A Parallel Group Study to Compare Sativex® With Placebo in the Treatment of Detrusor Overactivity in Patients With Multiple Sclerosis

NCT00678795 | Completed Phase 3 Results

• 1 other identifier: GWMS0208
• Study Type: interventional
• Target: 135
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Detrusor Overactivity; Multiple Sclerosis

Keywords

Detrusor overactivity; Multiple Sclerosis

Outcome Measures

Primary Outcomes (1)

• 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.

  0 - 10 weeks

Secondary Outcomes (7)

• Change From Baseline in the Mean Daily Episodes of Urgency at the End of Treatment

  Daily diary entries throughout 10 week study period

• Change From Baseline in the Mean Daily Episodes of Nocturia at the End of Treatment

  0 - 10 weeks

• Change From Baseline in the Mean Daily Number of Incontinence Pads Used at the End of Treatment

  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)

  0 - 10 weeks

• Change From Baseline in Mean Overall Bladder Condition 0-10 Numerical Rating Scale Score at the End of Treatment

  0 - 10 weeks

Study Arms (2)

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.

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.

Drug: Placebo

Interventions

Sativex® DRUG

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

Also known as: GW-10000-02

Sativex

Placebo DRUG

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.

Also known as: GW-4001-01

Placebo

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Jazz Pharmaceuticals: lead

Study Sites (1)

Division of Clinical Neurology, Queen's Medical Centre

Nottingham, Notts, NG7 2UH, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 20829244 RESULT

MeSH Terms

Conditions

Urinary Bladder, Overactive; Multiple Sclerosis

Interventions

nabiximols

Condition Hierarchy (Ancestors)

Urinary Bladder Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Mr Richard Potts, Clinical Operations Director
• Organization: GW Pharma Ltd.

rp@gwpharm.com

0044 1223 266800

Study Officials

• Cris Constantinescu, MD PhD

  Division of Clinical Neurology, Queen's Medical Centre

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: May 14, 2008
• First Posted: May 16, 2008
• Study Start: August 1, 2002
• Primary Completion: October 1, 2005
• Study Completion: October 1, 2005
• Last Updated: May 3, 2023
• Results First Posted: September 21, 2012

Record last verified: 2023-04

Locations

GB (1)