Research Site Cagliari Italy 09134
    114 Research Site Pavia Italy 27100
    115 Research Site Udine Italy 33100
    116 Research Site Kaunas Lithuania 50009
    117 Research Site Vilnius Lithuania 08661
    118 Research Site Delft Netherlands 2625 AD
    119 Research Site Deventer Netherlands 7416 SE
    120 Research Site Utrecht Netherlands 3584 CX
    121 Research Site Oslo Norway 0424
    122 Research Site Stavanger Norway 4011
    123 Research Site Bialystok Poland 15-276
    124 Research Site Gdansk Poland 80-952
    125 Research Site Krakow Poland 31-202
    126 Research Site Krakow Poland 31-501
    127 Research Site Lodz Poland 91-347
    128 Research Site Lublin Poland 20-954
    129 Research Site Wroclaw Poland 50-981
    130 Research Site Moscow Russian Federation 109240
    131 Research Site Moscow Russian Federation 111539
    132 Research Site Moscow Russian Federation 115093
    133 Research Site Moscow Russian Federation 117292
    134 Research Site Moscow Russian Federation 119620
    135 Research Site Moscow Russian Federation 119991
    136 Research Site Moscow Russian Federation 127299
    137 Research Site Moscow Russian Federation 127473
    138 Research Site Saint Petersburg Russian Federation 197341
    139 Research Site Saint-Petersburg Russian Federation 195067
    140 Research Site St Petersburg Russian Federation 198205
    141 Research Site St. Petersburg Russian Federation 199106
    142 Research Site St.-Petrsburg Russian Federation 196247
    143 Research Site Bratislava Slovakia 826 06
    144 Research Site Bratislava Slovakia 851 07
    145 Research Site Kosice Slovakia 040 66
    146 Research Site Nitra Slovakia 949 01
    147 Research Site Bristol United Kingdom BS2 8HW
    148 Research Site Cottingham United Kingdom HU16 5JQ
    149 Research Site Glasgow United Kingdom G11 6NT
    150 Research Site Harrow United Kingdom HA1 3UJ

    Sponsors and Collaborators

    • Cytokinetics

    Investigators

    • Study Director: MD, Amgen

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Cytokinetics
    ClinicalTrials.gov Identifier:
    NCT01300013
    Other Study ID Numbers:
    • 20100754
    First Posted:
    Feb 21, 2011
    Last Update Posted:
    Jul 27, 2021
    Last Verified:
    Jul 1, 2021

    Study Results

    No Results Posted as of Jul 27, 2021