Long Term Safety of Sativex Oromucosal Spray (Sativex®; Nabiximols) as Adjunctive Therapy in Patients With Uncontrolled Persistent Chronic Cancer Related Pain

A Multicenter, Non-comparative, Open-label Extension Study to Assess the Long Term Safety of Sativex® Oromucosal Spray (Sativex®; Nabiximols) as Adjunctive Therapy in Patients With Uncontrolled Persistent Chronic Cancer Related Pain

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01337089

Enrollment

660

Registered

2011-04-18

Start date

2011-01-19

Completion date

2016-01-27

Last updated

2023-04-12

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Advanced Cancer, Pain

Keywords

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

Brief summary

This was a six-month open-label extension (OLE) study to evaluate the safety of long-term nabiximols (Sativex®) therapy when used as an adjunctive treatment in participants with advanced cancer. The study provided continued availability of nabiximols to participants who completed a preceding Phase 3 study and new (de novo) participants.

Detailed description

This was a 6-month, multicenter, non-comparative, OLE study to evaluate the safety of long-term nabiximols use as an adjunctive measure in participants with advanced cancer. The study provided continued availability of nabiximols to participants who completed a preceding double-blind phase 3 study and de novo participants. Consenting eligible participants entered the extension study (Day 1) on the same day as the end of treatment visit of a parent study or within 7 days of the end of treatment visit or on the day of the safety follow-up visit of the parent study. The safety follow-up visit of a parent study was performed on the same day as Day 1, if the participant did not enter the OLE study on the same day as the end of treatment visit of a parent study. De novo participants attended a screening visit 3 to 14 days prior to enrollment (Day 1). All participants commenced dosing on Day 1. Further study visits took place after 2 weeks (Day 15), and every 4 weeks thereafter until the end of treatment period on Day 183 or earlier if the participant withdrew from the study. Treatment was started as a single spray in the evening on the first day (Day 1). Participants then gradually titrated by 1 additional spray per day to an individualized dose, balancing efficacy and tolerability. Participants had to complete titration within 14 days of their first dose of study drug and then continue at the same dose for the remainder of the study.

Interventions

DRUGNabiximols

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Participant had completed the parent study within the last seven days * Willing and able to give written informed consent * Willing and able to comply with all study requirements

Exclusion criteria

* The participant was using cannabis or cannabinoid based medications, other than the parent study investigational medicinal product (IMP), and was unwilling to abstain for the duration of the study * Any history or immediate family history of schizophrenia, other psychotic illness, severe personality disorder or other significant psychiatric disorder other than depression associated with their underlying condition * Any known or suspected history of a substance abuse/dependence disorder (including opiate abuse/dependence prior to the diagnosis of cancer), current heavy alcohol consumption (more than 60 grams \[g\] of pure alcohol per day for men, and more than 40 g of pure alcohol per day for women), current use of an illicit drug or current non-prescribed use of any prescription drug * Had poorly controlled epilepsy or recurrent seizures (for example, one or more seizure during the last year) * 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 at the end of treatment visit of the parent study * 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 3 months thereafter (however, a male condom should not have been used in conjunction with a female condom as this may not have proven effective)

Design outcomes

Primary

Measure	Time frame	Description
Percent Of Participants With Treatment-emergent Adverse Events	Baseline, Day 183	Treatment-emergent Adverse Events (TEAEs) were coded according to the Medical Dictionary for Regulatory Activities (MedDRA) dictionary version 17.0. A TEAE is defined as an adverse event with an onset after the start of study drug treatment. The percent of participants who experienced one or more TEAEs is reported.

Secondary

Measure	Time frame	Description
Change From Baseline In Mean NRS Average Pain During The Last Period	Baseline, Last Period (Days 156-183) or last 27 days of treatment	Participants indicated the level of pain experienced in the last 24 hours on an 11-point Numerical Rating Scale (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: Last Period NRS average pain score - Baseline NRS average pain score. A negative value indicates an improvement in average pain score from Baseline.
Change From Baseline In Mean Sleep Disruption NRS During The Last Period	Baseline, Last Period (Days 156-183) or last 27 days 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: Last Period sleep disruption NRS score - Baseline sleep disruption NRS score. A negative value indicates an improvement in sleep disruption score from Baseline.
Patient Satisfaction Questionnaire At Last Visit (Up To Day 183)	Last Visit (up to Day 183)	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.
Change From Baseline In NRS Constipation At Last Visit (Up To Day 183)	Baseline, Last Visit (up to Day 183)	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 - Baseline NRS constipation score. A negative value indicates improvement in condition from Baseline.

Countries

Australia, Belgium, Bulgaria, Czechia, Germany, Hungary, Israel, Italy, Latvia, Lithuania, Mexico, Poland, Puerto Rico, Romania, Spain, Taiwan, United Kingdom, United States

Participant flow

Recruitment details

Participants enrolled in this study included those who had taken part in studies NCT01262651 (GWCA0958), NCT01361607 (GWCA0962), and NCT01424566 (GWCA1103) and who chose to continue treatment by enrolling in this study, as well as new (de novo) participants who met all inclusion criteria and did not meet any of the exclusion criteria.

Pre-assignment details

For the de novo participants enrolled in this study, a screening visit took place 3 to 14 days prior to enrollment.

Participants by arm

Arm	Count
Nabiximols Nabiximols 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 6 months. Nabiximols oromucosal spray contained THC (27 mg/mL):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.	660
Total	660

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	237
Overall Study	Lost to Follow-up	2
Overall Study	Met Withdrawal Criteria	3
Overall Study	Withdrawal by Investigator	33
Overall Study	Withdrawal by Subject	129

Baseline characteristics

Characteristic	Nabiximols
Age, Continuous	60.2 years STANDARD_DEVIATION 11.1
Sex: Female, Male Female	313 Participants
Sex: Female, Male Male	347 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	291 / 660
serious Total, serious adverse events	301 / 660

Outcome results

Primary

Percent Of Participants With Treatment-emergent Adverse Events

Treatment-emergent Adverse Events (TEAEs) were coded according to the Medical Dictionary for Regulatory Activities (MedDRA) dictionary version 17.0. A TEAE is defined as an adverse event with an onset after the start of study drug treatment. The percent of participants who experienced one or more TEAEs is reported.

Time frame: Baseline, Day 183