A Study of Cannabis Based Medicine Extracts and Placebo in Patients With Pain Due to Spinal Cord Injury

Jazz Pharmaceuticals116 enrolled

Overview

A study to investigate the effects of sublingual cannabis based medicine extracts on neuropathic pain associated with spinal cord injury.

This was a multi-centre, double-blind, randomised, placebo-controlled, parallel-group study to evaluate the efficacy and tolerability of GW-1000-02 in central neuropathic pain associated with spinal cord injury. Patients were screened to determine eligibility and completed a seven to 21 day baseline period. Patients then returned to the centre for assessment, randomisation and initial dosing. Visits occurred at the end of treatment week one and at the end of the study (treatment week three) or upon withdrawal. Throughout the study, patients were permitted to take paracetamol as escape analgesic to relieve breakthrough pain. Patients in this study could elect to be screened for an open label extension study of GW-1000-02.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

116

Conditions

Pain

Interventions

GW-1000-02DRUG

Contained delta-9-tetrahydrocannabinol (THC) (27 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 2.7 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.

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Gave informed consent for participation in the study. * Male or Female, aged 18 years or above. * Diagnosis of non-acute spinal cord injury, with central neuropathic pain not wholly relieved by current therapy. * Central neuropathic pain with a mean severity Numerical Rating Scale score at least four during last seven days of the baseline period. * Relatively stable neurology during the preceding six months. * Stable medication regimen during the preceding four weeks. * 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. * Had not used cannabinoids for at least the preceding seven days and willing to abstain from any use of cannabinoids during the study. * Clinically acceptable laboratory results at Visit 2. * Ability (in the investigator's opinion) and willingness to comply with all study requirements. * Agreement for the UK Home Office, their general practitioner, 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. * 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 autonomic dysreflexia. * 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 therapy within the seven days leading to study entry. * If male, were receiving and were unwilling to stop sildenafil 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.

Locations (1)

The Royal National Orthopaedic Hospital

Middlesex, United Kingdom

Outcomes

Primary Outcomes

Change From Baseline in Mean Central Neuropathic Pain 11-Point Numerical Rating Scale Scores at the End of Treatment (up to 51 Days).

The Central Neuropathic Pain Numerical Rating Scale score was recorded three times daily, in the morning (on waking), at lunchtime and in the evening using the scale, 0 = 'No Pain' and 10 = 'Worst Possible Pain'. Patients were instructed to relate 'No Pain' to the time before the start of their spinal cord injury. End of Treatment was defined as the mean of the last seven days in the study or the mean of the last three days if the subject withdrew. A negative value indicates an improvement in pain score from baseline.

Time frame: Up to 51 days

Secondary Outcomes

Change From Baseline in the Mean Percentage of Days on Which Escape Medication Was Used at the End of Treatment

The percentage of days that subjects used escape medication was analysed and is presented as the mean change from baseline at the end of treatment. A negative value from baseline indicates an improvement.

Time frame: Up to 51 days

Change From Baseline in Mean Spasm Severity Numerical Rating Scale Score at the End of Treatment

Each day, just before going to bed, patients recorded in their patient diary whether they experienced any spasms that day and, if yes, recorded the overall level of the spasm(s) experienced using an Numerical Rating Scale spasm scale ranging from 0 = "Mildest ever spasm" to 10 = "Worst ever spasm". The mean spasm severity scores were summarised and analysed analogously to the primary endpoint. A negative value from baseline indicates an improvement.

Time frame: Up to 51 days

Change From Baseline in the Percentage of Days on Which Spasm Was Experienced at the End of Treatment

Each day, just before going to bed, patients recorded in their patient diary whether they experienced any spasms that day. The percentage of days on which spasm was experienced were summarised and analysed analogously to the primary endpoint. A negative value from baseline indicates an improvement.

Data from ClinicalTrials.gov

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