Long Term Safety of Sativex Oromucosal Spray (Sativex®; Nabiximols) as Adjunctive Therapy in Patients With Uncontrolled Persistent Chronic Cancer Related Pain

A Multicenter, Non-comparative, Open-label Extension Study to Assess the Long Term Safety of Sativex® Oromucosal Spray (Sativex®; Nabiximols) as Adjunctive Therapy in Patients With Uncontrolled Persistent Chronic Cancer Related Pain

This was a six-month open-label extension (OLE) study to evaluate the safety of long-term nabiximols (Sativex®) therapy when used as an adjunctive treatment in participants with advanced cancer. The study provided continued availability of nabiximols to participants who completed a preceding Phase 3 study and new (de novo) participants.

Study Overview

• Status: Completed
• Conditions: Pain; Advanced Cancer
• Intervention / Treatment: Drug: Nabiximols

Detailed Description

This was a 6-month, multicenter, non-comparative, OLE study to evaluate the safety of long-term nabiximols use as an adjunctive measure in participants with advanced cancer. The study provided continued availability of nabiximols to participants who completed a preceding double-blind phase 3 study and de novo participants. Consenting eligible participants entered the extension study (Day 1) on the same day as the "end of treatment" visit of a parent study or within 7 days of the "end of treatment" visit or on the day of the "safety follow-up visit" of the parent study. The "safety follow-up" visit of a parent study was performed on the same day as Day 1, if the participant did not enter the OLE study on the same day as the "end of treatment" visit of a parent study. De novo participants attended a screening visit 3 to 14 days prior to enrollment (Day 1). All participants commenced dosing on Day 1. Further study visits took place after 2 weeks (Day 15), and every 4 weeks thereafter until the end of treatment period on Day 183 or earlier if the participant withdrew from the study.

Treatment was started as a single spray in the evening on the first day (Day 1). Participants then gradually titrated by 1 additional spray per day to an individualized dose, balancing efficacy and tolerability. Participants had to complete titration within 14 days of their first dose of study drug and then continue at the same dose for the remainder of the study.

• Study Type: Interventional
• Enrollment (Actual): 660
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Parkville, Australia, 3050
• Belgium
  • Bruxelles, Belgium, 1000
• Bulgaria
  • Gabrovo, Bulgaria, 5300
  • Varna, Bulgaria, 9010
  • Vratsa, Bulgaria, 3000
• Czechia
  • Benešov, Czechia, 25601
  • Jablonec Nad Nisou, Czechia, 46601
  • Most, Czechia, 434 64
  • Nová Ves Pod Pleší, Czechia, 262 04
  • Ostrava, Czechia, 708 52
  • Plzen, Czechia, 304 60
  • Sokolov, Czechia, 356 01
  • Teplice, Czechia, 415 01
  • České Budějovice, Czechia, 370 01
  • České Budějovice, Czechia, 370 87
• Germany
  • Berlin, Germany, 10435
  • Frankfurt, Germany, 60311
  • Jena, Germany, 07747
  • Lunen, Germany, 44534
  • Stadtroda, Germany, 07646
  • Wetzlar, Germany, 35578
  • Wiesbaden, Germany, 65189
• Hungary
  • Deszk, Hungary, 6772
  • Komarom, Hungary, 2900
  • Miskolc, Hungary, 3501
  • Nyíregyháza, Hungary, 4412
  • Szekszard, Hungary, 7100
  • Szikszo, Hungary, 3800
• Israel
  • Beer Sheva, Israel, 84101
  • Haifa, Israel, 31096
  • Ramat Gan, Israel, 52621
  • Zerifin, Israel, 60930
• Italy
  • Garbagnate Milanese, Italy, 20024
  • Piacenza, Italy, 29100
  • Torino, Italy, 10126
• Latvia
  • Riga, Latvia, 1038
  • Rēzekne, Latvia, 4600
• Lithuania
  • Klaipeda, Lithuania, 92288
  • Siauliai, Lithuania, 76307
  • Vilnius, Lithuania, 08660
• Mexico
  • Chihuahua, Mexico, 31238
  • Distrito Federal, Mexico, 10700
• Poland
  • Białystok, Poland, 15-250
  • Bielsko-Biala, Poland, 43-300
  • Bydgoszcz, Poland, 85-796
  • Czeladz, Poland, 41-250
  • Częstochowa, Poland, 42-200
  • Częstochowa, Poland, 42-217
  • Działdowo, Poland, 13-200
  • Gdansk, Poland, 80-208
  • Gliwice, Poland, 44-101
  • Klodzko, Poland, 57-300
  • Opole, Poland, 45-272
  • Ostrowiec Swietokrzyski, Poland, 27-400
  • Poznan, Poland, 61-245
  • Warszawa, Poland, 02-781
  • Warszawa, Poland, 02-793
  • Wloclawek, Poland, 87-800
• Puerto Rico
  • Ponce, Puerto Rico, 00717
  • San Juan, Puerto Rico, 00927
• Romania
  • Baia Mare, Romania, 430031
  • Baia Mare, Romania, 430241
  • Braila, Romania, 810325
  • Bucuresti, Romania, 011461
  • Bucuresti, Romania, 010976
  • Cluj-Napoca, Romania, 400015
  • Constanţa, Romania, 900591
  • Craiova, Romania, 200385
  • Focsani, Romania, 620165
  • Iaşi, Romania, 700106
  • Oradea, Romania, 410469
  • Satu Mare, Romania, 440055
  • Sibiu, Romania, 550245
  • Suceava, Romania, 720237
  • Târgovişte, Romania, 130095
• Spain
  • Granada, Spain, 18014
• Taiwan
  • Taichung, Taiwan, 404
  • Tainan City, Taiwan, 73657
• United Kingdom
  • Bury, United Kingdom, BL9 7TD
  • Bury Saint Edmunds, United Kingdom, IP33 2QZ
  • Cheltenham, United Kingdom, GL53 0QJ
  • Crumpsall, United Kingdom, M8 5RB
  • Edinburgh, United Kingdom
  • Edinburgh, United Kingdom, EH4 2XR
  • Gorleston-on-Sea, United Kingdom, NR31 6LA
  • Leeds, United Kingdom, LS17 6QD
  • Manchester, United Kingdom, M20 4BX
  • Norwich, United Kingdom, NR4 7UY
  • Plymouth, United Kingdom, PL6 8DH
  • Weston-super-Mare, United Kingdom, BS23 4TQ
  • Withington, United Kingdom, M20 4BX
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85028
    • Phoenix, Arizona, United States, 85018
  • California
    • El Cajon, California, United States, 92020
    • Gilroy, California, United States, 95020
    • Glendale, California, United States, 91204
    • Santa Rosa, California, United States, 95403
  • Florida
    • Clearwater, Florida, United States, 33756
    • Daytona Beach, Florida, United States, 32117
    • Holiday, Florida, United States, 34691
    • Jacksonville, Florida, United States, 32257
    • Lynn Haven, Florida, United States, 32444
    • Miami, Florida, United States, 33136
    • Stuart, Florida, United States, 34994
    • Tampa, Florida, United States, 33609
    • Winter Park, Florida, United States, 32789
  • Georgia
    • Marietta, Georgia, United States, 30060
    • Newnan, Georgia, United States, 30265
    • Stockbridge, Georgia, United States, 30281
  • Illinois
    • Woodlawn, Illinois, United States, 62898
  • Kentucky
    • Ashland, Kentucky, United States, 41101
  • Louisiana
    • Bossier City, Louisiana, United States, 71111
    • Shreveport, Louisiana, United States, 71105
  • Minnesota
    • Saint Louis Park, Minnesota, United States, 55426
  • Missouri
    • Kansas City, Missouri, United States, 64132
  • Montana
    • Missoula, Montana, United States, 59802
  • New Jersey
    • Berlin, New Jersey, United States, 08009
  • New York
    • New York, New York, United States, 10003
    • New York, New York, United States, 10010
  • North Carolina
    • Flat Rock, North Carolina, United States, 28731
    • Winston-Salem, North Carolina, United States, 27103
  • Ohio
    • Cleveland, Ohio, United States, 44119
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19146
  • Texas
    • Houston, Texas, United States, 77089
    • Laredo, Texas, United States, 78041
  • Utah
    • Salt Lake City, Utah, United States, 84124
    • Salt Lake City, Utah, United States, 84112
  • Washington
    • Lacey, Washington, United States, 98503

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant had completed the parent study within the last seven days
• Willing and able to give written informed consent
• Willing and able to comply with all study requirements

Exclusion Criteria:

• The participant was using cannabis or cannabinoid based medications, other than the parent study investigational medicinal product (IMP), and was unwilling to abstain for the duration of the study
• 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 substance abuse/dependence disorder (including opiate abuse/dependence prior to the diagnosis of cancer), current heavy alcohol consumption (more than 60 grams [g] of pure alcohol per day for men, and more than 40 g of pure alcohol per day for women), current use of an illicit drug or current non-prescribed use of any prescription drug
• Had poorly controlled epilepsy or recurrent seizures (for example, one or more seizure during the last year)
• 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
• Had significantly impaired renal function
• Had significantly impaired hepatic function at the "end of treatment" visit of the parent study
• 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 should not have been used in conjunction with a female condom as this may not have proven effective)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Non-comparative, open-label 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 6 months. Nabiximols oromucosal spray contained delta-9-tetrahydrocannabinol (THC) (27 milligrams [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.

Drug: Nabiximols; Other Names: Sativex®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Of Participants With Treatment-emergent Adverse Events	Treatment-emergent Adverse Events (TEAEs) were coded according to the Medical Dictionary for Regulatory Activities (MedDRA) dictionary version 17.0. A TEAE is defined as an adverse event with an onset after the start of study drug treatment. The percent of participants who experienced one or more TEAEs is reported.	Baseline, Day 183

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline In Mean NRS Average Pain During The Last Period	Participants indicated the level of pain experienced in the last 24 hours on an 11-point Numerical Rating Scale (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: Last Period NRS average pain score - Baseline NRS average pain score. A negative value indicates an improvement in average pain score from Baseline.	Baseline, Last Period (Days 156-183) or last 27 days of treatment
Change From Baseline In Mean Sleep Disruption NRS During The Last Period	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: Last Period sleep disruption NRS score - Baseline sleep disruption NRS score. A negative value indicates an improvement in sleep disruption score from Baseline.	Baseline, Last Period (Days 156-183) or last 27 days of treatment
Patient Satisfaction Questionnaire At Last Visit (Up To Day 183)	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.	Last Visit (up to Day 183)
Change From Baseline In NRS Constipation At Last Visit (Up To Day 183)	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. 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.	Baseline, Last Visit (up to Day 183)

Collaborators and Investigators

• Sponsor: Jazz Pharmaceuticals
• Collaborators: Otsuka Pharmaceutical Development & Commercialization, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 19, 2011
• Primary Completion (Actual): January 27, 2016
• Study Completion (Actual): January 27, 2016

Study Registration Dates

• First Submitted: April 12, 2011
• First Submitted That Met QC Criteria: April 15, 2011
• First Posted (Estimate): April 18, 2011

Study Record Updates

• Last Update Posted (Actual): April 12, 2023
• Last Update Submitted That Met QC Criteria: April 7, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Cancer pain; Opioid therapy; Inadequate analgesia; Optimized chronic opioid therapy
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Cancer Pain; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Nabiximols
• Other Study ID Numbers: GWCA0999; 2009-016529-32 (EudraCT Number)