Trial Outcomes & Findings for PK and Tolerability of IV and Oral CK-1827452 in Patients With Ischemic Cardiomyopathy and Angina (NCT NCT00682565)

NCT ID: NCT00682565

Last Updated: 2018-08-21

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 94 participants
• Primary outcome timeframe: 1 day
• Results posted on: 2018-08-21

Participant Flow

Participant milestones

Measure	Mid Dose CK-1827452 CK-1827452 20 hour infusion followed by 6 days three times a day oral dose and a final single oral dose	High Dose CK-1827452 CK-1827452 20 hour infusion followed by 6 days three times a day oral dose and a final single oral dose	Placebo 20 hour infusion followed by 6 days three times a day oral dose and a final single oral dose
Overall Study STARTED	31	35	29
Overall Study COMPLETED	30	32	29
Overall Study NOT COMPLETED	1	3	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Mid Dose Active Drug n=31 Participants CK-1827452 20 hour infusion followed by 6 days three times a day oral dose and a final single oral dose	High Dose Active Drug n=34 Participants CK-1827452 20 hour infusion followed by 6 days three times a day oral dose and a final single oral dose	All Placebo n=29 Participants 20 hour infusion followed by 6 days three times a day oral dose and a final single oral dose	Total n=94 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Age, Categorical Between 18 and 65 years	11 Participants n=93 Participants	16 Participants n=4 Participants	17 Participants n=27 Participants	44 Participants n=483 Participants
Age, Categorical >=65 years	20 Participants n=93 Participants	18 Participants n=4 Participants	12 Participants n=27 Participants	50 Participants n=483 Participants
Age, Continuous	65.2 years STANDARD_DEVIATION 10.0 • n=93 Participants	62.6 years STANDARD_DEVIATION 8.1 • n=4 Participants	62.3 years STANDARD_DEVIATION 9.8 • n=27 Participants	63.4 years STANDARD_DEVIATION 9.3 • n=483 Participants
Sex: Female, Male Female	8 Participants n=93 Participants	5 Participants n=4 Participants	6 Participants n=27 Participants	19 Participants n=483 Participants
Sex: Female, Male Male	23 Participants n=93 Participants	29 Participants n=4 Participants	23 Participants n=27 Participants	75 Participants n=483 Participants
Region of Enrollment Russian Federation	0 participants n=93 Participants	14 participants n=4 Participants	7 participants n=27 Participants	21 participants n=483 Participants
Region of Enrollment Georgia	31 participants n=93 Participants	20 participants n=4 Participants	22 participants n=27 Participants	73 participants n=483 Participants

PRIMARY outcome

Timeframe: 1 day

Population: The Safety ETT Population consists of all patients in the Randomized Population who received any study drug and who performed ETT-3.

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.

Outcome measures

Measure	Mid Dose Active Drug n=31 Participants CK-1827452 20 hour infusion followed by 6 days three times a day oral dose and a final single oral dose	High Dose Active Drug n=34 Participants CK-1827452 20 hour infusion followed by 6 days three times a day oral dose and a final single oral dose	All Placebo n=29 Participants 20 hour infusion followed by 6 days three times a day oral dose and a final single oral dose
Participants Stopping Exercise Treadmill Test 3 (ETT-3) for Angina at Stage Earlier Than Baseline Exercise Treadmill Test (ETT-B)	0 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: 1 day

Population: The Safety ETT Population consists of all patients in the Randomized Population who received any study drug and who performed ETT-3.

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.

Outcome measures

Measure	Mid Dose Active Drug n=31 Participants CK-1827452 20 hour infusion followed by 6 days three times a day oral dose and a final single oral dose	High Dose Active Drug n=34 Participants CK-1827452 20 hour infusion followed by 6 days three times a day oral dose and a final single oral dose	All Placebo n=29 Participants 20 hour infusion followed by 6 days three times a day oral dose and a final single oral dose
Participants Stopping ETT-3 for Any Reason at Stage Earlier Than ETT-B	4 Participants	2 Participants	1 Participants

SECONDARY outcome

Timeframe: 1 day

Population: The Safety ETT Population consists of all patients in the Randomized Population who received any study drug and who performed ETT-3.

Outcome measures

Measure	Mid Dose Active Drug n=31 Participants CK-1827452 20 hour infusion followed by 6 days three times a day oral dose and a final single oral dose	High Dose Active Drug n=34 Participants CK-1827452 20 hour infusion followed by 6 days three times a day oral dose and a final single oral dose	All Placebo n=29 Participants 20 hour infusion followed by 6 days three times a day oral dose and a final single oral dose
Increase in Exercise Duration During ETT-3 vs. ETT-B	41.5 seconds Standard Deviation 113.1	40.5 seconds Standard Deviation 70.6	60.1 seconds Standard Deviation 71.2

SECONDARY outcome

Timeframe: 1 day

Population: The Safety ETT Population consists of all patients in the Randomized Population who received any study drug and who performed ETT-3.

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.

Outcome measures

Measure	Mid Dose Active Drug n=31 Participants CK-1827452 20 hour infusion followed by 6 days three times a day oral dose and a final single oral dose	High Dose Active Drug n=34 Participants CK-1827452 20 hour infusion followed by 6 days three times a day oral dose and a final single oral dose	All Placebo n=29 Participants 20 hour infusion followed by 6 days three times a day oral dose and a final single oral dose
Participants Stopping ETT-3 for Angina at Any Stage	0 Participants	7 Participants	2 Participants

SECONDARY outcome

Timeframe: 1 day

Population: 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.

ST Segment Depression measured by Electrocardiography while performing ETT-3.

Outcome measures

Measure	Mid Dose Active Drug n=10 Participants CK-1827452 20 hour infusion followed by 6 days three times a day oral dose and a final single oral dose	High Dose Active Drug n=12 Participants CK-1827452 20 hour infusion followed by 6 days three times a day oral dose and a final single oral dose	All Placebo n=7 Participants 20 hour infusion followed by 6 days three times a day oral dose and a final single oral dose
Participants With 1 mm ST Segment Depression During ETT-3	0 Participants	1 Participants	2 Participants

Adverse Events

Cohort 1 Active Drug

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Cohort 2 Active Drug

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

All Placebo

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Total

Serious events: 1 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Measure	Cohort 1 Active Drug n=31 participants at risk CK-1827452 20 hour infusion followed by 6 days three times a day oral dose and a final single oral dose	Cohort 2 Active Drug n=34 participants at risk CK-1827452 20 hour infusion followed by 6 days three times a day oral dose and a final single oral dose	All Placebo n=29 participants at risk 20 hour infusion followed by 6 days three times a day oral dose and a final single oral dose	Total n=94 participants at risk All Patients
Cardiac disorders Acute Coronary Syndrome	0.00% 0/31 • 2 - 3 weeks	2.9% 1/34 • Number of events 1 • 2 - 3 weeks	0.00% 0/29 • 2 - 3 weeks	1.1% 1/94 • Number of events 1 • 2 - 3 weeks
Injury, poisoning and procedural complications Post-procedural Myocardial Infarction	0.00% 0/31 • 2 - 3 weeks	2.9% 1/34 • Number of events 1 • 2 - 3 weeks	0.00% 0/29 • 2 - 3 weeks	1.1% 1/94 • Number of events 1 • 2 - 3 weeks

Other adverse events

Measure	Cohort 1 Active Drug n=31 participants at risk CK-1827452 20 hour infusion followed by 6 days three times a day oral dose and a final single oral dose	Cohort 2 Active Drug n=34 participants at risk CK-1827452 20 hour infusion followed by 6 days three times a day oral dose and a final single oral dose	All Placebo n=29 participants at risk 20 hour infusion followed by 6 days three times a day oral dose and a final single oral dose	Total n=94 participants at risk All Patients
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/31 • 2 - 3 weeks	8.8% 3/34 • Number of events 3 • 2 - 3 weeks	3.4% 1/29 • Number of events 1 • 2 - 3 weeks	4.3% 4/94 • Number of events 4 • 2 - 3 weeks
Vascular disorders Hypotension	3.2% 1/31 • Number of events 1 • 2 - 3 weeks	2.9% 1/34 • Number of events 1 • 2 - 3 weeks	0.00% 0/29 • 2 - 3 weeks	2.1% 2/94 • Number of events 2 • 2 - 3 weeks
General disorders Infusion Site Pain	3.2% 1/31 • Number of events 1 • 2 - 3 weeks	0.00% 0/34 • 2 - 3 weeks	3.4% 1/29 • Number of events 1 • 2 - 3 weeks	2.1% 2/94 • Number of events 2 • 2 - 3 weeks
Eye disorders Photopsia	0.00% 0/31 • 2 - 3 weeks	2.9% 1/34 • Number of events 1 • 2 - 3 weeks	3.4% 1/29 • Number of events 1 • 2 - 3 weeks	2.1% 2/94 • Number of events 2 • 2 - 3 weeks
Cardiac disorders Ventricular Extrasystoles	0.00% 0/31 • 2 - 3 weeks	5.9% 2/34 • Number of events 3 • 2 - 3 weeks	0.00% 0/29 • 2 - 3 weeks	2.1% 2/94 • Number of events 3 • 2 - 3 weeks

Additional Information

Medical Director

Cytokinetics, Inc.

Phone: 650-624-3053

Results disclosure agreements

• Principal investigator is a sponsor employee Sponsor intends to publish the results of the trial in collaboration with the Investigators.
• Publication restrictions are in place

Restriction type: OTHER