A Study of Sativex in the Treatment of Central Neuropathic Pain Due to Multiple Sclerosis

Jazz Pharmaceuticals66 enrolled

Overview

To investigate the ability of Sativex to relieve central neuropathic pain in multiple sclerosis subjects.

Multiple sclerosis subjects with a clinical diagnosis of central neuropathic pain entered a seven to ten day baseline period, followed by a four week double blind, randomised, parallel group comparison of Sativex, with placebo. The study medication was self-titrated to symptom resolution or maximum tolerated or allowed dose. Visits occurred at the end of weeks one and four (end of the study) or earlier if they withdrew. A follow-up visit occurred 30 - 40 days after completion or withdrawal.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Multiple Sclerosis Neuropathic Pain

Interventions

PlaceboDRUG

Contained peppermint oil, 0.05% (v/v), quinoline yellow, 0.005% (w/v), sunset yellow, 0.0025% (w/v), in ethanol:propylene glycol (50:50) excipient. Each actuation delivered 100 μl. The maximum permitted dose of study medication was eight actuations in any three hour period, and 48 actuations in any 24 hour period.

SativexDRUG

Contained delta-9-tetrahydrocannabinol (THC), (25 mg/ml):cannabidiol (CBD), (25 mg/ml) as extract of Cannabis sativa L., with peppermint oil, 0.05% (v/v), in ethanol:propylene glycol (50:50) excipient. Each actuation delivered 100 μl (THC 2.5 mg and CBD 2.5 mg). The maximum permitted dose of study medication was eight actuations in any three hour period, and 48 actuations in any 24 hour period.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Willing and able to give informed consent for participation in the study. * Male or female subjects aged 18 years or above. * Diagnosed with any disease sub-type of multiple sclerosis, with relapses/remission not expected to influence neuropathic pain. * Duration of multiple sclerosis greater than six months. * Central neuropathic pain, due to multiple sclerosis, of at least three months duration, for which a nociceptive, peripheral neuropathic or psychogenic cause appeared unlikely and was expected to remain stable for the duration of the study. * Pain score with a severity of four or more on at least four completed Numerical Rating Scale scores in the baseline week. * Regular medication regime for neuropathic pain had been stable during the previous two weeks, prior to reduction of tricyclic antidepressants, if applicable. * Willing to reduce the dosage of amitriptyline, or equivalent of other tricyclic antidepressants, to a maximum of 75 mg per day, if applicable. * No cannabinoid use (cannabis, Marinol or Nabilone) at least seven days before study entry and willing to abstain from any use of cannabis during the study. * Female subjects of child bearing potential or male subjects whose partner was of child bearing potential, who were willing to ensure that they or their partner used effective contraception during the study and for three months thereafter. * Able (in the investigators opinion) and willing to comply with all study requirements. * Willing for his or her name to be notified to the Home Office for participation in this study. * Willing for his or her general practitioner and consultant, if appropriate, to be notified of 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 illness such as diabetes mellitus that could have caused peripheral neuropathic pain. * Known or strongly suspected alcohol or substance abuse or considered to be at risk of alcohol or substance abuse by the investigator. * 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 or convulsions. * Significant renal or hepatic impairment as shown in medical history or indicated by clinical laboratory results from samples taken at baseline. * Elective surgery or other procedures requiring general anaesthesia scheduled during the study. * Terminal illness. * Any other significant disease or disorder which, in the opinion of the Investigator, could either have put the subject at risk because of participation in the study, or influenced the result of the study, or the subject's ability to participate in the study. * Female subjects who were pregnant, lactating or planning pregnancy during the course of the study. * Regular levodopa (Sinemet, Sinemet Plus, Levodopa, L-dopa, Madopar, Benserazide) therapy within seven days of study entry. * Known or suspected hypersensitivity to cannabinoids or any of the excipients of the study medications. * Known or suspected adverse reaction to cannabinoids. * Travel outside the UK planned during study. * Donation of blood during the study. * Participated in any other pharmacological clinical research study within 30 days of study entry. * Previously enrolled into this study.

Locations (1)

Walton Centre for Neurology and Neurosurgery

Liverpool, United Kingdom

Outcomes

Primary Outcomes

Change From Baseline in the Mean Pain 0-10 Numerical Rating Scale Score at the End of Treatment (4 Weeks)

The average pain Numerical Rating Scale was completed at the same time each day, i.e. bedtime in the evening. The patient was asked "on a scale of '0 to 10', please indicate the number that best describes your pain or average pain in the last 24 hours" where 0 = no pain and 10 = pain as bad as you can imagine. A negative value indicates an improvement in pain score from baseline.

Time frame: 0 - 4 weeks

Secondary Outcomes

Change From Baseline in the Mean 0-10 Numerical Rating Scale Sleep Score at the End of Treatment (4 Weeks)

Each day patients were asked to record in their subject diary, whether or not they were "woken due to nerve pain last night", using a 0-10 Numerical Rating Scale sleep score where zero equated with "did not disrupt sleep" and 10 meant "completely disrupts sleep (unable to sleep due to pain)". A decrease in score from baseline indicates an improvement.

Time frame: 0 - 4 weeks

Subject Global Impression of Change at Week 4

A 7-point Likert-type scale was used, with the question: 'Please assess the improvement in overall condition since the start of the study using the scale below' with the markers "very much improved, much improved, slightly improved, no change, slightly worse, much worse or very much worse". At Visit 2 (Baseline) patients wrote a brief description of their condition which was used at Week 4 to aid their memory regarding their symptoms at study start. For each of above markers the number of participants were reported.

Time frame: 4 weeks

Change From Baseline in the Mean Neuropathic Pain Scale 0-10 Numerical Rating Scale Score at the End of Treatment (Week 4)

The Neuropathic Pain Scale score is the 0-100 sum of 10 individual pain scores (0-10 Numerical Rating Scale, 0= no pain to 10 = worst pain imaginable). A negative change from baseline indicates an improvement in pain.

Data from ClinicalTrials.gov

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