Trial Outcomes & Findings for 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 (NCT NCT04970407)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

45 participants

Primary outcome timeframe

Baseline (Day 1) and Week 28

Results posted on

2025-02-19

Participant Flow

This Phase I, randomized, double-blind study was conducted in healthy adult male participants at a single investigational site in United Kingdom between 06 Jul 2021 and 08 Jun 2022. The purpose of this study was to compare the duration of action on compound muscle action potential (CMAP) of the extensor digitorum brevis (EDB) muscle injected with either Dysport 40 units (U), Botox 16 U or Xeomin 16 U.

This study consisted of a 14-day screening period, a double-blind period including treatment administration on Day 1, and follow-up period up to 40 weeks. A total of 45 male participants were randomized in a 1:1:1 ratio to receive treatment with Dysport 40 U, Botox 16 U or Xeomin 16 U respectively.

Participant milestones

Participant milestones
Measure	Dysport 40 U Participants received a single intramuscular (IM) injection of Dysport 40 U in the EDB muscle on Day 1.	Botox 16 U Participants received a single IM injection of Botox 16 U in the EDB muscle on Day 1.	Xeomin 16 U Participants received a single IM injection of Xeomin 16 U in the EDB muscle on Day 1.
Overall Study STARTED	15	15	15
Overall Study COMPLETED	15	15	15
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dysport 40 U n=15 Participants Participants received a single IM injection of Dysport 40 U in the EDB muscle on Day 1.	Botox 16 U n=15 Participants Participants received a single IM injection of Botox 16 U in the EDB muscle on Day 1.	Xeomin 16 U n=15 Participants Participants received a single IM injection of Xeomin 16 U in the EDB muscle on Day 1.	Total n=45 Participants Total of all reporting groups
Age, Continuous	36.2 years STANDARD_DEVIATION 11.3 • n=15 Participants	35.3 years STANDARD_DEVIATION 12.3 • n=15 Participants	34.8 years STANDARD_DEVIATION 13.9 • n=15 Participants	35.4 years STANDARD_DEVIATION 12.3 • n=45 Participants
Sex: Female, Male Female	0 Participants n=15 Participants	0 Participants n=15 Participants	0 Participants n=15 Participants	0 Participants n=45 Participants
Sex: Female, Male Male	15 Participants n=15 Participants	15 Participants n=15 Participants	15 Participants n=15 Participants	45 Participants n=45 Participants
Race and Ethnicity Not Collected	—	—	—	0 Participants Race and Ethnicity were not collected from any participant.

PRIMARY outcome

Timeframe: Baseline (Day 1) and Week 28

Population: The Pharmacodynamic (PD) analysis set consisted of all participants from the randomized set who received the appropriate dose of study treatment and had CMAP recorded for baseline and at least 1 post-baseline assessment.

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.

Outcome measures

Outcome measures
Measure	Dysport 40 U n=15 Participants Participants received a single IM injection of Dysport 40 U in the EDB muscle on Day 1.	Botox 16 U n=15 Participants Participants received a single IM injection of Botox 16 U in the EDB muscle on Day 1.	Xeomin 16 U n=15 Participants Participants received a single IM injection of Xeomin 16 U in the EDB muscle on Day 1.
Change From Baseline in Adjusted Mean (AM) Percentage (%) of CMAP Total Amplitude at Week 28	73.62 % of AM of CMAP total amplitude Standard Error 5.26	74.78 % of AM of CMAP total amplitude Standard Error 5.26	84.23 % of AM of CMAP total amplitude Standard Error 5.25

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 40

Population: The PD analysis set consisted of all participants from the randomized set who received the appropriate dose of study treatment and had CMAP recorded for baseline and at least 1 post-baseline assessment.

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.

Outcome measures

Outcome measures
Measure	Dysport 40 U n=15 Participants Participants received a single IM injection of Dysport 40 U in the EDB muscle on Day 1.	Botox 16 U n=15 Participants Participants received a single IM injection of Botox 16 U in the EDB muscle on Day 1.	Xeomin 16 U n=15 Participants Participants received a single IM injection of Xeomin 16 U in the EDB muscle on Day 1.
Change From Baseline in AM % of CMAP Total Amplitude at Week 40	77.10 % of AM of CMAP total amplitude Standard Error 5.09	81.83 % of AM of CMAP total amplitude Standard Error 5.10	92.01 % of AM of CMAP total amplitude Standard Error 5.09

SECONDARY outcome

Timeframe: At Weeks 28 and 40

Population: The PD analysis set consisted of all participants from the randomized set who received the appropriate dose of study treatment and had CMAP recorded for baseline and at least 1 post-baseline assessment. Only those participants who showed recovery at Weeks 28 and 40 were analyzed.

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.

Outcome measures

Outcome measures
Measure	Dysport 40 U n=15 Participants Participants received a single IM injection of Dysport 40 U in the EDB muscle on Day 1.	Botox 16 U n=15 Participants Participants received a single IM injection of Botox 16 U in the EDB muscle on Day 1.	Xeomin 16 U n=15 Participants Participants received a single IM injection of Xeomin 16 U in the EDB muscle on Day 1.
Percentage of Participants With Recovery of CMAP Total Amplitude Week 28	33.3 percentage of participants Interval 11.8 to 61.6	26.7 percentage of participants Interval 7.8 to 55.1	53.3 percentage of participants Interval 26.6 to 78.7
Percentage of Participants With Recovery of CMAP Total Amplitude Week 40	33.3 percentage of participants Interval 11.8 to 61.6	33.3 percentage of participants Interval 11.8 to 61.6	66.7 percentage of participants Interval 38.4 to 88.2

SECONDARY outcome

Timeframe: From Baseline (Day 1) up to Week 40

Population: The PD analysis set consisted of all participants from the randomized set who received the appropriate dose of study treatment and had CMAP recorded for baseline and at least 1 post-baseline assessment.

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.

Outcome measures

Outcome measures
Measure	Dysport 40 U n=15 Participants Participants received a single IM injection of Dysport 40 U in the EDB muscle on Day 1.	Botox 16 U n=15 Participants Participants received a single IM injection of Botox 16 U in the EDB muscle on Day 1.	Xeomin 16 U n=15 Participants Participants received a single IM injection of Xeomin 16 U in the EDB muscle on Day 1.
Time to Onset of Action of Study Intervention	1.00 weeks Interval 0.7 to 1.6	1.00 weeks Interval 0.7 to 1.1	1.00 weeks Interval 0.9 to 4.0

SECONDARY outcome

Timeframe: From Baseline (Day 1) up to Week 40

Population: The PD analysis set consisted of all participants from the randomized set who received the appropriate dose of study treatment and had CMAP recorded for baseline and at least 1 post-baseline assessment. Only those participants who showed recovery before the end of the study were analyzed.

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.

Outcome measures

Outcome measures
Measure	Dysport 40 U n=5 Participants Participants received a single IM injection of Dysport 40 U in the EDB muscle on Day 1.	Botox 16 U n=5 Participants Participants received a single IM injection of Botox 16 U in the EDB muscle on Day 1.	Xeomin 16 U n=10 Participants Participants received a single IM injection of Xeomin 16 U in the EDB muscle on Day 1.
Duration of Response	18.29 weeks Interval 7.0 to 19.0	10.86 weeks Interval 7.3 to 31.4	17.07 weeks Interval 3.1 to 38.6

SECONDARY outcome

Timeframe: Up to Week 40

Population: The PD analysis set consisted of all participants from the randomized set who received the appropriate dose of study treatment and had CMAP recorded for baseline and at least 1 post-baseline assessment.

Maximal inhibition was defined as the maximal measured inhibition of CMAP total amplitude of stimulated EDB.

Outcome measures

Outcome measures
Measure	Dysport 40 U n=15 Participants Participants received a single IM injection of Dysport 40 U in the EDB muscle on Day 1.	Botox 16 U n=15 Participants Participants received a single IM injection of Botox 16 U in the EDB muscle on Day 1.	Xeomin 16 U n=15 Participants Participants received a single IM injection of Xeomin 16 U in the EDB muscle on Day 1.
Percentage of Maximal Inhibition (Maximal Effect) of CMAP Total Amplitude	39.79 percentage of inhibition Interval 31.23 to 48.35	38.55 percentage of inhibition Interval 33.99 to 43.1	44.99 percentage of inhibition Interval 36.68 to 53.3

SECONDARY outcome

Timeframe: At Weeks 1, 4, 8 and 20

Population: The PD analysis set consisted of all participants from the randomized set who received the appropriate dose of study treatment and had CMAP recorded for baseline and at least 1 post-baseline assessment.

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.

Outcome measures

Outcome measures
Measure	Dysport 40 U n=15 Participants Participants received a single IM injection of Dysport 40 U in the EDB muscle on Day 1.	Botox 16 U n=15 Participants Participants received a single IM injection of Botox 16 U in the EDB muscle on Day 1.	Xeomin 16 U n=15 Participants Participants received a single IM injection of Xeomin 16 U in the EDB muscle on Day 1.
Number of Participants Who Achieved Maximal Effect of CMAP Total Amplitude Week 1	11 Participants	13 Participants	11 Participants
Number of Participants Who Achieved Maximal Effect of CMAP Total Amplitude Week 4	2 Participants	1 Participants	4 Participants
Number of Participants Who Achieved Maximal Effect of CMAP Total Amplitude Week 8	1 Participants	1 Participants	0 Participants
Number of Participants Who Achieved Maximal Effect of CMAP Total Amplitude Week 20	1 Participants	0 Participants	0 Participants

Adverse Events

Dysport 40 U

Serious events: 10 serious events

Other events: 11 other events

Deaths: 0 deaths

Botox 16 U

Serious events: 2 serious events

Other events: 10 other events

Deaths: 0 deaths

Xeomin 16 U

Serious events: 5 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Dysport 40 U n=15 participants at risk Participants received a single IM injection of Dysport 40 U in the EDB muscle on Day 1.	Botox 16 U n=15 participants at risk Participants received a single IM injection of Botox 16 U in the EDB muscle on Day 1.	Xeomin 16 U n=15 participants at risk Participants received a single IM injection of Xeomin 16 U in the EDB muscle on Day 1.
Infections and infestations Covid-19	66.7% 10/15 • Number of events 10 • Treatment-emergent adverse events were collected from the study drug administration (Day 1) up to Week 40 The Safety analysis set consisted of all participants who received at least 1 dose of study treatment.	13.3% 2/15 • Number of events 2 • Treatment-emergent adverse events were collected from the study drug administration (Day 1) up to Week 40 The Safety analysis set consisted of all participants who received at least 1 dose of study treatment.	26.7% 4/15 • Number of events 4 • Treatment-emergent adverse events were collected from the study drug administration (Day 1) up to Week 40 The Safety analysis set consisted of all participants who received at least 1 dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.00% 0/15 • Treatment-emergent adverse events were collected from the study drug administration (Day 1) up to Week 40 The Safety analysis set consisted of all participants who received at least 1 dose of study treatment.	0.00% 0/15 • Treatment-emergent adverse events were collected from the study drug administration (Day 1) up to Week 40 The Safety analysis set consisted of all participants who received at least 1 dose of study treatment.	6.7% 1/15 • Number of events 1 • Treatment-emergent adverse events were collected from the study drug administration (Day 1) up to Week 40 The Safety analysis set consisted of all participants who received at least 1 dose of study treatment.
Gastrointestinal disorders Enteritis	0.00% 0/15 • Treatment-emergent adverse events were collected from the study drug administration (Day 1) up to Week 40 The Safety analysis set consisted of all participants who received at least 1 dose of study treatment.	0.00% 0/15 • Treatment-emergent adverse events were collected from the study drug administration (Day 1) up to Week 40 The Safety analysis set consisted of all participants who received at least 1 dose of study treatment.	6.7% 1/15 • Number of events 1 • Treatment-emergent adverse events were collected from the study drug administration (Day 1) up to Week 40 The Safety analysis set consisted of all participants who received at least 1 dose of study treatment.

Other adverse events

Other adverse events
Measure	Dysport 40 U n=15 participants at risk Participants received a single IM injection of Dysport 40 U in the EDB muscle on Day 1.	Botox 16 U n=15 participants at risk Participants received a single IM injection of Botox 16 U in the EDB muscle on Day 1.	Xeomin 16 U n=15 participants at risk Participants received a single IM injection of Xeomin 16 U in the EDB muscle on Day 1.
Infections and infestations Viral infection	13.3% 2/15 • Number of events 2 • Treatment-emergent adverse events were collected from the study drug administration (Day 1) up to Week 40 The Safety analysis set consisted of all participants who received at least 1 dose of study treatment.	13.3% 2/15 • Number of events 3 • Treatment-emergent adverse events were collected from the study drug administration (Day 1) up to Week 40 The Safety analysis set consisted of all participants who received at least 1 dose of study treatment.	26.7% 4/15 • Number of events 4 • Treatment-emergent adverse events were collected from the study drug administration (Day 1) up to Week 40 The Safety analysis set consisted of all participants who received at least 1 dose of study treatment.
Injury, poisoning and procedural complications Soft tissue injury	0.00% 0/15 • Treatment-emergent adverse events were collected from the study drug administration (Day 1) up to Week 40 The Safety analysis set consisted of all participants who received at least 1 dose of study treatment.	13.3% 2/15 • Number of events 2 • Treatment-emergent adverse events were collected from the study drug administration (Day 1) up to Week 40 The Safety analysis set consisted of all participants who received at least 1 dose of study treatment.	6.7% 1/15 • Number of events 1 • Treatment-emergent adverse events were collected from the study drug administration (Day 1) up to Week 40 The Safety analysis set consisted of all participants who received at least 1 dose of study treatment.
Musculoskeletal and connective tissue disorders Pain in extremity	6.7% 1/15 • Number of events 1 • Treatment-emergent adverse events were collected from the study drug administration (Day 1) up to Week 40 The Safety analysis set consisted of all participants who received at least 1 dose of study treatment.	20.0% 3/15 • Number of events 3 • Treatment-emergent adverse events were collected from the study drug administration (Day 1) up to Week 40 The Safety analysis set consisted of all participants who received at least 1 dose of study treatment.	13.3% 2/15 • Number of events 2 • Treatment-emergent adverse events were collected from the study drug administration (Day 1) up to Week 40 The Safety analysis set consisted of all participants who received at least 1 dose of study treatment.
Musculoskeletal and connective tissue disorders Arthralgia	13.3% 2/15 • Number of events 2 • Treatment-emergent adverse events were collected from the study drug administration (Day 1) up to Week 40 The Safety analysis set consisted of all participants who received at least 1 dose of study treatment.	6.7% 1/15 • Number of events 1 • Treatment-emergent adverse events were collected from the study drug administration (Day 1) up to Week 40 The Safety analysis set consisted of all participants who received at least 1 dose of study treatment.	6.7% 1/15 • Number of events 1 • Treatment-emergent adverse events were collected from the study drug administration (Day 1) up to Week 40 The Safety analysis set consisted of all participants who received at least 1 dose of study treatment.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/15 • Treatment-emergent adverse events were collected from the study drug administration (Day 1) up to Week 40 The Safety analysis set consisted of all participants who received at least 1 dose of study treatment.	6.7% 1/15 • Number of events 1 • Treatment-emergent adverse events were collected from the study drug administration (Day 1) up to Week 40 The Safety analysis set consisted of all participants who received at least 1 dose of study treatment.	13.3% 2/15 • Number of events 2 • Treatment-emergent adverse events were collected from the study drug administration (Day 1) up to Week 40 The Safety analysis set consisted of all participants who received at least 1 dose of study treatment.
Nervous system disorders Headache	13.3% 2/15 • Number of events 2 • Treatment-emergent adverse events were collected from the study drug administration (Day 1) up to Week 40 The Safety analysis set consisted of all participants who received at least 1 dose of study treatment.	6.7% 1/15 • Number of events 1 • Treatment-emergent adverse events were collected from the study drug administration (Day 1) up to Week 40 The Safety analysis set consisted of all participants who received at least 1 dose of study treatment.	33.3% 5/15 • Number of events 7 • Treatment-emergent adverse events were collected from the study drug administration (Day 1) up to Week 40 The Safety analysis set consisted of all participants who received at least 1 dose of study treatment.
Nervous system disorders Hypoaesthesia	13.3% 2/15 • Number of events 2 • Treatment-emergent adverse events were collected from the study drug administration (Day 1) up to Week 40 The Safety analysis set consisted of all participants who received at least 1 dose of study treatment.	13.3% 2/15 • Number of events 2 • Treatment-emergent adverse events were collected from the study drug administration (Day 1) up to Week 40 The Safety analysis set consisted of all participants who received at least 1 dose of study treatment.	0.00% 0/15 • Treatment-emergent adverse events were collected from the study drug administration (Day 1) up to Week 40 The Safety analysis set consisted of all participants who received at least 1 dose of study treatment.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	13.3% 2/15 • Number of events 3 • Treatment-emergent adverse events were collected from the study drug administration (Day 1) up to Week 40 The Safety analysis set consisted of all participants who received at least 1 dose of study treatment.	6.7% 1/15 • Number of events 1 • Treatment-emergent adverse events were collected from the study drug administration (Day 1) up to Week 40 The Safety analysis set consisted of all participants who received at least 1 dose of study treatment.	0.00% 0/15 • Treatment-emergent adverse events were collected from the study drug administration (Day 1) up to Week 40 The Safety analysis set consisted of all participants who received at least 1 dose of study treatment.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/15 • Treatment-emergent adverse events were collected from the study drug administration (Day 1) up to Week 40 The Safety analysis set consisted of all participants who received at least 1 dose of study treatment.	6.7% 1/15 • Number of events 1 • Treatment-emergent adverse events were collected from the study drug administration (Day 1) up to Week 40 The Safety analysis set consisted of all participants who received at least 1 dose of study treatment.	13.3% 2/15 • Number of events 2 • Treatment-emergent adverse events were collected from the study drug administration (Day 1) up to Week 40 The Safety analysis set consisted of all participants who received at least 1 dose of study treatment.

Additional Information

Laurent Pons/Clinical Pharmacology Director

Ipsen Innovation

Phone: see email

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place