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

Phase 2
Completed
Conditions
Palliative Care
Pain
Cancer
Interventions
Registration Number
NCT00530764
Lead Sponsor
GW Pharmaceuticals Ltd
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
360
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Sativex Medium DoseSativex Medium DoseRange 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.
Sativex Low DoseSativex Low DoseRange 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.
Sativex High DoseSativex High DoseRange 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.
Primary Outcome Measures
NameTimeMethod
Number of Patients With at Least 30% Improvement in Numerical Rating Scale (NRS) Average Pain Score From Baseline5 Weeks: Baseline (first 3 days) - Week 5 (last 3 days)

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
NameTimeMethod
Change in Cumulative Average Pain Response CurvesBaseline to end of treatment (Week 5)

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).5 Weeks: Baseline (first 3 days) - End of Treatment (last 3 days of week 5)

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).5 Weeks: Baseline (first 3 days) - End of Treatment (last 3 days of week 5)

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 NRS5 Weeks: Baseline - End of Treatment (Last 3 days of Week 5)

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)Baseline (Visit 2) and End of Treatment (End of Week 5 or premature termination)

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)Baseline (Visit 2) and End of Treatment (Week 5 or premature termination)

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 - PGICEnd of Week 5

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)Baseline and End of Treatment (Week 5 or premature termination)

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.

Trial Locations

Locations (109)

Cancer Care Center of Tuscaloosa

🇺🇸

Tuscaloosa, Alabama, United States

Desert Oasis Cancer Center

🇺🇸

Casa Grande, Arizona, United States

Pacific Coast Hematology/Oncology Medical Group, Inc.

🇺🇸

Fountain Valley, California, United States

Office of Dr. Ronald Yanagihara

🇺🇸

Gilroy, California, United States

University of California San Diego

🇺🇸

La Jolla, California, United States

Loma Linda University

🇺🇸

Loma Linda, California, United States

Florida Institute of Medical Research

🇺🇸

Jacksonville, Florida, United States

Clinical Pharmacology Services

🇺🇸

Tampa, Florida, United States

Center of Hope for Cancer and Blood Disorders

🇺🇸

Riverdale, Georgia, United States

Louisiana Research Associates

🇺🇸

New Orleans, Louisiana, United States

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Cancer Care Center of Tuscaloosa
🇺🇸Tuscaloosa, Alabama, United States

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