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NCT01361607: SPRAY III

Sativex® for Relieving Persistent Pain in Patients With Advanced Cancer

Completed Phase 3 Results posted Last updated 12 April 2023
What this trial tests

Phase 3 trial testing Nabiximols in Pain in 399 participants. Completed in 24 November 2014.

Timeline
27 May 2011
Primary endpoint
24 November 2014
24 November 2014

Quick facts

Lead sponsorJazz Pharmaceuticals
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingtriple
Primary purposetreatment
Enrollment399
Start date27 May 2011
Primary completion24 November 2014
Estimated completion24 November 2014
Sites68 locations across United Kingdom, Germany, Hungary, Mexico, Poland, Romania, Puerto Rico, Bulgaria

Drugs / interventions tested

Conditions studied

Sponsor

Jazz Pharmaceuticals — full company profile →

Who can join

18 and older, any sex, with Pain or Advanced Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percent Improvement From Baseline In Mean NRS Average Pain At End Of Treatment Primary · Baseline, End of Treatment (Day 36)

Participants indicated level of pain in the last 24 hours on an 11-point Numerical Rating Scale (NRS), where a score of 0 was "no pain" and 10 was "pain as bad as you can imagine". Baseline = mean score from first day of 3-day eligibility period through to the day before first dose of study drug. End of Treatment = mean score over last (up to) 7 days to the final pain score at End of Treatment or up until Day 35, whichever is earlier, or final score available (prematurely terminated). Percentage improvement from baseline (Imp%) was calculated as: Imp% = (Baseline pain NRS mean - End of Treat

GroupValue95% CI
Nabiximols7.20.0 – 29.4
Placebo (GA-0034)9.50.0 – 34.5
Change From Baseline In Mean NRS Average Pain At End Of Treatment Secondary · Baseline, End of Treatment (Day 36)

Participants indicated the level of pain experienced in the last 24 hours on an 11-point NRS, where a score of 0 indicated "no pain" and a score of 10 indicated "pain as bad as you can imagine." Change in mean NRS average pain was calculated as: End of Treatment NRS average pain score - Baseline NRS average pain score. A negative value indicates an improvement in average pain score from Baseline.

GroupValue95% CI
Nabiximols-0.9± 1.5
Placebo (GA-0034)-1.0± 1.5
Change From Baseline In Mean NRS Worst Pain At End Of Treatment Secondary · Baseline, End of Treatment (Day 36)

Participants indicated the level of worst pain experienced in the last 24 hours on an 11-point NRS, where a score of 0 indicated "no pain" and a score of 10 indicated "pain as bad as you can imagine." Change in mean NRS worst pain was calculated as: End of Treatment NRS worst pain score - Baseline NRS worst pain score. A negative value indicates an improvement in worst pain score from Baseline.

GroupValue95% CI
Nabiximols-1.0± 1.7
Placebo (GA-0034)-1.2± 1.6
Change From Baseline In Mean Sleep Disruption NRS At End Of Treatment Secondary · Baseline, End of Treatment (Day 36)

Participants indicated the level of sleep disruption experienced in the last 24 hours on an 11-point NRS, where a score of 0 indicated "did not disrupt sleep" and a score of 10 indicated "completely disrupted (unable to sleep at all)." Change in mean sleep disruption NRS was calculated as: End of Treatment sleep disruption NRS score - Baseline sleep disruption NRS score. A negative value indicates an improvement in sleep disruption score from Baseline.

GroupValue95% CI
Nabiximols-0.9± 1.8
Placebo (GA-0034)-1.1± 1.7
Subject Global Impression Of Change At Last Visit (Up To Day 36) Secondary · Last visit (up to Day 36)

The Subject Global Impression of Change (SGIC) was used to assess the overall status of the participant related to their cancer pain, with the markers "very much improved, much improved, slightly improved, no change, slightly worse, much worse, or very much worse". The SGIC was assessed at Day 36 or at which a participant's last evaluation was performed, such as in the case of early termination. Last visit refers to the last visit that a participant completed the assessment; this could be either Day 22 or Day 36.

GroupValue95% CI
Nabiximols19
Placebo (GA-0034)11
Nabiximols36
Placebo (GA-0034)35
Nabiximols64
Placebo (GA-0034)51
Nabiximols38
Placebo (GA-0034)67
Physician Global Impression Of Change At Last Visit (Up To Day 36) Secondary · Last Visit (up to Day 36)

The Physician Global Impression of Change (PGIC) was used by the treating physician (investigator/sub-investigator) to assess if there was any change in the general functional abilities of the participant since prior to commencement of study medication, with the markers: "very much worse, much worse, slightly worse, no change, slightly improved, much improved, very much improved". Last visit refers to the last visit that a participant completed the assessment; this could be either Day 22 or Day 36.

GroupValue95% CI
Nabiximols13
Placebo (GA-0034)11
Nabiximols37
Placebo (GA-0034)32
Nabiximols62
Placebo (GA-0034)48
Nabiximols41
Placebo (GA-0034)78
Patient Satisfaction Questionnaire At Last Visit (Up To Day 36) Secondary · Last Visit (up to Day 36)

The Patient Satisfaction Questionnaire (PSQ) was used to assess level of satisfaction of the participant with the study drug, with the markers "extremely satisfied, very satisfied, slightly satisfied, neutral, slightly dissatisfied, very dissatisfied, extremely dissatisfied". Last visit refers to the last visit that a participant completed the assessment; this could be either Day 22 or Day 36.

GroupValue95% CI
Nabiximols18
Placebo (GA-0034)8
Nabiximols34
Placebo (GA-0034)43
Nabiximols55
Placebo (GA-0034)54
Nabiximols35
Placebo (GA-0034)52
Change From Baseline In Daily Total Opioid Use (Morphine Equivalent) At End Of Treatment Secondary · Baseline, End of Treatment (Day 36)

The total daily opioid use (in morphine equivalence) was the sum of morphine equivalence of daily maintenance dose and break-through dose. Change in daily total opioid use was calculated as: End of Treatment daily total opioid use - Baseline daily total opioid use. A negative value indicates a decrease in use from Baseline.

GroupValue95% CI
Nabiximols-6.5± 53.9
Placebo (GA-0034)2.3± 42.5
Change From Baseline In Daily Maintenance Opioid Dose (Morphine Equivalent) At End of Treatment Secondary · Baseline, End of Treatment (Day 36)

The prescribed daily quantity of opioid maintenance dose was calculated as the product of dose per use and daily frequency of use. Participants were asked: "Have you used your maintenance dose painkiller today as prescribed?" If the participant answered "No" to the question, the daily opioid maintenance dose usage on that day was set to 0. Change in daily maintenance opioid dose was calculated as: End of Treatment daily maintenance opioid dose - Baseline daily maintenance opioid dose. A negative value indicates a decrease in dose from Baseline.

GroupValue95% CI
Nabiximols-1.5± 38.2
Placebo (GA-0034)1.9± 34.3
Change From Baseline In Daily Break-through Opioid Dose (Morphine Equivalent) At End Of Treatment Secondary · Baseline, End of Treatment (Day 36)

Daily break-through opioid dose usage was calculated as the product of prescribed dose per use, and the number of uses per day. If participants took more than 1 different break-through opioid for more than 1 day, the sum of morphine equivalence dose usages for each break-through opioid was calculated for the summary. Change in daily break-through opioid dose was calculated as: End of Treatment daily break-through opioid dose - Baseline daily break-through opioid dose. A negative value indicates a decrease in dose from Baseline.

GroupValue95% CI
Nabiximols-4.4± 27.7
Placebo (GA-0034)0.5± 20.5
Change From Baseline In NRS Constipation At Last Visit (Up To Day 36) Secondary · Baseline, Last Visit (up to Day 36)

Participants indicated level of constipation on an 11-point NRS, where a score of 0 was "no constipation", and 10 was "constipation as bad as you can imagine." Last visit refers to the last visit that a participant completed the assessment; this could be either Day 22 or Day 36. Change in NRS constipation score was calculated as: Last Visit NRS constipation score - Baseline NRS constipation score. A negative value indicates improvement in condition from Baseline.

GroupValue95% CI
Nabiximols-0.4± 2.6
Placebo (GA-0034)-0.6± 2.7

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to Day 43 post-randomization. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Nabiximols
Serious: 35/199 (18%)
Deaths:
Placebo (GA-0034)
Serious: 44/198 (22%)
Deaths:

Serious adverse events (41 terms)

ReactionSystemNabiximolsPlacebo (GA-0034)
Neoplasm ProgressionNeoplasms benign, malignant and unspecified (incl cysts and polyps)
ConstipationGastrointestinal disorders
AnaemiaBlood and lymphatic system disorders
CoagulopathyBlood and lymphatic system disorders
Acute Myocardial InfarctionCardiac disorders
Cardiac Failure CongestiveCardiac disorders
TachycardiaCardiac disorders
VomitingGastrointestinal disorders
Chest PainGeneral disorders
Generalised OedemaGeneral disorders
BronchitisInfections and infestations
Device Related InfectionInfections and infestations
Device Related SepsisInfections and infestations
Groin AbscessInfections and infestations
Helicobacter GastritisInfections and infestations
Lobar PneumoniaInfections and infestations
PneumoniaInfections and infestations
Pseudomembranous ColitisInfections and infestations
PyelonephritisInfections and infestations
Staphylococcal SepsisInfections and infestations
Urinary Tract InfectionInfections and infestations
FallInjury, poisoning and procedural complications
Post Procedural HaemorrhageInjury, poisoning and procedural complications
Wound HaemorrhageInjury, poisoning and procedural complications
CachexiaMetabolism and nutrition disorders
Other adverse events (5 terms — click to expand)

ReactionSystemNabiximolsPlacebo (GA-0034)
SomnolenceNervous system disorders
NauseaGastrointestinal disorders
VomitingGastrointestinal disorders
DizzinessNervous system disorders
ConstipationGastrointestinal disorders

Most-reported serious reactions: Neoplasm Progression, Constipation, Anaemia, Coagulopathy, Acute Myocardial Infarction, Cardiac Failure Congestive, Tachycardia, Vomiting.

Data from ClinicalTrials.gov NCT01361607 adverse events section.

Sponsor's own description

This 9-week study aimed to determine the efficacy, safety, and tolerability of nabiximols (Sativex®) as an adjunctive treatment, compared with placebo in relieving uncontrolled persistent chronic pain in participants with advanced cancer. Eligible participants were not required to stop any of their current treatments or medications.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Sativex oromucosal spray as adjunctive therapy in advanced cancer patients with chronic pain unalleviated by optimized opioid therapy: two double-blind, randomized, placebo-controlled phase 3 studies.
    Fallon MT, Albert Lux E, McQuade R, Rossetti S, et al · · 2017 · cited 116× · PMID 28785408 · DOI 10.1177/2049463717710042
  2. Opioid-sparing effect of cannabinoids for analgesia: an updated systematic review and meta-analysis of preclinical and clinical studies.
    Nielsen S, Picco L, Murnion B, Winters B, et al · · 2022 · cited 61× · PMID 35459926 · DOI 10.1038/s41386-022-01322-4
  3. Perineural Invasion in Pancreatic Ductal Adenocarcinoma: From Molecules towards Drugs of Clinical Relevance.
    Selvaggi F, Melchiorre E, Casari I, Cinalli S, et al · · 2022 · cited 43× · PMID 36497277 · DOI 10.3390/cancers14235793
  4. A Balanced Approach for Cannabidiol Use in Chronic Pain.
    Argueta DA, Ventura CM, Kiven S, Sagi V, et al · · 2020 · cited 38× · PMID 32425793 · DOI 10.3389/fphar.2020.00561
  5. Cannabis-based medicines and medical cannabis for adults with cancer pain.
    Häuser W, Welsch P, Radbruch L, Fisher E, et al · · 2023 · cited 36× · PMID 37283486 · DOI 10.1002/14651858.cd014915.pub2
  6. Cannabidiol on the Path from the Lab to the Cancer Patient: Opportunities and Challenges.
    Olivas-Aguirre M, Torres-López L, Villatoro-Gómez K, Perez-Tapia SM, et al · · 2022 · cited 16× · PMID 35337163 · DOI 10.3390/ph15030366
  7. Role of Cannabidiol for Improvement of the Quality of Life in Cancer Patients: Potential and Challenges.
    Green R, Khalil R, Mohapatra SS, Mohapatra S. · · 2022 · cited 10× · PMID 36361743 · DOI 10.3390/ijms232112956
  8. Cannabinoids, Inner Ear, Hearing, and Tinnitus: A Neuroimmunological Perspective.
    Perin P, Mabou Tagne A, Enrico P, Marino F, et al · · 2020 · cited 8× · PMID 33329293 · DOI 10.3389/fneur.2020.505995

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing