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Trial record 4 of 13 for:    “omecamtiv mecarbil or CK-1827452 and heart failure”

Safety, PK, and Efficacy of Omecamtiv Mecarbil in Japanese Subjects With Heart Failure With Reduced Ejection Fraction

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02695420
Recruitment Status : Completed
First Posted : March 1, 2016
Results First Posted : January 31, 2020
Last Update Posted : January 31, 2020
Sponsor:
Information provided by (Responsible Party):
Amgen

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Heart Failure With Reduced Ejection Fraction
Interventions Drug: 25 mg Omecamtiv Mecarbil
Drug: Placebo
Drug: 37.5 mg Omecamtiv Mecarbil
Drug: 50 mg Omecamtiv Mecarbil
Enrollment 81
Recruitment Details Participants were enrolled at 31 research centers in Japan from 14 April 2016 to 16 December 2016.
Pre-assignment Details Participants were randomized at a ratio of 1:1:1:1 to twice daily (BID) placebo, 25 mg, 25 mg->37.5 mg Target Dose, or 25 mg->50 mg Target Dose, respectively. Randomization was stratified by presence or absence of atrial fibrillation/flutter.
Arm/Group Title Placebo BID Omecamtiv Mecarbil 25 mg BID Omecamtiv Mecarbil 25 mg to 37.5 mg BID Target Dose Omecamtiv Mecarbil 25 mg to 50 mg BID Target Dose
Hide Arm/Group Description Placebo for omecamtiv mecarbil BID Omecamtiv mecarbil 25 mg BID Omecamtiv mecarbil 25 mg BID up to Week 4 or Week 8 and 25 mg or 37.5 mg BID after Week 4 or Week 8, based on Week 2 PK Omecamtiv Mecarbil 25 mg BID up to Week 4 or Week 8 and 25 mg or 50 mg BID after Week 4 or Week 8, based on Week 2 PK
Period Title: Overall Study
Started 21 21 19 20
Completed 21 20 19 20
Not Completed 0 1 0 0
Reason Not Completed
Death             0             1             0             0
Arm/Group Title Placebo BID Omecamtiv Mecarbil 25 mg BID Omecamtiv Mecarbil 25 mg to 37.5 mg BID Target Dose Omecamtiv Mecarbil 25 mg to 50 mg BID Target Dose Total
Hide Arm/Group Description Placebo for omecamtiv mecarbil BID Omecamtiv mecarbil 25 mg BID Omecamtiv mecarbil 25 mg BID up to Week 4 or Week 8 and 25 mg or 37.5 mg BID after Week 4 or Week 8, based on Week 2 PK Omecamtiv Mecarbil 25 mg BID up to Week 4 or Week 8 and 25 mg or 50 mg BID after Week 4 or Week 8, based on Week 2 PK Total of all reporting groups
Overall Number of Baseline Participants 21 21 19 20 81
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 21 participants 21 participants 19 participants 20 participants 81 participants
64.6  (11.5) 66.9  (10.3) 63.6  (10.8) 66.5  (12.2) 65.4  (11.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 21 participants 21 participants 19 participants 20 participants 81 participants
Female
9
  42.9%
3
  14.3%
0
   0.0%
1
   5.0%
13
  16.0%
Male
12
  57.1%
18
  85.7%
19
 100.0%
19
  95.0%
68
  84.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 21 participants 21 participants 19 participants 20 participants 81 participants
Asian 21 21 19 20 81
Other 0 0 0 0 0
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 21 participants 21 participants 19 participants 20 participants 81 participants
Japanese 21 21 19 20 81
Other 0 0 0 0 0
Atrial Fibrillation/Flutter at Randomization   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 21 participants 21 participants 19 participants 20 participants 81 participants
Present 4 4 3 4 15
Absent 17 17 16 16 66
[1]
Measure Description: Randomization was stratified by presence or absence of atrial fibrillation/flutter via interactive voice-response system/interactive web-response (IVRS/IWRS) system.
1.Primary Outcome
Title Pharmacokinetics (PK): Concentration Before Morning Dose (Cpredose) Over Time
Hide Description [Not Specified]
Time Frame Before morning dose on Week 2 (Day 15), Week 4 (Day 28), Week 12 (Day 84), Week 16 (Day 112)
Hide Outcome Measure Data
Hide Analysis Population Description
PK Analysis Set: all randomized participants who received at least one dose of omecamtiv mecarbil and had at least one evaluable omecamtiv mecarbil PK concentration at given time point.
Arm/Group Title Omecamtiv Mecarbil 25 mg BID Omecamtiv Mecarbil 25 mg to 37.5 mg BID Target Dose Omecamtiv Mecarbil 25 mg to 50 mg BID Target Dose
Hide Arm/Group Description:
Omecamtiv mecarbil 25 mg BID
Omecamtiv mecarbil 25 mg BID up to Week 4 or Week 8 and 25 mg or 37.5 mg BID after Week 4 or Week 8, based on Week 2 PK
Omecamtiv Mecarbil 25 mg BID up to Week 4 or Week 8 and 25 mg or 50 mg BID after Week 4 or Week 8, based on Week 2 PK
Overall Number of Participants Analyzed 20 18 20
Mean (Standard Deviation)
Unit of Measure: ng/mL
Week 2 Number Analyzed 20 participants 18 participants 20 participants
239  (106) 179  (77.1) 208  (61.6)
Week 4 Number Analyzed 17 participants 17 participants 20 participants
222  (63.5) 196  (44) 209  (61.9)
Week 12 Number Analyzed 19 participants 17 participants 19 participants
217  (66.1) 228  (56.9) 282  (120)
Week 16 Number Analyzed 19 participants 17 participants 20 participants
206  (84.5) 244  (67.7) 292  (118)
2.Primary Outcome
Title PK: Area Under the Curve Until 8 Hours After Morning Dose at Week 8 (AUC0-8)
Hide Description [Not Specified]
Time Frame Week 8 (Day 56) at predose, at 2 hours ±30 minutes; 4 hours ±30 minutes; 6 hours ±30 minutes; 8 hours ±30 minutes after morning dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK Analysis Set: all randomized participants who received at least one dose of omecamtiv mecarbil and had at least one evaluable omecamtiv mecarbil PK concentration.
Arm/Group Title Omecamtiv Mecarbil 25 mg BID Omecamtiv Mecarbil 25 mg to 37.5 mg BID Target Dose Omecamtiv Mecarbil 25 mg to 50 mg BID Target Dose
Hide Arm/Group Description:
Omecamtiv mecarbil 25 mg BID
Omecamtiv mecarbil 25 mg BID up to Week 4 or Week 8 and 25 mg or 37.5 mg BID after Week 4 or Week 8, based on Week 2 PK
Omecamtiv Mecarbil 25 mg BID up to Week 4 or Week 8 and 25 mg or 50 mg BID after Week 4 or Week 8, based on Week 2 PK
Overall Number of Participants Analyzed 9 8 1
Mean (Standard Deviation)
Unit of Measure: hr*ng/mL
1850  (563) 1850  (383) 2360  (465)
3.Secondary Outcome
Title Change From Baseline at Week 16 in Systolic Ejection Time (SET)
Hide Description LS mean was from the repeated measures model, which included treatment group, stratification factor (from IVRS), scheduled visit, baseline value, and the interaction of treatment group with scheduled visit as covariates.
Time Frame Baseline, Week 16 (Day 112)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study drug with observed data. The 4 active treatment arms include only those participants who had a minimum investigational product exposure period of 25 days.
Arm/Group Title Placebo BID Omecamtiv Mecarbil 25 mg BID Omecamtiv Mecarbil 25 mg to 37.5 mg BID Target Dose Omecamtiv Mecarbil 25 mg to 50 mg BID Target Dose
Hide Arm/Group Description:
Placebo for omecamtiv mecarbil BID
Omecamtiv mecarbil 25 mg BID
Omecamtiv mecarbil 25 mg BID up to Week 4 or Week 8 and 25 mg or 37.5 mg BID after Week 4 or Week 8, based on Week 2 PK
Omecamtiv Mecarbil 25 mg BID up to Week 4 or Week 8 and 25 mg or 50 mg BID after Week 4 or Week 8, based on Week 2 PK
Overall Number of Participants Analyzed 20 19 17 17
Least Squares Mean (Standard Error)
Unit of Measure: msec
-1.7  (4.7) 20.5  (4.9) 27.6  (5.4) 23.8  (5.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo BID, Omecamtiv Mecarbil 25 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0008
Comments [Not Specified]
Method Repeated Measures Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 22.1
Confidence Interval (2-Sided) 95%
9.6 to 34.7
Parameter Dispersion
Type: Standard Error of the Mean
Value: 6.3
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo BID, Omecamtiv Mecarbil 25 mg to 37.5 mg BID Target Dose
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 29.3
Confidence Interval (2-Sided) 95%
16.3 to 42.3
Parameter Dispersion
Type: Standard Error of the Mean
Value: 6.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo BID, Omecamtiv Mecarbil 25 mg to 50 mg BID Target Dose
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 25.5
Confidence Interval (2-Sided) 95%
12.6 to 38.4
Parameter Dispersion
Type: Standard Error of the Mean
Value: 6.5
Estimation Comments [Not Specified]
4.Other Pre-specified Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Hide Description An adverse event (AE) is defined as any untoward medical occurrence. Serious AEs are defined as AEs that meets at least 1 of the following serious criteria: fatal, life threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, congenital anomaly/birth defect, other medically important serious event. AEs are graded as: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death. TEAEs are defined as events occurring after the first dose of study drug.
Time Frame From first dose of study drug up to Week 20 (Day 140 + 3 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set: all participants who received at least one dose of study drug.
Arm/Group Title Placebo BID Omecamtiv Mecarbil 25 mg BID Omecamtiv Mecarbil 25 mg to 37.5 mg BID Target Dose Omecamtiv Mecarbil 25 mg to 50 mg BID Target Dose
Hide Arm/Group Description:
Placebo for omecamtiv mecarbil BID
Omecamtiv mecarbil 25 mg BID
Omecamtiv mecarbil 25 mg BID up to Week 4 or Week 8 and 25 mg or 37.5 mg BID after Week 4 or Week 8, based on Week 2 PK
Omecamtiv Mecarbil 25 mg BID up to Week 4 or Week 8 and 25 mg or 50 mg BID after Week 4 or Week 8, based on Week 2 PK
Overall Number of Participants Analyzed 21 21 19 20
Measure Type: Count of Participants
Unit of Measure: Participants
All TEAEs
14
  66.7%
10
  47.6%
10
  52.6%
12
  60.0%
Grade >= 2 TEAEs
10
  47.6%
6
  28.6%
6
  31.6%
7
  35.0%
Grade >= 3 TEAEs
3
  14.3%
4
  19.0%
1
   5.3%
2
  10.0%
Grade >= 4 TEAEs
0
   0.0%
1
   4.8%
0
   0.0%
0
   0.0%
Serious AEs
3
  14.3%
4
  19.0%
1
   5.3%
3
  15.0%
TEAEs Leading to Withdrawal of Study Drug
0
   0.0%
2
   9.5%
1
   5.3%
0
   0.0%
Fata Adverse Events
0
   0.0%
1
   4.8%
0
   0.0%
0
   0.0%
Time Frame From first dose of study drug up to Week 20 (Day 140 + 3 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 Placebo BID Omecamtiv Mecarbil 25 mg BID Omecamtiv Mecarbil 25 mg to 37.5 mg BID Target Dose Omecamtiv Mecarbil 25 mg to 50 mg BID Target Dose
Hide Arm/Group Description Placebo for omecamtiv mecarbil BID Omecamtiv mecarbil 25 mg BID Omecamtiv mecarbil 25 mg BID up to Week 4 or Week 8 and 25 mg or 37.5 mg BID after Week 4 or Week 8, based on Week 2 PK Omecamtiv Mecarbil 25 mg BID up to Week 4 or Week 8 and 25 mg or 50 mg BID after Week 4 or Week 8, based on Week 2 PK
All-Cause Mortality
Placebo BID Omecamtiv Mecarbil 25 mg BID Omecamtiv Mecarbil 25 mg to 37.5 mg BID Target Dose Omecamtiv Mecarbil 25 mg to 50 mg BID Target Dose
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/21 (0.00%)   1/21 (4.76%)   0/19 (0.00%)   0/20 (0.00%) 
Hide Serious Adverse Events
Placebo BID Omecamtiv Mecarbil 25 mg BID Omecamtiv Mecarbil 25 mg to 37.5 mg BID Target Dose Omecamtiv Mecarbil 25 mg to 50 mg BID Target Dose
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/21 (14.29%)   4/21 (19.05%)   1/19 (5.26%)   3/20 (15.00%) 
Cardiac disorders         
Angina pectoris  1  0/21 (0.00%)  0/21 (0.00%)  0/19 (0.00%)  1/20 (5.00%) 
Cardiac failure  1  1/21 (4.76%)  1/21 (4.76%)  0/19 (0.00%)  1/20 (5.00%) 
Cardiac failure chronic  1  0/21 (0.00%)  1/21 (4.76%)  0/19 (0.00%)  1/20 (5.00%) 
Cardiac failure congestive  1  0/21 (0.00%)  1/21 (4.76%)  0/19 (0.00%)  0/20 (0.00%) 
Cardiac ventricular thrombosis  1  1/21 (4.76%)  0/21 (0.00%)  0/19 (0.00%)  0/20 (0.00%) 
Cardio-respiratory arrest  1  0/21 (0.00%)  1/21 (4.76%)  0/19 (0.00%)  0/20 (0.00%) 
Ventricular fibrillation  1  0/21 (0.00%)  1/21 (4.76%)  0/19 (0.00%)  0/20 (0.00%) 
General disorders         
Vascular stent restenosis  1  0/21 (0.00%)  0/21 (0.00%)  0/19 (0.00%)  1/20 (5.00%) 
Hepatobiliary disorders         
Hepatic function abnormal  1  0/21 (0.00%)  1/21 (4.76%)  0/19 (0.00%)  0/20 (0.00%) 
Infections and infestations         
Pneumonia  1  1/21 (4.76%)  0/21 (0.00%)  1/19 (5.26%)  0/20 (0.00%) 
Sepsis  1  0/21 (0.00%)  1/21 (4.76%)  0/19 (0.00%)  0/20 (0.00%) 
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo BID Omecamtiv Mecarbil 25 mg BID Omecamtiv Mecarbil 25 mg to 37.5 mg BID Target Dose Omecamtiv Mecarbil 25 mg to 50 mg BID Target Dose
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   10/21 (47.62%)   8/21 (38.10%)   10/19 (52.63%)   11/20 (55.00%) 
Blood and lymphatic system disorders         
Iron deficiency anaemia  1  0/21 (0.00%)  2/21 (9.52%)  0/19 (0.00%)  0/20 (0.00%) 
Cardiac disorders         
Bradycardia  1  0/21 (0.00%)  0/21 (0.00%)  1/19 (5.26%)  0/20 (0.00%) 
Cardiac failure congestive  1  0/21 (0.00%)  0/21 (0.00%)  1/19 (5.26%)  0/20 (0.00%) 
Supraventricular extrasystoles  1  0/21 (0.00%)  0/21 (0.00%)  1/19 (5.26%)  0/20 (0.00%) 
Ventricular extrasystoles  1  0/21 (0.00%)  0/21 (0.00%)  1/19 (5.26%)  0/20 (0.00%) 
General disorders         
Chest pain  1  0/21 (0.00%)  1/21 (4.76%)  1/19 (5.26%)  0/20 (0.00%) 
Oedema peripheral  1  0/21 (0.00%)  0/21 (0.00%)  0/19 (0.00%)  1/20 (5.00%) 
Hepatobiliary disorders         
Hepatic function abnormal  1  1/21 (4.76%)  0/21 (0.00%)  1/19 (5.26%)  0/20 (0.00%) 
Immune system disorders         
Seasonal allergy  1  0/21 (0.00%)  0/21 (0.00%)  0/19 (0.00%)  1/20 (5.00%) 
Infections and infestations         
Bronchitis  1  0/21 (0.00%)  1/21 (4.76%)  0/19 (0.00%)  1/20 (5.00%) 
Influenza  1  1/21 (4.76%)  2/21 (9.52%)  0/19 (0.00%)  0/20 (0.00%) 
Periodontitis  1  0/21 (0.00%)  1/21 (4.76%)  2/19 (10.53%)  0/20 (0.00%) 
Pharyngitis  1  1/21 (4.76%)  0/21 (0.00%)  0/19 (0.00%)  1/20 (5.00%) 
Viral upper respiratory tract infection  1  4/21 (19.05%)  1/21 (4.76%)  4/19 (21.05%)  4/20 (20.00%) 
Injury, poisoning and procedural complications         
Joint dislocation  1  0/21 (0.00%)  0/21 (0.00%)  1/19 (5.26%)  0/20 (0.00%) 
Tendon rupture  1  0/21 (0.00%)  0/21 (0.00%)  1/19 (5.26%)  0/20 (0.00%) 
Investigations         
Blood potassium increased  1  0/21 (0.00%)  0/21 (0.00%)  0/19 (0.00%)  1/20 (5.00%) 
Protein urine  1  0/21 (0.00%)  0/21 (0.00%)  1/19 (5.26%)  0/20 (0.00%) 
Troponin I increased  1  0/21 (0.00%)  0/21 (0.00%)  1/19 (5.26%)  0/20 (0.00%) 
Metabolism and nutrition disorders         
Dehydration  1  0/21 (0.00%)  2/21 (9.52%)  0/19 (0.00%)  0/20 (0.00%) 
Dyslipidaemia  1  1/21 (4.76%)  0/21 (0.00%)  0/19 (0.00%)  1/20 (5.00%) 
Hypoglycaemia  1  0/21 (0.00%)  0/21 (0.00%)  0/19 (0.00%)  1/20 (5.00%) 
Musculoskeletal and connective tissue disorders         
Arthralgia  1  0/21 (0.00%)  0/21 (0.00%)  0/19 (0.00%)  2/20 (10.00%) 
Muscle spasms  1  0/21 (0.00%)  0/21 (0.00%)  1/19 (5.26%)  0/20 (0.00%) 
Nervous system disorders         
Dizziness  1  1/21 (4.76%)  1/21 (4.76%)  0/19 (0.00%)  2/20 (10.00%) 
Headache  1  0/21 (0.00%)  0/21 (0.00%)  1/19 (5.26%)  0/20 (0.00%) 
Psychiatric disorders         
Depression  1  0/21 (0.00%)  0/21 (0.00%)  1/19 (5.26%)  0/20 (0.00%) 
Renal and urinary disorders         
Renal impairment  1  1/21 (4.76%)  0/21 (0.00%)  0/19 (0.00%)  1/20 (5.00%) 
Reproductive system and breast disorders         
Gynaecomastia  1  0/21 (0.00%)  0/21 (0.00%)  1/19 (5.26%)  0/20 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Cough  1  0/21 (0.00%)  0/21 (0.00%)  0/19 (0.00%)  1/20 (5.00%) 
Skin and subcutaneous tissue disorders         
Dermatitis  1  0/21 (0.00%)  2/21 (9.52%)  0/19 (0.00%)  0/20 (0.00%) 
Toxic skin eruption  1  0/21 (0.00%)  0/21 (0.00%)  1/19 (5.26%)  0/20 (0.00%) 
Vascular disorders         
Arteriosclerosis  1  0/21 (0.00%)  0/21 (0.00%)  1/19 (5.26%)  0/20 (0.00%) 
Hypertension  1  0/21 (0.00%)  0/21 (0.00%)  0/19 (0.00%)  1/20 (5.00%) 
Hypotension  1  0/21 (0.00%)  0/21 (0.00%)  2/19 (10.53%)  0/20 (0.00%) 
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Amgen Inc.
Phone: 866-572-6436
EMail: medinfo@amgen.com
Layout table for additonal information
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT02695420    
Other Study ID Numbers: 20120227
First Submitted: February 25, 2016
First Posted: March 1, 2016
Results First Submitted: January 23, 2020
Results First Posted: January 31, 2020
Last Update Posted: January 31, 2020