Clinical trial NCT01424566: A Two-Part Study of Sativex® Oromucosal Spray for Relieving Uncontrolled Persistent Pain in Patients With Advanced Cancer
Official 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pain
Advanced Cancer
Keywords: Cancer pain
Opioid therapy
Inadequate analgesia
Optimized chronic opioid therapy
Lead sponsor: Jazz Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Otsuka Pharmaceutical Development & Commercialization, Inc.
First posted: 2011-08-29
Enrollment: 406
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: This 11-week, multi-center, placebo-controlled study aimed to determine the efficacy, safety and tolerability of nabiximols administered as an adjunctive treatment for 5 weeks, versus placebo, assessed by a 2-part, randomized withdrawal design. The first part of the study (Part A) was single-blind (participants) and the second part of the study (Part B) was randomized, double-blind. Eligible participants had advanced cancer, with a clinical diagnosis of cancer related pain which was not wholly alleviated by their current optimized opioid treatment.

Qualifying participants entered the study at screening and commenced a 5- to 14-day eligibility period. During this period, eligible participants 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 participants underwent nabiximols titration during a single-blind treatment period lasting 10 days, followed by 4 days of therapy at the titrated dose. Participants who demonstrated an improvement of 15% or more on the score of the pain numerical rating scale were advanced to Part B, where they were randomized 1:1 to nabiximols or placebo in a double-blind fashion. Participants then received study treatments at their self-titrated doses for 5 weeks. After the end of the 5-week treatment period, participants were offered the option of entering an open-label extension (OLE) study; participants who entered the OLE up to 7 days after study completion had their follow-up assessments performed on the same day as their first OLE study visit. Participants that did not enter the OLE study had a safety follow up visit 14 days after treatment completion, which could be via telephone.

Eligibility 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

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)

Primary outcomes:
measure: Change From Randomization Baseline In Mean NRS Average Pain At End Of Treatment
timeFrame: Randomization Baseline, End of Treatment (Day 36 of the double-blind period)
Secondary outcomes:
measure: Percent Improvement From Eligibility Baseline In Mean NRS Average Pain Score At End Of Treatment
timeFrame: Eligibility Baseline, End of Treatment (Day 36 of the double-blind period)
measure: Change From Randomization Baseline In Mean NRS Worst Pain At End Of Treatment
timeFrame: Randomization Baseline, End of Treatment (Day 36 of the double-blind period)
measure: Change From Randomization Baseline In Mean Sleep Disruption NRS At End Of Treatment
timeFrame: Randomization Baseline, End of Treatment (Day 36 of the double-blind period)
measure: Subject Global Impression Of Change At Last Visit (Up To Day 36 Of The Double-blind Period)
timeFrame: Last Visit (up to Day 36 of the double-blind period)
measure: Physician Global Impression Of Change At Last Visit (Up To Day 36 Of The Double-blind Period)
timeFrame: Last Visit (up to Day 36 of the double-blind period)
measure: Patient Satisfaction Questionnaire At Last Visit (Up To Day 36 Of The Double-blind Period)
timeFrame: Last Visit (up to Day 36 of the double-blind period)
measure: Change From Randomization Baseline In Daily Total Opioid Use (Morphine Equivalent) At End Of Treatment
timeFrame: Randomization Baseline, End of Treatment (Day 36 of the double-blind period)
measure: Change From Randomization Baseline In Daily Maintenance Opioid Dose (Morphine Equivalent) At End Of Treatment
timeFrame: Randomization Baseline, End of Treatment (Day 36 of the double-blind period)
measure: Change From Randomization Baseline In Daily Break-through Opioid Dose (Morphine Equivalent) At End Of Treatment
timeFrame: Randomization Baseline, End of Treatment (Day 36 of the double-blind period)
measure: Change From Randomization Baseline In NRS Constipation At Last Visit (Up To Day 36 Of The Double-blind Period)
timeFrame: Randomization Baseline, Last Visit (up to Day 36 of the double-blind period)
Other outcomes:
Locations:
city: East Melbourne
country: Australia
city: Parkville
country: Australia
city: Shumen
country: Bulgaria
city: Varna
country: Bulgaria
city: Vratsa
country: Bulgaria
city: Lunen
country: Germany
city: Stadtroda
country: Germany
city: Wetzlar
country: Germany
city: Budapest
country: Hungary
city: Deszk
country: Hungary
city: Komárom
country: Hungary
city: Nyíregyháza
country: Hungary
city: Szikszó
country: Hungary
city: Bangalore
country: India
city: Jaipur
country: India
city: Pune
country: India
city: Ashkelon
country: Israel
city: Beer Sheva
country: Israel
city: Haifa
country: Israel
city: Jerusalem
country: Israel
city: Ramat Gan
country: Israel
city: Zerifin
country: Israel
city: Garbagnate Milanese
country: Italy
city: Piacenza
country: Italy
city: Torino
country: Italy
city: Klaipeda
country: Lithuania
city: Siauliai
country: Lithuania
city: Vilnius
country: Lithuania
city: Bydgoszcz
country: Poland
city: Czeladź
country: Poland
city: Gdansk
country: Poland
city: Gliwice
country: Poland
city: Klodzko
country: Poland
city: Opole
country: Poland
city: Ostrowiec Swietokrzyski
country: Poland
city: Poznan
country: Poland
city: Warszawa
country: Poland
city: Warszawa
country: Poland
city: Wloclawek
country: Poland
city: Alba Iulia
country: Romania
city: Baia Mare
country: Romania
city: Braila
country: Romania
city: Bucuresti
country: Romania
city: Focșani
country: Romania
city: Oradea
country: Romania
city: Satu Mare
country: Romania
city: Sibiu
country: Romania
city: Suceava
country: Romania
city: Cadiz
country: Spain
city: Granada
country: Spain
city: Madrid
country: Spain
city: Salamanca
country: Spain
city: Sevilla
country: Spain
city: Changhua City
country: Taiwan
city: Taichung
country: Taiwan
city: Tainan City
country: Taiwan
city: Taipei
country: Taiwan
city: Taipei
country: Taiwan
city: Taipei
country: Taiwan
city: Taipei
country: Taiwan
city: Bury Saint Edmunds
country: United Kingdom
city: Edinburgh
country: United Kingdom
city: Glasgow
country: United Kingdom
city: Manchester
country: United Kingdom
city: Norwich
country: United Kingdom
Study officials:
References:
citation: 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.