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Prospective, double-blind, placebo-controlled, randomized, multi-center study with an open-label lead-in tolerability period and an open-label extension period to investigate the efficacy and safety of NT 201 in the treatment of post-stroke spasticity of the lower limb

J-PLUS; Japan- Post-stroke spasticity of the Lower limb study on efficacy and Safety of NT 201

219

Lead-in tolerability period (LITP): 11 subjects, mean age 48.7 years. Main period (MP): 208 subjects, mean age 59.2 years. Open-label extension (OLEX) period: 202 subjects, mean age 58.7 years.

11 subjects were enrolled in LITP. 208 subjects in the MP (104 in the 400 U NT 201 group, 104 in the placebo group). 202 subjects who completed the LITP or MP were enrolled in the OLEX period.

Incidence rate of adverse events (AEs) was 72.7% in LITP, 48.1% and 49.0% (NT 201 vs. placebo) in the MP, and 64.9% in the OLEX period. The non-serious event Nasopharyngitis was the most frequently reported AE with 36.4% in the LITP, 18.3% and 13.5% in the MP (NT 201 vs. placebo), and 18.3% in the OLEX period.

Area under the curve (AUC) of the change from baseline in the modified Ashworth scale (MAS) plantar flexors score to the end of the MP (week 12): The LS mean difference between NT 201 versus placebo was statistically significant.

Change from baseline in MAS plantar flexors score to Weeks 4, 6, and 8: The LS mean differences were statistically significant at all these time points. The 1-point response rates in MAS plantar flexors score from baseline at Weeks 4, 6, and 8: The difference between the treatment groups was statistically significant at Weeks 6 and 8.

The study confirmed efficacy of NT 201 for lower limb spasticity. NT 201 (400 U) significantly improved the poststroke spasticity of lower limb as measured using AUC of changes in MAS score after a single injection over a period of 12 weeks. The study also confirmed the favorable safety and tolerability profile of NT 201 400 U in spasticity patients. No new or unexpected safety concerns were identified.

Dec. 15, 2018

https://www.sciencedirect.com/science/article/pii/S004101011830850X

No

Merz Pharmaceuticals GmbH

Clinicaltrials@Merz.de

Teijin Pharma Limited

clintrials@teijin.co.jp

completed

Nov. 24, 2015

Interventional

Prospective, double-blind, placebo-controlled, randomized

treatment purpose

3

-Female or male subjects from 20 to 80 (inclusive) years of age (less than 65 years during lead-in tolerability period).
-Body weight at least 50 kg.
-Unilateral lower-limb spasticity presenting with equinus foot deformity (condition of plantar flexion at the ankle joint) caused by a stroke at least 6 months before respective screening visit.
-Botulinum toxin-naive or pretreated patients with post-stroke spasticity of the LL (for pretreated subjects the last Botulinum toxin treatment must have been at least 16 weeks before the respective screening visit.
-Modified Ashworth Scale (MAS) score of plantar flexors at least 3.
-Spasticity is present in the clinical pattern pes equinus that contributes to the subject's gait impairment.

-Fixed contracture or other muscle hypertonia in the affected joint(s) intended to be treated.
-Bilateral lower-limb paresis, paralysis or tetraparesis.
-Surgery in the target limb for any indication within the 8 weeks before screening or within the screening period.
-Any previous and planned surgical treatment for spasticity in the target muscle(s).
-Severe atrophy of the target limb muscles.
-Any previous or planned treatment with phenol- or alcohol-injection into the target limb, as well as any planned treatment with phenol- or alcohol-injection in any body region scheduled for any time during the study.
-Treatment with parenterally administered drugs that interfere with neuromuscular transmission, aminoquinolines, or local anesthetics in the treated region within the two weeks before screening, within the screening period, and/or intended to be administered during the study.
-Antispastic medication with peripheral muscle relaxants administered within the two weeks before screening, within the screening period, or intended to be administered during the study.

Both

Post-stroke spasticity of the lower-limb

investigational material(s)
Generic name etc : NT 201
INN of investigational material : incobotulinumtoxinA
Therapeutic category code : 122 Skeletal muscle relaxants
Dosage and Administration for Investigational material : 400 U, intramuscular

control material(s)
Generic name etc : Placebo
INN of investigational material : -
Therapeutic category code : --- Other
Dosage and Administration for Investigational material : -

safety
efficacy
Area Under the Curve [AUC] of the change from baseline in Modified Ashworth Scale (MAS) of plantar flexors score to the end of the Main Period
From Baseline to week 12

safety
efficacy
Change from baseline in MAS plantar flexors score to Week 4
From Baseline to week 4

July. 22, 2015