Phase 3, 28-week, Randomized, Double-blind, Placebo-controlled Safety and Efficacy Study of Nabiximols as an add-on Therapy in Subjects With Spasticity Due to Multiple Sclerosis.

Jazz Pharmaceuticals

Status and phase: Withdrawn; Phase 3

Conditions: Spasticity; Multiple Sclerosis

Treatments: Drug: Placebo; Drug: Sativex

Study type: Interventional

Funder types: Industry

Identifiers

NCT01868048

GWMS1315

Details and patient eligibility

About

The purpose of this study is to determine the effective dose range and to demonstrate a non-effective dose range of Sativex compared with placebo in relieving symptoms of spasticity due to multiple sclerosis.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Willing and able to give written informed consent.
• The subject is at least 18 years of age or older.
• Diagnosed with any disease sub-type of multiple sclerosis of at least six months duration.
• Spasticity due to multiple sclerosis of at least six months duration, which is not wholly relieved with current anti-spasticity therapy, and which is expected to remain stable for the duration of the study.
• Subject must be receiving at least one of the following anti-spasticity therapies to be eligible: Baclofen, Tizanidine, Clonazepam, Diazepam, Dantrolene.
• Subject is willing to maintain anti-spasticity medication at a stable dose for the duration of the study and should be stable for 30 days prior to screening.
• If the subject is currently taking disease-modifying medication, this must be at a stable dose for at least three months prior to the screening visit; the dose must also remain stable for the duration of the study.

Exclusion criteria

• Has previously used Nabiximols or Sativex.
• The subject is currently using or has used cannabis or cannabinoid based medications within 30 days of study entry and is 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.
• In the opinion of the Investigator, any known or suspected history of a substance abuse disorder (including opiate abuse), current heavy alcohol consumption (more than 60g of pure alcohol per day for men, and more than 40g of pure alcohol per day for women), current use of an illicit drug or current non prescribed use of any prescription drug that should exclude the subject from participation.
• Has poorly controlled epilepsy or recurrent seizures (i.e. one or more seizure during the last year).
• Any known or suspected hypersensitivity to cannabinoids or any of the excipients of the study medication.
• Has experienced myocardial infarction or clinically significant cardiac dysfunction within the last 12 months or has a cardiac disorder that, in the opinion of the investigator would put the subject at risk of a clinically significant arrhythmia or myocardial infarction.
• Has significantly impaired renal function as evidenced by a creatinine clearance lower than 50mL/min at Visit 1.
• Has significantly impaired hepatic function at Visit 1 (Alanine Aminotransferase >5 times upper limit of normal (ULN) or bilirubin (TBL) > 2 times ULN). If the Alanine Aminotransferase or Aspartate Aminotransferase >3 times ULN and the TBL >2 times ULN (or International Normalized Ratio >1.5), this subject should not enter the study.
• Female subject of child-bearing potential and male subject whose partner is of child-bearing potential, unless willing to ensure that they or their partner use effective contraception or complete abstinence, for example, oral contraception, double barrier or intra-uterine device, during the study and for three months thereafter (however, a male condom should not be used in conjunction with a female condom as this may not prove effective).
• Female subject who is pregnant, lactating or planning pregnancy during the course of the study and for three months thereafter.
• Subjects who have received a non-approved investigational medicinal product within 30 days of Visit 1.
• Any other significant disease or disorder which, in the opinion of the investigator or sponsor, may either put the subject at risk because of participation in the study, or may influence the result of the study, or the subject's ability to participate in the study.
• Travel outside the country of residence planned during the study.
• Subjects previously enrolled into this study.

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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0 participants in 2 patient groups, including a placebo group

Sativex

Experimental group

Description:

Contains delta -9 tetrahydrocannabinol (THC), 27 mg/mL:cannabidiol (CBD), 25 mg/mL, in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring. Subjects received study medication delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose is 10 actuations per day. Each actuation delivers THC 2.7 mg and CBD 2.5 mg.

Treatment:

Drug: Sativex

Placebo

Placebo Comparator group

Description:

Oromucosal spray, containing no active drug but ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring and colorants. Maximum permitted dose is 10 actuations per day.

Treatment:

Drug: Placebo