SATIVEX® AS ADD-ON THERAPY VS. FURTHER OPTIMIZED FIRST-LINE ANTISPASTICS

Phase 1

• Conditions: Moderate to severe spasticity due to MS (multiple sclerosis).; MedDRA version: 19.0Level: HLTClassification code 10052785Term: Multiple sclerosis acute and progressiveSystem Organ Class: 100000004852; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2015-004451-40-AT
• Lead Sponsor: Almirall Hermal GmbH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-01-14
• Last Update Posted: 3 April 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 228

Inclusion Criteria

1.Male or female patients of at least 18 years of age.
2.Diagnosis of MS (any form) for at least 12 months.
3.If the patient is taking disease modifying medication or antispastic drugs other than oral baclofen, tizanidine or dantrolene, this must be at a stable dose for 3 months prior to the screening visit.
4.Moderate to severe spasticity, defined as a score of 4 or more on the MS spasticity 0-10 NRS scale as scored by the patient at the screening visit (considering the previous week), despite optimized previous and current treatment.
5.Existing MS spasticity symptoms for at least 12 months.
6.Eligible for treatment with Sativex according to the current SPC.
7.Previous treatment with at least 2 different optimized oral MS spasticity therapies before inclusion, which must include at least 1 of oral baclofen or oral tizanidine (mono- or combination therapy).
8.Currently receiving optimized treatment with at least 1 oral antispastic drug (baclofen and/or tizanidine and/or dantrolene as mono- or combination therapy), that has been stable for at least 3 months prior to the screening visit. Despite optimization, the patient does not have adequate relief of spasticity symptoms. Optimization is defined as having reached the most efficacious and best tolerated dose according to the relevant SPCs. The treating physician and the patient must confirm that the current treatment has been optimized.
9.Able (physical ability or supportive person) to comply with the study preparations correctly and to follow the study procedure and restrictions.
10.Written informed consent.
Additional inclusion criterion for treatment in Phase A (at Visit 2):
11.Moderate to severe spasticity, defined as a mean score of 4 or more on the MS spasticity 0-10 NRS scale as scored by the patient on the day of Visit 2 and recorded in the patient diary for the 6 previous days (i.e. considering the patient’s spasticity over the previous week during the screening period).
Additional inclusion criteria for continuation into the wash-out phase (at Visit 3):
12.Sativex responder during Phase A, i.e. spasticity symptoms reduced during Phase A by at least 20% on the MS spasticity 0-10 NRS score compared to the Phase A baseline score (i.e., mean of scores at Visit 2 and the 6 previous days).
13.Patient received Sativex treatment during Phase A according to the SPC as add-on to optimized standard therapy, and can tolerate the treatment.
Additional inclusion criterion for randomization in Phase B (at Visit 4):
14.After the 1 to 4 weeks wash-out phase, patients whose Phase A-improvement in MS spasticity NRS score has been reduced by at least 80% (i.e., mean of scores at Visit 4 and the 2 consecutive previous days).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 180
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 48

Exclusion Criteria

1.Contraindication to treatment with Sativex (according to the SPC).
2.Previous administration of Sativex.
3.Current consumption of cannabis herb or taking other cannabinoid-based drugs within 30 days prior to study entry, and/or unwillingness to avoid consumption over the study period.
4.Treatment with botulinum toxin injection for the relief of spasticity from within 6 months prior to the screening visit.
5.Any medical history or family history of schizophrenia, other psychotic disorders, severe personality disorder or other significant psychiatric disorder other than depression, which is associated with the underlying disease MS.
6.Current use of illegal drugs, non-prescribed, or off-label prescription drugs. A qualitative urine test for TCH will be performed at screening and after wash-out.
7.Any known or suspected history of a dependence disorder or current heavy alcohol consumption in the opinion of the investigator, and according to local guidelines.
8.Any known or suspected hypersensitivity to cannabinoids or any of the excipients of the involved IMPs.
9.Any concomitant disease or disorder (such as poorly controlled epilepsy or seizures) that may influence the patient’s level of cognition or mood.
10.Female patients of child bearing potential and male patients whose partner is of child bearing potential, unless willing to ensure that they or their partner use effective contraception during the study and for 3 months thereafter. A female is considered to be of childbearing potential unless she has had a hysterectomy, is at least 1 year post-menopausal or has undergone tubal ligation.
11.Female patient who is pregnant, lactating or planning pregnancy during the course of the study and for 3 months thereafter.
12.Concurrent participation in another clinical study or participation in another clinical study within 12 weeks prior to the screening visit.
13.History of myocardial infarction or clinically significant cardiac dysfunction within the last 12 months, or has a cardiac disorder which, in the opinion of the investigator, would put the patient at risk of a clinically significant arrhythmia or myocardial infarction.
14.Has known clinically significant impaired renal function or impaired hepatic function at baseline.
15.Any other significant disease or disorder which, in the opinion of the investigator, may either put the patient at risk because of participation in the study, may influence the result of the study, or the patient’s ability to participate in the study.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified