Status:
Not Yet Recruiting
Clinicaltrials.gov identifier:
Sponsor:
II-Yang Pharm. Co. Ltd
Enrollment:
40
Study Design:
This is a Phase 2, randomized, parallel assigned, double-blind, placebo-controlled study. The outcome is focused on the safety, tolerability, pharmacokinetics, and efficacy of Radotinib in PwP. The 40 individuals will be randomized to 4 dosing groups. In each dosing group, eight individuals will receive Radotinib, and two will receive matching placebo. The dose will be administered once daily for six months at each escalating dose level. The Radotinib doses being studied include 50mg/day, 100mg/day, 150mg/day and 200mg/day. The data monitoring committee will decide if the individual can be escalated to the next dose level. The study will include dopaminergic drug naïve PwP between 40-80 years of age with Hoehn and Yahr stage of 2.5. They will utilize the MDS clinical diagnostic criteria with a positive DAT scan for inclusion. In addition to standard exclusionary criteria, individuals on certain drugs will be excluded. The comprehensive list of exclusionary drugs includes strong CYP3A4 inhibitors and inducers, P-glycoprotein inducers, and medications that prolong QT interval. The study is being conducted across seven centers in France.
Rationale:
The primary outcome measure focuses on safety assessment by measuring the incidence and severity of adverse events 12 months after dose administration. The secondary outcome measures assess the effect in two main domains, pharmacokinetic and clinical. 1. Pharmacokinetic assessments will be done at 14 days after dose administration, and meas-urements include peak observed drug concentration, time to reach peak drug concen-tration, trough plasma concentration, the area under plasma concentration-time curve, elimination half-life, apparent total drug clearance, and apparent volume distribution; 2. Clinical assessment will include: a. Change in MDS-UPDRS parts I-III at 6 months; b. Time to initiation of dopamine replacement therapy assessed at 6 months; c. Patient reported outcome will include a change in the quality of life via PDQ-39 and the subject’s clinical global impression scale at 12 months. Other outcome measures will include the following: a. Change in Brain DaT SPECT scan; b. CSF concentration of the following at 6 months: alpha-synuclein, Tau, phospho-Tau (p-181), beta-amyloid peptide 1-42; c. CSF and plasma concentration of Radotinib; d. Serum concentration of NF-L.
Comments:
Radotinib is a potential c-Abl inhibitor alternative drug for PD owing to its superior brain penetration [2,3]. The current study is exploring doses lower than the approved dose for CML. Compared to other kinase inhibitors, Radotinib exerts its effect via c-Abl inhibition only [3]. It is undetermined whether the road to effective alpha-synuclein reduction is via multiple or selective kinase inhibition. While there is conflicting preclinical data regarding Radotinib efficacy, whether this translates to human efficacy is yet to be seen.
