Trial Outcomes & Findings for Pharmacokinetics of Oral CK-1827452 in Patients With Stable Heart Failure (NCT NCT00941681)

Results Overview

Area under the curve (AUC) measured in hours \* nanograms per milliliter (hr\*ng/mL) post first dose and pre second dose on day 1. Doses are approximately 12 hours apart in cohort 1 and 3 and 8 hours apart in cohort 2.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

35 participants

Primary outcome timeframe

1 day

Results posted on

2013-02-12

Participant Flow

Participant milestones

Participant milestones
Measure	Cohort 1: MR 50 mg BID Modified-release (MR) 50 mg dose of CK-1827452 twice a day (BID) for 10 days.	Cohort 2: IR 37.5 mg TID Immediate-release (IR) 37.5 mg dose of CK-1827452 three times a day (TID) for 10 days.	Cohort 3: MR 100 mg BID Modified-release (MR) 100 mg dose of CK-1827452 twice a day (BID) for 10 days
Overall Study STARTED	12	11	12
Overall Study COMPLETED	12	10	12
Overall Study NOT COMPLETED	0	1	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pharmacokinetics of Oral CK-1827452 in Patients With Stable Heart Failure

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1: MR 50 mg BID n=12 Participants Modified-release (MR) 50 mg dose of CK-1827452 twice a day (BID) for 10 days.	Cohort 2: IR 37.5 mg TID n=11 Participants Immediate-release (IR) 37.5 mg dose of CK-1827452 three times a day (TID) for 10 days.	Cohort 3: MR 100 mg BID n=12 Participants Modified-release (MR) 100 mg dose of CK-1827452 twice a day (BID) for 10 days	Total n=35 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	7 Participants n=5 Participants	8 Participants n=7 Participants	6 Participants n=5 Participants	21 Participants n=4 Participants
Age, Categorical >=65 years	5 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants	14 Participants n=4 Participants
Age Continuous	64.1 years STANDARD_DEVIATION 7.74 • n=5 Participants	61.1 years STANDARD_DEVIATION 7.97 • n=7 Participants	62.4 years STANDARD_DEVIATION 11.51 • n=5 Participants	62.6 years STANDARD_DEVIATION 9.08 • n=4 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants	11 Participants n=4 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	8 Participants n=7 Participants	8 Participants n=5 Participants	24 Participants n=4 Participants
Region of Enrollment Georgia	12 participants n=5 Participants	11 participants n=7 Participants	12 participants n=5 Participants	35 participants n=4 Participants

PRIMARY outcome

Timeframe: 1 day

Population: PK population (4 patients excluded from cohort 3 analysis due to improper dosing).

Maximum plasma concentration (C max) measured in nanograms per milliliter (ng/mL) post first dose and pre second dose on day 1. Doses are approximately 12 hours apart in cohort 1 and 3 and 8 hours apart in cohort 2.

Outcome measures

Outcome measures
Measure	Cohort 1: MR 50 mg BID n=12 Participants Modified-release (MR) 50 mg dose of CK-1827452 twice a day (BID) for 10 days.	Cohort 2: IR 37.5 mg TID n=11 Participants Immediate-release (IR) 37.5 mg dose of CK-1827452 three times a day (TID) for 10 days.	Cohort 3: MR 100 mg BID n=8 Participants Modified-release (MR) 100 mg dose of CK-1827452 twice a day (BID) for 10 days
C Max (Day 1, Dose 1)	58 ng/mL Standard Deviation 27	243 ng/mL Standard Deviation 148	209 ng/mL Standard Deviation 164

PRIMARY outcome

Timeframe: 1 day

Population: PK population (4 patients excluded from cohort 3 analysis due to improper dosing).

Time of observed maximum plasma concentration (T max) measured in hours (hr) post first dose and pre second dose on day 1. Doses are approximately 12 hours apart in cohort 1 and 3 and 8 hours apart in cohort 2.

Outcome measures

Outcome measures
Measure	Cohort 1: MR 50 mg BID n=12 Participants Modified-release (MR) 50 mg dose of CK-1827452 twice a day (BID) for 10 days.	Cohort 2: IR 37.5 mg TID n=11 Participants Immediate-release (IR) 37.5 mg dose of CK-1827452 three times a day (TID) for 10 days.	Cohort 3: MR 100 mg BID n=8 Participants Modified-release (MR) 100 mg dose of CK-1827452 twice a day (BID) for 10 days
T Max (Day 1, Dose 1)	3.5 hr Standard Deviation 2.9	3.7 hr Standard Deviation 3.7	3.5 hr Standard Deviation 3.9

PRIMARY outcome

Timeframe: 1 day

Population: PK population (4 patients excluded from cohort 3 analysis due to improper dosing).

Area under the curve (AUC) measured in hours \* nanograms per milliliter (hr\*ng/mL) post first dose and pre second dose on day 1. Doses are approximately 12 hours apart in cohort 1 and 3 and 8 hours apart in cohort 2.

Outcome measures

Outcome measures
Measure	Cohort 1: MR 50 mg BID n=12 Participants Modified-release (MR) 50 mg dose of CK-1827452 twice a day (BID) for 10 days.	Cohort 2: IR 37.5 mg TID n=11 Participants Immediate-release (IR) 37.5 mg dose of CK-1827452 three times a day (TID) for 10 days.	Cohort 3: MR 100 mg BID n=8 Participants Modified-release (MR) 100 mg dose of CK-1827452 twice a day (BID) for 10 days
AUC (Day 1, Dose 1)	446 hr*ng/mL Standard Deviation 206	1003 hr*ng/mL Standard Deviation 387	1650 hr*ng/mL Standard Deviation 1354

PRIMARY outcome

Timeframe: 1 day

Population: PK population (4 patients excluded from cohort 3 analysis due to improper dosing and 1 patient excluded from cohort 2 due to sudden death).

Maximum plasma concentration (C max) measured in nanograms per milliliter (ng/mL) post dose on day 10. Only one dose was administered on day 10 (final dose of study).

Outcome measures

Outcome measures
Measure	Cohort 1: MR 50 mg BID n=12 Participants Modified-release (MR) 50 mg dose of CK-1827452 twice a day (BID) for 10 days.	Cohort 2: IR 37.5 mg TID n=10 Participants Immediate-release (IR) 37.5 mg dose of CK-1827452 three times a day (TID) for 10 days.	Cohort 3: MR 100 mg BID n=8 Participants Modified-release (MR) 100 mg dose of CK-1827452 twice a day (BID) for 10 days
C Max (Day 10)	205 ng/mL Standard Deviation 111	420 ng/mL Standard Deviation 158	704 ng/mL Standard Deviation 494

PRIMARY outcome

Timeframe: 1 day

Population: PK population (4 patients excluded from cohort 3 analysis due to improper dosing and 1 patient excluded from cohort 2 due to sudden death).

Time of observed maximum plasma concentration (T max) measured in hours (hr) post dose on day 10. Only one dose was administered on day 10 (final dose of study).

Outcome measures

Outcome measures
Measure	Cohort 1: MR 50 mg BID n=12 Participants Modified-release (MR) 50 mg dose of CK-1827452 twice a day (BID) for 10 days.	Cohort 2: IR 37.5 mg TID n=10 Participants Immediate-release (IR) 37.5 mg dose of CK-1827452 three times a day (TID) for 10 days.	Cohort 3: MR 100 mg BID n=8 Participants Modified-release (MR) 100 mg dose of CK-1827452 twice a day (BID) for 10 days
T Max (Day 10)	1.8 hr Standard Deviation 0.9	1.8 hr Standard Deviation 1.1	2.7 hr Standard Deviation 1.6

PRIMARY outcome

Timeframe: 1 day

Population: PK population (4 patients excluded from cohort 3 analysis due to improper dosing and 1 patient excluded from cohort 2 due to sudden death).

Area under the curve (AUC) measured in hours \* nanograms per milliliter (hr\*ng/mL) post dose on day 10. Only one dose was administered on day 10 (final dose of study).

Outcome measures

Outcome measures
Measure	Cohort 1: MR 50 mg BID n=12 Participants Modified-release (MR) 50 mg dose of CK-1827452 twice a day (BID) for 10 days.	Cohort 2: IR 37.5 mg TID n=10 Participants Immediate-release (IR) 37.5 mg dose of CK-1827452 three times a day (TID) for 10 days.	Cohort 3: MR 100 mg BID n=8 Participants Modified-release (MR) 100 mg dose of CK-1827452 twice a day (BID) for 10 days
AUC (Day 10)	1886 hr*ng/mL Standard Deviation 1002	2118 hr*ng/mL Standard Deviation 623	6457 hr*ng/mL Standard Deviation 5147

SECONDARY outcome

Timeframe: 1 week

Outcome measures

Outcome data not reported

Adverse Events

Cohort 1: MR 50 mg BID

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Cohort 2: IR 37.5 mg TID

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Cohort 3: MR 100 mg BID

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cohort 1: MR 50 mg BID n=12 participants at risk Modified-release (MR) 50 mg dose of CK-1827452 twice a day (BID) for 10 days.	Cohort 2: IR 37.5 mg TID n=11 participants at risk Immediate-release (IR) 37.5 mg dose of CK-1827452 three times a day (TID) for 10 days.	Cohort 3: MR 100 mg BID n=12 participants at risk Modified-release (MR) 100 mg dose of CK-1827452 twice a day (BID) for 10 days
General disorders Sudden death	0.00% 0/12	9.1% 1/11 • Number of events 1	0.00% 0/12

Other adverse events

Other adverse events
Measure	Cohort 1: MR 50 mg BID n=12 participants at risk Modified-release (MR) 50 mg dose of CK-1827452 twice a day (BID) for 10 days.	Cohort 2: IR 37.5 mg TID n=11 participants at risk Immediate-release (IR) 37.5 mg dose of CK-1827452 three times a day (TID) for 10 days.	Cohort 3: MR 100 mg BID n=12 participants at risk Modified-release (MR) 100 mg dose of CK-1827452 twice a day (BID) for 10 days
Cardiac disorders Ventricular extrasystoles	0.00% 0/12	0.00% 0/11	8.3% 1/12 • Number of events 1
General disorders Influenza like illness	0.00% 0/12	0.00% 0/11	8.3% 1/12 • Number of events 1

Additional Information

Project Manager

Cytokinetics, Inc.

Phone: 650-624-2918

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