Closed after complete treatment of 32 patients after 21 months' recruitment.

The primary objective of this early-stage clinical study is to demonstrate an effect of single doses of CK-2017357 on measures of skeletal muscle function and fatigability in patients with generalized myasthenia gravis (MG).

This study is a Phase II, double-blind, randomized, three-way crossover, placebo-controlled, PD study of CK-2017357 in patients with generalized MG on standard therapy. 36 to 78 patients will be randomized at approximately 15 study centers to one of six different treatment sequences. Each treatment sequence consists of three dosing periods in which patients receive single oral doses of placebo, 250 mg, and 500 mg of CK-2017357. All six treatment sequences will enroll 6 patients. A wash out period of at least 7 days (to a maximum of 10 days) will be employed between the individual doses for each patient. This study is designed to assess the effects of CK-2017357 on the standardized Quantitative Myasthenia Gravis (QMG) score, Manual Muscle Test, Myasthenia Gravis Composite Assessment (MGCA) and Forced Vital Capacity. The pharmacokinetic (PK) and pharmacodynamic (PD) relationship of CK-2017357 after two single doses will be assessed versus placebo.

Inclusion criteria:

• Ability to comprehend and willing to sign an Informed Consent Form (ICF)
• Ability to understand written and oral English language
• Males and females between 18 and 80 years of age, inclusive
• Patient's signs and symptoms not better explained by another disease process
• Established diagnosis of MG defined as clinical evidence of muscle weakness and positive AChR-binding antibody titer (>0.02 nmol/L)
• Myasthenia Gravis Foundation of America (MGFA) clinical classification II or III
• Stable MG disease for 4 weeks prior to randomization
• Ability to refrain from IVIg treatments during the course of the study
• Ability to refrain from cholinesterase-inhibitors (e.g. pyridostigmine) for 12 hours before each dose
• Ability to perform all elements of the QMG
• 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
• Body mass index (BMI) of 18.0 to 36.0 kg/m2, inclusive
• 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
• 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)
• 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 to abstain from sexual intercourse for the duration of the study and 10 weeks after the end of the study

Exclusion criteria:

• History of chronic degenerative, psychiatric, or neurologic disorder other than MG that can produce weakness or fatigue
• Other major chronic or debilitating illnesses within six months prior to study entry
• Hepatic insufficiency (defined as ALT or AST > 3x ULN, or total bilirubin > 3 mg/dL)
• Renal insufficiency (defined as serum creatinine > 2.5 mg/dL or receiving dialysis)
• Other myasthenic syndromes (e.g. Lambert Eaton syndrome; inherited myasthenic syndrome)
• 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)
• Receipt of IVIg or plasmapheresis treatment within 6 weeks prior to the first dose of study drug
• Changes to immunosuppressive treatments (i.e., prednisone) within 6 weeks prior to the first dose of study drug
• Rituxan treatment within 3 months prior to study entry
• 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
• Any prior treatment with CK-2017357
• 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