Detrusor OveractivityPhase 3NCT00678795
A Parallel Group Study to Compare Sativex® With Placebo in the Treatment of Detrusor Overactivity in Patients With Multiple Sclerosis
A Phase 3 study testing Sativex® in people with Detrusor Overactivity and Multiple Sclerosis, run by Jazz Pharmaceuticals at 1 site in United Kingdom.
Trial summary
The purpose of this study is to evaluate the efficacy of Sativex® compared with placebo in reducing the daily number of episodes on incontinence. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Detrusor Overactivity, Multiple Sclerosis
- What is being tested?
- Sativex®
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 135 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Aug 2002to Oct 2005
- 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
- Willing and able to give informed consent.
- Male or female, aged 18 years or over.
- Diagnosed with MS and with detrusor overactivity not wholly relieved by current therapy.
- At least three incontinence episodes within five consecutive days during the baseline period
- Stable dose of anticholinergic medication for at least 14 days leading to study entry.
- Agreement, if female and of child bearing potential or if male with a partner of child bearing potential, to ensure that effective contraception is used during the study and for three months thereafter.
- Has not used cannabinoids (including cannabis, Marinol® or nabilone) for at least seven days before Visit 1 and willing to abstain from any use of cannabinoids during the study.
- Agreement for the UK Home Office, their general practitioner, and their consultant if appropriate, to be notified of their participation in the study.
Who cannot join
- A symptomatic UTI or any cause of detrusor overactivity other than neurogenic causes due to MS.
- Using ISC.
- A history of schizophrenia, other psychotic illness, severe personality disorder or other significant psychiatric disorder other than depression associated with their underlying condition.
- A history of alcohol or substance abuse.
- A severe cardiovascular disorder, such as ischaemic heart disease, arrhythmias (other than well controlled atrial fibrillation), poorly controlled hypertension or severe heart failure.
- A history of epilepsy.
Show all 16Show fewer
- If female, are pregnant of lactating, or are planning a pregnancy to occur during the course of the study.
- Significant renal or hepatic impairment.
- Elective surgery or other procedures requiring general anesthesia scheduled to occur during the study.
- Terminal illness or any other significant disease or disorder which, in the opinion of the investigator, may either put the subject at risk because of participation in the study or influence the result of the study, or the subjects ability to participate in the study.
- Regular levodopa (Sinement®, Sinement Plus®, Levodopa, L-dopa, Madopar®, Benserazide) within the seven days leading up to study entry.
- Receiving and unwilling to stop fentanyl for the duration of the study.
- Known or suspected hypersensitivity to cannabinoids or any of the excipients of the study medications.
- Intention to travel internationally or to donate blood during the study.
- Participation in another research study in the 12 weeks leading up to study entry.
- Previous randomization in to this study
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Division of Clinical Neurology, Queen's Medical Centre
Nottingham, Notts, NG7 2UH
About this study
Official title: A Double Blind, Randomised, Placebo Controlled, Parallel Group Study of Cannabis Based Medicine (CBM) Extract, in Patients Suffering Detrusor Overactivity Associated With Multiple Sclerosis.
The purpose of this study is to evaluate the efficacy of Sativex® compared with placebo in reducing the daily number of episodes on incontinence.
Read the detailed description
This is a ten week, multicentre, double blind, randomised, placebo controlled parallel group study to evaluate the efficacy of Sativex® on urge incontinence associated with neurogenic unstable bladder. Multiple sclerosis patients with incontinence symptoms are screened to determine eligibility and complete a two-week baseline period. They then return for a further eligibility check, randomisation and initial dosing. Subjects titrate and self-medicate with study medication between study visits at weeks two and five. They will also complete efficacy assessments in their diary-books and at visits.
- Conditions
- Detrusor Overactivity, Multiple Sclerosis
- Being tested
- Sativex®, Placebo
- Keywords
- Detrusor overactivity, Multiple Sclerosis
- Medical subject headings
- Urinary Bladder, Overactive, Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sativex®Drug
Also called GW-10000-02
Containing ∆9 tetrahydrocannabinol (THC), 27 mg/ml and cannabidiol (CBD), 25 mg/ml as extract of Cannabis sativa L.
Subjects received study medication delivered in 100 µl actuations by a pump action oromucosal spray. Maximum permitted dose was eight actuations in any three-hour period and 48 actuations (THC 130 mg:CBD 120 mg) in 24 hours
PlaceboDrug
Also called GW-4001-01
containing excipients only. Subjects received study medication delivered in 100 µl actuations from a pump action oromucosal spray. Maximum permitted dose was eight actuations in any three-hour period and 48 actuations in 24 hours.
| Study group | Role | What they receive |
|---|---|---|
| Sativex | Experimental | Each 100 ul actuation contains 27 mg delta-9-tetrahydrocannabinol (THC) and 25 mg cannabidiol (CBD). A maximum of 48 actuations (130 mg of THC and 120 mg of CBD) was permitted in any 24 hour period. Receives: Drug: Sativex® |
| Placebo | Placebo comparator | Each 100 ul actuation contains the colorants plus excipients. A maximum of 48 actuations was permitted in any 24 hour period. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in the Mean Daily Number of Incontinence Episodes at the End of Treatment
To assess the effect of Sativex in neurogenic overactive bladder, the incontinence episode frequency was selected as the primary endpoint. Baseline was the average of all available data recorded during the 14 days immediately prior to the randomisation visit. End of Treatment was the last average available from Week 3, Week 5, and Weeks 7-8. A negative value indicates an improvement in score from baseline.
Measured: 0 - 10 weeks
Secondary outcomes (7)
Change From Baseline in the Mean Daily Episodes of Urgency at the End of Treatment
Subjects documented in the daily subject diary each instance of urgency, and the time that each took place, as for the recording of incontinence episode frequency. Baseline was the average of all available data recorded during the 14 days immediately prior to the randomisation visit. End of Treatment was the last average available from Week 3, Week 5, and Weeks 7-8. A negative value indicates an improvement in score from baseline.
Measured: Daily diary entries throughout 10 week study period
Change From Baseline in the Mean Daily Episodes of Nocturia at the End of Treatment
Subjects documented in the daily subject diary each instance of nocturia, and the time that each took place (as for the recording of incontinence episode frequency). Baseline was the average of all available data recorded during the 14 days immediately prior to the randomisation visit. End of Treatment was the last average available from Week 3, Week 5, and Weeks 7-8. A negative value indicates an improvement in score from baseline.
Measured: 0 - 10 weeks
Change From Baseline in the Mean Daily Number of Incontinence Pads Used at the End of Treatment
Subjects documented in the daily subject diary, the total number of incontinence pads they had used each day. Baseline was the average of all available data recorded during the 14 days immediately prior to the randomisation visit. End of Treatment was the last average available from Week 3, Week 5, and Weeks 7-8. A negative value indicates an improvement in score from baseline.
Measured: 0 - 10 weeks
Change From Baseline in Mean Total Incontinence Quality of Life (I-QOL) Questionnaire Score at the End of Treatment (Completion or Withdrawal)
The I-QOL consists of 22 items from three subscales; avoidance/limiting behaviour (eight items), psychosocial impact (nine items) and social embarrassment (five items). The responses to each of the 22 items were summed and averaged for a total score and then transformed to a 0-100 scale for ease of interpretation. The transformation formula used for the I-QOL total scores is: Transformed score = 100 x (the sum of the items - lowest possible score) / Possible raw score range. An increase in score indicates an improvement in QOL.
Measured: 0 - 10 weeks
Change From Baseline in Mean Overall Bladder Condition 0-10 Numerical Rating Scale Score at the End of Treatment
Subjects subjectively assessed the severity of their urinary incontinence and general bladder symptoms by responding to the following question on a Numerical Rating Scale: My bladder condition, taking everything into account, causes me: 0 = "no problems" and 10 = "intolerable problems". Baseline was the average of all available data recorded during the 14 days immediately prior to the randomisation visit. End of Treatment was the last average available from Week 3, Week 5, and Weeks 7-8. A negative value indicates an improvement in score from baseline.
Measured: 0 - 10 weeks
Patient's Global Impression of Change
Subjects were asked at completion or withdrawal to give their impression of the overall change in their condition since entry into the study using the following seven-point scale: 1 = 'Very Much Improved', 2 = 'Much Improved', 3 = 'Minimally Improved', 4 = 'No Change', 5 = 'Minimally Worse', 6 = 'Much Worse', 7 = 'Very Much Worse'. The numbers who scored 1, 2, or 3 are presented.
Measured: 0 - 10 weeks
Change From Baseline in the Mean Number of Daily Voids at the End of Treatment
Baseline was the average of all available data recorded during the 14 days immediately prior to the randomisation visit. End of Treatment was the last average available from Week 3, Week 5, and Weeks 7-8. A negative value indicates an improvement in score from baseline.
Measured: 0 - 10 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2008 (estimated)
- Study startAug 2002
- Primary completionOct 2005
- Study completionOct 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Detrusor OveractivityStudies of the same condition, open and under way.
- More trials run by Jazz PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 135 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jazz Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Cris Constantinescu, MD PhD, Principal investigator, Division of Clinical Neurology, Queen's Medical Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00678795
- Sponsor's protocol ID
- GWMS0208
- Status last verified
- Apr 2023
- First submitted
- 14 May 2008
- Last updated
- 3 May 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Kavia RB, De Ridder D, Constantinescu CS, Stott CG, Fowler CJ. Randomized controlled trial of Sativex to treat detrusor overactivity in multiple sclerosis. Mult Scler. 2010 Nov;16(11):1349-59. doi: 10.1177/1352458510378020. Epub 2010 Sep 9.
PubMed 20829244
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double Blind, Randomised, Placebo Controlled, Parallel Group Study of Cannabis Based Medicine (CBM) Extract, in Patients Suffering Detrusor Overactivity Associated With Multiple Sclerosis.
- ClinicalTrials.gov ID
- NCT00678795
- Acronym / sponsor ID
- GWMS0208
- Conditions
- Detrusor Overactivity, Multiple Sclerosis
- Keywords
- Detrusor overactivity, Multiple Sclerosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 135 participants (actual)
- Lead sponsor
- Jazz PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Aug 2002
- Primary completion
- Oct 2005 (actual)
- Study completion
- Oct 2005 (actual)
- First posted
- 16 May 2008 (estimated)
- Results
- Posted 21 Sep 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the efficacy of Sativex® compared with placebo in reducing the daily number of episodes on incontinence.
Detailed description
This is a ten week, multicentre, double blind, randomised, placebo controlled parallel group study to evaluate the efficacy of Sativex® on urge incontinence associated with neurogenic unstable bladder. Multiple sclerosis patients with incontinence symptoms are screened to determine eligibility and complete a two-week baseline period. They then return for a further eligibility check, randomisation and initial dosing. Subjects titrate and self-medicate with study medication between study visits at weeks two and five. They will also complete efficacy assessments in their diary-books and at visits.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sativex | Experimental | Drug: Sativex®Each 100 ul actuation contains 27 mg delta-9-tetrahydrocannabinol (THC) and 25 mg cannabidiol (CBD). A maximum of 48 actuations (130 mg of THC and 120 mg of CBD) was permitted in any 24 hour period. |
| Placebo | Placebo comparator | Drug: PlaceboEach 100 ul actuation contains the colorants plus excipients. A maximum of 48 actuations was permitted in any 24 hour period. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Willing and able to give informed consent.
- Male or female, aged 18 years or over.
- Diagnosed with MS and with detrusor overactivity not wholly relieved by current therapy.
- At least three incontinence episodes within five consecutive days during the baseline period
- Stable dose of anticholinergic medication for at least 14 days leading to study entry.
Key exclusion criteria (16 listed)
- A symptomatic UTI or any cause of detrusor overactivity other than neurogenic causes due to MS.
- Using ISC.
- A history of schizophrenia, other psychotic illness, severe personality disorder or other significant psychiatric disorder other than depression associated with their underlying condition.
- A history of alcohol or substance abuse.
- A severe cardiovascular disorder, such as ischaemic heart disease, arrhythmias (other than well controlled atrial fibrillation), poorly controlled hypertension or severe heart failure.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sativex®Also: GW-10000-02Containing ∆9 tetrahydrocannabinol (THC), 27 mg/ml and cannabidiol (CBD), 25 mg/ml as extract of Cannabis sativa L. Subjects received study medication delivered in 100 µl actuations by a pump action oromucosal spray. Maximum permitted dose was eight actuations in any three-hour period and 48 actuations (THC 130 mg:CBD 120 mg) in 24 hours | Drug | Sativex |
| PlaceboAlso: GW-4001-01containing excipients only. Subjects received study medication delivered in 100 µl actuations from a pump action oromucosal spray. Maximum permitted dose was eight actuations in any three-hour period and 48 actuations in 24 hours. | Drug | Placebo |
Primary outcome
Change From Baseline in the Mean Daily Number of Incontinence Episodes at the End of Treatment
Time frame: 0 - 10 weeks
To assess the effect of Sativex in neurogenic overactive bladder, the incontinence episode frequency was selected as the primary endpoint. Baseline was the average of all available data recorded during the 14 days immediately prior to the randomisation visit. End of Treatment was the last average available from Week 3, Week 5, and Weeks 7-8. A negative value indicates an improvement in score from baseline.
7 secondary outcomes
Change From Baseline in the Mean Daily Episodes of Urgency at the End of Treatment
Time frame: Daily diary entries throughout 10 week study period
Change From Baseline in the Mean Daily Episodes of Nocturia at the End of Treatment
Time frame: 0 - 10 weeks
Change From Baseline in the Mean Daily Number of Incontinence Pads Used at the End of Treatment
Time frame: 0 - 10 weeks
Change From Baseline in Mean Total Incontinence Quality of Life (I-QOL) Questionnaire Score at the End of Treatment (Completion or Withdrawal)
Time frame: 0 - 10 weeks
Change From Baseline in Mean Overall Bladder Condition 0-10 Numerical Rating Scale Score at the End of Treatment
Time frame: 0 - 10 weeks
Patient's Global Impression of Change
Time frame: 0 - 10 weeks
Change From Baseline in the Mean Number of Daily Voids at the End of Treatment
Time frame: 0 - 10 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 May 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 20829244Kavia RB, De Ridder D, Constantinescu CS, Stott CG, Fowler CJ. Randomized controlled trial of Sativex to treat detrusor overactivity in multiple sclerosis. Mult Scler. 2010 Nov;16(11):1349-59. doi: 10.1177/1352458510378020. Epub 2010 Sep 9.
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Neurogenic Detrusor Overactivity, Spinal Cord Injuries
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TTNS in SCI Patients With Neurogenic Detrusor Overactivity
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Cris Constantinescu, MD PhD principal investigator
Division of Clinical Neurology, Queen's Medical Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Sativex® in people with Detrusor Overactivity and Multiple Sclerosis, run by Jazz Pharmaceuticals at 1 site in United Kingdom.
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 8 inclusion and 16 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 3 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. 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 21 Sep 2012). 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?
Change From Baseline in the Mean Daily Number of Incontinence Episodes at the End of Treatment (time frame: 0 - 10 weeks). 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 NCT00678795, 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 3 May 2023.