Clinical trial NCT01606189: A Study to Compare Sublingual Cannabis Based Medicine Extracts With Placebo to Treat Brachial Plexus Injury Pain
Official title: A Double Blind, Randomised, Three Way Crossover Study Comparing Two Different Sublingual Cannabis Based Medicine Extracts With Placebo, in Patients With Chronic Pain Due to Brachial Plexus Injury.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pain
Lead sponsor: Jazz Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2012-05-25
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: A study to compare the efficacy of two sublingual cannabinoid based medicine extracts with placebo in the treatment of chronic pain due to brachial plexus injury.

Detailed description: This study used a three way crossover study design. Eligible patients recorded their symptoms during a one to two week baseline period, then entered a three period, double blind, randomised crossover of GW-1000-02, GW-2000-02 and placebo. Each period lasted two weeks, with no washout between periods. There were six possible treatment sequences. The primary analysis was based on Box Scale-11 pain severity scores recorded throughout the study in patient daily diary booklets. Blood samples were taken from patient-volunteers at the beginning of each period, for measurement of plasma cannabinoid concentration.

Eligibility criteria: Inclusion Criteria:

* Aged 18 years or above.
* Brachial plexus pain, at least 18 months after the initial injury.
* Reported weekly brachial plexus pain at the required severity at Visits 1 and 2; a Box Scale-11 pain severity score of four boxes or above.
* A pattern of pain that in the Investigator's opinion had been stable during the four weeks before study entry.
* Stable regular medication during the four weeks before study entry.
* A maximum tricyclic antidepressant dose of 75 mg per day, if applicable.
* No cannabinoid use (cannabis, Marinol® or Nabilone) at least seven days before study entry or during the study.
* If sexually active; was either using effective contraception during the study and for three months thereafter or had been surgically sterilised or, if female, was post-menopausal. All patients agreed to use a barrier method of contraception in addition to their usual form of oral or depot contraception.
* Willing and able to undertake and comply with all study requirements.
* Willing and able to consider and understand the patient information leaflet and consent form and to give informed consent. Those patients unable to read or to sign the document were managed as detailed in the Declaration of Helsinki.
* Willing for his or her general practitioner, and consultant if appropriate, to be informed of study participation.
* Willing for his or her name to be notified to Home Office for participation in the study.

Exclusion Criteria:

* Abuse or strong suspicion of drug abuse, including alcohol or cannabis, or in the investigator's opinion had a tendency to drug dependency or substance abuse. Patients with a history of abuse could have been included at the discretion of the investigator.
* Known or suspected adverse reaction to cannabinoids.
* Known or suspected hypersensitivity to cannabinoids or any of the excipients of the study medication.
* History of any type of schizophrenia, any other psychotic illness, or other significant psychiatric illness other than depression associated with chronic illness.
* Regular levodopa therapy (Sinemet®, Sinemet plus®, Levodopa®, L-dopa®, Madopar®, Benserazide®) within seven days of study entry.
* Serious cardiovascular disorder including recent angina, uncontrolled hypertension or an uncontrolled symptomatic cardiac arrhythmia.
* History of significant renal or hepatic impairment as shown in medical history or indicated by clinical laboratory results from samples.
* History of active epilepsy or convulsions.
* Nerve surgery within six months of study entry or any other surgery within two months of study entry.
* Elective surgery, other procedures requiring general anaesthesia, or a planned hospital admission that would have taken place during the study, other than a hospital admission under the care of the study investigator.
* Terminal illness.
* Pregnancy, lactation or expected non-compliance with the contraceptive measures called for by the protocol.
* Participation in any other pharmacological clinical research study in the 12 weeks before study entry.
* Planned travel outside the UK between study entry and the end of the crossover phase.

Primary outcomes:
measure: Change From Baseline in the Mean Box Scale-11 Pain Review Score at the End of Each Treatment Period (Each Lasting 14-20 Days)
timeFrame: Up to 74 days
Secondary outcomes:
measure: Change From Baseline in the Mean Sleep Disturbance Score at the End of Each Treatment Period (Each Lasting 14-20 Days).
timeFrame: Up to 74 days
measure: Change From Baseline in the Mean Box Scale-11 Sleep Quality Score at the End of Each Treatment Period (Each Lasting 14-20 Days).
timeFrame: Up to 74 days
measure: Change From Baseline in the Mean McGill Pain Questionnaire Part 1 Score for 'Total Pain Intensity' at the End of Each Treatment Period (Each Lasting 14-20 Days)
timeFrame: Up to 74 days
measure: Change From Baseline in the Mean McGill Pain Questionnaire Part 2 Score for 'Intensity of Pain' at the End of Each Treatment Period (Each Lasting 14-20 Days)
timeFrame: Up to 74 days
measure: Change From Baseline in the Number of Patients Who Reported 'No Pain' or 'Mild Pain' Using a McGill Pain Questionnaire Part 3 Score for 'Strength of Pain at Present' at the End of Each Treatment Period (Each Lasting 14-20 Days)
timeFrame: Up to 74 days
measure: Change From Baseline in the Mean Pain Disability Index Score at the End of Each Treatment Period (Each Lasting 14-20 Days).
timeFrame: Up to 74 days
measure: Change From Baseline in the Mean 12-Item General Health Questionnaire Score at the End of Each Treatment Period (Each Lasting 14-20 Days).
timeFrame: Up to 74 days
measure: Incidence of Adverse Events as a Measure of Patient Safety.
timeFrame: Up to 114 days
Other outcomes:
Locations:
city: Middlesex
country: United Kingdom
facility: The Royal National Orthopaedic Hospital
Study officials:
References:
citation: Berman JS, Symonds C, Birch R. Efficacy of two cannabis based medicinal extracts for relief of central neuropathic pain from brachial plexus avulsion: results of a randomised controlled trial. Pain. 2004 Dec;112(3):299-306. doi: 10.1016/j.pain.2004.09.013.