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

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ClinicalTrials.gov Identifier: NCT01337089
Recruitment Status : Completed
First Posted : April 18, 2011
Results First Posted : April 23, 2018
Last Update Posted : April 23, 2018
Sponsor:
Collaborator:
Otsuka Pharmaceutical Development & Commercialization, Inc.
Information provided by (Responsible Party):
GW Pharmaceuticals Ltd.

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Pain Advanced Cancer Drug: Nabiximols Phase 3

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  (Clinical Trial)
Actual Enrollment : 660 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : January 19, 2011
Actual Primary Completion Date : January 27, 2016
Actual Study Completion Date : January 27, 2016

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 Name: Sativex®



Primary Outcome Measures :
  1. Percent Of Participants With Treatment-emergent Adverse Events [ Time Frame: Baseline, Day 183 ]
    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.


Secondary Outcome Measures :
  1. Change From Baseline In Mean NRS Average Pain During The Last Period [ Time Frame: Baseline, Last Period (Days 156-183) or last 27 days of treatment ]

    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.


  2. Change From Baseline In Mean Sleep Disruption NRS During The Last Period [ Time Frame: Baseline, Last Period (Days 156-183) or last 27 days of treatment ]

    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.


  3. Patient Satisfaction Questionnaire At Last Visit (Up To Day 183) [ Time Frame: 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.

  4. Change From Baseline In NRS Constipation At Last Visit (Up To Day 183) [ Time Frame: Baseline, 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.




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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01337089


  Hide Study Locations
Locations
United States, Arizona
Phoenix, Arizona, United States, 85018
Phoenix, Arizona, United States, 85028
United States, California
El Cajon, California, United States, 92020
Gilroy, California, United States, 95020
Glendale, California, United States, 91204
Santa Rosa, California, United States, 95403
United States, 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
United States, Georgia
Marietta, Georgia, United States, 30060
Newnan, Georgia, United States, 30265
Stockbridge, Georgia, United States, 30281
United States, Illinois
Woodlawn, Illinois, United States, 62898
United States, Kentucky
Ashland, Kentucky, United States, 41101
United States, Louisiana
Bossier City, Louisiana, United States, 71111
Shreveport, Louisiana, United States, 71105
United States, Minnesota
Saint Louis Park, Minnesota, United States, 55426
United States, Missouri
Kansas City, Missouri, United States, 64132
United States, Montana
Missoula, Montana, United States, 59802
United States, New Jersey
Berlin, New Jersey, United States, 08009
United States, New York
New York, New York, United States, 10003
New York, New York, United States, 10010
United States, North Carolina
Flat Rock, North Carolina, United States, 28731
Winston-Salem, North Carolina, United States, 27103
United States, Ohio
Cleveland, Ohio, United States, 44119
United States, Pennsylvania
Philadelphia, Pennsylvania, United States, 19146
United States, Texas
Houston, Texas, United States, 77089
Laredo, Texas, United States, 78041
United States, Utah
Salt Lake City, Utah, United States, 84112
Salt Lake City, Utah, United States, 84124
United States, Washington
Lacey, Washington, United States, 98503
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, 010976
Bucuresti, Romania, 011461
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 Saint Edmunds, United Kingdom, IP33 2QZ
Bury, United Kingdom, BL9 7TD
Cheltenham, United Kingdom, GL53 0QJ
Crumpsall, United Kingdom, M8 5RB
Edinburgh, United Kingdom, EH4 2XR
Edinburgh, United Kingdom
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
Sponsors and Collaborators
GW Pharmaceuticals Ltd.
Otsuka Pharmaceutical Development & Commercialization, Inc.

Responsible Party: GW Pharmaceuticals Ltd.
ClinicalTrials.gov Identifier: NCT01337089     History of Changes
Other Study ID Numbers: GWCA0999
2009-016529-32 ( EudraCT Number )
First Posted: April 18, 2011    Key Record Dates
Results First Posted: April 23, 2018
Last Update Posted: April 23, 2018
Last Verified: March 2018

Keywords provided by GW Pharmaceuticals Ltd.:
Cancer pain
Opioid therapy
Inadequate analgesia
Optimized chronic opioid therapy

Additional relevant MeSH terms:
Cancer Pain
Pain
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms