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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01424566




Registration number
NCT01424566
Ethics application status
Date submitted
25/08/2011
Date registered
29/08/2011
Date last updated
12/04/2023

Titles & IDs
Public title
A Two-Part Study of Sativex® Oromucosal Spray for Relieving Uncontrolled Persistent Pain in Patients With Advanced Cancer
Scientific title
A Two-part, Placebo-controlled, Study of the Safety and Efficacy of Sativex® Oromucosal Spray (Sativex®; Nabiximols) as Adjunctive Therapy in Relieving Uncontrolled Persistent Chronic Pain in Patients With Advanced Cancer, Who Have Inadequate Analgesia Even With Optimized Chronic Opioid Therapy.
Secondary ID [1] 0 0
2010-022905-17
Secondary ID [2] 0 0
GWCA1103
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pain 0 0
Advanced Cancer 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Nabiximols
Treatment: Drugs - Placebo (GA-0034)

Experimental: 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 2 or 7 weeks. 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.

Placebo Comparator: 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.


Treatment: Drugs: Nabiximols


Treatment: Drugs: Placebo (GA-0034)
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Randomization Baseline In Mean NRS Average Pain At End Of Treatment
Timepoint [1] 0 0
Randomization Baseline, End of Treatment (Day 36 of the double-blind period)
Secondary outcome [1] 0 0
Percent Improvement From Eligibility Baseline In Mean NRS Average Pain Score At End Of Treatment
Timepoint [1] 0 0
Eligibility Baseline, End of Treatment (Day 36 of the double-blind period)
Secondary outcome [2] 0 0
Change From Randomization Baseline In Mean NRS Worst Pain At End Of Treatment
Timepoint [2] 0 0
Randomization Baseline, End of Treatment (Day 36 of the double-blind period)
Secondary outcome [3] 0 0
Change From Randomization Baseline In Mean Sleep Disruption NRS At End Of Treatment
Timepoint [3] 0 0
Randomization Baseline, End of Treatment (Day 36 of the double-blind period)
Secondary outcome [4] 0 0
Subject Global Impression Of Change At Last Visit (Up To Day 36 Of The Double-blind Period)
Timepoint [4] 0 0
Last Visit (up to Day 36 of the double-blind period)
Secondary outcome [5] 0 0
Physician Global Impression Of Change At Last Visit (Up To Day 36 Of The Double-blind Period)
Timepoint [5] 0 0
Last Visit (up to Day 36 of the double-blind period)
Secondary outcome [6] 0 0
Patient Satisfaction Questionnaire At Last Visit (Up To Day 36 Of The Double-blind Period)
Timepoint [6] 0 0
Last Visit (up to Day 36 of the double-blind period)
Secondary outcome [7] 0 0
Change From Randomization Baseline In Daily Total Opioid Use (Morphine Equivalent) At End Of Treatment
Timepoint [7] 0 0
Randomization Baseline, End of Treatment (Day 36 of the double-blind period)
Secondary outcome [8] 0 0
Change From Randomization Baseline In Daily Maintenance Opioid Dose (Morphine Equivalent) At End Of Treatment
Timepoint [8] 0 0
Randomization Baseline, End of Treatment (Day 36 of the double-blind period)
Secondary outcome [9] 0 0
Change From Randomization Baseline In Daily Break-through Opioid Dose (Morphine Equivalent) At End Of Treatment
Timepoint [9] 0 0
Randomization Baseline, End of Treatment (Day 36 of the double-blind period)
Secondary outcome [10] 0 0
Change From Randomization Baseline In NRS Constipation At Last Visit (Up To Day 36 Of The Double-blind Period)
Timepoint [10] 0 0
Randomization Baseline, Last Visit (up to Day 36 of the double-blind period)

Eligibility
Key inclusion criteria
Inclusion Criteria (abbreviated):

- The participant had advanced cancer for which there is no known curative therapy

- The participant had a clinical diagnosis of cancer related pain, which was not
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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria (abbreviated):

- 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 currently using or had used cannabis or cannabinoid-based
medications within 30 days of study entry and was unwilling to abstain for the
duration of the study

- 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

- 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 three months thereafter (however, a
male condom was not to be used in conjunction with a female condom as this may not
have proven effective)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
29/06/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
28/12/2015
Sample size
Target
Accrual to date
Final
406
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
- East Melbourne
Recruitment hospital [2] 0 0
- Parkville
Recruitment postcode(s) [1] 0 0
3002 - East Melbourne
Recruitment postcode(s) [2] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
Bulgaria
State/province [1] 0 0
Shumen
Country [2] 0 0
Bulgaria
State/province [2] 0 0
Varna
Country [3] 0 0
Bulgaria
State/province [3] 0 0
Vratsa
Country [4] 0 0
Germany
State/province [4] 0 0
Lunen
Country [5] 0 0
Germany
State/province [5] 0 0
Stadtroda
Country [6] 0 0
Germany
State/province [6] 0 0
Wetzlar
Country [7] 0 0
Hungary
State/province [7] 0 0
Budapest
Country [8] 0 0
Hungary
State/province [8] 0 0
Deszk
Country [9] 0 0
Hungary
State/province [9] 0 0
Komárom
Country [10] 0 0
Hungary
State/province [10] 0 0
Nyíregyháza
Country [11] 0 0
Hungary
State/province [11] 0 0
Szikszó
Country [12] 0 0
India
State/province [12] 0 0
Bangalore
Country [13] 0 0
India
State/province [13] 0 0
Jaipur
Country [14] 0 0
India
State/province [14] 0 0
Pune
Country [15] 0 0
Israel
State/province [15] 0 0
Ashkelon
Country [16] 0 0
Israel
State/province [16] 0 0
Beer Sheva
Country [17] 0 0
Israel
State/province [17] 0 0
Haifa
Country [18] 0 0
Israel
State/province [18] 0 0
Jerusalem
Country [19] 0 0
Israel
State/province [19] 0 0
Ramat Gan
Country [20] 0 0
Israel
State/province [20] 0 0
Zerifin
Country [21] 0 0
Italy
State/province [21] 0 0
Garbagnate Milanese
Country [22] 0 0
Italy
State/province [22] 0 0
Piacenza
Country [23] 0 0
Italy
State/province [23] 0 0
Torino
Country [24] 0 0
Lithuania
State/province [24] 0 0
Klaipeda
Country [25] 0 0
Lithuania
State/province [25] 0 0
Siauliai
Country [26] 0 0
Lithuania
State/province [26] 0 0
Vilnius
Country [27] 0 0
Poland
State/province [27] 0 0
Bydgoszcz
Country [28] 0 0
Poland
State/province [28] 0 0
Czeladz
Country [29] 0 0
Poland
State/province [29] 0 0
Gdansk
Country [30] 0 0
Poland
State/province [30] 0 0
Gliwice
Country [31] 0 0
Poland
State/province [31] 0 0
Klodzko
Country [32] 0 0
Poland
State/province [32] 0 0
Opole
Country [33] 0 0
Poland
State/province [33] 0 0
Ostrowiec Swietokrzyski
Country [34] 0 0
Poland
State/province [34] 0 0
Poznan
Country [35] 0 0
Poland
State/province [35] 0 0
Warszawa
Country [36] 0 0
Poland
State/province [36] 0 0
Wloclawek
Country [37] 0 0
Romania
State/province [37] 0 0
Alba Iulia
Country [38] 0 0
Romania
State/province [38] 0 0
Baia Mare
Country [39] 0 0
Romania
State/province [39] 0 0
Braila
Country [40] 0 0
Romania
State/province [40] 0 0
Bucuresti
Country [41] 0 0
Romania
State/province [41] 0 0
Foc?ani
Country [42] 0 0
Romania
State/province [42] 0 0
Oradea
Country [43] 0 0
Romania
State/province [43] 0 0
Satu Mare
Country [44] 0 0
Romania
State/province [44] 0 0
Sibiu
Country [45] 0 0
Romania
State/province [45] 0 0
Suceava
Country [46] 0 0
Spain
State/province [46] 0 0
Cadiz
Country [47] 0 0
Spain
State/province [47] 0 0
Granada
Country [48] 0 0
Spain
State/province [48] 0 0
Madrid
Country [49] 0 0
Spain
State/province [49] 0 0
Salamanca
Country [50] 0 0
Spain
State/province [50] 0 0
Sevilla
Country [51] 0 0
Taiwan
State/province [51] 0 0
Changhua City
Country [52] 0 0
Taiwan
State/province [52] 0 0
Taichung
Country [53] 0 0
Taiwan
State/province [53] 0 0
Tainan City
Country [54] 0 0
Taiwan
State/province [54] 0 0
Taipei
Country [55] 0 0
United Kingdom
State/province [55] 0 0
Bury Saint Edmunds
Country [56] 0 0
United Kingdom
State/province [56] 0 0
Edinburgh
Country [57] 0 0
United Kingdom
State/province [57] 0 0
Glasgow
Country [58] 0 0
United Kingdom
State/province [58] 0 0
Manchester
Country [59] 0 0
United Kingdom
State/province [59] 0 0
Norwich

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Jazz Pharmaceuticals
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Otsuka Pharmaceutical Development & Commercialization, Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The primary objective of this study was to evaluate the efficacy of nabiximols (Sativex®),
compared with placebo, when used as an adjunctive measure in relieving uncontrolled
persistent chronic pain (not breakthrough pain) in participants with advanced cancer, who had
inadequate analgesia even with optimized chronic opioid therapy.

This multi-center study was conducted in two parts. All participants enrolled into the trial
received nabiximols during one of two parts of the study, but they did not know which part.

Eligible participants were not required to stop any of their current treatments or
medications.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01424566
Trial related presentations / publications
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.
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries