lenrispodun as adjunctive therapy in the treatment of patients with motor fluctuations due to parkinson's disease

Conditions: Parkinson Disease

Summary: this is a multicenter, randomized, double-blind, placebo-controlled, parallel-group, fixed-dose study in patients with a diagnosis of parkinson's disease consistent with the uk parkinson's disease society (ukpds) brain bank diagnostic criteria, who are experiencing wearing off symptoms and levodopa-induced dyskinesia.

the study will be conducted in three periods: * screening period (up to 4 weeks) during which patient eligibility will be assessed; * double-blind treatment period (4 weeks) in which all patients will be randomized to receive placebo or lenrispodun 30 mg/day in 1:1 ratio. * safety follow-up period (1 week) in which all patients will return to the clinic for a safety follow-up visit approximately one week after the last dose of study treatment.

Eligibility criteria:
inclusion criteria: 1. male or female between 40 years of age and older 2. body mass index of 19.0-40.0 kg/m2; 3. diagnosis of pd that is consistent with the uk parkinson's disease society (ukpds) brain bank diagnostic criteria; 4. hoehn and yahr scale stage classification of 2 or 3 when in the on state; 5. have a clinically meaningful response to levodopa (levodopa + ddci combination) based on investigator assessment, and meet the following: 1. have been on a stable and optimal dose of levodopa (levodopa + ddci combination: minimum dose of levodopa equivalent to 100 mg three times daily) for at least 4 weeks prior to screening, and are expected to continue the same dose regimen throughout the double-blind treatment period; 2. if taking other anti-parkinsonian medications (mao-b \[monoamine oxidase b\] inhibitor, comt \[catechol-o-methyltransferase\] inhibitor, dopamine agonist) in addition to levodopa, have been on a stable dose for at least 4 weeks prior to screening and are expected to continue the same dose regimen throughout the double-blind treatment period; 7. have wearing-off symptoms and levodopa-induced dyskinesia as per investigator judgment; 8. properly complete and return a self-reported home diary for motor function status (hauser diary) during the screening period, which confirms 3 days (ie, 3 consecutive, 24-hour periods) immediately prior to baseline, each with at least 2½ hours of off time during waking hours. 9. has a caregiver to assist with study participation, if determined by the investigator to be necessary. exclusion criteria: 1. medical history indicating parkinsonism other than idiopathic pd, including but not limited to, progressive supranuclear gaze palsy, multiple system atrophy, drug-induced parkinsonism, essential tremor, primary dystonia; 2. has late-stage pd, severe peak-dose dyskinesia, clinically significant end-dose or biphasic dyskinesia, and/or unpredictable or widely swinging fluctuations in their symptoms as assessed by the investigator; 3. exhibits clinical signs of dementia as indicated by the mini-mental state examination, 2nd edition: standard version (mmse-2:sv) score of ≤ 24; 4. use of moderate or strong cyp3a4 inhibitors within 5 half-lives of baseline or cyp3a4 inducers within 2 weeks of baseline; 5. daily use of nonsteroidal anti-inflammatory drugs (nsaids), with the exception of acetylsalicylic acid (asa); 6. use of mao-a inhibitors, phosphodiesterase type 5 (pde5) inhibitors, or alpha blockers including tamsulosin, within 5 half-lives of baseline;

Keywords: levodopa-induced dyskinesia on and off state