Sativex® for Relieving Persistent Pain in Patients With Advanced Cancer (SPRAY III)

Tracking Information
First Submitted Date ICMJE	May 25, 2011
First Posted Date ICMJE	May 27, 2011
Last Update Posted Date	July 6, 2016
Study Start Date ICMJE	May 2011
Actual Primary Completion Date	October 2014 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: May 26, 2011)	The primary endpoint is the percent improvement from baseline to the end of treatment in NRS average pain score. [ Time Frame: 5 weeks ]
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT01361607 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: May 26, 2011)	Change from baseline in mean NRS average pain [ Time Frame: 5 weeks ]; Change from baseline in mean NRS worst pain [ Time Frame: 5 weeks ]; Change from baseline in mean Sleep Disruption NRS [ Time Frame: 5 weeks ]
Original Secondary Outcome Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Sativex® for Relieving Persistent Pain in Patients With Advanced Cancer
Official Title ICMJE	A Double Blind, Randomized, Placebo-controlled, Parallel Group Study of Sativex® Oromucosal Spray (Sativex®; Nabiximols) as Adjunctive Therapy in Relieving Uncontrolled Persistent Chronic Pain in Patients With Advanced Cancer, Who Experience Inadequate Analgesia During Optimized Chronic Opioid Therapy
Brief Summary	This 9-week study aimed to determine the efficacy, safety and tolerability of Sativex® (Nabiximols) as an adjunctive treatment, compared with placebo in relieving uncontrolled persistent chronic pain in patients with advanced cancer. Eligible patients 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 Sativex administered as an adjunctive treatment for 5 weeks, vs. placebo. Eligible patients had advanced cancer, with a clinical diagnosis of cancer related pain which was not wholly alleviated by their current optimized opioid treatment. Qualifying patients entered the study at Visit 1 and commenced a 5-14 day eligibility period. During this period, eligible patients 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 patients returned for a randomization visit (Visit 2, Day 1) and were randomized to either Sativex or placebo using a 1:1 allocation ratio. Patients began an initial titration period lasting up to 14 days; the titration schedule required dosing to a minimum of 3 sprays per day, after which patients were allowed to individualize their dose (3-10 sprays per day) by Day 14, and that dose was then fixed for the remainder of the study. Patients returned at Visit 3 (Day 22) and Visit 4 (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, patients were offered the option of entering an open-label extension (OLE) study; a safety follow up visit (Visit 5) was not required if the patient entered the OLE on the same day as Visit 4. Patients who entered the OLE up to 7 days after Visit 4 had their Visit 5 assessments performed on the same day as their first OLE study visit. Patients that did not enter the OLE study had a safety follow up visit (Visit 5) 14 days after treatment completion, which could be via telephone.
Study Type ICMJE	Interventional
Study Phase	Phase 3
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
Condition ICMJE	Pain; Advanced Cancer
Intervention ICMJE	Drug: Sativex® Other Name: Nabiximols; Drug: Placebo (GA-0034)
Study Arms	Placebo Comparator: Placebo (GA-0034) Placebo oromucosal spray. 100 μl administered twice daily up to a maximum of 10 sprays per day. Intervention: Drug: Placebo (GA-0034); Experimental: Sativex® Sativex oromucosal spray. 100 μl administered twice daily up to a maximum of 10 sprays per day. Intervention: Drug: Sativex®
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: December 17, 2014)	399
Original Estimated Enrollment ICMJE; (submitted: May 26, 2011)	380
Actual Study Completion Date	November 2014
Actual Primary Completion Date	October 2014 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria (abbreviated): The patient has advanced cancer for which there is no known curative therapy; The patient has a clinical diagnosis of cancer related pain, which is not alleviated with their current optimized opioid treatment; The patient is receiving an optimized maintenance dose of Step III 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 patient is receiving a daily maintenance dose Step III 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 patient is using no more than one type of break-through opioid analgesia Exclusion Criteria (abbreviated): Have any planned clinical interventions that would affect their pain (e.g., chemotherapy or radiation therapy where, in the clinical judgment of the investigator, these would be expected to affect pain); The patient is currently using or has used cannabis or cannabinoid based medications within 30 days of study entry and is unwilling to abstain for the duration of the study; Has experienced myocardial infarction or clinically significant cardiac dysfunction within the last 12 months or has a cardiac disorder that, in the opinion of the investigator would put the patient at risk of a clinically significant arrhythmia or myocardial infarction; Has significantly impaired renal function; Has significantly impaired hepatic function; Female patients of child-bearing potential and male patients whose partner is of child-bearing potential, unless willing to ensure that they or their partner use effective contraception, for example, oral contraception, double barrier, intra-uterine device, during the study and for three months thereafter (however, a male condom should not be used in conjunction with a female condom as this may not prove effective)
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Bulgaria, Czech Republic, Germany, Hungary, Mexico, Poland, Puerto Rico, Romania, United Kingdom, United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01361607
Other Study ID Numbers ICMJE	GWCA0962; 2009-016065-29 ( EudraCT Number )
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	GW Pharmaceuticals Ltd.
Study Sponsor ICMJE	GW Pharmaceuticals Ltd.
Collaborators ICMJE	Otsuka Pharmaceutical Development & Commercialization, Inc.
Investigators ICMJE	Not Provided
PRS Account	GW Pharmaceuticals Ltd.
Verification Date	July 2016
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP