Study to Compare the Safety and Tolerability of Sativex® in Patients With Cancer Related Pain

• Sponsor: Jazz Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00675948
• Collaborator: (none)
• Enrollment: 43
• Location: 1
• Arms: 2
• Duration (Months): 53
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the safety and tolerability of long term therapy with Sativex® and GW-2000-02.

Condition or Disease	Intervention/Treatment	Phase
Pain; Cancer	Drug: Sativex; Drug: GW-2000-02	Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 43 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: An Open-label, Extension Study, to Investigate the Long-term Safety and Tolerability of Cannabis Based Medicine Extracts in Patients With Cancer-related Pain.
• Study Start Date: Apr 1, 2002
• Actual Primary Completion Date: Sep 1, 2006
• Actual Study Completion Date: Sep 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sativex Active treatment	Drug: Sativex; 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.; Other Names: GW-1000-02
Experimental: GW-2000-02 Active treatment	Drug: GW-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.

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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 exclusion criteria.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Shropshire and Mid-Wales Hospice	Shrewsbury		United Kingdom	SY3 8HS

Sponsors and Collaborators

• Jazz Pharmaceuticals

Investigators

• Principal Investigator: Jeremy R Johnson, MB ChB, Shropshire and Mid-Wales Hospice

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jazz Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00675948
• Other Study ID Numbers: GWEXT0101
• First Posted: May 12, 2008
• Last Update Posted: Jun 24, 2013
• Last Verified: Jun 1, 2013

• Keywords provided by Jazz Pharmaceuticals: Palliative Care; Pain; Cancer
• Additional relevant MeSH terms: Cancer Pain; Nabiximols

Study Results

Participant Flow

Recruitment Details	The first subject was recruited on the 30th April 2002

Arm/Group Title	Sativex	THC Alone
Arm/Group Description	Each 100 μl actuation of Sativex delivered a dose containing 2.7 mg THC and 2.5 mg CBD	Each 100 μl actuation of THC alone delivered a dose containing 2.7 mg THC
Period Title: Overall Study
STARTED	39	4
COMPLETED	0	1
NOT COMPLETED	39	3

Baseline Characteristics

Arm/Group Title	Sativex	THC Alone	Total
Arm/Group Description	Each 100 μl actuation of Sativex delivered a dose containing 2.7 mg THC and 2.5 mg CBD	Each 100 μl actuation of THC alone delivered a dose containing 2.7 mg THC	Total of all reporting groups
Overall Participants	39	4	43
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	29 74.4%	4 100%	33 76.7%
>=65 years	10 25.6%	0 0%	10 23.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.5 (13.5)	58.6 (6.28)	57.6 (12.94)
Sex: Female, Male (Count of Participants)
Female	16 41%	3 75%	19 44.2%
Male	23 59%	1 25%	24 55.8%
Region of Enrollment (participants) [Number]
United Kingdom	31 79.5%	3 75%	34 79.1%
Belgium	8 20.5%	1 25%	9 20.9%

Outcome Measures

1. Primary Outcome

Title	The Incidence of Adverse Events as a Measure of Subject Safety
Description	The number of subjects who experienced an adverse event in this study is presented.
Time Frame	0 - 657 days

Outcome Measure Data

Analysis Population Description

All subjects who took at least one dose of study medication and yielded on-treatment efficacy data were classed as the safety population.

Arm/Group Title	Sativex	THC Alone
Arm/Group Description	Each 100 μl actuation of Sativex delivered a dose containing 2.7 mg delta-9-tetrahydrocannabinol (THC) and 2.5 mg cannabidiol (CBD)	Each 100 μl actuation of THC alone delivered a dose containing 2.7 mg THC
Measure Participants	39	4
Number [participants]	37 94.9%	4 100%

2. Secondary Outcome

Title	Change From Baseline in the Mean Brief Pain Inventory (Short Form) - Pain Severity Score at the End of Treatment
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Sativex	THC Alone
Arm/Group Description	Each 100 μl actuation of Sativex delivered a dose containing 2.7 mg THC and 2.5 mg CBD	Each 100 μl actuation of THC alone delivered a dose containing 2.7 mg THC
Measure Participants	17	0
Mean (Standard Deviation) [units on a scale]	-0.53 (1.28)

3. Secondary Outcome

Title	Change From Baseline in the Mean EORTC Quality of Life-C30 Questionnaire - Global Health Status Score at the End of Treatment
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Sativex	THC Alone
Arm/Group Description	Each 100 μl actuation of Sativex delivered a dose containing 2.7 mg THC and 2.5 mg CBD	Each 100 μl actuation of THC alone delivered a dose containing 2.7 mg THC
Measure Participants	17	0
Mean (Standard Deviation) [units on a scale]	-2.0 (28.34)

Adverse Events

Time Frame	All adverse events (AEs) occurring from the time of consent to post study follow up (2 - 521 days) were collected. All deaths and serious adverse events (SAEs) occurring within 28 days of the final dose of study medication were also collected.
Adverse Event Reporting Description	All AEs occurring during the study were reported on the running logs at the back of the study case report form.
Arm/Group Title	Sativex		THC Alone
Arm/Group Description	Each 100 μl actuation of Sativex delivered a dose containing 2.7 mg THC and 2.5 mg CBD		Each 100 μl actuation of THC alone delivered a dose containing 2.7 mg THC
All Cause Mortality
	Sativex		THC Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Sativex		THC Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/39 (51.3%)		1/4 (25%)
Blood and lymphatic system disorders
Anaemia NOS aggravated	1/39 (2.6%)		0/4 (0%)
Cardiac disorders
Atrial fibrillation	1/39 (2.6%)		0/4 (0%)
Gastrointestinal disorders
Haematemesis	2/39 (5.1%)		0/4 (0%)
Diarrhoea NOS	1/39 (2.6%)		0/4 (0%)
Intestinal obstruction NOS	1/39 (2.6%)		0/4 (0%)
Nausea	1/39 (2.6%)		0/4 (0%)
Vomiting NOS	1/39 (2.6%)		0/4 (0%)
General disorders
General physical health deterioration	1/39 (2.6%)		0/4 (0%)
Weakness	1/39 (2.6%)		0/4 (0%)
Infections and infestations
Pneumonia	1/39 (2.6%)		0/4 (0%)
Pyelonephritis NOS	1/39 (2.6%)		0/4 (0%)
Sepsis NOS	1/39 (2.6%)		0/4 (0%)
Urinary tract infection NOS	1/39 (2.6%)		0/4 (0%)
Injury, poisoning and procedural complications
Accident NOS	1/39 (2.6%)		0/4 (0%)
Investigations
Blood creatinine increased	1/39 (2.6%)		0/4 (0%)
Blood potassium increased	1/39 (2.6%)		0/4 (0%)
Blood urea increased	1/39 (2.6%)		0/4 (0%)
Gamma-glutamyltransferase increased	1/39 (2.6%)		0/4 (0%)
Metabolism and nutrition disorders
Dehydration	1/39 (2.6%)		0/4 (0%)
Musculoskeletal and connective tissue disorders
Back pain	1/39 (2.6%)		0/4 (0%)
Pain in limb	1/39 (2.6%)		0/4 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression	8/39 (20.5%)		1/4 (25%)
Metastases to brain	1/39 (2.6%)		0/4 (0%)
Non-small cell lung cancer NOS	1/39 (2.6%)		0/4 (0%)
Tumour pain	1/39 (2.6%)		0/4 (0%)
Nervous system disorders
Loss of consciousness	1/39 (2.6%)		0/4 (0%)
Neuropathic pain	1/39 (2.6%)		0/4 (0%)
Somnolence	1/39 (2.6%)		0/4 (0%)
Psychiatric disorders
Confusion	2/39 (5.1%)		0/4 (0%)
Renal and urinary disorders
Dysuria	1/39 (2.6%)		0/4 (0%)
Renal Failure NOS	1/39 (2.6%)		0/4 (0%)
Urinary incontinence	1/39 (2.6%)		0/4 (0%)
Urinary retention	1/39 (2.6%)		0/4 (0%)
Respiratory, thoracic and mediastinal disorders
Respiratory depression	1/39 (2.6%)		0/4 (0%)
Other (Not Including Serious) Adverse Events
	Sativex		THC Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	37/39 (94.9%)		4/4 (100%)
Blood and lymphatic system disorders
Anaemia	4/39 (10.3%)		0/4 (0%)
Cardiac disorders
Atrial fibrillation	2/39 (5.1%)		0/4 (0%)
Gastrointestinal disorders
Nausea	10/39 (25.6%)		0/4 (0%)
Vomiting	10/39 (25.6%)		1/4 (25%)
Dry mouth	5/39 (12.8%)		0/4 (0%)
Diarrhoea	4/39 (10.3%)		0/4 (0%)
Dyspepsia	2/39 (5.1%)		0/4 (0%)
Gastritis NOS	2/39 (5.1%)		0/4 (0%)
Haematemesis	2/39 (5.1%)		0/4 (0%)
General disorders
Fatigue	2/39 (5.1%)		0/4 (0%)
Thirst	2/39 (5.1%)		0/4 (0%)
Weakness	2/39 (5.1%)		0/4 (0%)
Hepatobiliary disorders
Cholelithiasis	0/39 (0%)		1/4 (25%)
Infections and infestations
Lower respiratory tract infection NOS	2/39 (5.1%)		0/4 (0%)
Oral candidiasis	2/39 (5.1%)		0/4 (0%)
Cellulitis	0/39 (0%)		1/4 (25%)
Urinary tract infection	5/39 (12.8%)		1/4 (25%)
Injury, poisoning and procedural complications
Therapeutic agent toxicity	0/39 (0%)		1/4 (25%)
Investigations
Liver function tests abnormal	2/39 (5.1%)		1/4 (25%)
Metabolism and nutrition disorders
Anorexia	2/39 (5.1%)		0/4 (0%)
Musculoskeletal and connective tissue disorders
Pain in limb	8/39 (20.5%)		0/4 (0%)
Arthralgia	0/39 (0%)		1/4 (25%)
Pain in back	2/39 (5.1%)		0/4 (0%)
Muscle spasms	2/39 (5.1%)		0/4 (0%)
Peripheral swelling	0/39 (0%)		1/4 (25%)
Joint swelling	2/39 (5.1%)		0/4 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression	11/39 (28.2%)		1/4 (25%)
Metastasis to bone	0/39 (0%)		1/4 (25%)
Nervous system disorders
Dizziness	8/39 (20.5%)		1/4 (25%)
Somnolence	8/39 (20.5%)		0/4 (0%)
Headache	2/39 (5.1%)		1/4 (25%)
Memory impairment	0/39 (0%)		1/4 (25%)
Jerky movement	2/39 (5.1%)		0/4 (0%)
Clonic convulsions	0/39 (0%)		1/4 (25%)
Psychiatric disorders
Confusion	7/39 (17.9%)		1/4 (25%)
Anxiety	2/39 (5.1%)		0/4 (0%)
Confusional state	2/39 (5.1%)		0/4 (0%)
Depression	2/39 (5.1%)		0/4 (0%)
Disorientation	2/39 (5.1%)		0/4 (0%)
Hallucination NOS	2/39 (5.1%)		0/4 (0%)
Affect lability	2/39 (5.1%)		0/4 (0%)
Renal and urinary disorders
Haematuria	0/39 (0%)		1/4 (25%)
Urinary incontinence	3/39 (7.7%)		0/4 (0%)
Renal failure NOS	0/39 (0%)		1/4 (25%)
Renal Impairment NOS	0/39 (0%)		1/4 (25%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea NOS	3/39 (7.7%)		0/4 (0%)
Skin and subcutaneous tissue disorders
Rash NOS	0/39 (0%)		1/4 (25%)
Hot flushes NOS	0/39 (0%)		1/4 (25%)
Vascular disorders
Skin lesion NOS	0/39 (0%)		1/4 (25%)
Hypotension NOS	2/39 (5.1%)		0/4 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Publication Policy: GW will coordinate the dissemination of data from this study and may solicit input and assistance from the principal investigator. All publications for example, manuscripts, abstracts, oral/slide presentations or book chapters based on this study, must be submitted to GW for corporate review before release.