Research Project
9163715
Title of Study: CC100B: Safety and Tolerability of Multiple Doses in Subjects with ALS Number of Planned, Randomized Subjects: 21 Phase of Development: 1 Objectives: Primary objective: to assess the safety and tolerability of multiple doses of orally administered CC100 in subjects with amyotrophic lateral sclerosis (ALS). Secondary objectives: to determine pharmacokinetics and pharmacodynamics of CC100 in plasma after single and after multiple doses; and to determine short-term effects of CC100 on potential blood-cell ALS biomarkers. Study Design: Phase 1 double-blind, randomized, placebo-controlled multiple-dose of three CC100-dose cohorts. Approximately 18 subjects will receive CC100. Approximately 3 subjects will be randomized to placebo (across 3 cohorts). Periodic Assessment Committee safety reviews. Main Criteria for Inclusion and Exclusions: Subjects ?18 and <65 years of age and ?113 kg (250 lbs) with definite or probable stable ALS as described by the World Federation of Neurology ad hoc committee. Subjects must have forced vital capacity of >60% predicted. Riluzole is allowed, providing dose has been stable for ?30 days. Men must be willing to practice a reliable method of birth control. Women must be non- fertile or post-menopausal. Excluded are subjects who have asthma or severe drug allergies/hypersensitivity; have known or existing evidence of serious systemic or local infection; or are immuno-compromised; have lymphoproliferative disease or malignant disease; or have serious or unstable/uncontrolled illnesses (except ALS) that could interfere with the analyses of safety. Note: Participation will not exclude subjects from future CC100 studies Criteria for Evaluation: Safety Endpoints: Adverse events, blood chemistry, hematology, urinalysis, vital signs, 12-lead ECGs. Pharmacokinetic (PK)/Pharmacodynamic (PD): Plasma for CC100 concentrations (PK). Blood collected at baseline and after each subject?s last dose will be assayed for potential biomarker(s). Stored specimens will be de-identified or combined for validating diagnostic tools/assays related to ALS. Statistical Methods: A minimum of 6 subjects per CC100 dose group and 3 placebo-dosed subjects (total across cohorts) are considered sufficient to evaluate initial safety and tolerability for the cohorts. Pharmacokinetic parameter estimates will be calculated by standard noncompartmental methods of analysis. Absolute bioavailability of administration will be estimated based on the total area under the time- concentration curve (AUC0-?).
