not applicable

• Register: EUCTR
• Last refreshed on: 2 December 2013
• Main ID: EUCTR2011-002901-31-HU
• Date of registration: 13/10/2011
• Prospective Registration: Yes
• Primary sponsor: Mundipharma Research GmbH & Co. KG
• Public title: not applicable
• Scientific title: A multicentre, double-blind, randomised, placebo controlled study to determine the efficacy and tolerability of OXN PR for the treatment of severe Parkinson’s disease associated pain - A randomised placebo controlled study of OXN PR for severe Parkinson’s disease associated pain
• Date of first enrolment: 21/12/2011
• Target sample size: 210
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-002901-31
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: Double-blind phase is followed by open-label phase If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Czech Republic, Germany, Hungary, Spain, United Kingdom

Contacts

• Name: Michael Hopp
• Affiliation: Mundipharma Research GmbH & Co. KG

• Name: Michael Hopp
• Affiliation: Mundipharma Research GmbH & Co. KG

Key inclusion & exclusion criteria

Inclusion criteria:
Screening/Double-Blind Phase Inclusion Criteria
1. Males and females, age of 25 years or over (the Double-Blind Phase rescue medication is not licensed for use in under 25 year olds)
2. Able to provide written informed consent
3. Primary diagnosis of Parkinson‘s disease diagnosed by an expert as determined by the UK Parkinson's Disease Society Brain Bank Clinical Diagnostic Criteria (1992)
4. Parkinson‘s disease Stage II-IV (Hoehn & Yahr staging system)
5. Severe pain graded in at least 1 of the sub sections of the Chaudhuri and Schapira (2009) pain classification system
6. An average pain score of 6 or above on an 11 point NRS, over the previous 7 days determined using diary scores of averaged 24 hour pain in the 7 days leading up to Randomisation (assessed at Visit 2)
7. Female subjects less than one year post-menopausal must have a negative serum or urine pregnancy test recorded prior to the first dose of study medication, be non-lactating, and willing to use an adequate and highly effective method of contraception throughout the study. A highly effective method of birth control is defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as sterilisation, implants, injectables, combined oral contraceptives, some IUDs (hormonal), sexual abstinence or vasectomised partner. Subjects who have had a hysterectomy, sterilisation or who the Investigator is certain to be post-menopausal (e.g. are elderly) do not need to be tested.
8. Subjects who, based on the Investigators‘ judgement, are likely to benefit from WHO step III opioid therapy for the duration of the study (see Appendix 18.3. )
9. Subjects must not have received opioid containing medication in the last 6 months on a regular basis (i.e. prescribed medication or more than occasional self medication use for cough, cold etc.)
10. Receiving stable treatment for Parkinson‘s disease for at least 4 weeks prior to randomisation, the dose of which is expected to remain consistent throughout the Double-Blind Phase
11. In the Investigator‘s opinion, the subject does not have visual or auditory impairments that would reduce their ability to complete study questionnaires or be unable to receive instructions for these
12. Concomitant medication (including co-analgesic) use anticipated to remain stable throughout the Double-Blind Phase of the study
13. Subjects willing and able to participate in all aspects of the study and comply with the use of study medication.

Open-Label Extension Inclusion Criteria
The aim of the Open-Label Phase is to ensure a safe transfer of all subjects to a subsequent pain treatment after the study. Subjects must:
1. Still meet general inclusion criteria for Double-Blind Phase; subjects do not have to meet inclusion 5, 6, 9 & 12
2. Have completed the Double-Blind Phase or discontinued early but have had at least 8 weeks treatment with study medication.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 105
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 105

Exclusion criteria:
Medical Conditions
1. Cognitive impairment as assessed with the MMSE scoring 24 or less
2. History of psychosis (hallucinations, delusions, etc.)
3. History of drug or alcohol abuse or current compulsive addictive use of drugs or alcohol
4. Parkinsonian-like disease secondary to drug therapy side-effects e.g. due to exposure to medications that deplete dopamine (reserpine, tetrabenazine) or block dopamine receptors (neuroleptics, antiemetics)
5. Parkinson-plus syndromes e.g. progressive supranuclear palsy (PSP) and the multiple system atrophies (MSA)
6. Females who are pregnant (positive ß-hCG test) or lactating
7. Any other contraindications to use of the opioid study medication(s) as per the SmPC/IB:
? Hypersensitivity to the active substances or to any of the excipients
? Any situation where opioids are contraindicated
? Severe respiratory depression with hypoxia and/or hypercapnia
? Severe chronic obstructive pulmonary disease
? Cor pulmonale
? Severe bronchial asthma
? Non-opioid induced paralytic ileus
? Moderate to severe hepatic impairment (see exclusion criterion 16)
8. Any other contraindications to use of the study Double-Blind Phase rescue medication as per the SmPC:
? known hypersensitivity to levodopa or benserazide
? contra-indicated in narrow-angle glaucoma (it may be used in wide-angle glaucoma provided that the intra-ocular pressure remains under control); severe psychoneuroses or psychoses; severe endocrine, renal, hepatic or cardiac disorders
? should not be given in conjunction with, or within 2 weeks of withdrawal of, monoamine oxidase (MAO) inhibitors, except selective MAO-B inhibitors (e.g. selegiline) or selective MAO-A inhibitors (e.g. moclobemide) unless selective MAO inhibitors are given in combination in which case it is contraindicated
? not be used in persons who have a history of, or who may be suffering from, a malignant melanoma
9. Subjects with any of the following as determined by medical history, clinical laboratory tests, ECG results, and physical examination, that would place the subject at risk upon exposure to the study medication:
? myxoedema
? untreated hypothyroidism
? Addison`s disease
? increase of intracranial pressure
? uncontrolled seizures or convulsive disorder
? evidence of clinically significant cardiovascular, renal, hepatic, gastrointestinal (e.g. paralytic ileus), or psychiatric disease (subjects with controlled co-morbidities may be included following agreement with the Medical Monitor)
Contraindicated Treatments
10. Treatment with Deep Brain Stimulation
11. Subjects receiving hypnotics or other central nervous system (CNS) depressants that, in the Investigator‘s opinion, may pose a risk of additional CNS depression with opioids study medication
12. Subjects presently taking, or who have taken, naloxone or naltrexone ? 30 days prior to the Screening Visit
13. Subjects who have received an investigational medicinal product within 30 days of study entry (defined as the start of the Screening Phase)
14. Any current use of an opioid other than the study medication provided
15. Subjects with a positive urine drug test at Screening Visit 1, which indicates unreported illicit drug use or unreported use of a concomitant medication not required to treat the Subjects‘ medical condition(s)
Laboratory Exclusions
16. Abnormal parameters as defined:
? aspartate aminotransferase (AST; SGOT) > 3 times the upper limit of normal
? alanine aminotransferase (ALT

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Subjects will have idiopathic Parkinson's disease and be suffering from severe PD associated pain.
MedDRA version: 14.1 Level: LLT Classification code 10013113 Term: Disease Parkinson's System Organ Class: 100000004852

Intervention(s)

Trade Name: Targinact 5 mg/2.5 mg prolonged-release tablets
Product Name: oxycodone/naloxone prolonged release tablets 5 mg /2.5 mg
Product Code: OXN 5 mg/2.5 mg PR
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: Oxycodone hydrochloride
CAS Number: 124-90-3
Other descriptive name: OXYCODONE HYDROCHLORIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5.0-
INN or Proposed INN: Naloxone Hydrochloride Dihydrate
CAS Number: 357-08-4
Current Sponsor code: 51481-60-8
Other descriptive name: NALOXONE HYDROCHLORIDE DIHYDRATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.5-
Pharmaceutical form of the placebo: Prolonged-release tablet
Route of administration of the placebo: Oral use

Trade Name: Targinact 10 mg/5 mg prolonged-release tablets
Product Name: oxycodone/naloxone prolonged release tablets 10 mg /5 mg
Product Code: OXN 10 mg / 5 mg PR
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: Oxycodone Hydrochloride
CAS Number: 124-90-3
Other descriptive name: OXYCODONE HYDROCHLORIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10.0-
INN or Proposed INN: Naloxone Hydrochloride Dihydrate
CAS Number: 357-08-4
Current Sponsor code: 51481-60-8
Other descriptive name: NALOXONE HYDROCHLORIDE DIHYDRATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5.0-
Pharmaceutical form of the placebo: Prolonged-release tablet
Route of administration of the placebo: Oral use

Trade Name: Targinact 20 mg/10 mg prolonged-release tablets
Product Name: oxycodone/naloxone prolonged release tablets 20 mg /10 mg
Product Code: OXN 20 mg / 10 mg PR
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: OXYCODONE HYDROCHLORIDE
CAS Number: 124-90-3
Other descriptive name: OXYCODONE HYDROCHLORIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20.0-
INN or Proposed INN: NAL

Primary Outcome(s)

Secondary Objective: ? To demonstrate improvement in the subject's condition, relative to baseline, as measured on the Clinical Global Impression – Improvement scale (CGI-I) and separately the Patient Global Impression – Improvement scale (PGI-I)
? To assess the effect of OXN PR on motor symptoms of PD
? To assess the effect of OXN PR on non-motor symptoms of PD
? To assess the effect of OXN PR on dyskinesia
? To assess the effect of OXN PR on sleep
? To assess the effect of OXN PR on Quality of Life
? To assess the tolerability of OXN PR
? To assess the frequency of rescue medication intake

Primary end point(s): The primary endpoint for the primary comparison of OXN PR vs. placebo:
? Averaged 24 hour pain scores collected for 7 days preceding the study clinic visit (week 16)

Timepoint(s) of evaluation of this end point: Evaluation after study end. No interim analysis planned

Main Objective: To demonstrate superiority of OXN PR compared to placebo with respect to analgesic efficacy in subjects with chronic severe pain associated with Parkinson's disease (PD), as assessed by averaged 24 hour pain scores collected for 7 days prior to the clinic visits

Secondary Outcome(s)

Secondary end point(s): The following key secondary endpoints for the primary comparison of OXN PR vs. placebo will be tested in a hierarchical testing strategy:
? Averaged 24 hour pain scores collected for the 7 days preceding individual clinic visits during the Double-Blind Phase
? Percentage of responders (defined as a =30% reduction from baseline) in averaged 24 hour pain scores collected for 7 days preceding the study clinic visit at week 16
? CGI-I: Percentage of responders (defined as a response of 'Much improved‘ or 'Very much improved‘) on the CGI-I scale (as defined by the Investigator)

Other exploratory endpoints:
? Percentage of responders (defined as a response of ‘Much improved’ or ‘Very much improved’) on the PGI-I scale (as defined by the subject)
? Change from baseline in the total score and domains of the Non Motor Symptom Assessment Scale for Parkinson’s Disease to the end of the Double-Blind Phase (week 16)
? Change from baseline in the total score of the UPDRS Part III/IV Motor Examination to the end of the Double-Blind Phase (week 16)
? Change from baseline in percentage of subjects meeting wearing off criteria (defined as the presence of at least one symptom in the WOQ-9 with improvement after the next dose of anti-Parkinsonian medication)
? Change from baseline in the total score of the CISI-PD to the end of the Double-Blind Phase (week 16)
? Frequency of rescue medication use during the Double-Blind Phase
? Change from baseline in the total score of the PDSS-2 to the end of the Double-Blind Phase (week 16)
? Change from baseline in the total score of the PDQ-8 to the end of the Double-Blind Phase (week 16)
? Change from baseline in EQ-5D index score to the end of the Double-Blind Phase (week 16)
? Change from baseline in the anxiety domain score of the HADS to the end of the Double-Blind Phase (week 16)
? Change from baseline in the depression domain score of the HADS to the end of the Double-Blind Phase (week 16)

Timepoint(s) of evaluation of this end point: Evaluation after study end. No interim analysis planned

Secondary ID(s)

2011-002901-31-GB

OXN2504

Source(s) of Monetary Support

Mundipharma Research GmbH & Co. KG