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

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

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)

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Biological: Botulinum toxin type A; Biological: Botulinum toxin type A

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Manchester, United Kingdom
    • Mac Research Clinical research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Adjusted Mean (AM) Percentage (%) of CMAP Total Amplitude at Week 28	The CMAP procedure was performed on the injected foot by a neurophysiologist. Percentage relative to baseline was calculated as (value at Week 28 [mean of the 3 measurements]/baseline value) multiplied by (*) 100. The adjusted mean was obtained from a mixed-effects model for repeated measures (MMRM) model with Fisher scoring. Baseline was defined as the last non-missing measurement taken prior to study drug administration. Baseline value used for this analysis was the average of 6 measurements, the 3 measurements at screening and the 3 measurements at baseline.	Baseline (Day 1) and Week 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in AM % of CMAP Total Amplitude at Week 40	The CMAP procedure was performed on the injected foot by a neurophysiologist. It was measured as percentage relative to baseline defined as CMAP at the corresponding visit (mean of the 3 measurements)/CMAP at baseline (mean of the 6 measurements)*100. The adjusted mean was obtained from a MMRM model with Fisher scoring. Baseline was defined as the last non-missing measurement taken prior to study drug administration. Baseline value used for this analysis was the average of 6 measurements, the 3 measurements at screening and the 3 measurements at baseline.	Baseline (Day 1) and Week 40
Percentage of Participants With Recovery of CMAP Total Amplitude	The recovery was considered to be reached for all the visits occurring after the time to recovery, that is (i.e.) the first visit for which CMAP total amplitude returned to at least 85% of the baseline value. Percentage of participants with recovery of CMAP total amplitude was analyzed at Weeks 28 and 40.	At Weeks 28 and 40
Time to Onset of Action of Study Intervention	Time to onset of action was defined as the first timepoint when EDB CMAP total amplitude was less or equal to 85% of the baseline value.	From Baseline (Day 1) up to Week 40
Duration of Response	Duration of response was calculated as time to recovery of CMAP total amplitude - time to onset. Time to recovery was defined as the first timepoint where EDB CMAP total amplitude returned to at least 85% of the baseline value.	From Baseline (Day 1) up to Week 40
Percentage of Maximal Inhibition (Maximal Effect) of CMAP Total Amplitude	Maximal inhibition was defined as the maximal measured inhibition of CMAP total amplitude of stimulated EDB.	Up to Week 40
Number of Participants Who Achieved Maximal Effect of CMAP Total Amplitude	Time to maximal effect was defined on an individual basis as the time between baseline and the timepoint of maximal inhibition of CMAP amplitude of stimulated EDB. Participants with maximal effect of CMAP total amplitude were reported.	At Weeks 1, 4, 8 and 20

Collaborators and Investigators

• Sponsor: Ipsen
• Investigators: Study Director: Ipsen Medical Director, Ipsen

Publications and helpful links

Helpful Links

• Lay language results summary

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2021
• Primary Completion (Actual): March 16, 2022
• Study Completion (Actual): June 8, 2022

Study Registration Dates

• First Submitted: July 2, 2021
• First Submitted That Met QC Criteria: July 20, 2021
• First Posted (Actual): July 21, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 18, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Neurotransmitter Agents; Membrane Transport Modulators; Cholinergic Agents; Neuromuscular Agents; Acetylcholine Release Inhibitors; Botulinum Toxins, Type A; abobotulinumtoxinA; Botulinum Toxins; incobotulinumtoxinA
• Other Study ID Numbers: D-FR-52120-279; 2021-000802-14 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes