Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT00941681 | Pharmacokinetics of Oral CK-1827452 in Patients With Stable Heart Failure | PHASE2 | COMPLETED | 35 | — | — | Apr 1, 2009 | Oct 1, 2009 | Feb 12, 2013 | 3 | Georgia |
| NCT00682565 | PK and Tolerability of IV and Oral CK-1827452 in Patients With Ischemic Cardiomyopathy and Angina | PHASE2 | COMPLETED | 94 | — | — | Apr 1, 2008 | Mar 1, 2009 | Aug 21, 2018 | 14 | Georgia, Russia |
| NCT00624442 | A Study of CK-1827452 Infusion in Stable Heart Failure | PHASE2 | COMPLETED | 45 | — | — | Apr 1, 2007 | Feb 1, 2009 | May 14, 2021 | 17 | United States, Georgia +2 |
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.
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.
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.
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).
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).
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).
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.
Pooled analysis of the echocardiographic measure systolic ejection time from echocardiograms taken at all timepoints. The systolic ejection time is the period during which the aortic valve is open and blood is flowing across the valve. Echocardiograms from cohorts 1,2,3,4 and 5 (564 echocardiograms) were binned into either placebo group or 1 of 6 groups based on plasma concentration of CK-1827452.
Pooled analysis of the echocardiographic measure fractional shortening from echocardiograms taken at all timepoints. Fractional shortening is the percentage of change from baseline in the left ventricular cavity dimension with systole. Echocardiograms from cohorts 1,2,3,4 and 5 (564 echocardiograms) were binned into either placebo group or 1 of 6 groups based on plasma concentration of CK-1827452.
| Arm | Type | Description |
|---|---|---|
| Cohort 1: MR 50 mg BID | EXPERIMENTAL | Modified-release (MR) 50 mg dose of CK-1827452 twice a day (BID) for 10 days. |
| Cohort 2: IR 37.5 mg TID | EXPERIMENTAL | Immediate-release (IR) 37.5 mg dose of CK-1827452 three times a day (TID) for 10 days. |
| Cohort 3: MR 100 mg BID | EXPERIMENTAL | Modified-release (MR) 100 mg dose of CK-1827452 twice a day (BID) for 10 days |
| Mid Dose CK-1827452 or Placebo | EXPERIMENTAL | CK-1827452 I.V. infusion for 2 hours at 24mg/hr followed by 18 hours at 6mg/hr or placebo, followed by 6 days three times a day oral dose and a final single oral dose |
| High Dose CK-1827452 or Placebo | EXPERIMENTAL | CK-1827452 I.V. infusion for 2 hours at 48mg/hr followed by 18 hours at 11mg/hr or placebo, followed by 6 days three times a day oral dose and a final single oral dose |
| Cohort 1 | EXPERIMENTAL | 4 treatment periods with a 2 hour infusion. The 4 treatment periods consist of 3 escalating dose levels of CK-1827452 and 1 placebo treatment randomized into the dose escalation sequence. Treatment periods occur at least 7 days apart. |
| Cohort 2 | EXPERIMENTAL | 4 treatment periods with a 2 hour infusion. The 4 treatment periods consist of 3 escalating dose levels of CK-1827452 and 1 placebo treatment randomized into the dose escalation sequence. Treatment periods occur at least 7 days apart. |
| Cohort 3 | EXPERIMENTAL | 4 treatment periods with a 24 hour infusion. The 4 treatment periods consist of 3 escalating dose levels of CK-1827452 and 1 placebo treatment randomized into the dose escalation sequence. Treatment periods occur at least 7 days apart. |
| Cohort 4 | EXPERIMENTAL | 4 treatment periods with a 24 hour infusion. The 4 treatment periods consist of 3 escalating dose levels of CK-1827452 and 1 placebo treatment randomized into the dose escalation sequence. Treatment periods occur at least 7 days apart. |
| Cohort 5 | EXPERIMENTAL | 2 treatment periods with a 72 hour infusion. The 2 treatment periods are randomly assigned and consist of 1 dose level of CK-1827452 (with dose de-escalation possible depending on tolerability) and 1 placebo treatment. Treatment period 2 occurs at least 7 days after the conclusion of period 1. |
| Name | Type | Description |
|---|---|---|
| CK-1827452 | DRUG | 50 mg MR CK-1827452 BID for 10 days |
| CK-1827452 24mg and 6 mg iv infusion | DRUG | I.V. infusion for 2 hours at 24mg/hr followed by 18 hours at 6mg/hr |
| CK-1827452 12.5mg capsule | DRUG | 12.5mg oral immediate release capsule |
| CK-1827452 48 mg and 11 mg iv infusion | DRUG | I.V. infusion for 2 hours at 48mg/hr followed by 18 hours at 11mg/hr |
| CK-1827452 25mg capsule | DRUG | 25mg oral immediate release capsule |
| Placebo iv infusion | DRUG | Matching placebo iv infusion |
| Placebo capsule | DRUG | Matching placebo oral immediate release capsule |
| Placebo | DRUG | IV infusion for 2 hours |
Inclusion Criteria: 1. The patient has signed an Informed Consent Form/Patient Information Sheet for this study approved by the governing Institutional Review Board (IRB) or Independent Ethics Committee (IEC) 2. The patient is at least 18 years old at the time of consent 3. Left ventricular ejectio...