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

Neuraltus Pharmaceuticals

Status and phase

Completed

Phase 2

Phase 1

Conditions

Parkinson's Disease

Treatments

Other: placebo comparator

Drug: nicotine

Study type

Interventional

Funder types

Industry

Identifiers

NCT00957918

NP002-09-001

Details and patient eligibility

About

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?

Full 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.

Enrollment

65 patients

Sex

All

Ages

30 to 83 years old

Volunteers

No Healthy Volunteers

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.