A Study of CK-1827452 Infusion in Stable Heart Failure
Condition: Heart Failure
MeSH terms: Heart Failure
Intervention: CK-1827452; CK-1827452; CK-1827452; CK-1827452; CK-1827452; CK-1827452; CK-1827452; CK-1827452; Placebo; Placebo; CK-1827452; Placebo; CK-1827452; CK-1827452; CK-1827452; CK-1827452
Intervention description: IV infusion for 1 hour at 0.125 mg/kg/h followed by 1 hour at 0.0625 mg/kg/h; IV infusion for 1 hour at 0.25 mg/kg/h followed by 1 hour at 0.125 mg/kg/h; IV infusion for 1 hour at 0.5 mg/kg/h followed by 1 hour at 0.25 mg/kg/h; IV infusion for 1 hour at 0.75 mg/kg/h followed by 1 hour at 0.375 mg/kg/h; IV infusion for 1 hour at 1.0 mg/kg/h followed by 1 hour at 0.5 mg/kg/h; 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; 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; 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; IV infusion for 2 hours; IV infusion for 24 hours; 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; IV infusion for 72 hours; 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; IV infusion for 1 hour at 0.25 mg/kg/h followed by 23 hours at 0.025 mg/kg/h; IV infusion for 1 hour at 0.5 mg/kg/h followed by 23 hours at 0.05 mg/kg/h; IV infusion for 1 hour at 1.0 mg/kg/h followed by 23 hours at 0.1 mg/kg/h
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 45.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This study will assess the safety, tolerability, and pharmacodynamics of CK-1827452 infusion
      in patients with stable heart failure.
    

Eligibility criteria:

        Inclusion Criteria

          1. Patient is male, or female of non-childbearing potential (two years post-menopausal or
             surgically sterilized)

          2. Female patients must have a negative urine pregnancy test prior to entry into the
             study

          3. Patient is 18 years old or greater

          4. Patient has given signed informed consent

          5. Patient is considered to be in suitable health in the opinion of the investigator, as
             determined by:

               -  A pre-study physical examination with no clinical abnormalities which in the
                  opinion of the investigator would preclude participation in the study other than
                  physical symptoms or signs consistent with stable heart failure

               -  An electrocardiogram (ECG) with no abnormalities in the opinion of the
                  investigator that would impair assessment of stopping criteria

          6. 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)

          7. Patient has a documented diagnosis of heart failure with an ejection fraction of less
             than 40%

          8. 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

          9. Patient is currently in sinus rhythm

         10. Patient has interpretable echocardiographic images on a screening echocardiogram

        Exclusion Criteria

          1. Patient has been hospitalized for heart failure, myocardial infarction, coronary
             revascularization, or another cardiac indication within the last 6 weeks

          2. Patient has a current history of alcohol use which in the opinion of the investigator
             would preclude participation in the study

          3. Patient has a current history of drug abuse

          4. Patient has donated blood or blood products within 30 days prior to screening

          5. Patient has Canadian Cardiovascular Society (CCS) Class III or IV angina

          6. Patient has significant obstructive valvular disease or significant congenital heart
             disease

          7. Patient has had a valve replacement

          8. Patient is pacemaker dependent

          9. Patient is on chronic anti-arrhythmic therapy, with the exception of amiodarone

         10. Patient is currently taking, or has taken in the last 7 days, a CYP3A4 inhibitor or
             inducer medication

         11. Patient has a history of hypertrophic obstructive cardiomyopathy

         12. Patient weighs > 120 kg

         13. Patient has a supine resting systolic blood pressure < 95 mmHg after 3 minutes rest

         14. Patient has a supine resting heart rate ≥ 100 beats per minute after 3 minutes rest

         15. Patient has an Modification of Diet in Renal Disease (MDRD) estimate of Glomerular
             Filtration Rate (GFR) ≤ 35 ml/min/1.73 m2

         16. Patient has a potassium < 3.5 mEq/L or > 5.5 mEq/L

         17. Patient has a sodium ≤ 133 mEq/L

         18. Patient has a urea > 15 mmole/L

         19. Patient has a troponin I or T at screening that is detectable at the investigative
             site's clinical laboratory

         20. Patient has a hemoglobin < 11 gm/dL in males or < 10 gm/dL in females

         21. Patient has an alanine transaminase (ALT), aspartate transaminase (AST), alkaline
             phosphatase (ALKP) or total bilirubin (TBILI) > 3 times the upper limit of normal

         22. Patient is, in the opinion of the investigator, not suitable to participate in the
             study

         23. Patient has participated in any clinical study with an investigational drug within
             three months prior to the first day of dosing with the exception of coronary stent
             studies Patient has ever received CK-1827452