Effects of PR Oxycodone and of Levodopa, vs Placebo, on Central Neuropathic Pain in Parkinson's Disease (OXYDOPA)

Evaluation of the Analgesic Effects of Prolonged-release Oxycodone and of Levodopa, Versus Placebo, on Central Neuropathic Pain in Parkinson's Disease: OXYDOPA Trial

This study will be conducted in three parallel groups receiving oxycodone, levodopa or placebo, administered as an add-on therapy, in addition to the usual antiparkinsonian treatment. As this study focuses on chronic central neuropathic pain caused by PD, the effects of study treatments will be evaluated after a 10-week treatment period

Study Overview

• Status: Completed
• Conditions: Parkinson Disease
• Intervention / Treatment: Drug: PR Oxycodone; Drug: Levodopa placebo; Drug: Levodopa; Drug: Oxycodone Placebo

Detailed Description

The treatment period (11 weeks) will be divided into three periods:

1. A titration phase of two weeks, during which of the doses of the treatments will be gradually increased in three steps:

   Level 1 (from D1 to D5):

   • Oxycodone: 10 mg PR/day bid (5 mg PR/5 mg PR)
   • Levodopa: 100 mg/day bid (50 mg/50 mg)

   Level 2 (from D6 to D10):

   • Oxycodone: 20 mg PR/day tid (10 mg/0 mg/10 mg)
   • Levodopa: 150 mg/day tid (50 mg/50 mg/50 mg)

   Level 3 (from D11to D15):

   • Oxycodone: 40 mg PR/day tid (20 mg/0 mg/20 mg)
   • Levodopa: 200 mg/day tid (100 mg/50 mg/50 mg)
2. A fixed dose period: the level 3 dose will be maintained for 8 weeks (from D16 to D71). The study treatment will be administered as an add-on therapy, with the usual antiparkinsonian treatment. If patients have side effects at the level 3 dose, a return to the level 2 dose will be authorized.
3. A withdrawal period: The dose of the study treatment will gradually be reduced, over an eight-day period:

For patients treated with the level 3 dose for 8 weeks: decrease to the level 2 dose over the first 3 days (from D72 to D74) ; then a decrease to the level 1 dose over the next 3 days (from D75 to D77). The treatment will be stopped completely on D78. The last visit will take place on D79, 2 days after the end of treatment.

For patients treated with the level 2 dose: decrease to the level 1 dose over the first 3 days (from D72 to D74), with stopping of the treatment on D75. The last visit will take place on D79, 5 days after the end of treatment.

• Study Type: Interventional
• Enrollment (Actual): 67
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• France
  • Aix-en-Provence, France, 13616
    • Hospital of Aix-en-Provence
  • Amiens, France, 80054
    • CHU Amiens
  • Bordeaux, France, 33076
    • University Hospital of Bordeaux
  • Clermont-Ferrand, France, 63003
    • University Hospital of Clermont-Ferrand
  • Créteil, France, 94010
    • Henri Mondor Hospital
  • Lille, France, 59037
    • University Hospital of Lille
  • Limoges, France, 87042
    • University Hospital of Limoges
  • Lyon, France
    • Hospital Pierre Wertheimer
  • Marseille, France, 13385
    • University Hospital of Marseille
  • Nancy, France
    • University Hospital of Nancy
  • Nantes, France
    • University Hospital of Nantes
  • Nîmes, France
    • University Hospital of Nîmes - Caremeau
  • Paris, France, 75651
    • Pitié-Salpêtrière Hospital
  • Poitiers, France, 86021
    • University hospital of Poitiers
  • Rennes, France, 35033
    • University Hospital of Rennes
  • Rouen, France, 76031
    • University Hospital of Rouen
  • Strasbourg, France, 67098
    • University Hospital of Strasbourg
  • Toulouse, France, 31059
    • Chu Toulouse

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 36 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with Parkinson's disease according to the UKPDSBB (United Kingdom Parkinson's Disease Society Brain Bank) criteria
• Patients suffering from chronic pain (lasting for more than 3 months)
• Patients suffering from central neuropathic pain caused by PD,
• Patients with a PD-related central neuropathic pain intensity of at least 3 points on the VAS (average intensity over the last month),
• Patients with both types of pain (neuropathic and nociceptive) will be included if the neuropathic pain predominates
• Patients treated with a stable regimen of dopaminergic drugs (levodopa and/or dopamine agonists) for at least 4 weeks before the study dan throughout the study
• Patients with a stable step 1 analgesic (NSAIDS, acetaminophen) or coanalgesic (antidepressants, antiepileptic) treatment for at least 4 weeks before the study and throughout the study

Exclusion Criteria:

• Patients suffering from another parkinsonian syndrome
• De Novo patients (patients never before treated with dopaminergic drugs)
• Patients with intercurrent acute pain
• Patients suffering from a chronic disease causing pain (rheumatoid arthritis, ankylosing spondylitis, diabetic neuropathy, cancer etc.)
• Patients treated with neuroleptics
• Patients with clinically detectable behavioural disorders and addiction
• Patients with disabling dyskinesias
• Patients with painful restless legs syndrome
• Patients with cognitive impairment (MMS < 25) or unable to complete the various scales used in the study
• Hypersensitivity to oxycodone, levodopa, benserazide or a combination of these drugs
• Patients treated with opioid drugs (step 2 and 3)
• Patients treated with non-selective monoamine oxidase inhibitors (MAOI)
• Patients with severe hepatocellular insufficiency
• Patients with uncontrolled cardiovascular and pulmonary diseases
• Persistent constipation that has already resulted in a subocclusive state
• Patients treated with antiemetic neuroleptics
• Patients with angle-closure glaucoma

Exclusion criteria relating to MRI:

• Patients with claustrophobia
• Patients with a hearing aid, cardiac prosthesis, pacemaker, surgical clip
• Patients refusing to be informed of abnormalities are detected on MRI

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PR oxycodone; A titration phase of two weeks, in three steps: Level 1 (from D1 to D5): Oxycodone : 10 mg PR/day bid (5 mg PR/5 mg PR); Levodopa placebo 100 mg/day bid (50 mg/50 mg) Level 2 (from D6 to D10): Oxycodone : 20 mg PR/day tid (10 mg/0 mg/10 mg); Levodopa placebo: 150 mg/day tid (50 mg/50 mg/50 mg) Level 3 (from D11to D15): Oxycodone: 40 mg PR/day tid (20 mg/0 mg/20 mg); Levodopa placebo: 200 mg/day tid (100 mg/50 mg/50 mg)A fixed dose period: the level 3 dose will be maintained for 8 weeks (from D16 to D71).A withdrawal period:	Drug: PR Oxycodone; PR Oxycodone; Other Names: PR Oxycontin; Drug: Levodopa placebo
Active Comparator: levodopa; A titration phase of two weeks, in three steps: Level 1 (from D1 to D5): Oxycodone placebo : 10 mg PR/day bid (5 mg PR/5 mg PR); Levodopa 100 mg/day bid (50 mg/50 mg) Level 2 (from D6 to D10): Oxycodone placebo: 20 mg PR/day tid (10 mg/0 mg/10 mg); Levodopa : 150 mg/day tid (50 mg/50 mg/50 mg) Level 3 (from D11to D15): Oxycodone placebo: 40 mg PR/day tid (20 mg/0 mg/20 mg); Levodopa : 200 mg/day tid (100 mg/50 mg/50 mg)A fixed dose period: the level 3 dose will be maintained for 8 weeks (from D16 to D71).A withdrawal period:	Drug: Levodopa; Levodopa; Other Names: Modopar; Drug: Oxycodone Placebo; Placebo of PR Oxycodone
Placebo Comparator: Placebo; A titration phase of two weeks, in three steps: Level 1 (from D1 to D5): Oxycodone placebo : 10 mg PR/day bid (5 mg PR/5 mg PR); Levodopa placebo 100 mg/day bid (50 mg/50 mg) Level 2 (from D6 to D10): Oxycodone placebo: 20 mg PR/day tid (10 mg/0 mg/10 mg); Levodopa placebo: 150 mg/day tid (50 mg/50 mg/50 mg) Level 3 (from D11to D15): Oxycodone placebo: 40 mg PR/day tid (20 mg/0 mg/20 mg); Levodopa placebo: 200 mg/day tid (100 mg/50 mg/50 mg)A fixed dose period: the level 3 dose will be maintained for 8 weeks (from D16 to D71).A withdrawal period:	Drug: Levodopa placebo; Drug: Oxycodone Placebo; Placebo of PR Oxycodone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average pain intensity	Change in average pain rated on visual analog scale (VAS) intensity between baseline and after 8 weeks	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximal pain intensity	Change of maximal pain intensity over the preceding week rated on the VAS	8 weeks
Functional impact of pain" of the Brief Pain Inventory (BPI)	Change in scores between Day 0 and Day 71(Day 71= 8 weeks of treatment)	8 weeks
Neuropathic Pain Symptoms Inventory (NPSI)	Change in scores between Day 0 and Day 71(Day 71= 8 weeks of treatment)	8 weeks
McGill pain questionnaire (SFMPQ)	Change in scores between Day 0 and Day 71(Day 71= 8 weeks of treatment)	8 weeks
Depression and anxiety: the Hospital Depression and Anxiety (HAD) scale	Change in scores between Day 0 and Day 71(Day 71= 8 weeks of treatment)	8 weeks
Apathy: the Lille Apathy Rating Scale (LARS)	Change in scores between Day 0 and Day 71(Day 71= 8 weeks of treatment)	8 weeks
Fatigue : the Parkinson fatigue scale	Change in scores between Day 0 and Day 71(Day 71= 8 weeks of treatment)	8 weeks
Sleep : the Pittsburgh sleep quality index	Change in scores between Day 0 and Day 71(Day 71= 8 weeks of treatment)	8 weeks
Motor assessment and motor fluctuations: MDS UPDRS (MDS Movement Disorder Society - UPDRS Unified Parkinson Disease Rating Scale)	Change in scores between Day 0 and Day 71(Day 71= 8 weeks of treatment)	8 weeks
Quality of life: Parkinson's Disease Questionnaire 39 items (PDQ-39)	Change in scores between Day 0 and Day 71(Day 71= 8 weeks of treatment)	8 weeks
Acetaminophen consumption reported in diary	number of pills or capsules reported in patients diary	8 weeks
Adverse events	Adverse events, evaluated with an open-ended questionnaire	Day 5, Day 10, Day 15, Day 43, Day 71, Day 79
changes in Resting-state brain network (3T fMRI)	changes in resting-state cerebral networks between Day 0 and Day 71, as assessed by 3T fMRI.	Day 0 /Day 71(Day 71= 8 weeks of treatment)

Collaborators and Investigators

• Sponsor: University Hospital, Toulouse
• Investigators: Principal Investigator: Christine Brefel-Courbon, MD, University Hospital, Toulouse; Study Chair: Claire THALAMAS, MD, University Hospital, Toulouse

Publications and helpful links

General Publications

• Lawn T, Rukavina K, Malcangio M, Howard M, Chaudhuri KR. Response to Mylius et al. Pain. 2022 Mar 1;163(3):e496-e497. doi: 10.1097/j.pain.0000000000002445. No abstract available.
• Brefel-Courbon C, Harroch E, Marques A, Devos D, Thalamas C, Rousseau V, Ory-Magne F, Fabbri M, Maltete D, Rouaud T, Drapier S, Tir M, Thobois S, Salhi H, Corvol JC, Castelnovo G, Lagha-Boukbiza O, Fluchere F, Frismand S, Ansquer S, Sommet A, Rascol O. Oxycodone or Higher Dose of Levodopa for the Treatment of Parkinsonian Central Pain: OXYDOPA Trial. Mov Disord. 2024 Sep;39(9):1533-1543. doi: 10.1002/mds.29878. Epub 2024 Jun 8.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2016
• Primary Completion (Actual): November 1, 2020
• Study Completion (Actual): November 1, 2020

Study Registration Dates

• First Submitted: August 17, 2015
• First Submitted That Met QC Criteria: November 9, 2015
• First Posted (Estimated): November 10, 2015

Study Record Updates

• Last Update Posted (Actual): May 4, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Parkinson Disease; Amino Acids, Peptides, and Proteins; Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Amines; Amino Acids; Catechols; Phenols; Benzene Derivatives; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Catecholamines; Dihydroxyphenylalanine; Tyrosine; Levodopa; benserazide, levodopa drug combination
• Other Study ID Numbers: 14 7440 01

Drug and device information, study documents

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