Clinical trial NCT01361607: Sativex® for Relieving Persistent Pain in Patients With Advanced Cancer
Official title: A Double Blind, Randomized, Placebo-controlled, Parallel Group Study of Sativex Oromucosal Spray (Sativex®; Nabiximols) as Adjunctive Therapy in Relieving Uncontrolled Persistent Chronic Pain in Patients With Advanced Cancer, Who Experience Inadequate Analgesia During Optimized Chronic Opioid Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pain
Advanced Cancer
Keywords: Cancer pain
Opioid therapy
Inadequate analgesia
Optimized chronic opioid therapy
Lead sponsor: Jazz Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Otsuka Pharmaceutical Development & Commercialization, Inc.
First posted: 2011-05-27
Enrollment: 399
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: This 9-week, multi-center, double-blind, randomized, placebo-controlled study aimed to determine the efficacy, safety and tolerability of nabiximols, administered as an adjunctive treatment for 5 weeks, versus placebo. Eligible participants had advanced cancer, with a clinical diagnosis of cancer related pain that was not wholly alleviated by their current optimized opioid treatment.

Qualifying participants entered the study at screening and commenced a 5 to 14 day eligibility period. During this period, eligible participants had 3 consecutive days where pain severity remained within defined parameters, break-through opioid usage had not exceeded an average of 4 episodes per day, and maintenance opioid medication and dose had not changed. Eligible participants returned for randomization on Day 1 and were randomized to either the nabiximols or placebo treatment arm using a 1:1 allocation ratio. Participants began an initial titration period that lasted up to 14 days. The titration schedule required dosing to a minimum of 3 sprays per day, after which participants were allowed to individualize their dose (3 to 10 sprays per day) until Day 14 when that dose was then fixed for the remainder of the study. Participants returned at Day 22 and Day 36 (end of the randomized treatment period), or earlier if they terminated prematurely from the study. After the end of the 5-week treatment period, participants were offered the option of entering an open-label extension (OLE) study; a safety follow up visit (up to Day 43) was not required if the participant entered the OLE on Day 36. Participants who entered the OLE, up to 7 days after study completion had their follow-up assessments performed on the same day as their first OLE study visit. Participants that did not enter the OLE study had a safety follow up visit 14 days after treatment completion, which could be via telephone.

Eligibility criteria: Inclusion Criteria (abbreviated):

* The participant had advanced cancer for which there was no known curative therapy
* The participant had a clinical diagnosis of cancer related pain, which was not wholly alleviated with their current optimized opioid treatment
* The participant received an optimized maintenance dose of Step 3 opioid therapy, preferably with a sustained release preparation, but also allowing a regular maintenance dose of around-the-clock use of immediate release preparations
* The participant received a daily maintenance dose Step 3 opioid therapy of less than or equal to a total daily opioid dose of 500 mg/day of morphine equivalence (including maintenance and break-through opioids)
* The participant was using no more than one type of break-through opioid analgesia

Exclusion Criteria (abbreviated):

* The participant had any planned clinical interventions that would have affected their pain (for example, chemotherapy or radiation therapy where, in the clinical judgment of the investigator, these would be expected to affect pain)
* The participant was using or had used cannabis or cannabinoid-based medications within 30 days of study entry and is unwilling to abstain for the duration of the study
* The participant had experienced myocardial infarction or clinically significant cardiac dysfunction within the last 12 months or had a cardiac disorder that, in the opinion of the investigator, would have put the participant at risk of a clinically significant arrhythmia or myocardial infarction
* The participant had significantly impaired renal function
* The participant had significantly impaired hepatic function
* Female participants of child-bearing potential and male participants whose partner was of child-bearing potential, unless willing to ensure that they or their partner used effective contraception, for example, oral contraception, double barrier, intra-uterine device, during the study and for 3 months thereafter (however, a male condom was not to be used in conjunction with a female condom as this may not have proven effective)

Primary outcomes:
measure: Percent Improvement From Baseline In Mean NRS Average Pain At End Of Treatment
timeFrame: Baseline, End of Treatment (Day 36)
Secondary outcomes:
measure: Change From Baseline In Mean NRS Average Pain At End Of Treatment
timeFrame: Baseline, End of Treatment (Day 36)
measure: Change From Baseline In Mean NRS Worst Pain At End Of Treatment
timeFrame: Baseline, End of Treatment (Day 36)
measure: Change From Baseline In Mean Sleep Disruption NRS At End Of Treatment
timeFrame: Baseline, End of Treatment (Day 36)
measure: Subject Global Impression Of Change At Last Visit (Up To Day 36)
timeFrame: Last visit (up to Day 36)
measure: Physician Global Impression Of Change At Last Visit (Up To Day 36)
timeFrame: Last Visit (up to Day 36)
measure: Patient Satisfaction Questionnaire At Last Visit (Up To Day 36)
timeFrame: Last Visit (up to Day 36)
measure: Change From Baseline In Daily Total Opioid Use (Morphine Equivalent) At End Of Treatment
timeFrame: Baseline, End of Treatment (Day 36)
measure: Change From Baseline In Daily Maintenance Opioid Dose (Morphine Equivalent) At End of Treatment
timeFrame: Baseline, End of Treatment (Day 36)
measure: Change From Baseline In Daily Break-through Opioid Dose (Morphine Equivalent) At End Of Treatment
timeFrame: Baseline, End of Treatment (Day 36)
measure: Change From Baseline In NRS Constipation At Last Visit (Up To Day 36)
timeFrame: Baseline, Last Visit (up to Day 36)
Other outcomes:
Locations:
city: Glendale
country: United States
state: California
city: Santa Rosa
country: United States
state: California
city: Clearwater
country: United States
state: Florida
city: Holiday
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Stuart
country: United States
state: Florida
city: Marietta
country: United States
state: Georgia
city: Newnan
country: United States
state: Georgia
city: Stockbridge
country: United States
state: Georgia
city: Gurnee
country: United States
state: Illinois
city: Mount Vernon
country: United States
state: Illinois
city: Ashland
country: United States
state: Kentucky
city: Bossier City
country: United States
state: Louisiana
city: Shreveport
country: United States
state: Louisiana
city: Missoula
country: United States
state: Montana
city: Berlin
country: United States
state: New Jersey
city: New York
country: United States
state: New York
city: New York
country: United States
state: New York
city: Cleveland
country: United States
state: Ohio
city: Lacey
country: United States
state: Washington
city: Vratsa
country: Bulgaria
city: Benešov
country: Czechia
city: Jablonec Nad Nisou
country: Czechia
city: Plzen
country: Czechia
city: Sokolov
country: Czechia
city: Teplice
country: Czechia
city: České Budějovice
country: Czechia
city: České Budějovice
country: Czechia
city: Berlin
country: Germany
city: Frankfurt
country: Germany
city: Fulda
country: Germany
city: Hannover
country: Germany
city: Jena
country: Germany
city: Wiesbaden
country: Germany
city: Komarom
country: Hungary
city: Nyíregyháza
country: Hungary
city: Mexico
country: Mexico
state: DF
city: Chihuahua
country: Mexico
city: Monterrey
country: Mexico
city: Bydgoszcz
country: Poland
city: Czestochowa
country: Poland
city: Czestochowa
country: Poland
city: Dzialdowo
country: Poland
city: Gdansk
country: Poland
city: Klodzko
country: Poland
city: Ostrowiec Swietokrzyski
country: Poland
city: Poznan
country: Poland
city: Warszawa
country: Poland
city: Ponce
country: Puerto Rico
city: Targoviste
country: Romania
state: Dambovita
city: Baia Mare
country: Romania
city: Braila
country: Romania
city: Brasov
country: Romania
city: Bucuresti
country: Romania
city: Cluj-Napoca
country: Romania
city: Constanta
country: Romania
city: Focșani
country: Romania
city: Iasi
country: Romania
city: Sibiu
country: Romania
city: Suceava
country: Romania
city: Cheltenham
country: United Kingdom
state: Gloucestershire
city: Withington
country: United Kingdom
state: Manchester
city: Great Yarmouth
country: United Kingdom
state: Norfolk
city: Coventry
country: United Kingdom
city: Glasgow
country: United Kingdom
city: Manchester
country: United Kingdom
city: Norwich
country: United Kingdom
city: Plymouth
country: United Kingdom
Study officials:
References:
citation: Fallon MT, Albert Lux E, McQuade R, Rossetti S, Sanchez R, Sun W, Wright S, Lichtman AH, Kornyeyeva E. 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. Br J Pain. 2017 Aug;11(3):119-133. doi: 10.1177/2049463717710042. Epub 2017 May 17.