A Two-Part Study of Sativex® Oromucosal Spray for Relieving Uncontrolled Persistent Pain in Patients With Advanced Cancer

NCT01424566 | Completed Phase 3 Results DMC

• 2 other identifiers: GWCA11032010-022905-17
• Study Type: interventional
• Target: 406
• Locations: 13 countries
• Sites: 65

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.

Conditions

Pain; Advanced Cancer

Keywords

Cancer pain; Opioid therapy; Inadequate analgesia; Optimized chronic opioid therapy

Outcome Measures

Primary Outcomes (1)

• 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.

  Randomization Baseline, End of Treatment (Day 36 of the double-blind period)

Secondary Outcomes (10)

• Percent Improvement From Eligibility Baseline In Mean NRS Average Pain Score At End Of Treatment

  Eligibility Baseline, End of Treatment (Day 36 of the double-blind period)

• Change From Randomization Baseline In Mean NRS Worst Pain At End Of Treatment

  Randomization Baseline, End of Treatment (Day 36 of the double-blind period)

• Change From Randomization Baseline In Mean Sleep Disruption NRS At End Of Treatment

  Randomization Baseline, End of Treatment (Day 36 of the double-blind period)

• Subject Global Impression Of Change At Last Visit (Up To Day 36 Of The Double-blind Period)

  Last Visit (up to Day 36 of the double-blind period)

• Physician Global Impression Of Change At Last Visit (Up To Day 36 Of The Double-blind Period)

  Last Visit (up to Day 36 of the double-blind period)

Study Arms (2)

Nabiximols

EXPERIMENTAL

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.

Drug: Nabiximols

Placebo (GA-0034)

PLACEBO COMPARATOR

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.

Drug: Placebo (GA-0034)

Interventions

Nabiximols DRUG

Also known as: Sativex®

Nabiximols

Placebo (GA-0034) DRUG

Placebo (GA-0034)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Jazz Pharmaceuticals: lead
• Otsuka Pharmaceutical Development & Commercialization, Inc.: collaborator

Study Sites (65)

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East Melbourne, 3002, Australia

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Parkville, 3050, Australia

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Shumen, 9700, Bulgaria

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Varna, 9010, Bulgaria

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Vratsa, 3000, Bulgaria

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Lünen, 44534, Germany

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Stadtroda, 07646, Germany

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Wetzlar, 35578, Germany

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Budapest, 1135, Hungary

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Deszk, 6772, Hungary

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Komárom, 2900, Hungary

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Nyíregyháza, 4412, Hungary

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Szikszó, 3800, Hungary

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Bangalore, 560034, India

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Jaipur, 302017, India

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Pune, 411004, India

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Ashkelon, 78306, Israel

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Beersheba, 84101, Israel

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Haifa, 31096, Israel

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Jerusalem, 91120, Israel

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Ramat Gan, 52621, Israel

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Ẕerifin, 60930, Israel

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Garbagnate Milanese, 20024, Italy

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Piacenza, 29100, Italy

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Torino, 10126, Italy

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Klaipėda, 92288, Lithuania

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Šiauliai, 76307, Lithuania

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Vilnius, 08660, Lithuania

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Bydgoszcz, 85-796, Poland

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Czeladź, 41-250, Poland

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Gdansk, 80-208, Poland

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Gliwice, 44-101, Poland

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Kłodzko, 57-300, Poland

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Opole, 45-272, Poland

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Ostrowiec Świętokrzyski, 27-400, Poland

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Poznan, 61-245, Poland

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Warsaw, 02-781, Poland

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Warsaw, 02-793, Poland

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Włocławek, 87-800, Poland

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Alba Iulia, 510077, Romania

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Baia Mare, 430241, Romania

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Brăila, 810325, Romania

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Bucharest, 010976, Romania

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Focşani, 620165, Romania

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Oradea, 410469, Romania

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Satu Mare, 440055, Romania

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Sibiu, 550245, Romania

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Suceava, 720237, Romania

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Cadiz, 11009, Spain

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Granada, 18014, Spain

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Madrid, 28050, Spain

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Salamanca, 37129, Spain

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Seville, 41013, Spain

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Changhua, 500, Taiwan

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Taichung, 404, Taiwan

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Tainan, 73657, Taiwan

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Taipei, 10002, Taiwan

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Taipei, 10099, Taiwan

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Taipei, 11213, Taiwan

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Taipei, 11490, Taiwan

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Bury St Edmunds, IP33 2QZ, United Kingdom

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Edinburgh, EH4 2XR, United Kingdom

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Glasgow, G12 0YN, United Kingdom

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Manchester, M20 4BX, United Kingdom

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Norwich, NR4 7UY, United Kingdom

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Related Publications (1)

• 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.

  PMID: 28785408 BACKGROUND

MeSH Terms

Conditions

Pain; Cancer Pain

Interventions

nabiximols

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Medical Enquiries
• Organization: GW Pharmaceuticals Ltd.

medinfo.USA@gwpharm.com

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2011
• First Posted: August 29, 2011
• Study Start: June 29, 2012
• Primary Completion: July 10, 2015
• Study Completion: December 28, 2015
• Last Updated: April 12, 2023
• Results First Posted: April 23, 2018

Record last verified: 2023-04

Locations

DE (3); IT (3); BU (3); PL (11); ES (5); RO (9); HU (5); TW (7); LI (3); GB (5); AU (2); IL (6); IN (3)