Clinical trial NCT01767129: Safety and Efficacy of AVP-923 in the Treatment of Levodopa-induced Dyskinesia in Parkinson's Disease Patients
Official title: A Phase 2a, Double-blind, Randomized, Placebo-controlled, Crossover Study to Evaluate the Safety and Efficacy of AVP-923 (Dextromethorphan/Quinidine) in the Treatment of Levodopa-induced Dyskinesia in Parkinson's Disease Patients.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Dyskinesia
Parkinson's Disease
Keywords: levodopa
dyskinesia
parkinson's disease
AVP-923
dextromethorphan
quinidine
Lead sponsor: Avanir Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Michael J. Fox Foundation for Parkinson's Research
First posted: 2013-01-14
Enrollment: 14
Sex: ALL
Minimum age (years): 30
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: To evaluate the efficacy, safety, and tolerability of AVP-923 capsules containing 45 mg dextromethorphan and 10 mg quinidine (AVP-923-45) compared to placebo for the treatment of levodopa-induced dyskinesia (LID) in patients with Parkinson's disease (PD).

Detailed description: Proof-of-concept phase 2a, double-blind, randomized, placebo-controlled, crossover study.

Eligibility criteria: Inclusion Criteria:

* Males and females 30 to 80 years of age, inclusive.
* Diagnosis of idiopathic PD meeting the United Kingdom Parkinson's disease Society Brain Bank criteria.
* Levodopa-induced dyskinesia present greater than 25% of the day as per MDS-UPDRS.
* Dyskinesia of at least moderate severity as per MDS-UPDRS
* Amantadine and Monoamine Oxidase (MAO) inhibitors must be discontinued at least three weeks prior to randomization.
* Subjects currently receiving anti-parkinsonian medications, including all Levodopa preparations are eligible provided they have been on a stable dose of these medications for at least 1 month prior to randomization.
* Concomitant use of antidepressants such as selective serotonin reuptake inhibitors are allowed, provided the dose has been stable for at least 1 month prior to randomization.

Exclusion Criteria:

* Subject had a prior surgery for PD except Deep Brain Stimulation (Deep Brain Stimulation must not have been performed within one year of screening)
* Hoehn and Yahr score of 5 when "off".
* Subject with Cognitive impairment and/or history of psychiatric manifestations or active hallucinations.
* Subjects with any history of complete heart block, QTc prolongation, or torsades de pointes.
* Subjects with any family history of congenital QT interval prolongation syndrome.
* Subjects with history of postural syncope, or any history of unexplained syncope within the last 12 months.
* Subjects with a history of substance and/or alcohol abuse within the past 2 years.

Primary outcomes:
measure: Least Squares Mean Dyskinesia Severity Area Under the Curve (AUC) Score As Assessed By Modified Movement Disorder Society-Unified Dyskinesia Rating Scale (MDS-UDysRS) Part 3
timeFrame: Over the 2-hour levodopa infusion period on the last day of each treatment period (Day 14 and Day 42)
Secondary outcomes:
measure: Least Squares Mean Disability Area Under the Curve (AUC) Score As Assessed By Modified Movement Disorder Society-Unified Dyskinesia Rating Scale (MDS-UDysRS) Part 4
timeFrame: Over the 2-hour levodopa infusion period on the last day of each treatment period (Day 14 and Day 42)
measure: Least Squares Mean Motor Movement Area Under the Curve Score As Assessed by Modified Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Part III
timeFrame: Over the 2-hour levodopa infusion period on the last day of each treatment period (Day 14 and Day 42)
measure: Least Squares Mean Timed Finger Tapping Area Under the Curve (AUC) Score
timeFrame: Over the 2-hour levodopa infusion period on the last day of each treatment period (Day 14 and Day 42)
measure: Change From Baseline in MDS-UPDRS Scores for Part I, II, and IV
timeFrame: Baseline (Day 1); Post-Baseline (Day 14 or 42)
measure: Change From Baseline in MDS-UDysRS Scores for Part 1 and 2
timeFrame: Baseline (Day 1); Post-Baseline (Day 14 or 42)
measure: Change From Baseline in PD Motor Diary Ratings Of Duration Of "On-time Without Bothersome Dyskinesia"
timeFrame: Baseline; Post-Baseline (Days 14 and 42)
measure: Change From Baseline in Parkinson's Disease Questionnaire-39 (PDQ-39) Domain Scores at the End of Each Treatment Period
timeFrame: Baseline; Post-Baseline (Day 14 or 42)
measure: Change From Baseline in PDQ-39 Single Index (PDQ-39-SI) Scores at the End of Each Treatment Period
timeFrame: Baseline; Post-Baseline (Day 14 or 42)
measure: Change From Screening in the Montreal Cognitive Assessment (MoCA) Calculated Score at the End of Each Treatment Period
timeFrame: Screening (Day -28); End of each treatment period (Days 14 or 42)
measure: Change From Baseline in the Dyskinesia and Other PD Symptoms Score As Assessed by Patient Global Impression of Change (PGIC)
timeFrame: Baseline; Post-Baseline (Days 14 and 42)
Other outcomes:
Locations:
city: Chicago
country: United States
state: Illinois
city: Portland
country: United States
state: Oregon
city: Toronto
country: Canada
state: Ontario
Study officials:
References:
citation: Fox SH, Metman LV, Nutt JG, Brodsky M, Factor SA, Lang AE, Pope LE, Knowles N, Siffert J. Trial of dextromethorphan/quinidine to treat levodopa-induced dyskinesia in Parkinson's disease. Mov Disord. 2017 Jun;32(6):893-903. doi: 10.1002/mds.26976. Epub 2017 Mar 30.