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PainPhase 3NCT01262651

Sativex® for Relieving Persistent Pain in Participants With Advanced Cancer

A Phase 3 study testing Nabiximols in people with Pain and Advanced Cancer, run by GW Pharmaceuticals Ltd at 72 sites in 12 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This 9-week study aimed to determine the efficacy, safety and tolerability of nabiximols (Sativex®) as an adjunctive treatment, compared with placebo in relieving uncontrolled persistent chronic pain in participants with advanced cancer. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Pain, Advanced Cancer
What is being tested?
Nabiximols
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
397 participants
Where
72 sitesin 12 countries
Study dates
25 Nov 2010to 2 Jul 2015
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • The participant had advanced cancer for which there was no known curative therapy
  • The participant had a clinical diagnosis of cancer related pain, which was not wholly 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

Who cannot join

  • The participant 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 using or had used cannabis or cannabinoid-based medications within 30 days of study entry and is unwilling to abstain for the duration of the study
  • The participant 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
  • The participant had significantly impaired renal function
  • The participant 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 3 months thereafter (however, a male condom was not to be used in conjunction with a female condom as this may not have proven effective)

Trial locations and contacts

72 sites in 12 countries.

72 sites in 12 countries

United States25 sites

  • Study site

    Berlin, New Jersey, 08009

  • Study site

    Brandon, Florida, 33511

  • Study site

    Daytona Beach, Florida, 32117

  • Study site

    El Cajon, California, 92020

  • Study site

    Gilroy, California, 95020

  • Study site

    Hendersonville, North Carolina, 28739

  • Study site

    Holiday, Florida, 34691

  • Study site

    Houston, Texas, 77024

  • Study site

    Houston, Texas, 77089

  • Study site

    Jacksonville, Florida, 32257

  • Study site

    Kansas City, Missouri, 64132

  • Study site

    Laredo, Texas, 78041

  • Study site

    Lynn Haven, Florida, 32444

  • Study site

    Newnan, Georgia, 30265

  • Study site

    Philadelphia, Pennsylvania, 19146

  • Study site

    Phoenix, Arizona, 85027

  • Study site

    Phoenix, Arizona, 85028

  • Study site

    Saint Louis Park, Minnesota, 55426

  • Study site

    Salt Lake City, Utah, 84112

  • Study site

    Salt Lake City, Utah, 84124

  • Study site

    Shreveport, Louisiana, 71105

  • Study site

    Stockbridge, Georgia, 30281

  • Study site

    Stuart, Florida, 34994

  • Study site

    Winston-Salem, North Carolina, 27103

  • Study site

    Winter Park, Florida, 32789

Other trials in United States

United Kingdom8 sites

  • Study site

    Bury, BL9 7TD

  • Study site

    Bury St Edmunds, IP33 2QZ

  • Study site

    Edinburgh, EH4 2XR

  • Study site

    Glasgow, G12 0YN

  • Study site

    Manchester, M8 5RB

  • Study site

    Norwich, NR4 7UY

  • Study site

    Weston-super-Mare, BS23 4TQ

  • Study site

    Wolverhampton, WV10 0QP

Other trials in United Kingdom

Czechia7 sites

  • Study site

    České Budějovice, 370 01

  • Study site

    České Budějovice, 370 87

  • Study site

    Hradec Králové, 500 05

  • Study site

    Most, 434 64

  • Study site

    Nová Ves pod Pleší, 262 04

  • Study site

    Ostrava-Poruba, 708 52

  • Study site

    Pilsen, 304 60

Other trials in Czechia

Romania7 sites

  • Study site

    Baia Mare, 430031

  • Study site

    Brăila, 810325

  • Study site

    Bucharest, 010976

  • Study site

    Craiova, 200385

  • Study site

    Oradea, 410469

  • Study site

    Satu Mare, 440055

  • Study site

    Suceava, 720237

Other trials in Romania

Hungary6 sites

  • Study site

    Deszk, H-6772

  • Study site

    Kecskemét, H-6000

  • Study site

    Komárom, H-2900

  • Study site

    Miskolc, H-3501

  • Study site

    Nyíregyháza, H-4412

  • Study site

    Szekszárd, H-7100

Other trials in Hungary

Poland5 sites

  • Study site

    Bialystok, 15-250

  • Study site

    Bielsko-Biala, 43-300

  • Study site

    Gliwice, 44-101

  • Study site

    Poznan, 61-245

  • Study site

    Warsaw, 02-781

Other trials in Poland

Bulgaria3 sites

  • Study site

    Gabrovo, 5300

  • Study site

    Shumen, 9700

  • Study site

    Varna, 9010

Other trials in Bulgaria

Germany3 sites

  • Study site

    Lünen, 44534

  • Study site

    Stadtroda, 07646

  • Study site

    Wetzlar, 35578

Other trials in Germany

Lithuania3 sites

  • Study site

    Klaipėda, LT-92288

  • Study site

    Šiauliai, LT-76307

  • Study site

    Vilnius, LT-08660

Other trials in Lithuania

Latvia2 sites

  • Study site

    Rēzekne, LV-4600

  • Study site

    Riga, LV-1079

Other trials in Latvia

Puerto Rico2 sites

  • Study site

    Ponce, 00717

  • Study site

    San Juan, 00927

Other trials in Puerto Rico

Belgium1 site

  • Study site

    Brussels, 1000

Other trials in Belgium

About this study

Official title: 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

This 9-week study aimed to determine the efficacy, safety and tolerability of nabiximols (Sativex®) as an adjunctive treatment, compared with placebo in relieving uncontrolled persistent chronic pain in participants with advanced cancer.

Eligible participants were not required to stop any of their current treatments or medications.

Read the detailed description

This 9-week, multi-center, double-blind, randomized, placebo-controlled study aimed to determine the efficacy, safety and tolerability of nabiximols, administered as an adjunctive treatment for 5 weeks, versus placebo. 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 returned for randomization on Day 1 and were randomized to either the nabiximols or placebo treatment arm using a 1:1 allocation ratio. Participants began an initial titration period that lasted up to 14 days. The titration schedule required dosing to a minimum of 3 sprays per day, after which participants were allowed to individualize their dose (3 to 10 sprays per day) until Day 14 when that dose was then fixed for the remainder of the study. Participants returned at Day 22 and 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, participants were offered the option of entering an open-label extension (OLE) study; a safety follow up visit (up to Day 43) was not required if the participant entered the OLE on Day 36. 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.

Being tested
Nabiximols, Placebo (GA-0034)
Keywords
Cancer pain, Opioid therapy, Inadequate analgesia, Optimized chronic opioid therapy
Medical subject headings
Pain, Cancer Pain

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NabiximolsDrug

    Also called Sativex®

  • Placebo (GA-0034)Drug

Study groups in NCT01262651
Study groupRoleWhat they receive
NabiximolsExperimentalNabiximols 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 5 weeks. Nabiximols oromucosal spray contained delta-9-tetrahydrocannabinol (THC) (27 milligram [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.
Receives: Drug: Nabiximols
Placebo (GA-0034)Placebo comparatorPlacebo 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)
Receives: Drug: Placebo (GA-0034)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percent Improvement From Baseline In Mean NRS Average Pain At End Of Treatment

    Participants indicated level of pain in the last 24 hours on an 11-point Numerical Rating Scale (NRS), where a score of 0 was "no pain" and 10 was "pain as bad as you can imagine". Baseline = mean score from first day of 3-day eligibility period through to the day before first dose of study drug. End of Treatment = mean score over last (up to) 7 days to the final pain score at End of Treatment or up until Day 35, whichever is earlier, or final score available (prematurely terminated).

    Percentage improvement from baseline (Imp%) was calculated as:

    Imp% = (Baseline pain NRS mean - End of Treatment pain NRS mean)/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 (no diary data from Day 33 onwards), Imp% was zero for participants whose Imp% value was positive and it was Imp% for participants whose Imp% value was not positive.

    Measured: Baseline, End of Treatment (Day 36)

Secondary outcomes (10)

  1. Change From 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 - Baseline NRS average pain score.

    A negative value indicates an improvement in average pain score from Baseline.

    Measured: Baseline, End Of Treatment (Day 36)

  2. Change From 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 - Baseline NRS worst pain score.

    A negative value indicates an improvement in worst pain score from Baseline.

    Measured: Baseline, End of Treatment (Day 36)

  3. Change From 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 - Baseline sleep disruption NRS score.

    A negative value indicates an improvement in sleep disruption score from Baseline.

    Measured: Baseline, End of Treatment (Day 36)

  4. Subject Global Impression Of Change At Last Visit (Up To Day 36)

    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 or 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.

    Measured: Last Visit (up to Day 36)

  5. Physician Global Impression Of Change At Last Visit (Up To Day 36)

    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.

    Measured: Last Visit (up to Day 36)

  6. Patient Satisfaction Questionnaire At Last Visit (Up To Day 36)

    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.

    Measured: Last Visit (up to Day 36)

  7. Change From 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 equivalents of daily maintenance dose and break-through dose.

    Change in daily total opioid use was calculated as: End of Treatment daily total opioid use - Baseline daily total opioid use.

    A negative value indicates a decrease in use from Baseline.

    Measured: Baseline, End of Treatment (Day 36)

  8. Change From 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 - Baseline daily maintenance opioid dose.

    A negative value indicates a decrease in dose from Baseline.

    Measured: Baseline, End of Treatment (Day 36)

  9. Change From 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 equivalents 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 - Baseline daily break-through opioid dose.

    A negative value indicates a decrease in dose from Baseline.

    Measured: Baseline, End of Treatment (Day 36)

  10. Change From Baseline In NRS Constipation At Last Visit (Up To Day 36)

    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; this could be either Day 22 or Day 36.

    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.

    Measured: Baseline, Last Visit (up to Day 36)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Dec 2010 (estimated)
  2. Study start25 Nov 2010
  3. Primary completion2 Jul 2015
  4. Study completion2 Jul 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
397 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01262651
Sponsor's protocol ID
GWCA0958
Other IDs
2009-016064-36, 2009
Status last verified
Mar 2018
First submitted
16 Dec 2010
Last updated
23 Apr 2018
Data monitoring committee
Yes

Publications

  • Lichtman AH, Lux EA, McQuade R, Rossetti S, Sanchez R, Sun W, Wright S, Kornyeyeva E, Fallon MT. Results of a Double-Blind, Randomized, Placebo-Controlled Study of Nabiximols Oromucosal Spray as an Adjunctive Therapy in Advanced Cancer Patients with Chronic Uncontrolled Pain. J Pain Symptom Manage. 2018 Feb;55(2):179-188.e1. doi: 10.1016/j.jpainsymman.2017.09.001. Epub 2017 Sep 18.

    PubMed 28923526

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Nabiximols in people with Pain and Advanced Cancer, run by GW Pharmaceuticals Ltd at 72 sites in 12 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 72 sites in United States, United Kingdom, Czechia, Romania, Hungary and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Apr 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percent Improvement From Baseline In Mean NRS Average Pain At End Of Treatment (time frame: Baseline, End of Treatment (Day 36)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01262651, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Apr 2018.

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