Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This study will assess the safety, tolerability, and pharmacodynamics of CK-1827452 infusion in patients with stable heart failure.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CK-1827452 | Drug | IV infusion for 1 hour at 0.125 mg/kg/h followed by 1 hour at 0.0625 mg/kg/h |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline of Systolic Ejection Time at Various CK-1827452 Plasma Concentrations | 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. | 4 days |
| Change From Baseline of Fractional Shortening at Various CK-1827452 Plasma Concentrations | 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. | 4 days |
| Measure | Description | Time Frame |
|---|---|---|
| CK-1827452 Maximum Observed Plasma Concentration (Cmax) | Determined by evaluation of plasma concentrations from blood samples collected prior to dosing and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 12, 24 and 48 hours after initiation of study drug infusion | 2 days |
| CK-1827452 Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Plasma Concentration (AUClast) |
Not provided
Inclusion Criteria
Patient is male, or female of non-childbearing potential (two years post-menopausal or surgically sterilized)
Female patients must have a negative urine pregnancy test prior to entry into the study
Patient is 18 years old or greater
Patient has given signed informed consent
Patient is considered to be in suitable health in the opinion of the investigator, as determined by:
Patient has pre-study clinical laboratory findings that are within normal range, or if outside of the normal range, should not preclude participation in the study in the opinion of the investigator (see Exclusion Criteria, below, for exceptions)
Patient has a documented diagnosis of heart failure with an ejection fraction of less than 40%
Patient has been on a stable dose of a beta blocker and an ACE (angiotensin-converting enzyme) inhibitor or an ARB (angiotensin II receptor blocker) for at least 4 weeks. If prescribed, diuretics must have been administered according to a consistent regimen for at least 4 weeks
Patient is currently in sinus rhythm
Patient has interpretable echocardiographic images on a screening echocardiogram
Exclusion Criteria
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California, San Diego Medical Center | San Diego | California | 92103 | United States | ||
| Christiana Care Health Services, Inc. |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25951506 | Derived | Vu T, Ma P, Xiao JJ, Wang YM, Malik FI, Chow AT. Population pharmacokinetic-pharmacodynamic modeling of omecamtiv mecarbil, a cardiac myosin activator, in healthy volunteers and patients with stable heart failure. J Clin Pharmacol. 2015 Nov;55(11):1236-47. doi: 10.1002/jcph.538. Epub 2015 Jul 14. | |
| 21856481 | Derived |
Not provided
Not provided
Not provided
The recruitment period was from April 2007 to January 2009.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1 | 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. |
| FG001 | Cohort 2 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| 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. |
|
| CK-1827452 |
| Drug |
IV infusion for 1 hour at 0.25 mg/kg/h followed by 1 hour at 0.125 mg/kg/h |
|
| CK-1827452 | Drug | IV infusion for 1 hour at 0.5 mg/kg/h followed by 1 hour at 0.25 mg/kg/h |
|
| CK-1827452 | Drug | IV infusion for 1 hour at 0.75 mg/kg/h followed by 1 hour at 0.375 mg/kg/h |
|
| CK-1827452 | Drug | IV infusion for 1 hour at 1.0 mg/kg/h followed by 1 hour at 0.5 mg/kg/h |
|
| CK-1827452 | Drug | IV infusion for 1 hour at 0.25 mg/kg/h followed by 1 hour at 0.125 mg/kg/h followed by 22 hours at 0.025 mg/kg/h |
|
| CK-1827452 | Drug | IV infusion for 1 hour at 0.5 mg/kg/h followed by 1 hour at 0.25 mg/kg/h followed by 22 hours at 0.05 mg/kg/h |
|
| CK-1827452 | Drug | IV infusion for 1 hour at 1.0 mg/kg/h followed by 1 hour at 0.5 mg/kg/h followed by 22 hours at 0.1 mg/kg/h |
|
| Placebo | Drug | IV infusion for 2 hours |
|
| Placebo | Drug | IV infusion for 24 hours |
|
| CK-1827452 | Drug | IV infusion for 1 hour at 1.0 mg/kg/h followed 1 hour at 0.5 mg/kg/h followed by 70 hours at 0.1 mg/kg/h |
|
| Placebo | Drug | IV infusion for 72 hours |
|
| CK-1827452 | Drug | IV infusion for 1 hour at 0.75 mg/kg/h followed 1 hour at 0.5 mg/kg/h followed by 70 hours at 0.1 mg/kg/h |
|
| CK-1827452 | Drug | IV infusion for 1 hour at 0.25 mg/kg/h followed by 23 hours at 0.025 mg/kg/h |
|
| CK-1827452 | Drug | IV infusion for 1 hour at 0.5 mg/kg/h followed by 23 hours at 0.05 mg/kg/h |
|
| CK-1827452 | Drug | IV infusion for 1 hour at 1.0 mg/kg/h followed by 23 hours at 0.1 mg/kg/h |
|
Determined by evaluation of plasma concentrations from blood samples collected prior to dosing and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 12, 24 and 48 hours after initiation of study drug infusion |
| 2 days |
| Newark |
| Delaware |
| 19713 |
| United States |
| Diagnostic Services Clinic | Tbilisi | Georgia |
| Russian Cardiological Research and Production Complex | Moscow | 121552 | Russia |
| Dzhanelidze Research Institute for Emergency Medical Care | Saint Petersburg | 192242 | Russia |
| Almazov Federal Heart, Blood and Endocrinology Center | Saint Petersburg | 194156 | Russia |
| St. Petersburg State Medical University | Saint Petersburg | 197089 | Russia |
| Castle Hill Hospital, University of Hull | Hull | England | HU16 5JQ | United Kingdom |
| King's College Hospital | London | England | SE5 9RS | United Kingdom |
| St. George's Hospital | London | England | SW17 ORE | United Kingdom |
| St. Mary's Hospital & Imperial College | London | England | W2 1LA | United Kingdom |
| Manchester Heart Centre, Manchester Royal Infirmary | Manchester | England | M13 9WL | United Kingdom |
| ICON Development Solutions | Manchester | England | M15 6SH | United Kingdom |
| Wythenshawe Hospital | Manchester | England | M23 9LT | United Kingdom |
| Northwick Park Hospital | Middlesex | England | HA1 3UJ | United Kingdom |
| Ninewells Hospital and Medical School | Dundee | Scotland | DD1 9SY | United Kingdom |
| BHF Cardiovascular Centre | Glasgow | Scotland | G12 8TA | United Kingdom |
| Cleland JG, Teerlink JR, Senior R, Nifontov EM, Mc Murray JJ, Lang CC, Tsyrlin VA, Greenberg BH, Mayet J, Francis DP, Shaburishvili T, Monaghan M, Saltzberg M, Neyses L, Wasserman SM, Lee JH, Saikali KG, Clarke CP, Goldman JH, Wolff AA, Malik FI. The effects of the cardiac myosin activator, omecamtiv mecarbil, on cardiac function in systolic heart failure: a double-blind, placebo-controlled, crossover, dose-ranging phase 2 trial. Lancet. 2011 Aug 20;378(9792):676-83. doi: 10.1016/S0140-6736(11)61126-4. |
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. |
| FG002 | Cohort 3 | 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. |
| FG003 | Cohort 4 | 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 sequence. Treatment periods occur at least 7 days apart. |
| FG004 | Cohort 5 | 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. |
| COMPLETED |
|
| NOT COMPLETED |
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1 | 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. |
| BG001 | Cohort 2 | 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. |
| BG002 | Cohort 3 | 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. |
| BG003 | Cohort 4 | 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 sequence. Treatment periods occur at least 7 days apart. |
| BG004 | Cohort 5 | 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. |
| BG005 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline of Systolic Ejection Time at Various CK-1827452 Plasma Concentrations | 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. | Pharmacodynamic Population. 4-way crossover design for cohorts 1-4 and 2-way crossover for cohort 5 requires multiple dosing events per participant. Also, multiple PK/PD assessments occur per dosing event. | Posted | Least Squares Mean | Standard Error | msec | 4 days |
|
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary | Change From Baseline of Fractional Shortening at Various CK-1827452 Plasma Concentrations | 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. | Pharmacodynamic Population. 4-way crossover design for cohorts 1-4 and 2-way crossover for cohort 5 requires multiple dosing events per participant. Also, multiple PK/PD assessments occur per dosing event. | Posted | Least Squares Mean | Standard Error | Percentage of change | 4 days |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | CK-1827452 Maximum Observed Plasma Concentration (Cmax) | Determined by evaluation of plasma concentrations from blood samples collected prior to dosing and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 12, 24 and 48 hours after initiation of study drug infusion | Posted | Mean | Standard Deviation | nanogram/milliliter | 2 days |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | CK-1827452 Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Plasma Concentration (AUClast) | Determined by evaluation of plasma concentrations from blood samples collected prior to dosing and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 12, 24 and 48 hours after initiation of study drug infusion | Posted | Mean | Standard Deviation | hour x nanogram/milliliter | 2 days |
|
5 weeks
Participants were placed in bins based on their first hour loading dose or placebo. Because multiple dosing events occurred in all cohorts and some loading dose overlap occurs between Cohort 1 and 2 as well as between Cohort 3 and 4, participant numbers in this section do not match the numbers in the participant flow section.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | 0 | 41 | 8 | 41 | |||
| EG001 | Cohorts 1 and/or 2, Loading Dose of 0.125 mg/kg/hr | Loading dose is the first hour of IV infusion. | 0 | 8 | 1 | 8 | ||
| EG002 | Cohorts 1 and/or 2, Loading Dose of 0.25 mg/kg/hr | Loading dose is the first hour of IV infusion. | 0 | 9 | 0 | 9 | ||
| EG003 | Cohorts 1 and/or 2, Loading Dose of 0.5 mg/kg/hr | Loading dose is the first hour of IV infusion. | 0 | 16 | 1 | 16 | ||
| EG004 | Cohorts 1 and/or 2, Loading Dose of 1.0 mg/kg/hr | Loading dose is first hour of IV infusion. | 0 | 6 | 4 | 6 | ||
| EG005 | Cohorts 1 and/or 2, Loading Dose of 0.75 mg/kg/hr | Loading dose is the first hour of IV infusion. | 0 | 8 | 0 | 8 | ||
| EG006 | Cohort 2, Loading Dose of 2.2 mg/kg/hr | Loading dose is first hour of IV infusion. This dose level occurred in 1 patient due to accidental overdose. | 1 | 1 | 1 | 1 | ||
| EG007 | Cohorts 3 and 4, Loading Dose of 0.25 mg/kg/hr | Loading dose is first hour of IV infusion. | 1 | 18 | 6 | 18 | ||
| EG008 | Cohorts 3 and 4, Loading Dose of 0.5 mg/kg/hr | Loading dose is first hour of IV infusion. | 1 | 18 | 4 | 18 | ||
| EG009 | Cohorts 3 and 4, Loading Dose of 1.0 mg/kg/hr | Loading dose is first hour of IV infusion. | 0 | 16 | 1 | 16 | ||
| EG010 | Cohort 5, Loading Dose of 0.75 mg/kg/hr | Loading dose is first hour of IV infusion. | 0 | 2 | 1 | 2 | ||
| EG011 | Cohort 5, Loading Dose of 1.0 mg/kg/hr | Loading dose is first hour of IV infusion. | 0 | 8 | 2 | 8 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Non ST elevation MI in patient with drug overdose | Cardiac disorders | MedDRA 10.0 | Non-systematic Assessment |
| |
| Septicemia in setting of diabetic foot ulcer | Metabolism and nutrition disorders | MedDRA 10.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 10.0 | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Orthostatic hypotension | Vascular disorders | MedDRA 10.0 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 10.0 | Systematic Assessment |
| |
| Somnolence | Nervous system disorders | MedDRA 10.0 | Systematic Assessment |
| |
| Troponin increased | Investigations | MedDRA 10.0 | Systematic Assessment |
| |
| Dizziness postural | Nervous system disorders | MedDRA 10.0 | Systematic Assessment |
| |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | MedDRA 10.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 10.0 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA 10.0 | Systematic Assessment |
| |
| Infusion site pain | General disorders | MedDRA 10.0 | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 10.0 | Systematic Assessment |
| |
| Sinus bradycardia | Cardiac disorders | MedDRA 10.0 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 10.0 | Systematic Assessment |
|
Other Adverse Event table shows treatment emergent adverse events that occurred in two or more patients. Total for Other Adverse Events is the number of patients affected by an adverse event where an adverse event occurred in two or more patients.
Sponsor intends to publish the results of the trial in collaboration with the Investigators.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director | Cytokinetics, Inc. | (650) 624-3011 |
| ID | Term |
|---|---|
| D006333 | Heart Failure |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C547293 | omecamtiv mecarbil |
Not provided
Not provided
Not provided
| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
|
| Georgia |
|
| Russian Federation |
|
| United Kingdom |
|
| Ejection Fraction msec Change from Baseline |
|
| Placebo corrected change from baseline least squares mean +/- the standard error of the mean | ANCOVA | ANCOVA analysis is based on the following model: CFB Parameter = Bin Group + Baseline + Error, treating patients as a random effect. | <0.0001 | p-value is not adjusted for multiple comparison Threshold for statistical significance: p<0.05 | LSM placebo corrected diff from baseline | 18 | 2-Sided | 95 | 10 | 27 | Superiority or Other (legacy) |
| Placebo corrected change from baseline least squares mean +/- the standard error of the mean | ANCOVA | ANCOVA analysis is based on the following model: CFB Parameter = Bin Group + Baseline + Error, treating patients as a random effect. | <0.0001 | p-value is not adjusted for multiple comparison Threshold for statistical significance: p<0.05 | LSM placebo corrected diff from baseline | 47 | 95 | 38 | 56 | Superiority or Other (legacy) |
| Placebo corrected change from baseline least squares mean +/- the standard error of the mean | ANCOVA | ANCOVA analysis is based on the following model: CFB Parameter = Bin Group + Baseline + Error, treating patients as a random effect. | <0.0001 | p-value is not adjusted for multiple comparison Threshold for statistical significance: p<0.05 | LSM placebo corrected diff from baseline | 58 | 2-Sided | 95 | 46 | 70 | Superiority or Other (legacy) |
| Placebo corrected change from baseline least squares mean +/- the standard error of the mean | ANCOVA | ANCOVA analysis is based on the following model: CFB Parameter = Bin Group + Baseline + Error, treating patients as a random effect. | <0.0001 | p-value is not adjusted for multiple comparison Threshold for statistical significance: p<0.05 | LSM placebo corrected diff from baseline | 59 | 2-Sided | 95 | 47 | 72 | Superiority or Other (legacy) |
| Placebo corrected change from baseline least squares mean +/- the standard error of the mean | ANCOVA | ANCOVA analysis is based on the following model: CFB Parameter = Bin Group + Baseline + Error, treating patients as a random effect. | <0.0001 | p-value is not adjusted for multiple comparison Threshold for statistical significance: p<0.05 | LSM placebo corrected diff from baseline | 80 | 2-Sided | 95 | 71 | 89 | Superiority or Other (legacy) |
| All available concentration data are used in the model as a continuous variable. p-value based on individual plasma concentration of CK-1827452 vs. corresponding systolic ejection time PD assessment (not binned based on plasma concentration) | ANCOVA | ANCOVA analysis based on the following model: Change from baseline = Concentration + Baseline + Error, treating patients as random effect | <0.0001 | Threshold for statistical significance: p<0.05 | 95 | Superiority or Other (legacy) |
| OG003 | >300-400 ng/mL | Measurements pooled by plasma concentration of CK-1827452 at time of pharmacodynamic measure. Measurements at any dose level or timepoint could contribute to this bin. |
| OG004 | >400-500 ng/mL | Measurements pooled by plasma concentration of CK-1827452 at time of pharmacodynamic measure. Measurements at any dose level or timepoint could contribute to this bin. |
| OG005 | >500 ng/mL | Measurements pooled by plasma concentration of CK-1827452 at time of pharmacodynamic measure. Measurements at any dose level or timepoint could contribute to this bin. |
|
|
|
| OG004 | Cohort 1/2: 1.0 mg/kg/h + 0.5 mg/kg/h | Subjects received the following CK-1827452 regimen: 1.0 mg/kg/h IV for 1 hour (loading) + 0.5 mg/kg/h IV for 1 hour (maintenance) |
| OG005 | Cohort 3: 0.25 mg/kg/h + 0.025 mg/kg/h | Subjects received the following CK-1827452 regimen: 0.25 mg/kg/h IV for 1 hour (loading) + 0.025 mg/kg/h IV for 23 hours (maintenance) |
| OG006 | Cohort 3: 0.5 mg/kg/h + 0.05 mg/kg/h | Subjects received the following CK-1827452 regimen: 0.50 mg/kg/h IV for 1 hour (loading) + 0.05 mg/kg/h IV for 23 hours (maintenance) |
| OG007 | Cohort 3: 1.0 mg/kg/h + 0.1 mg/kg/h | Subjects received the following CK-1827452 regimen: 1.0 mg/kg/h IV for 1 hour (loading) + 0.1 mg/kg/h IV for 23 hours (maintenance) |
| OG008 | Cohort 4: 0.25 mg.kg.h + 0.125 mg/kg/h + 0.025 mg/kg/h | Subjects received the following CK-1827452 regimen: 0.25 mg/kg/h IV for 1 hour + 0.125 mg/kg/h IV for 1 hour + 0.025 mg/kg/h IV for 22 hours |
| OG009 | Cohort 4: 0.5 mg/kg/h + 0.25 mg/kg/h + 0.05 mg/kg/h | Subjects received the following CK-1827452 regimen: 0.5 mg/kg/h IV for 1 hour + 0.25 mg/kg/h IV for 1 hour + 0.05 mg/kg/h IV for 22 hours |
| OG010 | Cohort 4: 1.0 mg/kg/h + 0.5 mg/kg/h + 0.1 mg/kg/h | Subjects received the following CK-1827452 regimen: 1.0 mg/kg/h IV for 1 hour + 0.5 mg/kg/h IV for 1 hour + 0.1 mg/kg/h IV for 22 hours |
| OG011 | Cohort 5: 1.0 mg/kg/h + 0.5 mg/kg/h + 0.1 mg/kg/h | Subjects received the following CK-1827452 regimen: 1.0 mg/kg/h IV for 1 hour + 0.5 mg/kg/h IV for 1 hour + 0.1 mg/kg/h IV for 70 hours |
| OG012 | Cohort 5: 0.75 mg/kg/h + 0.375 mg/kg/h + 0.075 mg/kg/h | Subjects received the following CK-1827452 regimen: 0.75 mg/kg/h IV for 1 hour + 0.375 mg/kg/h IV for 1 hour + 0.075 mg/kg/h IV for 70 hours |
|
|
Subjects received the following CK-1827452 regimen: 0.75 mg/kg/h IV for 1 hour (loading) + 0.375 mg/kg/h IV for 1 hour (maintenance)
| OG004 | Cohort 1/2: 1.0 mg/kg/h + 0.5 mg/kg/h | Subjects received the following CK-1827452 regimen: 1.0 mg/kg/h IV for 1 hour (loading) + 0.5 mg/kg/h IV for 1 hour (maintenance) |
| OG005 | Cohort 3: 0.25 mg/kg/h + 0.025 mg/kg/h | Subjects received the following CK-1827452 regimen: 0.25 mg/kg/h IV for 1 hour (loading) + 0.025 mg/kg/h IV for 23 hours (maintenance) |
| OG006 | Cohort 3: 0.5 mg/kg/h + 0.05 mg/kg/h | Subjects received the following CK-1827452 regimen: 0.50 mg/kg/h IV for 1 hour (loading) + 0.05 mg/kg/h IV for 23 hours (maintenance) |
| OG007 | Cohort 3: 1.0 mg/kg/h + 0.1 mg/kg/h | Subjects received the following CK-1827452 regimen: 1.0 mg/kg/h IV for 1 hour (loading) + 0.1 mg/kg/h IV for 23 hours (maintenance) |
| OG008 | Cohort 4: 0.25 mg.kg.h + 0.125 mg/kg/h + 0.025 mg/kg/h | Subjects received the following CK-1827452 regimen: 0.25 mg/kg/h IV for 1 hour + 0.125 mg/kg/h IV for 1 hour + 0.025 mg/kg/h IV for 22 hours |
| OG009 | Cohort 4: 0.5 mg/kg/h + 0.25 mg/kg/h + 0.05 mg/kg/h | Subjects received the following CK-1827452 regimen: 0.5 mg/kg/h IV for 1 hour + 0.25 mg/kg/h IV for 1 hour + 0.05 mg/kg/h IV for 22 hours |
| OG010 | Cohort 4: 1.0 mg/kg/h + 0.5 mg/kg/h + 0.1 mg/kg/h | Subjects received the following CK-1827452 regimen: 1.0 mg/kg/h IV for 1 hour + 0.5 mg/kg/h IV for 1 hour + 0.1 mg/kg/h IV for 22 hours |
| OG011 | Cohort 5: 1.0 mg/kg/h + 0.5 mg/kg/h + 0.1 mg/kg/h | Subjects received the following CK-1827452 regimen: 1.0 mg/kg/h IV for 1 hour + 0.5 mg/kg/h IV for 1 hour + 0.1 mg/kg/h IV for 70 hours |
| OG012 | Cohort 5: 0.75 mg/kg/h + 0.375 mg/kg/h + 0.075 mg/kg/h | Subjects received the following CK-1827452 regimen: 0.75 mg/kg/h IV for 1 hour + 0.375 mg/kg/h IV for 1 hour + 0.075 mg/kg/h IV for 70 hours |
|
|