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

Primary Purpose

Parkinson Disease

Status
Completed
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
PR Oxycodone
Levodopa
Oxycodone Placebo
Levodopa placebo
Sponsored by
University Hospital, Toulouse
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Parkinson Disease

Eligibility Criteria

40 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Hospital of Aix-en-Provence
  • CHU Amiens
  • University Hospital of Bordeaux
  • University Hospital of Clermont-Ferrand
  • Henri Mondor Hospital
  • University Hospital of Lille
  • University Hospital of Limoges
  • Hospital Pierre Wertheimer
  • University Hospital of Marseille
  • University Hospital of Nancy
  • University Hospital of Nantes
  • University Hospital of Nîmes - Caremeau
  • Pitié-Salpêtrière Hospital
  • University Hospital of Poitiers
  • University Hospital of Rennes
  • University Hospital of Rouen
  • University Hospital of Strasbourg
  • Chu Toulouse

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Placebo Comparator

Arm Label

PR oxycodone

levodopa

Placebo

Arm Description

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:

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:

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:

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Maximal pain intensity
Change of maximal pain intensity over the preceding week rated on the VAS
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)
Neuropathic Pain Symptoms Inventory (NPSI)
Change in scores between Day 0 and Day 71(Day 71= 8 weeks of treatment)
McGill pain questionnaire (SFMPQ)
Change in scores between Day 0 and Day 71(Day 71= 8 weeks of treatment)
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)
Apathy: the Lille Apathy Rating Scale (LARS)
Change in scores between Day 0 and Day 71(Day 71= 8 weeks of treatment)
Fatigue : the Parkinson fatigue scale
Change in scores between Day 0 and Day 71(Day 71= 8 weeks of treatment)
Sleep : the Pittsburgh sleep quality index
Change in scores between Day 0 and Day 71(Day 71= 8 weeks of treatment)
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)
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)
Acetaminophen consumption reported in diary
number of pills or capsules reported in patients diary
Adverse events
Adverse events, evaluated with an open-ended questionnaire
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.

Full Information

First Posted
August 17, 2015
Last Updated
February 28, 2022
Sponsor
University Hospital, Toulouse
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1. Study Identification

Unique Protocol Identification Number
NCT02601586
Brief Title
Effects of PR Oxycodone and of Levodopa, vs Placebo, on Central Neuropathic Pain in Parkinson's Disease
Acronym
OXYDOPA
Official Title
Evaluation of the Analgesic Effects of Prolonged-release Oxycodone and of Levodopa, Versus Placebo, on Central Neuropathic Pain in Parkinson's Disease: OXYDOPA Trial
Study Type
Interventional

2. Study Status

Record Verification Date
February 2022
Overall Recruitment Status
Completed
Study Start Date
September 2016 (Actual)
Primary Completion Date
November 2020 (Actual)
Study Completion Date
November 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Toulouse

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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
Detailed Description
The treatment period (11 weeks) will be divided into three periods: 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) 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
67 (Actual)

8. Arms, Groups, and Interventions

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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christine BREFEL-COURBON, MD
Organizational Affiliation
CHU Toulouse
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Claire THALAMAS, MD
Organizational Affiliation
CHU Toulouse
Official's Role
Study Chair
Facility Information:
Facility Name
Hospital of Aix-en-Provence
City
Aix-en-Provence
ZIP/Postal Code
13616
Country
France
Facility Name
CHU Amiens
City
Amiens
ZIP/Postal Code
80054
Country
France
Facility Name
University Hospital of Bordeaux
City
Bordeaux
ZIP/Postal Code
33076
Country
France
Facility Name
University Hospital of Clermont-Ferrand
City
Clermont-Ferrand
ZIP/Postal Code
63003
Country
France
Facility Name
Henri Mondor Hospital
City
Créteil
ZIP/Postal Code
94010
Country
France
Facility Name
University Hospital of Lille
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
University Hospital of Limoges
City
Limoges
ZIP/Postal Code
87042
Country
France
Facility Name
Hospital Pierre Wertheimer
City
Lyon
Country
France
Facility Name
University Hospital of Marseille
City
Marseille
ZIP/Postal Code
13385
Country
France
Facility Name
University Hospital of Nancy
City
Nancy
Country
France
Facility Name
University Hospital of Nantes
City
Nantes
Country
France
Facility Name
University Hospital of Nîmes - Caremeau
City
Nîmes
Country
France
Facility Name
Pitié-Salpêtrière Hospital
City
Paris
ZIP/Postal Code
75651
Country
France
Facility Name
University Hospital of Poitiers
City
Poitiers
ZIP/Postal Code
86021
Country
France
Facility Name
University Hospital of Rennes
City
Rennes
ZIP/Postal Code
35033
Country
France
Facility Name
University Hospital of Rouen
City
Rouen
ZIP/Postal Code
76031
Country
France
Facility Name
University Hospital of Strasbourg
City
Strasbourg
ZIP/Postal Code
67098
Country
France
Facility Name
Chu Toulouse
City
Toulouse
ZIP/Postal Code
31059
Country
France

12. IPD Sharing Statement

Citations:
PubMed Identifier
35148289
Citation
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.
Results Reference
derived

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

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