A Pharmacodynamics and Safety Study of DSP-9632P in Patients With Levodopa-Induced Dyskinesia in Parkinson's Disease

NCT05435729 | Completed Phase 1

• 2 other identifiers: DD701105jRCT2031220051
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Levodopa-induced Dyskinesia; Parkinson's Disease

Outcome Measures

Primary Outcomes (2)

• Binding potential of 11C-raclopride and Dopamine D2 receptor occupancy by Positron Emission Tomography (PET) in Part A

  Evaluate the amount of striatal dopamine release derived from levodopa following single transdermal administration of DSP-9632P using 11C-raclopride PET in patients with levodopa-induced dyskinesia in Parkinson's disease

  1 day

• Incidence of adverse events (AEs), serious adverse events (SAEs), and AEs leading to treatment discontinuation in Part B

  Evaluate the Incidence of AEs, SAEs, and AEs leading to treatment discontinuation of DSP-9632P following multiple once-daily transdermal administration for 7 days in patients with levodopa-induced dyskinesia in Parkinson's disease transdermal administration for 7 days in patients with levodopa-induced dyskinesia in Parkinson's disease

  7 days

Secondary Outcomes (15)

• Change from baseline in Unified Dyskinesia Rating Scale (UDysRS) score in Part A

  1 days

• Change from baseline in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) score in Part A

  1 days

• Incidence of adverse events (AEs), serious adverse events (SAEs), and AEs leading to treatment discontinuation in Part A

  1 days

• Cmax of levodopa in Part A

  1 days

• Time of occurrence of Cmax (tmax) of levodopa in Part A

  1 days

Other Outcomes (3)

• Absolute value and change from baseline in EuroQol 5 dimensions 5-level (EQ-5D-5L) total score in Part B

  7 days

• Absolute value and change from baseline in Parkinson's Disease Questionnaire-39 (PDQ-39) total score, score of 8 domains, and summary index score in Part B

  7 days

• Change from baseline in eye movement parameters (e.g. eye-blink rates) in Part B

  7 days

Study Arms (3)

DSP-9632P 27.5 mg in Periods 3 of Part A

EXPERIMENTAL

Single dose of DSP-9632P 27.5 mg in patients with levodopa-induced dyskinesia in Parkinson's disease

Drug: DSP-9632P 27.5 mg; Drug: Levodopa formulation

DSP-9632P 82.5 mg in Periods 4 of Part A

EXPERIMENTAL

Single dose of DSP-9632P 82.5 mg in patients with levodopa-induced dyskinesia in Parkinson's disease

Drug: DSP-9632P 82.5 mg; Drug: Levodopa formulation

DSP-9632P 55.0 mg in Period 1 or 2 of Part B

EXPERIMENTAL

Multiple dose of DSP-9632P 55.0 mg in patients with levodopa-induced dyskinesia in Parkinson's disease

Drug: Placebo; Drug: DSP-9632P 55.0 mg; Drug: Levodopa formulation

Interventions

DSP-9632P 27.5 mg DRUG

Single dose of DSP-9632P 27.5 mg

DSP-9632P 27.5 mg in Periods 3 of Part A

DSP-9632P 82.5 mg DRUG

Single dose of DSP-9632P 82.5 mg

DSP-9632P 82.5 mg in Periods 4 of Part A

Placebo DRUG

Placebo for DSP-9632P

DSP-9632P 55.0 mg in Period 1 or 2 of Part B

DSP-9632P 55.0 mg DRUG

Multiple dose of DSP-9632P 55.0 mg

DSP-9632P 55.0 mg in Period 1 or 2 of Part B

Levodopa formulation DRUG

Single dose of Levodopa formulation

DSP-9632P 27.5 mg in Periods 3 of Part A; DSP-9632P 55.0 mg in Period 1 or 2 of Part B; DSP-9632P 82.5 mg in Periods 4 of Part A

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject whose age is ≥ 50 and \< 80 years at the time of informed consent.
• Subject who is fully informed and understands the objectives, procedures, anticipated drug effects/pharmacological action and risks of the study and who voluntarily provides written consent to participate in the study.
• Subject who has clinically established Parkinson's disease diagnosed by MDS clinical diagnostic criteria for Parkinson's disease (2015).
• Subject who has a response to levodopa at screening in the opinion of the investigator.
• Subject who is confirmed to have dopaminergic denervation with a specific binding ratio in the striatum, obtained by dopamine transporter SPECT (123I-FP-CIT, DAT scan®) performed prior to the study or at screening, that is lower than the lower limit of 95% confidence interval of healthy adults.
• Subject who has a Hoehn \& Yahr stage ≤ III in the ON state at screening.
• Subject who has MDS-UPDRS Part IV-1 ≥ 2 and Part IV-2 ≥ 2 at screening.
• Subject who is on treatment with levodopa formulation at least 3 times daily at screening.
• Subject who is able to receive 11C-raclopride PET scans (Part A only).
• Subject who has a score of ≥ 2 in any of questions of UDysRS Part 1B at screening (Part B only).
• Subjects who can wear the glasses-type wearable device and agree to wear it (Part B only).
• Subject who is able to comply with the study requirements, including physical examination, assessments, and reporting symptoms.
• Subject who is willing to practice abstinence or use appropriate contraception as part of the subject's lifestyle from signing informed consent through 30 days after the last dose of study drug.
• Subject who is on treatment with levodopa formulation at least 3 times daily and is treated with levodopa formulation with a fixed dosing regimen for at least 28 days prior to Period 1 (Part A) or prior to admission (Part B).
• Subject who is in the ON state with dyskinesia every day for at least 30 minutes twice or more daily based on the PD home diary during the placebo lead-in period (Part B only).

You may not qualify if:

• 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:
• Heart rate \> 100 bpm or \< 50 bpm
• QRS interval \> 120 msec
• QTcF \> 450 msec (male) or \> 470 msec (female)
• PR interval \> 200 msec
• 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.

Sponsors & Collaborators

• Sumitomo Pharma Co., Ltd.: lead

Study Sites (1)

Nippon Medical School Hospital

Bunkyo, Tokyo, Japan

Location

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Periods 1 and 2 in Part B will be conducted in a double-blinded manner. The subjects, all study staff including the investigator, drug concentration-measuring facility, drug residual amount-measuring facility, safety review team, and the Sponsor are kept blinded to the assignment of treatment during the period from the initiation of the study to database lock.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 13, 2022
• First Posted: June 28, 2022
• Study Start: May 31, 2022
• Primary Completion: November 30, 2022
• Study Completion: December 2, 2022
• Last Updated: August 9, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

JP (1)