A Phase II, Double-Blind, Randomized, Three-Way Crossover, Placebo-Controlled, Pharmacodynamic Study of CK-2017357 in Patients With Generalized Myasthenia Gravis on Standard Therapy
Overview
- Phase
- Phase 2
- Intervention
- Placebo
- Conditions
- Myasthenia Gravis
- Sponsor
- Cytokinetics
- Enrollment
- 32
- Locations
- 15
- Primary Endpoint
- Pulmonary Function Test (VC in liters)
- Status
- Terminated
- Last Updated
- 6 years ago
Overview
Brief Summary
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).
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Treatment Sequence 1
Dosing Period 1 Placebo; Dosing Period 2 CK-2017357 250 mg; Dosing Period 3 CK-2017357 500 mg
Intervention: Placebo
Treatment Sequence 1
Dosing Period 1 Placebo; Dosing Period 2 CK-2017357 250 mg; Dosing Period 3 CK-2017357 500 mg
Intervention: 250 mg CK-2017357
Treatment Sequence 3
Dosing Period 1 CK-2017357 250 mg; Dosing Period 2 Placebo; Dosing Period 3 CK-2017357 500 mg
Intervention: Placebo
Treatment Sequence 1
Dosing Period 1 Placebo; Dosing Period 2 CK-2017357 250 mg; Dosing Period 3 CK-2017357 500 mg
Intervention: 500 mg CK-2017357
Treatment Sequence 2
Dosing Period 1 Placebo; Dosing Period 2 CK-2017357 500 mg; Dosing Period 3 CK-2017357 250 mg
Intervention: Placebo
Treatment Sequence 2
Dosing Period 1 Placebo; Dosing Period 2 CK-2017357 500 mg; Dosing Period 3 CK-2017357 250 mg
Intervention: 250 mg CK-2017357
Treatment Sequence 2
Dosing Period 1 Placebo; Dosing Period 2 CK-2017357 500 mg; Dosing Period 3 CK-2017357 250 mg
Intervention: 500 mg CK-2017357
Treatment Sequence 3
Dosing Period 1 CK-2017357 250 mg; Dosing Period 2 Placebo; Dosing Period 3 CK-2017357 500 mg
Intervention: 250 mg CK-2017357
Treatment Sequence 3
Dosing Period 1 CK-2017357 250 mg; Dosing Period 2 Placebo; Dosing Period 3 CK-2017357 500 mg
Intervention: 500 mg CK-2017357
Treatment Sequence 4
Dosing Period 1 CK-2017357 250 mg; Dosing Period 2 CK-2017357 500 mg; Dosing Period 3 Placebo
Intervention: Placebo
Treatment Sequence 4
Dosing Period 1 CK-2017357 250 mg; Dosing Period 2 CK-2017357 500 mg; Dosing Period 3 Placebo
Intervention: 250 mg CK-2017357
Treatment Sequence 4
Dosing Period 1 CK-2017357 250 mg; Dosing Period 2 CK-2017357 500 mg; Dosing Period 3 Placebo
Intervention: 500 mg CK-2017357
Treatment Sequence 5
Dosing Period 1 CK-2017357 500 mg; Dosing Period 2 Placebo; Dosing Period 3 CK-2017357 250 mg
Intervention: Placebo
Treatment Sequence 5
Dosing Period 1 CK-2017357 500 mg; Dosing Period 2 Placebo; Dosing Period 3 CK-2017357 250 mg
Intervention: 250 mg CK-2017357
Treatment Sequence 5
Dosing Period 1 CK-2017357 500 mg; Dosing Period 2 Placebo; Dosing Period 3 CK-2017357 250 mg
Intervention: 500 mg CK-2017357
Treatment Sequence 6
Dosing Period 1 CK-2017357 500 mg; Dosing Period 2 CK-2017357 250 mg; Dosing Period 3 Placebo
Intervention: Placebo
Treatment Sequence 6
Dosing Period 1 CK-2017357 500 mg; Dosing Period 2 CK-2017357 250 mg; Dosing Period 3 Placebo
Intervention: 250 mg CK-2017357
Treatment Sequence 6
Dosing Period 1 CK-2017357 500 mg; Dosing Period 2 CK-2017357 250 mg; Dosing Period 3 Placebo
Intervention: 500 mg CK-2017357
Outcomes
Primary Outcomes
Pulmonary Function Test (VC in liters)
Time Frame: 1 day
Forced Vital Capacity
Manual Muscle Test (MMT)
Time Frame: 1 day
Sum of strength or function values assessed by physician on the neck, shoulder, hip and ankle
Quantitative Myasthenia Gravis score (QMG)
Time Frame: 1 day
A quantitative motor assessment of muscular weakness on a scale of 0 to 3 with 0 representing "none" and 3 representing "severe". Muscular assessments included in the overall score are effects on double vision, ptosis, facial muscles, swallowing, speech, outstretched arms and legs, forced vital capacity, hand grip strength, and ability to lift head.
Secondary Outcomes
- Characterize dose and plasma concentrations of CK-2017357 and QMG(2 days)
- Characterize dose and plasma concentrations of CK-2017357 and Manual Muscle Test (MMT)(2 days)
- Number of patients with adverse events(4 weeks)
- Patient Global Assessment(2 days)
- Investigator Global Assessment(2 days)
- Modified MG Symptom Score(2 days)
- Characterize dose and plasma concentrations of CK-2017357 and Forced Vital Capacity (FVC)(2 days)