A Study of Sativex® for Pain Relief in Patients With Advanced Malignancy. - Full Text View

Sponsor:	GW Pharmaceuticals Ltd.
Collaborator:	Quintiles
Information provided by (Responsible Party):	GW Pharmaceuticals Ltd.
ClinicalTrials.gov Identifier:	NCT00530764

Purpose

The purpose of this study is to determine the effective dose range and to demonstrate a non-effective dose range of Sativex in patients with advanced cancer, who experience inadequate pain relief even though they are on optimized chronic opioid therapy.

Condition	Intervention	Phase
Palliative Care Pain Cancer	Drug: Sativex Low Dose Drug: Sativex Medium Dose Drug: Sativex High Dose	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Supportive Care
Official Title:	A Double Blind, Randomized, Placebo Controlled, Parallel Group Dose-range Exploration Study of Sativex® in Relieving Pain in Patients With Advanced Cancer, Who Experience Inadequate Analgesia During Optimized Chronic Opioid Therapy.

Resource links provided by NLM:

MedlinePlus related topics: Cancer Palliative Care

Drug Information available for: Dronabinol

U.S. FDA Resources

Further study details as provided by GW Pharmaceuticals Ltd.:

Primary Outcome Measures:

Number of Patients With at Least 30% Improvement in Numerical Rating Scale (NRS) Average Pain Score From Baseline [ Time Frame: 5 Weeks: Baseline (first 3 days) - Week 5 (last 3 days) ] [ Designated as safety issue: No ]
A positive 30% pain response is defined as a reduction of at least 30% in the mean NRS average pain score from baseline to week 5 (last 3 days). The patient was asked "on a scale of '0 to 10', please indicate the number that best describes your pain or average pain in the last 24 hours" where 0 = no pain and 10 = pain as bad as you can imagine. No pain relates to the time prior to the onset of pain due to cancer. The average pain NRS was completed at the same time each day, i.e. bedtime in the evening.

Secondary Outcome Measures:

Change in Cumulative Average Pain Response Curves [ Time Frame: Baseline to end of treatment (Week 5) ] [ Designated as safety issue: No ]
The cumulative response to treatment is the percentage changes from baseline in the mean NRS pain score as defined as the 30% response.

The pain NRS was completed at the same time each day, i.e. bedtime in the evening. The patient was asked "on a scale of '0 to 10', please indicate the number that best describes your pain or average pain in the last 24 hours" where 0 = no pain and 10 = pain as bad as you can imagine. No pain relates to the time prior to the onset of pain due to cancer.
Change in Mean Daily NRS Pain Score (Average Pain). [ Time Frame: 5 Weeks: Baseline (first 3 days) - End of Treatment (last 3 days of week 5) ] [ Designated as safety issue: No ]
The average pain NRS was complete at the same time each day, i.e. bedtime in the evening. The patient was asked "on a scale of '0 to 10', please indicate the number that best describes your pain or average pain in the last 24 hours" where 0 = no pain and 10 = pain as bad as you can imagine. No pain relates to the time prior to the onset of pain due to cancer. A negative value indicates an improvement in pain score from baseline.
Change in Mean Daily NRS Pain Score (Worst Pain). [ Time Frame: 5 Weeks: Baseline (first 3 days) - End of Treatment (last 3 days of week 5) ] [ Designated as safety issue: No ]
The worst pain NRS was completed at the same time each day, i.e. bedtime in the evening. The patient was asked "on a scale of '0 to 10', please indicate the number that best describes your worst pain in the last 24 hours" where 0 = no pain and 10 = pain as bad as you can imagine. No pain relates to the time prior to the onset of pain due to cancer. A negative value indicates an improvement in worst pain score from baseline.
Change in Sleep Disruption NRS [ Time Frame: 5 Weeks: Baseline - End of Treatment (Last 3 days of Week 5) ] [ Designated as safety issue: No ]
The sleep disruption NRS was completed at the same time each day, i.e. bedtime in the evening. The patient was asked "on a scale of '0 to 10', please indicate how your pain disrupted your sleep last night?" where 0 = did not disrupt sleep and 10 = completely disrupted (unable to sleep at all). A negative value indicates an improvement in sleep disruption score from baseline.
Change in Brief Pain Inventory - Short Form (BPI-SF) [ Time Frame: Baseline (Visit 2) and End of Treatment (End of Week 5 or premature termination) ] [ Designated as safety issue: No ]
The BPI-SF is a 14-item questionnaire that asks patients 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 higher score represents a poor outcome.
Change in Patient Assessment of Constipation Quality of Life (PAC-QoL) [ Time Frame: Baseline (Visit 2) and End of Treatment (Week 5 or premature termination) ] [ Designated as safety issue: No ]
The PAC-QoL questionnaire consists of 28 questions divided into the following areas: 4 questions on physical discomfort, 8 questions on psychosocial discomfort, 11 questions on worries/concerns and 5 questions on satisfaction. The PAC-QoL was completed at baseline and then at the end of treatment. An overall score (range 0-4) was calculated at each visit and the difference determined. A positive difference in score represents an improvement.
Change in Patient Global Impression of Change - PGIC [ Time Frame: End of Week 5 ] [ Designated as safety issue: No ]
A 7-point Likert-type scale was used, with the question: 'Please assess the status of your pain due to cancer since entry into the study using the scale below' with the markers "very much improved, much improved, slightly improved, no change, slightly worse, much worse or very much worse". At Visit 2 (Baseline) patients wrote a brief description of their pain caused by cancer which was used at Week 5 to aid their memory regarding their symptoms at study start. For each of above markers the number of participants were reported.
Change in Montgomery Asberg Depression Rating Scale (MADRS) [ Time Frame: Baseline and End of Treatment (Week 5 or premature termination) ] [ Designated as safety issue: Yes ]
The MADRS comprises of 10 questions that are completed by the patient to determine their depression level. The MADRS was completed at Visit 2 (Baseline) prior to receiving the study drug and at Visit 4 (Week 5 or premature termination). Each item is scored on a 0-6 scale , where 0=no sadness to 6=extreme and continuous gloom and despondency, and the MADRS score is the sum of the 10 item scores (range 0-60). The higher the score the more severe the depression.

Enrollment:	360
Study Start Date:	November 2007
Study Completion Date:	January 2010
Primary Completion Date:	January 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Sativex Low Dose Range of 1 to 4 sprays per day. Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). Thus maximum daily dose is 10.8mg THC and 10mg CBD.	Drug: Sativex Low Dose Range of 1 to 4 sprays per day. Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). Thus maximum daily dose is 10.8mg THC and 10mg CBD. Other Name: GW-1000-02
Experimental: Sativex Medium Dose Range of 6 to 10 sprays per day. Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). Thus maximum daily dose is 27mg THC and 25mg CBD.	Drug: Sativex Medium Dose Range of 6 to 10 sprays per day. Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). Thus maximum daily dose is 27mg THC and 25mg CBD. Other Name: GW-1000-02
Experimental: Sativex High Dose Range of 11 to 16 sprays per day. Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). Thus maximum daily dose is 43.2mg THC and 40mg CBD.	Drug: Sativex High Dose Range of 11 to 16 sprays per day. Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). Thus maximum daily dose is 43.2mg THC and 40mg CBD. Other Name: GW-1000-02
No Intervention: Placebo Range of 1-16 sprays per day of placebo spray.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

The patient has advanced active cancer for which there is no known curative therapy.
The patient is able (in the investigators opinion) and willing to comply with all study requirements.
The patient has a clinical diagnosis of cancer related pain, which is not wholly alleviated with their current opioid treatment.
The patient is receiving a sustained release (SR) fixed dose of opioid therapy (excluding Methadone). N.B. The opiate therapy must be Step III according to the World Health Organization (WHO) analgesic ladder.
The patient is willing to continue to take their regular daily baseline opioid regimen (SR) at the same dose, throughout the duration of study.

Exclusion Criteria:

The patient should be excluded from entering study if they have received or are due to receive during the study period; chemotherapy, hormone therapy or radiotherapy, which, in the opinion of the investigator will affect their pain.
Any history or immediate family history of schizophrenia, other psychotic illness, severe personality disorder or other significant psychiatric disorder other than depression associated with their underlying condition.
Any known or suspected history of a diagnosed dependence disorder, current heavy alcohol consumption, current use of an illicit drug or current non prescribed use of any prescription drug.
The patient has poorly controlled epilepsy or recurrent seizures (i.e. at least one year since last seizure).
The patient has experienced myocardial infarction or clinically relevant cardiac dysfunction within the last 12 months or has a cardiac disorder that, in the opinion of the investigator would put the patient at risk of a clinically relevant arrhythmia or myocardial infarction.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00530764

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Sponsors and Collaborators

GW Pharmaceuticals Ltd.

Quintiles

More Information

No publications provided

Responsible Party:	GW Pharmaceuticals Ltd.
ClinicalTrials.gov Identifier:	NCT00530764 History of Changes
Other Study ID Numbers:	GWCA0701
Study First Received:	September 13, 2007
Results First Received:	March 2, 2011
Last Updated:	May 24, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by GW Pharmaceuticals Ltd.:

Pain
Cancer
Palliative

Additional relevant MeSH terms:

Tetrahydrocannabinol
Hallucinogens
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses

Psychotropic Drugs
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on May 24, 2012