Study of NP002 in Subjects With Idiopathic Parkinson's Disease to Treat Dyskinesias Due to Levodopa Therapy - Full Text View

Sponsor:	Neuraltus Pharmaceuticals, Inc.
Information provided by:	Neuraltus Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:	NCT00957918

Purpose

The study is designed to answer the question: will nicotine at doses that do not cause serious side effects, show feasibility in treatment of levodopa-induced dyskinesia in patients with Parkinson's disease?

Condition	Intervention	Phase
Parkinson's Disease	Drug: nicotine Other: placebo comparator	Phase I Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Randomized, Double-Blind, Parallel Group, Placebo Controlled Safety, Tolerability and Efficacy Study of NP002 in Subjects With Idiopathic Parkinson's Disease With Dyskinesias Due to Levodopa Therapy

Resource links provided by NLM:

Genetics Home Reference related topics: familial paroxysmal nonkinesigenic dyskinesia Parkinson disease

MedlinePlus related topics: Parkinson's Disease

Drug Information available for: Levodopa Nicotine tartrate Nicotine polacrilex

U.S. FDA Resources

Further study details as provided by Neuraltus Pharmaceuticals, Inc.:

Primary Outcome Measures:

frequency and severity of adverse events, active vs placebo [ Time Frame: Every two weeks during dosing (week 0 to week 12) and weekly thereafter for 2 weeks following cessation of dosing ] [ Designated as safety issue: Yes ]
measure of impulse control (rMIDI), active vs placebo [ Time Frame: at screening and 4 weeks, 10 weeks, 12 weeks and 14 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

measure of frequency and severity of dyskinesia (USDysRS), active vs placebo [ Time Frame: At screen and every two weeks through week 10 ] [ Designated as safety issue: Yes ]
Parkinson's disease severity (UPDRS part II,III,IV), active vs placebo [ Time Frame: At screen and every two weeks through week 10 ] [ Designated as safety issue: No ]

Estimated Enrollment:	60
Study Start Date:	October 2009
Estimated Study Completion Date:	September 2010
Estimated Primary Completion Date:	September 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Nicotine: Experimental Active drug is nicotine dihydrate bitartrate, provided as an oral capsule at escalating doses, 1 mg to 6 mg, once every 6 hours	Drug: nicotine Oral capsule self administered in escalating doses from 1 mg to 6 mg, 4 times a day. Each dose is is taken for two weeks, except the highest dose, which is taken for 4 weeks. At the end of 10 weeks, the dose is tapered down over 9 days. Subject is continued on study through week 14.
placebo: Placebo Comparator Subjects in this arm receive placebo capsules orally	Other: placebo comparator oral capsules containing only excipient will be self-administered with the same regimen as the active drug, 4 times a day, approximately every 6 hours for 10 weeks and nine days. Study is continued through week 14.

Detailed Description:

Nicotine will be employed at daily doses lower than those available OTC as smoking-cessation patches, in parkinsonian patients experiencing disabling dyskinesias due to their levodopa treatment. The principal adverse effect from this dose level of nicotine is expected to be nausea on acute administration to nicotine-naive patients. Because tolerance to the effects of nicotine is achieved by repeated dose, the study is designed to gradually escalate from 6 to 24 mg per day, taken in 6 separate oral doses of 6 mg each. The study is designed to see if doses which can be tolerated by parkinsonian patients will also reduce the severity and frequency of the dyskinesias experienced following administration of levodopa, the gold standard medication for Parkinson's disease.

Eligibility

Ages Eligible for Study:	30 Years to 83 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

clinical diagnosis of probable idiopathic Parkinson's disease
in stable health
male and female aged 30-83 yrs
Hoehn and Yahr stage II through IV inclusive
levodopa-induced dyskinesias present greater than 25% of waking day; rating equal or greater than 2 on item 32 of UPDRS
dyskinesias moderately or severely disabling as determined by a rating of equal or greater than 2 on item 33 of UPDRS
Mini-Mental state (MMSE) score of equal or greater than 26
on a stable dose of levodopa for at least 30 days
if subjects are taking dopamine antagonists, amantadine, MAO-B inhibitors (rasagiline only) or COMT inhibitors, doses must have been stable for at least 30 days

Exclusion Criteria:

Secondary or non-idiopathic Parkinson's disease
Subjects with parkinsonian symptoms who do not respond to levodopa therapy
history of schizophrenia, or other DSM-IV TR axis 1 diagnosis sufficient to interfere with or affect study conduct or interpretation of results
any history (past 5 years) of suicide or suicide attempt or thoughts or urges of suicide on direct questioning
subjects who score 2 or higher on a single module of the Jay MIDI scale
moderate or severe hallucinations, psychoses or delusions
any medical condition or lab abnormality presenting an unwarranted risk in the opinion of the Investigator
history of HIV positivity, AIDS, or active hepatitis determined by subject report
female who is pregnant or breastfeeding
female of childbearing potential not using double barrier method of birth control throughout the duration of the study
receipt of a neurosurgical intervention (e.g. brain surgery)related to Parkinson's disease or any neurosurgical procedure sufficient to interfere with study conduct or interpretation of results
must not have systolic blood pressure ≥150; diastolic ≥95.
must not have ECG at screening judged clinically significantly abnormal by investigator
must not have QTc > 450 msec at ECG screen
must not have current angina pectoris, history of ventricular arrhythmias, uncontrolled hyperthyroidism, known or suspected pheochromocytoma, symptomatic vasospastic disease, or active peptic ulcer
must not have a history of stroke, transient ischemic attack (TIA) or myocardial infarction within the last 2 years
must not have current drug or alcohol abuse within the last two years. Acceptable alcohol use is no more than 3 ounces of alcohol, 3 beers or 2 glasses of wine per day.
must not be participating in another drug trial or have participated in another drug study in the last 30 days. Observational trials with no intervention are acceptable provided permission is obtained from the other study sponsor in writing.
must not be unwilling or unable to swallow capsules
must not have a positive urine test for cotinine at screening
must not be a smoker, previous (less than 5 years since cessation) smoker or have regular exposure to second hand smoke
must not be allergic to capsule excipients
must not be allergic to ondansetron. If allergic, they may participate provided they understand there is no rescue medication for potential nausea or vomiting during the study
must not have known sensitivity to nicotine or nicotine-containing products
must not be taking any of the following medications or substances within a minimum of 30 days: nicotine, any form; CYP2A6 inducers or inhibitors during the course of the study or within 30 days of the planned initial dose (your investigator will have a full list of these drugs); Monoamine oxidase inhibitors (with the exception of rasagiline, which is allowed)(your investigator will have a full list of these drugs); apokyn (apomorphine), due to its contraindication with ondansetron); warfarin.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00957918

Locations

United States, Arizona
Barrow Neurology Clinics at St. Joseph's Hospital and Medical Center
Phoenix, Arizona, United States, 85013
United States, California
Keck/USC School of Medicine -Department of Neurology
Los Angelis, California, United States, 90033
Pacific Neuroscience Medical Group
Oxnard, California, United States, 93030
United States, Colorado
Colorado Neurological Institute
Englewood, Colorado, United States, 80113
United States, Florida
Parkinson's Disease & Movement Disorders Ctr of Boca Raton
Boca Raton, Florida, United States, 33486
Collier Neurologic Specialists, LLC
Naples, Florida, United States, 34102
United States, Minnesota
Strurers Parkinson's Center
Golden Valley, Minnesota, United States, 55427
United States, New York
David L. Kreitzman, M.D., P.C.
Commack, New York, United States, 11725
108-14 72nd Ave, Second floor
Forest Hills, New York, United States, 11375
United States, North Carolina
Duke University Medical Center, Department of Neurology
Durham, North Carolina, United States, 27705
United States, Oklahoma
The Movement Disordedr Clinic of Oklahoma
Tusla, Oklahoma, United States, 74137
United States, Pennsylvania
Parkinson's Disease and Movement Center, Penn Comprehensive Neuroscience Center
Philadelphia, Pennsylvania, United States, 19107

Sponsors and Collaborators

Neuraltus Pharmaceuticals, Inc.

Investigators

Principal Investigator:

Abrahan N Lieberman, MD

St. Joseph's Hospital and Medical Center, Barrow Neurology Clinics

More Information

No publications provided

Responsible Party:	Neuraltus ( Nancy Isaac/Vice President, Regulatory Affairs )
ClinicalTrials.gov Identifier:	NCT00957918 History of Changes
Other Study ID Numbers:	NP002-09-001
Study First Received:	August 11, 2009
Last Updated:	June 22, 2010
Health Authority:	United States: Food and Drug Administration

Keywords provided by Neuraltus Pharmaceuticals, Inc.:

levodopa-induced dyskinesia
Parkinson's disease
parkinsonian
levodopa-induced dyskinesias in Parkinson's disease

Additional relevant MeSH terms:

Dyskinesias
Parkinson Disease
Movement Disorders
Central Nervous System Diseases
Nervous System Diseases
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Neurodegenerative Diseases
Anti-Dyskinesia Agents
Neurologic Manifestations
Signs and Symptoms
Levodopa
Nicotine

Antiparkinson Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Ganglionic Stimulants
Autonomic Agents
Peripheral Nervous System Agents
Nicotinic Agonists
Cholinergic Agonists
Cholinergic Agents

ClinicalTrials.gov processed this record on September 07, 2010