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

Toulouse University Hospital

Status and phase: Completed; Phase 3; Phase 2

Conditions: Parkinson Disease

Treatments: Drug: Levodopa; Drug: PR Oxycodone; Drug: Oxycodone Placebo; Drug: Levodopa placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT02601586

14 7440 01

Details and patient eligibility

About

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

Full 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.

Enrollment: 67 patients

Sex: All

Ages: 40 to 75 years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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67 participants in 3 patient groups, including a placebo group

PR oxycodone

Experimental group

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:

Treatment:

Drug: Levodopa placebo

Drug: PR Oxycodone

levodopa

Active Comparator group

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:

Treatment:

Drug: Oxycodone Placebo

Drug: Levodopa

Placebo

Placebo Comparator group

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:

Treatment:

Drug: Levodopa placebo

Drug: Oxycodone Placebo