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PK and Tolerability of IV and Oral CK-1827452 in Patients With Ischemic Cardiomyopathy and Angina

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ClinicalTrials.gov Identifier: NCT00682565
Recruitment Status : Completed
First Posted : May 22, 2008
Results First Posted : February 25, 2010
Last Update Posted : August 21, 2018
Sponsor:
Information provided by (Responsible Party):
Cytokinetics

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Heart Failure
Myocardial Ischemia
Angina Pectoris
Interventions Drug: CK-1827452 24mg and 6 mg iv infusion
Drug: CK-1827452 12.5mg capsule
Drug: CK-1827452 48 mg and 11 mg iv infusion
Drug: CK-1827452 25mg capsule
Drug: Placebo iv infusion
Drug: Placebo capsule
Enrollment 94
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Mid Dose CK-1827452 High Dose CK-1827452 Placebo
Hide Arm/Group Description CK-1827452 20 hour infusion followed by 6 days three times a day oral dose and a final single oral dose CK-1827452 20 hour infusion followed by 6 days three times a day oral dose and a final single oral dose 20 hour infusion followed by 6 days three times a day oral dose and a final single oral dose
Period Title: Overall Study
Started 31 35 29
Completed 30 32 29
Not Completed 1 3 0
Arm/Group Title Mid Dose Active Drug High Dose Active Drug All Placebo Total
Hide Arm/Group Description CK-1827452 20 hour infusion followed by 6 days three times a day oral dose and a final single oral dose CK-1827452 20 hour infusion followed by 6 days three times a day oral dose and a final single oral dose 20 hour infusion followed by 6 days three times a day oral dose and a final single oral dose Total of all reporting groups
Overall Number of Baseline Participants 31 34 29 94
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 31 participants 34 participants 29 participants 94 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
11
  35.5%
16
  47.1%
17
  58.6%
44
  46.8%
>=65 years
20
  64.5%
18
  52.9%
12
  41.4%
50
  53.2%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 31 participants 34 participants 29 participants 94 participants
65.2  (10.0) 62.6  (8.1) 62.3  (9.8) 63.4  (9.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 31 participants 34 participants 29 participants 94 participants
Female
8
  25.8%
5
  14.7%
6
  20.7%
19
  20.2%
Male
23
  74.2%
29
  85.3%
23
  79.3%
75
  79.8%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 31 participants 34 participants 29 participants 94 participants
Russian Federation 0 14 7 21
Georgia 31 20 22 73
1.Primary Outcome
Title Participants Stopping Exercise Treadmill Test 3 (ETT-3) for Angina at Stage Earlier Than Baseline Exercise Treadmill Test (ETT-B)
Hide Description The Modified Naughton Exercise Treadmill Test was employed in this study. Exercise Treadmill Test 3 (ETT-3) was performed during the last 2 hours of the 20-hour infusion of study drug or placebo. Baseline Exercise Treadmill Test (ETT-B) was performed prior to dosing.
Time Frame 1 day
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety ETT Population consists of all patients in the Randomized Population who received any study drug and who performed ETT-3.
Arm/Group Title Mid Dose Active Drug High Dose Active Drug All Placebo
Hide Arm/Group Description:
CK-1827452 20 hour infusion followed by 6 days three times a day oral dose and a final single oral dose
CK-1827452 20 hour infusion followed by 6 days three times a day oral dose and a final single oral dose
20 hour infusion followed by 6 days three times a day oral dose and a final single oral dose
Overall Number of Participants Analyzed 31 34 29
Measure Type: Number
Unit of Measure: Participants
0 0 1
2.Secondary Outcome
Title Participants Stopping ETT-3 for Any Reason at Stage Earlier Than ETT-B
Hide Description The Modified Naughton Exercise Treadmill Test was employed in this study. Exercise Treadmill Test 3 (ETT-3) was performed during the last 2 hours of the 20-hour infusion of study drug or placebo. Baseline Exercise Treadmill Test (ETT-B) was performed prior to dosing.
Time Frame 1 day
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety ETT Population consists of all patients in the Randomized Population who received any study drug and who performed ETT-3.
Arm/Group Title Mid Dose Active Drug High Dose Active Drug All Placebo
Hide Arm/Group Description:
CK-1827452 20 hour infusion followed by 6 days three times a day oral dose and a final single oral dose
CK-1827452 20 hour infusion followed by 6 days three times a day oral dose and a final single oral dose
20 hour infusion followed by 6 days three times a day oral dose and a final single oral dose
Overall Number of Participants Analyzed 31 34 29
Measure Type: Number
Unit of Measure: Participants
4 2 1
3.Secondary Outcome
Title Increase in Exercise Duration During ETT-3 vs. ETT-B
Hide Description [Not Specified]
Time Frame 1 day
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety ETT Population consists of all patients in the Randomized Population who received any study drug and who performed ETT-3.
Arm/Group Title Mid Dose Active Drug High Dose Active Drug All Placebo
Hide Arm/Group Description:
CK-1827452 20 hour infusion followed by 6 days three times a day oral dose and a final single oral dose
CK-1827452 20 hour infusion followed by 6 days three times a day oral dose and a final single oral dose
20 hour infusion followed by 6 days three times a day oral dose and a final single oral dose
Overall Number of Participants Analyzed 31 34 29
Mean (Standard Deviation)
Unit of Measure: seconds
41.5  (113.1) 40.5  (70.6) 60.1  (71.2)
4.Secondary Outcome
Title Participants Stopping ETT-3 for Angina at Any Stage
Hide Description

This Outcome Measure includes all participants who stopped ETT-3 for angina at any stage, not only those who stopped at a stage earlier than ETT-B.

Note: All 9 subjects who stopped ETT-3 for angina also stopped ETT-B for angina.

Time Frame 1 day
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety ETT Population consists of all patients in the Randomized Population who received any study drug and who performed ETT-3.
Arm/Group Title Mid Dose Active Drug High Dose Active Drug All Placebo
Hide Arm/Group Description:
CK-1827452 20 hour infusion followed by 6 days three times a day oral dose and a final single oral dose
CK-1827452 20 hour infusion followed by 6 days three times a day oral dose and a final single oral dose
20 hour infusion followed by 6 days three times a day oral dose and a final single oral dose
Overall Number of Participants Analyzed 31 34 29
Measure Type: Number
Unit of Measure: Participants
0 7 2
5.Secondary Outcome
Title Participants With 1 mm ST Segment Depression During ETT-3
Hide Description ST Segment Depression measured by Electrocardiography while performing ETT-3.
Time Frame 1 day
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety ETT Population consists of all patients in the Randomized Population who received any study drug and who performed ETT-3. However, majority of patients did not have ECGs assessable (per protocol) for 1 mm ST depression.
Arm/Group Title Mid Dose Active Drug High Dose Active Drug All Placebo
Hide Arm/Group Description:
CK-1827452 20 hour infusion followed by 6 days three times a day oral dose and a final single oral dose
CK-1827452 20 hour infusion followed by 6 days three times a day oral dose and a final single oral dose
20 hour infusion followed by 6 days three times a day oral dose and a final single oral dose
Overall Number of Participants Analyzed 10 12 7
Measure Type: Number
Unit of Measure: Participants
0 1 2
Time Frame 2 - 3 weeks
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Cohort 1 Active Drug Cohort 2 Active Drug All Placebo Total
Hide Arm/Group Description CK-1827452 20 hour infusion followed by 6 days three times a day oral dose and a final single oral dose CK-1827452 20 hour infusion followed by 6 days three times a day oral dose and a final single oral dose 20 hour infusion followed by 6 days three times a day oral dose and a final single oral dose All Patients
All-Cause Mortality
Cohort 1 Active Drug Cohort 2 Active Drug All Placebo Total
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Cohort 1 Active Drug Cohort 2 Active Drug All Placebo Total
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/31 (0.00%)      1/34 (2.94%)      0/29 (0.00%)      1/94 (1.06%)    
Cardiac disorders         
Acute Coronary Syndrome  1 [1]  0/31 (0.00%)  0 1/34 (2.94%)  1 0/29 (0.00%)  0 1/94 (1.06%)  1
Injury, poisoning and procedural complications         
Post-procedural Myocardial Infarction  1 [2]  0/31 (0.00%)  0 1/34 (2.94%)  1 0/29 (0.00%)  0 1/94 (1.06%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (10.1)
[1]
Reported as unrelated to treatment by Investigator but upgraded to possibly related by the sponsor.
[2]
Reported as unrelated to treatment by Investigator.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Cohort 1 Active Drug Cohort 2 Active Drug All Placebo Total
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/31 (6.45%)      7/34 (20.59%)      3/29 (10.34%)      12/94 (12.77%)    
Cardiac disorders         
Ventricular Extrasystoles  1  0/31 (0.00%)  0 2/34 (5.88%)  3 0/29 (0.00%)  0 2/94 (2.13%)  3
Eye disorders         
Photopsia  1  0/31 (0.00%)  0 1/34 (2.94%)  1 1/29 (3.45%)  1 2/94 (2.13%)  2
General disorders         
Infusion Site Pain  1  1/31 (3.23%)  1 0/34 (0.00%)  0 1/29 (3.45%)  1 2/94 (2.13%)  2
Respiratory, thoracic and mediastinal disorders         
Dyspnea  1  0/31 (0.00%)  0 3/34 (8.82%)  3 1/29 (3.45%)  1 4/94 (4.26%)  4
Vascular disorders         
Hypotension  1  1/31 (3.23%)  1 1/34 (2.94%)  1 0/29 (0.00%)  0 2/94 (2.13%)  2
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (10.1)
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.
Sponsor intends to publish the results of the trial in collaboration with the Investigators.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Director
Organization: Cytokinetics, Inc.
Phone: 650-624-3053
Layout table for additonal information
Responsible Party: Cytokinetics
ClinicalTrials.gov Identifier: NCT00682565     History of Changes
Other Study ID Numbers: CY 1221
First Submitted: May 20, 2008
First Posted: May 22, 2008
Results First Submitted: November 30, 2009
Results First Posted: February 25, 2010
Last Update Posted: August 21, 2018