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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 two different doses of NT 201 in the treatment of post-stroke spasticity of the upper limb.

J-PURE; Japan- Post-stroke spasticity of the Upper limb study on Efficacy and Safety of NT 201

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Lead-in tolerability period (LITP): 11 subjects, mean age 52.4 years. Main period (MP): 100 subjects, mean age 59.7 years. Open-label extension (OLEX) period: 100 subjects, mean age 58.5 years.

11 subjects were enrolled in the LITP, 100 subjects in the MP (44 in the high-dose [400 U] NT 201 group, 22 in the high-dose placebo group; 23 in the low dose [250 U] NT 201 group, 11 in the low dose placebo group). 100 subjects who completed the LITP or MP were enrolled in the OLEX period.

Incidence rate of adverse events (AEs) was 45.5% in LITP, 47.8% and 36.4% in the MP (NT 201 arms vs. placebo), and 65% in the OLEX period. 7 serious AEs occurred during the entire study (1 in the placebo group of the MP). None of these were assessed as related to injection of study drug. . The non-serious event Nasopharyngitis was the most frequently reported AE with 27.3% in the LITP, 17.9% and 6.1% in the MP (NT 201 arms vs. placebo arms), and 14.0% in the OLEX period.

Area under the curve (AUC) of the change from baseline in the modified Ashworth scale (MAS) wrist score to the end of the MP (week 12): Mean AUC was 13.09 for high dose NT 201, 5.65 for high dose placebo, 11.27 for low dose NT 201 and 3.86 for low dose placebo. Both the LS mean difference between high dose NT 201 versus high-dose placebo as well as between low dose NT 201 versus low dose placebo were statistically significant.

Change from baseline in MAS wrist score to Week 4: Mean change in the MAS wrist score from baseline to Week 4 was 1.35 for high dose NT 201, 0.52 for high dose placebo, 1.11 for low dose NT 201, and 0.27 for low dose placebo.

The study confirmed efficacy of NT 201 for upper limb spasticity. Both high (400 U) and low (250 U) doses of NT 201 significantly improved the poststroke spasticity of upper 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 Pharmaceutical GmbH

Clinicaltrials@Merz.de

Teijin Pharma Limited

clintrials@teijin.co.jp

completed

Nov. 18, 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 40 kg.
-Unilateral upper-limb spasticity of wrist and fingers caused by a stroke at least 6 months before respective screening visit.
-Botulinum toxin-naïve or pretreated subjects with post-stroke spasticity of the upper limb. For pretreated subjects the last Botulinum toxin treatment must have been at least 16 weeks before the respective screening visit.
-Wrist flexor muscle tone is ≥ 3 and finger flexor muscle tone of at least 2 on the Modified Asworth Scale (MAS).
-At least one functional disability domain with a rating of at least 2 on the Disability Assessment Scale (DAS).

-Fixed contracture or other muscle hypertonia in the affected joint(s) intended to be treated.
-Bilateral upper-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 upper-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 wrist score to the end of the Main Period
From Baseline to week 12

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

July. 22, 2015