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

Phase 1

Completed

• Conditions: Healthy Participants
• Interventions: Biological: Botulinum toxin type A

• Registration Number: NCT04970407
• Lead Sponsor: Ipsen

Brief Summary

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)

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-07-02
• Study Start: 2021-07-06
• Study First Submitted QC: 2021-07-20
• Study First Posted: 2021-07-21
• Primary Completion: 2022-03-16
• Study Completion: 2022-06-08
• Results First Submitted: 2023-05-18
• Status Verified: 2024-02
• Results First Submitted QC: 2024-02-21
• Last Update Submitted: 2024-02-21
• Results First Posted: 2024-08-01
• Last Update Posted: 2024-08-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 45

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).

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Botox®	Botulinum toxin type A	16U IM at day 1.
Xeomin®	Botulinum toxin type A	16U IM at day 1.
Dysport®	Botulinum toxin type A	40 Units (U) Intramuscular (IM) injection at day 1.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Adjusted Mean (AM) Percentage (%) of CMAP Total Amplitude at Week 28	Baseline (Day 1) and 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.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in AM % of CMAP Total Amplitude at Week 40	Baseline (Day 1) and 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.
Percentage of Participants With Recovery of CMAP Total Amplitude	At Weeks 28 and 40	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.
Time to Onset of Action of Study Intervention	From Baseline (Day 1) up to Week 40	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.
Percentage of Maximal Inhibition (Maximal Effect) of CMAP Total Amplitude	Up to Week 40	Maximal inhibition was defined as the maximal measured inhibition of CMAP total amplitude of stimulated EDB.
Number of Participants Who Achieved Maximal Effect of CMAP Total Amplitude	At Weeks 1, 4, 8 and 20	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.
Duration of Response	From Baseline (Day 1) up to Week 40	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.

Trial Locations

Locations (1)

Mac Research Clinical research Unit; 🇬🇧 Manchester, United Kingdom