Pharmacodynamic Study of CK-2017357 in Patients With Generalized Myasthenia Gravis

Patients who meet the following criteria may be included in the study:

1. Ability to comprehend and willing to sign an Informed Consent Form (ICF)
2. Ability to understand written and oral English language
3. Males and females between 18 and 80 years of age, inclusive
4. Patient's signs and symptoms not better explained by another disease process
5. Established diagnosis of MG defined as clinical evidence of muscle weakness and positive AChR-binding antibody titer (>0.02 nmol/L)
6. Myasthenia Gravis Foundation of America (MGFA) clinical classification II or III
7. Stable MG disease for 4 weeks prior to randomization
8. Ability to refrain from IVIg treatments during the course of the study
9. Ability to refrain from cholinesterase-inhibitors (e.g. pyridostigmine) for 12 hours before each dose
10. Ability to perform all elements of the QMG
11. Grade of 2 or 3 in two or more of the following muscle groups as measured by QMG: right or left arm flexion, head lift, and right or left leg raise at 45° Note: Patients may re-screen if they fail due to inadequate weakness from taking pyridostigmine within 12 hours of screening
12. Body mass index (BMI) of 18.0 to 36.0 kg/m2, inclusive
13. Pre-study clinical laboratory findings (including troponin I [TnI] and creatine phosphokinase [CPK]) within the normal range, or if outside of the normal range, deemed not clinically significant by the Investigator

14. For female patients only: Agreement

    • to use a double barrier during sexual intercourse (1 hormonal, plus 1 barrier method, or 2 simultaneous barrier methods) birth control (birth control pills, male condom, female condom, intrauterine device, Norplant, tubal ligation, or other sterilization procedures)

15. For male patients only: Agreement either

    • to use a condom during sexual intercourse with female partners who are of reproductive potential and to have female partners use an additional effective means of contraception (e.g., diaphragm plus spermicide, or oral contraceptives) for the duration of the study and 10 weeks after the end of the study or b. to abstain from sexual intercourse for the duration of the study and 10 weeks after the end of the study

The following criteria exclude potential patients from the study:

1. History of chronic degenerative, psychiatric, or neurologic disorder other than MG that can produce weakness or fatigue
2. Other major chronic or debilitating illnesses within six months prior to study entry
3. Hepatic insufficiency (defined as ALT or AST > 3x ULN, or total bilirubin > 3 mg/dL)
4. Renal insufficiency (defined as serum creatinine > 2.5 mg/dL or receiving dialysis)
5. Other myasthenic syndromes (e.g. Lambert Eaton syndrome; inherited myasthenic syndrome)
6. Female patients who are premenopausal and are: (a) pregnant on the basis of a serum pregnancy test, (b) breast-feeding, or (c) not using an effective method of double barrier (1 hormonal plus 1 barrier method or 2 simultaneous barrier methods) birth control (birth control pills, male condom, female condom, intrauterine device, Norplant, tubal ligation, or other sterilization procedures)
7. Receipt of IVIg or plasmapheresis treatment within 6 weeks prior to the first dose of study drug
8. Changes to immunosuppressive treatments (i.e., prednisone) within 6 weeks prior to the first dose of study drug
9. Rituxan treatment within 3 months prior to study entry
10. Participation in any other investigational study drug or device trial in which receipt of an investigational study drug or device occurred within 30 days prior to dosing
11. Any prior treatment with CK-2017357
12. Recent history of alcoholism or drug abuse, or significant behavioral or psychiatric problems, or other conditions which in the Investigator's opinion may impair ability to adequately comply with the requirements of the study