A Pharmacodynamics and Safety Study of DSP-9632P in Patients With Levodopa-Induced Dyskinesia in Parkinson's Disease
A Pharmacodynamics and Safety Study of DSP-9632P in Patients With Levodopa-Induced Dyskinesia in Parkinson's Disease
This study is an open-label of single transdermal dose of DSP-9632P to evaluate the dopamine release derived from levodopa in brain, and a randomized, double-blind, placebo-controlled, 2-way crossover of multiple transdermal doses of DSP-9632P to evaluate the safety and tolerability in patients with levodopa-induced dyskinesia in Parkinson's disease.
This study consists of Part A and Part B. Part A is an open-label part to evaluate the amount of striatal dopamine release derived from levodopa following single transdermal administration of DSP-9632P using 11Craclopride PET in patients with levodopa-induced dyskinesia in Parkinson's disease. Part A consists of screening, Period 1, Period 2, Period 3, Period 4, and follow-up period. Each period consists of 2 days, Day 1 and Day 2. There will be a 7-day or longer washout of DSP-9632P between Periods 3 and 4. Subjects will be hospitalized in each period.
Part B is a randomized, double-blind, placebo-controlled, crossover part to evaluate the safety and tolerability of DSP-9632P following multiple transdermal administration in patients with levodopa-induced dyskinesia in Parkinson's disease. Part B consists of screening, placebo lead-in period, baseline period, Period 1, Period 2, and follow-up period. Period 1 and Period 2 consist of 9 days. Subjects will be hospitalized for 10 days 9 nights from baseline period to Period 1 and for 9 days 8 nights in Period 2. There will be a 7-day or longer washout of DSP-9632P between Periods 1 and 2.
Subjects will concomitantly use any of the levodopa formulation from the time of informed consent to the end of study.
Inclusion Criteria:
Exclusion Criteria:
Subject with a clinically significant history of cardiovascular, hepatic, renal, endocrine, gastrointestinal, hematological, respiratory, or neurologic disease other than Parkinson's disease, determined by the investigator.
Subject who has a disorder or history of a condition that may interfere with drug metabolism or excretion including clinically significant abnormality of the hepatic or renal systems.
Subject with a history of epilepsy, convulsions, unexplained syncope or other unexplained loss of consciousness (except a single incident), or head trauma with loss of consciousness lasting more than 5 minutes.
Subject with a clinically significant abnormal 12-lead ECG or a screening 12-lead ECG for safety assessment that demonstrates any one of the following:
Subject with dermatosis or skin abnormality (eg, dermatitis, eczema, or dyschromatosis) at application sites.
Subject with a history of drug allergy or skin allergy.
Subject with a known sensitivity to any transdermal patch.
Subject with a history of drug abuse or narcotic abuse, or a positive urine drug screening at screening.
Subject who has a positive immunology at screening.
Subject with any clinically significant abnormal clinical laboratory value (hematology test, serum chemistry test, urinalysis, coagulation test, or lipid test) determined by the investigator at screening.
Subject with a history of biphasic dyskinesia, myoclonus, or apathy.
Subject with a current or history of psychiatric illness (eg, schizophrenia, bipolar disorder, depression) based on the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5).
Subject with Mini-Mental State Examination (MMSE) score of ≤ 23 at screening.
Subject who has received surgical therapy related to Parkinson's disease.
Subject who has previously received levodopa-carbidopa intestinal gel.
Subject who has previously received DSP-9632P.
Subject who has participated in any clinical study and received any investigational drug during the 90 days prior to screening visit, or who is currently participating in another clinical trial.
Subject who has experienced significant blood loss or donated blood (≥ 400 mL) during the 90 days prior to screening or donated 200 mL of blood or more during the 30 days prior to screening; has donated blood components during the 14 days prior to screening or intends to donate blood components or blood during the 30 days after the last study visit.
Subject who is in the opinion of the investigator unsuitable in any other way to participate in this study.
Subject who has a positive urine drug screening at admission.
Subject who has consumed caffein or smoked in 2 days prior to the admission or has consumed alcohol in 1 day prior to the admission (Part A only).
Subject who answers "yes" to "Suicidal Ideation" Items 4 or 5 on the C-SSRS at admission.
Subject who has used dopamine receptor antagonists (antipsychotics, metoclopramide, domperidone) within 14 days prior to Period 1.
Subject who has used serotonergic 5-HT1A/1B agonists/antagonists (tandospirone, sumatriptan, zolmitriptan, eletriptan, rizatriptan, naratriptan, Yokukansan) during the 14 days prior to Period 1.
Subject who has used therapeutic agents (monoamine oxidase B [MAO-B] inhibitors, zonisamide, istradefylline, anticholinergics) for Parkinson's disease other than levodopa formulations, dopamine receptor agonists and COMT inhibitors within 28 days prior to Period 1.
Subject who has used amantadine hydrochloride during the 28 days prior to Period 1.
Subject who has used antidepressants (tricyclic antidepressants, tetracyclic antidepressants, selective serotonin reuptake inhibitors [SSRI], serotonin/norepinephrine reuptake inhibitors [SNRI], or noradrenergic and specific serotonergic antidepressants [NaSSA], etc.) during the 28 days prior to Period 1.
Subject with a positive severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) nucleic acid amplification test to be performed between screening and admission in Period 1, or clinical symptoms suggestive of infection with SARSCoV-2 before admission.
Bunkyo, Tokyo, Japan