A Comparative Study to Evaluate the Effects and Mechanism of Action of Dysport®, Botox® and Xeomin® in the Extensor Digitorum Brevis Model in Healthy Adult Male Participants

Study Overview
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Brief Summary
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Study aimed at comparing the pharmacodynamic profile (including duration of action) of three commercialized toxins by measuring the action potential of the injected muscle (extensor digitorum brevis)

Official Title
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A Phase I, Randomised, Double-blind, Parallel-group, Single-centre Comparative Study to Evaluate the Pharmacodynamic Profile of Dysport®, Botox®, and Xeomin® in the Extensor Digitorum Brevis (EDB) Model in Healthy Adult Male Participants

Conditions
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Healthy Participants

Intervention / Treatment
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* Biological: Botulinum toxin type A
* Biological: Botulinum toxin type A
* Biological: Botulinum toxin type A


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant must be between18 to 65 years of age inclusive, at the time of signing the informed consent Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, vital signs and cardiac monitoring A body mass index (BMI) within the range 18 and 30 kg/m2 (inclusive). Exclusion Criteria: Any medical condition that may put the participant at risk with exposure to BoNT, including diagnosed myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, or any other disease that might interfere with neuromuscular function Previous treatment with botulinum toxin (BoNT) (any serotype) during the past 6 months Known hypersensitivity to any of the components of the Dysport/ Botox/ Xeomin formulation (which includes human serum albumin, lactose, sucrose) or allergy to cow's milk protein Use of agents that could interfere with neuromuscular transmission, including calcium channel blockers, penicillamine, aminoglycosides, lincosamides, polymixins, magnesium sulphate, anticholinesterases, succinylcholine and quinidine

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dysport®<br>40 Units (U) Intramuscular (IM) injection at day 1. | Biological: Botulinum toxin type A<br>* Intramuscular Injection, concentration 300 units (U)<br>* Other names: abobotulinumtoxinA (Dysport®);|
| Active Comparator: Botox®<br>16U IM at day 1. | Biological: Botulinum toxin type A<br>* Intramuscular Injection, concentration 50 U<br>* Other names: onabotulinumtoxinA (Botox®);|
| Active Comparator: Xeomin®<br>16U IM at day 1. | Biological: Botulinum toxin type A<br>* Intramuscular Injection, concentration 50 U<br>* Other names: incobotulinumtoxinA (Xeomin®);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CMAP total amplitude measured as relative change from Baseline (%) |  | week 28. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CMAP total amplitude measured as relative change from Baseline (%). |  | Week 40. | 
| Incidence of recovery of CMAP total amplitude, defined as total amplitude return to at least 85% of the Baseline value. |  | Week 28. | 
| Incidence of recovery of CMAP total amplitude. |  | Week 40. | 
| Time to onset of action defined as first timepoint where EDB CMAP total amplitude is 85% or lower than the Baseline value. |  | From baseline to week 40. | 
| Duration of response defined as time period between time to onset and time to recovery. | Time to recovery is defined as the first timepoint (post time to onset of action and assuming that % of baseline value keeps on decreasing) where EDB CMAP total amplitude returns to at least 85% of the baseline value. | From baseline to week 40. | 
| Maximal inhibition (maximal effect) reached. | Maximal Effect for each participant is defined as the maximal measured inhibition of CMAP amplitude of stimulated EDB. Maximal Effect will be analysed descriptively. | From baseline to week 40. | 
| Time to maximal effect on the CMAP total amplitude of stimulated EDB. |  | From baseline to week 40. | 
| Type, incidence and severity of TEAEs, SAEs, AEs (or SAEs) leading to withdrawals |  | From baseline to week 40. |