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Trial details imported from ClinicalTrials.gov

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




Trial ID
NCT01424566
Ethics application status
Date submitted
25/08/2011
Date registered
25/08/2011
Date last updated
23/03/2018

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 - Participants indicated the level of pain experienced in the last 24 hours on an 11-point 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: End of Treatment NRS average pain score - Randomization (Part B) Baseline NRS average pain score. The participant's Randomization (Part B) baseline pain 0-10 NRS value was the mean over the last 4 consecutive days of the single-blind treatment period (Part A; pre-randomization). A negative value indicates an improvement in average pain score from Randomization (Part B) Baseline.
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 - Participants indicated level of pain in the last 24 hours on an 11-point NRS, where a score of 0 was "no pain" and 10 was "pain as bad as you can imagine". Eligibility Baseline = mean score from the 3-day eligibility period. End of Treatment = mean score over last (up to) 4 days to the final pain score at End of Treatment or up until Day 36 of the double-blind period, whichever is earlier, or final score available (prematurely terminated).
Percentage improvement from baseline (Imp%) was calculated as:
Imp% = (Eligibility Baseline pain NRS mean - End of Treatment pain NRS mean)/Eligibility Baseline pain NRS mean * 100.
For participants who died or withdrew due to disease progression, Imp% values were used. For participants who died or withdrew unrelated to disease progression before end of Week 5, Imp% was zero for participants whose Imp% value was positive and it was Imp% for participants whose Imp% value was not positive.
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 - Participants indicated the level of worst pain experienced in the last 24 hours on an 11-point 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 worst pain was calculated as: End of Treatment NRS worst pain score - Randomization (Part B) Baseline NRS worst pain score. The participant's Randomization (Part B) baseline worst pain 0-10 NRS value was the mean over the last 4 consecutive days of the single-blind treatment period (Part A; pre-randomization). A negative value indicates an improvement in worst pain score from Randomization (Part B) Baseline.
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 - 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: End of Treatment sleep disruption NRS score - Randomization (Part B) Baseline sleep disruption NRS score. The participant's Randomization (Part B) baseline sleep disruption 0-10 NRS value was the mean over the last 4 consecutive days of the single-blind treatment period (Part A; pre-randomization). A negative value indicates an improvement in sleep disruption score from Randomization (Part B) Baseline.
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) - The Subject Global Impression of Change (SGIC) was used to assess the overall status of the participant related to their cancer pain, with the markers "very much improved, much improved, slightly improved, no change, slightly worse, much worse, or very much worse". The SGIC was assessed at Day 36 of the double-blind period or the day at which a participant's last evaluation was performed, such as in the case of early termination. Last visit refers to the last visit that a participant completed the assessment; this could be either Day 22 or 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) - The Physician Global Impression of Change (PGIC) was used by the treating physician (investigator/sub-investigator) to assess if there was any change in the general functional abilities of the participant since prior to commencement of study medication, with the markers: "very much worse, much worse, slightly worse, no change, slightly improved, much improved, very much improved". Last visit refers to the last visit that a participant completed the assessment; this could be either Day 22 or 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) - 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; this could be either Day 22 or 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 - The total daily opioid use (in morphine equivalence) was the sum of morphine equivalence of daily maintenance dose and break-through dose.
Change in daily total opioid use was calculated as: End of Treatment daily total opioid use - Randomization (Part B) Baseline daily total opioid use. The participant's Randomization (Part B) baseline daily total opioid use value was the mean over the last 4 consecutive days of the single-blind treatment period (Part A; pre-randomization). A negative value indicates a decrease in use from Randomization (Part B) Baseline.
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 - The prescribed daily quantity of opioid maintenance dose was calculated as the product of dose per use and daily frequency of use. Participants were asked: "Have you used your maintenance dose painkiller today as prescribed?" If the participant answered "No" to the question, the daily opioid maintenance dose usage on that day was set to 0.
Change in daily maintenance opioid dose was calculated as: End of Treatment daily maintenance opioid dose - Randomization (Part B) Baseline daily maintenance opioid dose. The participant's Randomization (Part B) baseline daily maintenance opioid dose value was the mean over the last 4 consecutive days of the single-blind treatment period (Part A; pre-randomization). A negative value indicates a decrease in dose from Randomization (Part B) Baseline.
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 - Daily break-through opioid dose usage was calculated as the product of prescribed dose per use, and the number of uses per day. If participants took more than 1 different break-through opioid for more than 1 day, the sum of morphine equivalence dose usages for each break-through opioid was calculated for the summary.
Change in daily break-through opioid dose was calculated as: End of Treatment daily break-through opioid dose - Randomization (Part B) Baseline daily maintenance opioid dose. The participant's Randomization (Part B) baseline daily break-through opioid dose value was the mean over the last 4 consecutive days of the single-blind treatment period (Part A; pre-randomization). A negative value indicates a decrease in dose from Randomization (Part B) Baseline.
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) - 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 - Randomization (Part B) Baseline NRS constipation score. The participant's Randomization (Part B) baseline constipation NRS value was the last evaluation (including unscheduled visits) in the single-blind treatment period (Part A) prior to the first dose of study drug in the double-blind treatment period (Part B). A negative value indicates improvement in condition from Randomization (Part B) Baseline.
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
Gender
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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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
GW Pharmaceuticals Ltd.
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/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