Clinical trial NCT00711880: A Study of Sativex® for Relief of Peripheral Neuropathic Pain Associated With Allodynia.
Official title: A Double Blind, Randomised, Placebo Controlled Parallel Group Study of Cannabis Based Medicine Extract (CBME), in the Treatment of Peripheral Neuropathic Pain Characterised by Allodynia.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pain
Peripheral Neuropathy
Keywords: Pain
Peripheral Neuropathy
Lead sponsor: Jazz Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2008-07-09
Enrollment: 125
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: The purpose of this study is to evaluate the efficacy of Sativex® compared with placebo in relieving peripheral neuropathic pain associated with allodynia.

Detailed description: This was a six week, multicentre, double blind, randomised, placebo controlled parallel group study to evaluate the efficacy of Sativex®. Subjects with peripheral neuropathic pain characterised by allodynia, were screened to determine eligibility and entered a seven day baseline period. Subjects then returned to the centre for randomisation and dose introduction, and received either placebo or Sativex in a double blind manner for five weeks, with a follow up visit 7 to 10 days after the end of the treatment period. The primary efficacy measure was the difference in pain severity at the end of treatment, measured using a peripheral neuropathic pain 0 to 10 numerical rating scale.

Eligibility criteria: Inclusion Criteria:

* Willing and able to give informed consent.
* Male or female, aged 18 years or above.
* Chronic peripheral neuropathic pain of at least six months duration.
* Presence of mechanical allodynia within the territory of the affected nerve(s).
* Evidence of sensory change in the affected nerve by simple clinical tests.
* Peripheral neuropathic pain with a severity score of four or more on at least four completed NRS during the baseline week.
* Stable dose of analgesic medication for at least two weeks leading to study entry.
* Agreement, if female and of child bearing potential or if male with a partner of child bearing potential, to ensure that effective contraception was used during the study and for three months thereafter.
* Have not used cannabinoids (including cannabis, Marinol or Nabilone) for at least seven days before Visit 1 and were willing to abstain from any use of cannabinoids during the study.
* Ability (in the investigator's opinion) and willingness to comply with all study requirements.
* Agreement for the UK Home Office, their primary care physician, and their consultant if appropriate, to be notified of their participation in the study.

Exclusion Criteria:

* History of schizophrenia, other psychotic illness, severe personality disorder or other significant psychiatric disorder other than depression associated with their underlying condition.
* Concomitant severe non-neuropathic pain or the presence of cancer related neuropathic pain or neuropathic pain resulting from diabetes mellitus.
* Known history of alcohol or substance abuse.
* Severe cardiovascular disorder, such as ischaemic heart disease, arrhythmias (other than well controlled atrial fibrillation), poorly controlled hypertension or severe heart failure.
* History of epilepsy.
* If female, were pregnant or lactating, or were planning a pregnancy to occur during the course of the study.
* Significant renal or hepatic impairment.
* Elective surgery or other procedures requiring general anaesthesia scheduled to occur during the study.
* Terminal illness or were considered inappropriate for placebo medication.
* Any other significant disease or disorder which, in the opinion of the investigator, may have either put the subject at risk because of participation in the study, or may influenced the result of the study, or the subject's ability to participate in the study.
* Regular levodopa (Sinemet®, Sinement Plus®, Levodopa®, L-dopa®, Madopar®, Benserazide®) therapy within the seven days leading to study entry.
* If male, were receiving and were unwilling to stop sildenafil (Viagra®) for the duration of the study.
* Known or suspected hypersensitivity to cannabinoids or any of the excipients of the study medications.
* Known or suspected adverse reaction to cannabinoids.
* Intention to travel internationally during the study.
* Intention to donate blood during the study.
* Participation in another research study in the 12 weeks leading to study entry.
* Previous randomisation into this study

Primary outcomes:
measure: Change From Baseline in the Mean Daily Peripheral Neuropathic Pain on a 0-10 Numerical Rating Scale Score During the Last Seven Days of Treatment (End of Treatment)
timeFrame: Day 0 to Day 42
Secondary outcomes:
measure: Change From Baseline in Mean Neuropathic Pain Scale Score at the End of Treatment
timeFrame: Day 0 to Day 42
measure: Change From Baseline in Mean Sleep Quality at the End of Treatment
timeFrame: Day 7 - Day 42
measure: Change From Baseline in the Mean Pain Disability Index Score at the End of Treatment
timeFrame: Day 0 - Day 42
measure: Change From Baseline in Mean Dynamic Allodynia Test Score at the End of Treatment
timeFrame: Day 7 and Day 42
measure: Change From Baseline in Mean Static Allodynia Test Score at the End of Treatment
timeFrame: Day 0 - Day 42
measure: Change From Baseline in Mean Total General Health Questionnaire Score at the End of Treatment
timeFrame: Day 7 and Day 42
measure: Change From Baseline in the Mean Brief Repeatable Battery of Neuropsychological Test Score for 'Selective Reminding' at the End of Treatment
timeFrame: Day 7 and Day 42
measure: Change From Baseline in the Mean Brief Repeatable Battery of Neuropsychological Test Score for '10/36 Spatial Recall' at the End of Treatment
timeFrame: Day 7 and Day 42
measure: Change From Baseline in the Mean Brief Repeatable Battery of Neuropsychological Test Score for 'Symbol Digit Modalities' at the End of Treatment
timeFrame: Day 7 and Day 42
measure: Change From Baseline in the Mean Brief Repeatable Battery of Neuropsychological Test Score for 'Paced Auditory Serial Addition Task' at the End of Treatment
timeFrame: Day 7 and Day 42
measure: Change From Baseline in the Mean Brief Repeatable Battery of Neuropsychological Test Score for 'Word List Generation' at the End of Treatment
timeFrame: Day 7 and Day 42
measure: Subject Global Impression of Change in the Severity of Peripheral Neuropathic Pain at the End of Treatment
timeFrame: Day 42
measure: Change From Pre-dose in Mean Intoxication 100 mm Visual Analogue Scale Score at the End of Treatment
timeFrame: Day 0 - Day 42
measure: Subject Global Impression of Change in the Severity of Allodynia in Their Chosen Allodynic Area at the End of Treatment
timeFrame: Day 0 - 42
measure: Incidence of Adverse Events as a Measure of Subject Safety
timeFrame: Day 0 - Day 42
Other outcomes:
Locations:
city: Fazakerley
country: United Kingdom
facility: Clinical Trials Unit, The Walton Centre
state: Liverpool
Study officials:
affiliation: Clinical Trials Unit, The Walton Centre
name: Turo Nurmikko, MB BS PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Nurmikko TJ, Serpell MG, Hoggart B, Toomey PJ, Morlion BJ, Haines D. Sativex successfully treats neuropathic pain characterised by allodynia: a randomised, double-blind, placebo-controlled clinical trial. Pain. 2007 Dec 15;133(1-3):210-20. doi: 10.1016/j.pain.2007.08.028. Epub 2007 Nov 7.