A Study of Sativex® for Pain Relief in Patients With Advanced Malignancy

The purpose of this study is to determine whether Sativex® and GW-2000-02 are effective in the management of subjects with intractable cancer-related pain.

This is a two week (two days baseline and two weeks treatment period), multicentre, double blind, randomised, placebo controlled, parallel group study to evaluate the efficacy of Sativex® and GW-2000-02 in subjects with cancer-related pain. Subjects are screened to determine eligibility and completed a two-day baseline period. Subjects then return to the centre for assessment, randomisation and dose introduction. All subjects are allowed to continue using all their current medications, provided that the dose remains stable throughout the study period. Their progress is reviewed after seven to 10 days and at the end of the study (day 14 to 20), or upon withdrawal. Subjects in this study are given the opportunity to be enrolled in an open label extension study (GWEXT0101).

Eligibility Criteria:
Inclusion Criteria:

* Willing and able to give informed consent.
* Male or female, age 18 years or above.
* Diagnosed with cancer of any type, which is considered to be terminal.
* Diagnosed with cancer-related pain which is not wholly alleviated with their current strong opioid treatment and whose level of pain measured on a NRS is ³four on at least one occasion per day, during the two day run-in period, leading up to visit 1.
* On strong opioid maintenance therapy for at least seven days prior to the screening visit.
* Willing to abstain from any use of cannabis during the study, other than the study medication.
* No cannabinoids use (cannabis, Marinol® or Nabilone) for at least seven days before Visit 1 and willing to abstain from any use of cannabis during the study.
* Clinically acceptable blood results at the screening visit.
* Able (in the investigators opinion) and willing to undertake and comply with all study requirements.
* Willing to allow their own general practitioner, and consultant if appropriate, to be informed of study participation.
* Willing for the Home Office to be notified of his or her participation in the study (applicable to the UK centres only).

Exclusion Criteria:

* Know history of substance misuse.
* Known or suspected to have had an adverse reaction to cannabinoids causing psychosis or other severe psychiatric illness.
* Received any epidural analgesia within 48 hours prior to study entry.
* Either received, within two weeks of study entry, or due to receive chemotherapy or radiotherapy during the study.
* Unable to give informed consent.
* History of any type of schizophrenia, any other psychotic illness, a serious personality disorder, or other significant psychiatric illness other than depression associated with their chronic pain and/or in response to the underlying condition.
* Currently taking levodopa (Sinemet®, Sinemet plus®, Levodopa®, L-dopa®, Madopar®, Benserazide®).
* Had a serious cardiovascular disorder, including angina, uncontrolled hypertension, or an uncontrolled symptomatic cardiac arrhythmia.
* Significant renal or hepatic impairment, who in the opinion of the investigator, were unsuitable for treatment with study medication.
* History of epilepsy.
* Had oral cavity cancers or whose previous treatments had included radiotherapy to the floor of the mouth.
* Female subjects who were pregnant or lactating or of child-bearing potential and were inadequately protected against conception during the study and for three months thereafter.
* Male subjects who were sexually active and who were not using adequate forms of contraception during the study and for three months thereafter.
* Subjects who had participated in a clinical research study in the past four weeks, prior to study entry.
* Planned travel outside the UK during the study (applicable to the UK centres only).
* Subjects who, in the opinion of the investigator, were unsuitable to participate in the study for any other reason, not mentioned in the entry criteria.