Cancer, Pain
Conditions
Keywords
Palliative Care, Pain, Cancer
Brief summary
The purpose of this study is to assess the safety and tolerability of long term therapy with Sativex® and GW-2000-02.
Detailed description
Subjects who have previously participated in GWCA0101, 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® (containing delta-9-tetrahydrocannabinol \[THC\] and cannabidiol \[CBD\]) and GW-2000-02 (containing THC alone) in subjects with cancer-related pain are screened, and if eligible begin dosing with open-label Sativex®. They are allowed to self-titrate their study medication to symptom resolution or maximum tolerated/allowable dose of 130 mg THC and 120 mg CBD and have the opportunity to request a change from Sativex® to GW-2000-02 if they or the investigator consider their response less than optimal. Subjects are reviewed for tolerability and evidence of clinical benefit at 7-10 days after Visit 1 and then every four weeks. Continuation within the study is conditional on satisfactory reports of tolerability, efficacy and dosing regime.
Interventions
DRUGSativex
Containing delta-9-tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml; both as extract of Cannabis sativa L. Subjects received study medication delivered in 100 µl actuations by a pump action oromucosal spray. Maximum permitted dose was eight actuations in any three hour period and 48 actuations (THC 130 mg:CBD 120 mg) in 24 hours.
DRUGGW-2000-02
Containing THC, 27 mg/ml, as extract of Cannabis sativa L. Subjects received study medication delivered in 100 µl actuations by a pump action oromucosal spray. Maximum permitted dose was eight actuations in any three hour period and 48 actuations (THC 130 mg) in 24 hours.
Sponsors
Jazz Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Willing and eligible to continue into the extension study from GWCA0101. * Complied adequately with the study requirements, as detailed in GWCA0101. * In the investigator's opinion able to undertake and comply with all of the study requirements (it is understood that progress of the disease may accelerate and affect this ability). * Willing and able to read, consider and understand the subject information and consent form and to give written informed consent in compliance with the Declaration of Helsinki1. * Willing to allow their own general practitioner, and consultant if appropriate, to be informed of study participation. * Willing for their name to be notified to the Home Office for participation in the trial.
Exclusion criteria
* Have not participated in GWCA0101. * Have not complied adequately with the study requirements, as detailed in GWCA0101. * Experienced an unacceptable adverse event, whilst participating in GWCA0101. * Known or suspected to have had an adverse reaction to cannabinoids causing psychosis or other severe psychiatric illness. * 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®). * Has a serious cardiovascular disorder, including angina, uncontrolled hypertension, or an uncontrolled symptomatic cardiac arrhythmia. * Has significant renal or hepatic impairment, which in the opinion of the investigator, are unsuitable for treatment with Investigational Medicinal Product. * History of epilepsy. * Female subjects of child bearing potential and male subjects whose partner is of child bearing potential, unless willing to ensure that they or their partner use effective contraception during the study and for three months thereafter. * If female, are pregnant or lactating, or are planning pregnancy during the course of the study and for three months thereafter. * Have oral cavity cancers or whose previous treatments had included radiotherapy to the floor of the mouth. * In the opinion of the investigator, are unsuitable to participate in the study for any other reason, not mentioned in the inclusion and
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Incidence of Adverse Events as a Measure of Subject Safety | 0 - 657 days | The number of subjects who experienced an adverse event in this study is presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Mean Brief Pain Inventory (Short Form) - Pain Severity Score at the End of Treatment | 0 - 657 days | The Brief Pain Inventory (Short Form) is a 14-item questionnaire that asks subjects to rate pain over the prior week and the degree to which it interferes with activities on a 0 to 10 scale, where 0=no pain and 10=pain as bad as you can imagine. Severity is measured as worst pain, least pain, average pain, and pain right now. The severity composite score was calculated as the arithmetic mean of the four severity items (range 0-10). The minimum value is zero and maximum is 10. A negative value indicates an improvement in score from baseline. The end of treatment was classed as study completion or withdrawal, if this occurred sooner. Calculation of the mean Brief Pain Inventory (Short Form) score was only carried out when data was available for 10 or more subjects at the relevant study visits. As such, no mean scores were calculated for subjects taking THC alone. |
| Change From Baseline in the Mean EORTC Quality of Life-C30 Questionnaire - Global Health Status Score at the End of Treatment | 0 - 657 days | The EORTC Quality of Life-C30 Health Status visual analogue scale was a self-reported score where subjects rated their health state from: 0 = worst health state imaginable to 100 = best health state imaginable. An increase in score from baseline indicates an improvement in condition. The end of treatment was classed as study completion or withdrawal, if this occurred sooner. Calculation of mean EORTC Quality of Life-C30 Health Status scores was only produced when data was available for 10 or more subjects at the relevant study visits. As such, no mean scores were calculated for subjects taking THC alone. |
Countries
United Kingdom
Participant flow
Recruitment details
The first subject was recruited on the 30th April 2002
Participants by arm
| Arm | Count |
|---|---|
| Sativex Each 100 μl actuation of Sativex delivered a dose containing 2.7 mg THC and 2.5 mg CBD | 39 |
| THC Alone Each 100 μl actuation of THC alone delivered a dose containing 2.7 mg THC | 4 |
| Total | 43 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 23 | 1 |
| Overall Study | Lack of Efficacy | 3 | 0 |
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Pain under control | 1 | 0 |
| Overall Study | Patient died | 1 | 0 |
| Overall Study | Patient feels unable to take medication | 0 | 1 |
| Overall Study | Patient unable to comply with diaries | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Sponsor decision | 0 | 1 |
| Overall Study | Withdrawal by Subject | 7 | 0 |
Baseline characteristics
| Characteristic | THC Alone | Total | Sativex |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 10 Participants | 10 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 33 Participants | 29 Participants |
| Age, Continuous | 58.6 years STANDARD_DEVIATION 6.28 | 57.6 years STANDARD_DEVIATION 12.94 | 57.5 years STANDARD_DEVIATION 13.5 |
| Region of Enrollment Belgium | 1 participants | 9 participants | 8 participants |
| Region of Enrollment United Kingdom | 3 participants | 34 participants | 31 participants |
| Sex: Female, Male Female | 3 Participants | 19 Participants | 16 Participants |
| Sex: Female, Male Male | 1 Participants | 24 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 37 / 39 | 4 / 4 |
| serious Total, serious adverse events | 20 / 39 | 1 / 4 |
Outcome results
Primary
The Incidence of Adverse Events as a Measure of Subject Safety
The number of subjects who experienced an adverse event in this study is presented.
Time frame: 0 - 657 days
Population: All subjects who took at least one dose of study medication and yielded on-treatment efficacy data were classed as the safety population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sativex | The Incidence of Adverse Events as a Measure of Subject Safety | 37 participants |
| THC Alone | The Incidence of Adverse Events as a Measure of Subject Safety | 4 participants |
Secondary
Change From Baseline in the Mean Brief Pain Inventory (Short Form) - Pain Severity Score at the End of Treatment
The Brief Pain Inventory (Short Form) is a 14-item questionnaire that asks subjects to rate pain over the prior week and the degree to which it interferes with activities on a 0 to 10 scale, where 0=no pain and 10=pain as bad as you can imagine. Severity is measured as worst pain, least pain, average pain, and pain right now. The severity composite score was calculated as the arithmetic mean of the four severity items (range 0-10). The minimum value is zero and maximum is 10. A negative value indicates an improvement in score from baseline. The end of treatment was classed as study completion or withdrawal, if this occurred sooner. Calculation of the mean Brief Pain Inventory (Short Form) score was only carried out when data was available for 10 or more subjects at the relevant study visits. As such, no mean scores were calculated for subjects taking THC alone.
Time frame: 0 - 657 days
Population: The efficacy analyses were conducted on data from all subjects who entered the study, who were randomised, who received at least one dose of study medication and who yielded on-treatment efficacy data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sativex | Change From Baseline in the Mean Brief Pain Inventory (Short Form) - Pain Severity Score at the End of Treatment | -0.53 units on a scale | Standard Deviation 1.28 |
Secondary
Change From Baseline in the Mean EORTC Quality of Life-C30 Questionnaire - Global Health Status Score at the End of Treatment
The EORTC Quality of Life-C30 Health Status visual analogue scale was a self-reported score where subjects rated their health state from: 0 = worst health state imaginable to 100 = best health state imaginable. An increase in score from baseline indicates an improvement in condition. The end of treatment was classed as study completion or withdrawal, if this occurred sooner. Calculation of mean EORTC Quality of Life-C30 Health Status scores was only produced when data was available for 10 or more subjects at the relevant study visits. As such, no mean scores were calculated for subjects taking THC alone.
Time frame: 0 - 657 days
Population: The efficacy analyses were conducted on data from all randomised subjects who received at least one dose of study medication and who yielded on-treatment efficacy data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sativex | Change From Baseline in the Mean EORTC Quality of Life-C30 Questionnaire - Global Health Status Score at the End of Treatment | -2.0 units on a scale | Standard Deviation 28.34 |