Sativex® for Relieving Persistent Pain in Patients With Advanced Cancer

NCT ID: NCT01361607

Last Updated: 2023-04-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 399 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-05-27
• Study Completion Date: 2014-11-24

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.

Conditions

Pain; Advanced Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Nabiximols

Nabiximols was self-administered by participants as a 100 microliter (μL) oromucosal spray in the morning and evening, up to a maximum of 10 sprays per day for 5 weeks. Nabiximols oromucosal spray contained delta-9-tetrahydrocannabinol (THC) (27 milligram \[mg\]/milliliter \[mL\]):cannabidiol (CBD) (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD.

Group Type: EXPERIMENTAL

Nabiximols

Intervention Type: DRUG

Placebo (GA-0034)

Placebo was self-administered by participants as a 100 μL oromucosal spray in the morning and evening, up to a maximum of 10 sprays per day for 5 weeks. Placebo oromucosal spray contained ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring and colorings.

Group Type: PLACEBO_COMPARATOR

Placebo (GA-0034)

Intervention Type: DRUG

Interventions

Nabiximols

Intervention Type: DRUG

Placebo (GA-0034)

Intervention Type: DRUG

Other Intervention Names

Sativex®

Eligibility Criteria

Inclusion Criteria

• 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

• 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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Otsuka Pharmaceutical Development & Commercialization, Inc.

INDUSTRY

Sponsor Role: collaborator

Jazz Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Glendale, California, United States

Santa Rosa, California, United States

Clearwater, Florida, United States

Holiday, Florida, United States

Miami, Florida, United States

Stuart, Florida, United States

Marietta, Georgia, United States

Newnan, Georgia, United States

Stockbridge, Georgia, United States

Gurnee, Illinois, United States

Mount Vernon, Illinois, United States

Ashland, Kentucky, United States

Bossier City, Louisiana, United States

Shreveport, Louisiana, United States

Missoula, Montana, United States

Berlin, New Jersey, United States

New York, New York, United States

New York, New York, United States

Cleveland, Ohio, United States

Lacey, Washington, United States

Vratsa, , Bulgaria

Benešov, , Czechia

České Budějovice, , Czechia

České Budějovice, , Czechia

Jablonec nad Nisou, , Czechia

Pilsen, , Czechia

Sokolov, , Czechia

Teplice, , Czechia

Berlin, , Germany

Frankfurt, , Germany

Fulda, , Germany

Hanover, , Germany

Jena, , Germany

Wiesbaden, , Germany

Komárom, , Hungary

Nyíregyháza, , Hungary

Mexico City, Mexico City, Mexico

Chihuahua City, , Mexico

Monterrey, , Mexico

Bydgoszcz, , Poland

Częstochowa, , Poland

Częstochowa, , Poland

Działdowo, , Poland

Gdansk, , Poland

Kłodzko, , Poland

Ostrowiec Świętokrzyski, , Poland

Poznan, , Poland

Warsaw, , Poland

Ponce, , Puerto Rico

Târgovişte, Dâmbovița County, Romania

Baia Mare, , Romania

Brasov, , Romania

Brăila, , Romania

Bucharest, , Romania

Cluj-Napoca, , Romania

Constanța, , Romania

Focşani, , Romania

Iași, , Romania

Sibiu, , Romania

Suceava, , Romania

Cheltenham, Gloucestershire, United Kingdom

Withington, Manchester, United Kingdom

Great Yarmouth, Norfolk, United Kingdom

Coventry, , United Kingdom

Glasgow, , United Kingdom

Manchester, , United Kingdom

Norwich, , United Kingdom

Plymouth, , United Kingdom

Countries

United States; Bulgaria; Czechia; Germany; Hungary; Mexico; Poland; Puerto Rico; Romania; United Kingdom

References

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.

Reference Type: BACKGROUND

PMID: 28785408 (View on PubMed)

Other Identifiers

2009-016065-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GWCA0962

Identifier Type: -

Identifier Source: org_study_id