Preliminary Study of Piclozotan in Patients With Motor Complications Associated With Parkinson's Disease

A Double-Blind, Placebo-Controlled, Preliminary Study of the Efficacy, Safety, and Tolerability of Intravenous SUN N4057 in Patients With Motor Complications Associated With Parkinson's Disease

The purpose of this study is to obtain preliminary information on the effect of piclozotan on motor complications associated with Parkinson's Disease.

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease
• Intervention / Treatment: Drug: piclozotan; Drug: 0.9% sodium chloride (normal saline)

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2

Contacts and Locations

Study Locations

• Guatemala
  • Guatemala, Guatemala
    • Hospital Multimedica
• Romania
  • Oradea, Romania
    • Hospital Clinic of Neurology and Psychiatry Oradea
• United States
  • California
    • Fountain Valley, California, United States, 92708
      • The Parkinson's and Movement Disorder Institute
  • Florida
    • Tampa, Florida, United States, 33606
      • University of South Florida, Parkinson's Disease and Movement Disorders Center
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Emory University--Wesley Woods Health Center
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • UMDNJ-Robert Wood Johnson Medical School
  • New York
    • Brooklyn, New York, United States, 11203
      • SUNY Downstate Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Main Inclusion Criteria:

• Idiopathic Parkinson's disease for at least 5 years
• Presence of motor fluctuations and dyskinesia
• Stable regimen of levodopa/carbidopa for 30 days
• At least 25% response/improvement in Unified Parkinson's Disease Rating Scale (UPDRS) part III scores after dosing with regular Parkinson's disease (PD) medications
• Mini-Mental State Examination (MMSE) score of 25 or higher

Main Exclusion Criteria:

• Atypical or secondary parkinsonism.
• Prior use of neuroleptic agents.
• History of intracranial procedures for PD.
• Active psychosis.
• History of drug or alcohol abuse in past 12 months.
• Cardiac conduction system abnormality.
• Predisposing medical condition that causes nausea or vomiting or routine use of an anti-emetic.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: piclozotan; Participants will be randomized to receive two 12-hour intravenous (IV) infusions of piclozotan administered at a plasma level of 30 ng/mL over 2 inpatient days.	Drug: piclozotan; piclozotan, intravenous (IV) infusion; Other Names: SUN N4057
Placebo Comparator: 0.9 % sodium chloride (normal saline); Participants will be randomized to receive two 12-hour intravenous (IV) infusions of 0.9 % sodium chloride (normal saline) administered at a plasma level of 30 ng/mL over 2 inpatient days.	Drug: 0.9% sodium chloride (normal saline); 0.9% sodium chloride (normal saline) intravenous (IV) infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Percentage of "On" Time Without Dyskinesia Averaged Over Days 1 and 2 in Participants Treated With SUN N4057 and Those Treated With a Placebo	Improvement in motor complications associated with Parkinson's disease are measured as "on" (good medication response); OR "on with dyskinesia" (good medication response, but with superimposed involuntary movements that interfere with activities), OR "off" (poor medication response).	Baseline (Day-7) up to 2 days post-dose.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline up to Day 2 in the Percentage of "on" Time Without Dyskinesia, as Assessed Over Hours 1 to 8 for Each Time Point in Participants Treated With SUN N4057 and Those Treated With a Placebo	Improvement in motor complications associated with Parkinson's disease are measured as "on" (good medication response); OR "on with dyskinesia" (good medication response, but with superimposed involuntary movements that interfere with activities), OR "off" (poor medication response).	Baseline (Day -7), Day 1, and Day 2 post-dose.
Percentage of "on" Time With Dyskinesia at Baseline up to Day 2, and the Change From Baseline in Participants Treated With SUN N4057 and Those Treated With a Placebo	Improvement in motor complications associated with Parkinson's disease are measured as "on" (good medication response); OR "on with dyskinesia" (good medication response, but with superimposed involuntary movements that interfere with activities), OR "off" (poor medication response). Negative values indicate a decrease in "on" time from baseline to measured time point.	Baseline (Day -7), Day 1, and Day 2 post-dose.
Percentage of "on" Time With Dyskinesia for the Average of Days 1 and 2, and the Change From Baseline in Participants Treated With SUN N4057 and Those Treated With a Placebo	Improvement in motor complications associated with Parkinson's disease are measured as "on" (good medication response); OR "on with dyskinesia" (good medication response, but with superimposed involuntary movements that interfere with activities), OR "off" (poor medication response). Negative values indicate a decrease in "on" time from baseline to measured time point.	Baseline (Day -7), Day 1, and Day 2 post-dose.
Percentage of "on" Time With or Without Dyskinesia at Baseline up to Day 2, and the Change From Baseline in Participants Treated With SUN N4057 and Those Treated With a Placebo	Improvement in motor complications associated with Parkinson's disease are measured as "on" (good medication response); OR "on with dyskinesia" (good medication response, but with superimposed involuntary movements that interfere with activities), OR "off" (poor medication response). Negative values indicate a decrease in "on" time from baseline to measured time point.	Baseline (Day -7), Day 1 and Day 2 post-dose.
Percentage of "on" Time With or Without Dyskinesia for the Average of Days 1 and 2, and the Change From Baseline in Participants Treated With SUN N4057 and Those Treated With a Placebo	Improvement in motor complications associated with Parkinson's disease are measured as "on" (good medication response); OR "on with dyskinesia" (good medication response, but with superimposed involuntary movements that interfere with activities), OR "off" (poor medication response). Negative values indicate a decrease in "on" time from baseline to measured time point.	Baseline (Day -7), Day 1 and Day 2 post-dose.
Percentage of "Off" Time at Baseline up to Day 2, and the Change From Baseline in Participants Treated With SUN N4057 and Those Treated With a Placebo	Improvement in motor complications associated with Parkinson's disease are measured as "on" (good medication response); OR "on with dyskinesia" (good medication response, but with superimposed involuntary movements that interfere with activities), OR "off" (poor medication response). Negative values indicate a decrease in "off" time from baseline to measured time point.	Baseline (Day -7), Day 1, and Day 2 post-dose.
Percentage of "Off" Time for the Average of Days 1 and 2, and the Change From Baseline in Participants Treated With SUN N4057 and Those Treated With a Placebo	Improvement in motor complications associated with Parkinson's disease are measured as "on" (good medication response); OR "on with dyskinesia" (good medication response, but with superimposed involuntary movements that interfere with activities), OR "off" (poor medication response). Negative values indicate a decrease in "off" time from baseline to measured time point.	Baseline (Day -7), Day 1, and Day 2 post-dose.
Change From Baseline up to Day 2 in the Average Abnormal Involuntary Movement Scale (AIMS) Total Score in Participants Treated With SUN N4057 and Those Treated With a Placebo	The Abnormal Involuntary Movement Scale (AIMS) is an assessment of dyskinesia in patients with movement disorders. The AIMS was originally developed to assess neuroleptic-induced extrapyramidal symptoms but has also been applied to the assessment of dyskinesia in patients with Parkinson's disease. AIMS questions 1 to 7 rate the degree of dyskinesia on a 0 to 4 scale in the extremities, trunk, and face, where 0 is no dyskinesia (better outcome) and 4 is severe dyskinesia (worse outcome). The total score range is 0 (better outcome) to 28 (worse outcome). Higher scores indicate a worse outcome.	Baseline (Day -7), Day 1, and Day 2 post-dose.
Average of Days 1 and 2 in the Average Abnormal Involuntary Movement Scale (AIMS) Total Score in Participants Treated With SUN N4057 and Those Treated With a Placebo	The Abnormal Involuntary Movement Scale (AIMS) is an assessment of dyskinesia in patients with movement disorders. The AIMS was originally developed to assess neuroleptic-induced extrapyramidal symptoms but has also been applied to the assessment of dyskinesia in patients with Parkinson's disease. AIMS questions 1 to 7 rate the degree of dyskinesia on a 0 to 4 scale in the extremities, trunk, and face, where 0 is no dyskinesia (better outcome) and 4 is severe dyskinesia (worse outcome). The total score range is 0 (better outcome) to 28 (worse outcome). Higher scores indicate a worse outcome.	Day 1 and Day 2 post-dose.
Mean SUN N4057 Plasma Concentrations Over Time Following Treatment With SUN N4057	The mean concentration of study drug, SUN N4057, in participant blood plasma samples drawn during infusions.	Day 1 pre-dose (Hour 0), 1 hour, 6 hours, 12 hours; Day 2 pre-dose (Hour 24), 1 hour (Hour 25), 6 hours (Hour 30), 12 hours (Hour 36), and Day 3 Hour 0 (Hour 48) post-dose.
Mean SUN N4057 Plasma Pharmacokinetic Parameter of Observed Maximum Concentration (Cmax) Following Treatment With SUN N4057	Cmax is the observed maximum concentration of SUN N4057 in the participant blood plasma sample after drug administration.	Baseline (Day 1 pre-dose) up to Hour 24, and Hour 48 post-dose.
Mean SUN N4057 Plasma Pharmacokinetic Parameter of Observed Minimum Concentration (Cmin) Following Treatment With SUN N4057	Cmin is the observed minimum concentration of SUN N4057 in the participant blood plasma sample after drug administration. Average of C24 and C48 [ie, 24 hours after the initiation of infusion on Days 1 and 2. Cmin = average of (C24 and C48)	Day 1 pre-dose (Hour 0) up to Hour 24, and Hour 48 post-dose.
Mean SUN N4057 Plasma Pharmacokinetic Parameter of Observed Mean Concentration (Caverage) Following Treatment With SUN N4057	Caverage is the mean concentration of SUN N4057 in the participant blood plasma sample obtained from the observed concentrations during the 2-day drug infusions (average of C1, C6, C12, C25, C30, and C36 [ie, Hours 1, 6, 12, 25, 30, and 36 after the initiation of infusion on Day 1]). Caverage = average of (C1, C6, C12, C25, C30, and C36)	Day 1 at 1 hour, 6 hours, and12 hours; Day 2 at 25 hours, 30 hours, and 36 hours post-dose.
Mean SUN N4057 Pharmacokinetic Parameter of Area Under the Drug Concentration vs Time Curve (AUCt) Following Treatment With SUN N4057	AUCt is defined as the area under the drug concentration vs time curve from zero up to the last sampling point with a quantifiable drug concentration which is above the lower limit of quantification.	Baseline (Day 1 pre-dose) up to Hour 0, Hour 1, Hour 6, Hour 12, Hour 24, Hour 25, Hour 30, Hour 36, and Hour 48 post-dose.
Treatment-Related Treatment-Emergent Adverse Events Reported Following Treatment With SUN N4057 or Placebo	A treatment-emergent adverse event (TEAE) was defined as an Adverse Event (AE) that was new in onset or aggravated in severity or frequency following administration of the investigational agent. This included any change from the screening physical examination findings or results of diagnostic procedures (eg, laboratory test, ECG) that were clinically significant, eg, required diagnostic or therapeutic intervention beyond confirmation alone.	Baseline up to Day 16 post-dose, up to approximately a total 12 months.

Collaborators and Investigators

• Sponsor: Daiichi Sankyo, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 13, 2007
• Primary Completion (Actual): July 17, 2008
• Study Completion (Actual): July 17, 2008

Study Registration Dates

• First Submitted: January 2, 2008
• First Submitted That Met QC Criteria: February 19, 2008
• First Posted (Estimate): February 26, 2008

Study Record Updates

• Last Update Posted (Actual): March 11, 2021
• Last Update Submitted That Met QC Criteria: February 17, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Parkinson's Disease; dyskinesia; motor complications; Motor complications associated with Parkinson's
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Serotonin Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Piclozotan
• Other Study ID Numbers: ASBI-501

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
• IPD Sharing Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• IPD Sharing Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No