Clinical trial NCT01262651: Sativex® for Relieving Persistent Pain in Participants 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: GWPharm
Sponsor class: UNKNOWN
Collaborators: name: Otsuka Pharmaceutical Development & Commercialization, Inc.
First posted: 2010-12-17
Enrollment: 397
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 which 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: Phoenix
country: United States
state: Arizona
city: Phoenix
country: United States
state: Arizona
city: El Cajon
country: United States
state: California
city: Gilroy
country: United States
state: California
city: Brandon
country: United States
state: Florida
city: Daytona Beach
country: United States
state: Florida
city: Holiday
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: Lynn Haven
country: United States
state: Florida
city: Stuart
country: United States
state: Florida
city: Winter Park
country: United States
state: Florida
city: Newnan
country: United States
state: Georgia
city: Stockbridge
country: United States
state: Georgia
city: Shreveport
country: United States
state: Louisiana
city: Saint Louis Park
country: United States
state: Minnesota
city: Kansas City
country: United States
state: Missouri
city: Berlin
country: United States
state: New Jersey
city: Hendersonville
country: United States
state: North Carolina
city: Winston-Salem
country: United States
state: North Carolina
city: Philadelphia
country: United States
state: Pennsylvania
city: Houston
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Laredo
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: Salt Lake City
country: United States
state: Utah
city: Bruxelles
country: Belgium
city: Gabrovo
country: Bulgaria
city: Shumen
country: Bulgaria
city: Varna
country: Bulgaria
city: Ceske Budejovice
country: Czechia
city: Ceske Budejovice
country: Czechia
city: Hradec Kralove
country: Czechia
city: Most
country: Czechia
city: Nová Ves Pod Pleší
country: Czechia
city: Ostrava-Poruba
country: Czechia
city: Plzen
country: Czechia
city: Lunen
country: Germany
city: Stadtroda
country: Germany
city: Wetzlar
country: Germany
city: Deszk
country: Hungary
city: Kecskemét
country: Hungary
city: Komarom
country: Hungary
city: Miskolc
country: Hungary
city: Nyíregyháza
country: Hungary
city: Szekszard
country: Hungary
city: Rezekne
country: Latvia
city: Riga
country: Latvia
city: Klaipeda
country: Lithuania
city: Siauliai
country: Lithuania
city: Vilnius
country: Lithuania
city: Bialystok
country: Poland
city: Bielsko-Biala
country: Poland
city: Gliwice
country: Poland
city: Poznan
country: Poland
city: Warszawa
country: Poland
city: Ponce
country: Puerto Rico
city: San Juan
country: Puerto Rico
city: Baia Mare
country: Romania
city: Braila
country: Romania
city: Bucuresti
country: Romania
city: Craiova
country: Romania
city: Oradea
country: Romania
city: Satu Mare
country: Romania
city: Suceava
country: Romania
city: Bury Saint Edmunds
country: United Kingdom
city: Bury
country: United Kingdom
city: Edinburgh
country: United Kingdom
city: Glasgow
country: United Kingdom
city: Manchester
country: United Kingdom
city: Norwich
country: United Kingdom
city: Weston Super Mare
country: United Kingdom
city: Wolverhampton
country: United Kingdom
Study officials:
References:
citation: Lichtman AH, Lux EA, McQuade R, Rossetti S, Sanchez R, Sun W, Wright S, Kornyeyeva E, Fallon MT. Results of a Double-Blind, Randomized, Placebo-Controlled Study of Nabiximols Oromucosal Spray as an Adjunctive Therapy in Advanced Cancer Patients with Chronic Uncontrolled Pain. J Pain Symptom Manage. 2018 Feb;55(2):179-188.e1. doi: 10.1016/j.jpainsymman.2017.09.001. Epub 2017 Sep 18.