Trial Outcomes & Findings for Dysport in Hallux Abducto Valgus (HAV) Phase IIa (NCT NCT03569098)

NCT ID: NCT03569098

Last Updated: 2021-07-02

Results Overview

The NPRS is a widely used and validated unidimensional measure of pain intensity in adults. Participants were asked to rate the intensity of their foot pain during physical activity (example, walking, standing or running) based on an 11-point scale ranging from 0 to 10, where 0 represents "no pain" and 10 represents "worst possible pain". Higher scores indicate a worse outcome. Daily pain intensities were recorded by the participant using an electronic diary (eDiary) for 7 consecutive days prior to each study visit. Baseline was defined as the daily NPRS score averaged over the 7 consecutive days prior to the Baseline visit (Day 1).

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 186 participants
• Primary outcome timeframe: Baseline and Week 8 in the double-blind treatment period
• Results posted on: 2021-07-02

Participant Flow

This Phase II double-blind study was conducted at 27 sites in the United States between 19 June 2018 and 22 May 2020 in adult participants suffering from clinically significant hallux abducto valgus (HV) who have not undergone surgery for their condition.

The study consisted of a screening period (up to 3 weeks), followed by a double-blind treatment period (Cycle 1). From Week 12, retreatment criteria were evaluated every 4 weeks to determine eligibility to receive treatment in the open-label period (Cycles 2 and 3). Total study duration was a maximum of 36 weeks. A total of 186 participants were randomized in a 1:1:1 ratio to 1 of 3 treatment groups (placebo, Dysport 300 units (U) and Dysport 500 U) in the double-blind treatment period.

Participant milestones

Measure	Placebo On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of placebo (matching with Dysport) intramuscular injection distributed between 4 injection points in the 4 targeted muscles of the study foot. Following the double-blind treatment period, all participants who met retreatment criteria were treated during the open-label period with Dysport 300 U on Cycle 2 Day 1 and either Dysport 300 U or 500 U on Cycle 3 Day 1. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.	Dysport 300 U On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of Dysport 300 U intramuscular injection distributed between 4 injection points (75 U each) in the 4 targeted muscles of the study foot. Following the double-blind treatment period, all participants who met retreatment criteria were treated during the open-label period with Dysport 300 U on Cycle 2 Day 1 and either Dysport 300 U or 500 U on Cycle 3 Day 1. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.	Dysport 500 U On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of Dysport 500 U intramuscular injection distributed between 4 injection points (125 U each) in the 4 targeted muscles of the study foot. Following the double-blind treatment period, all participants who met retreatment criteria were treated during the open-label period with Dysport 300 U on Cycle 2 Day 1 and either Dysport 300 U or 500 U on Cycle 3 Day 1. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.
Double-Blind Treatment Cycle 1 STARTED	63	63	60
Double-Blind Treatment Cycle 1 Received Study Medication	61	63	56
Double-Blind Treatment Cycle 1 COMPLETED	55	53	49
Double-Blind Treatment Cycle 1 NOT COMPLETED	8	10	11
Open-Label Treatment Cycle 2 STARTED	0	146	0
Open-Label Treatment Cycle 2 COMPLETED	0	111	0
Open-Label Treatment Cycle 2 NOT COMPLETED	0	35	0
Open-Label Treatment Cycle 3 STARTED	0	8	56
Open-Label Treatment Cycle 3 COMPLETED	0	7	50
Open-Label Treatment Cycle 3 NOT COMPLETED	0	1	6

Reasons for withdrawal

Measure	Placebo On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of placebo (matching with Dysport) intramuscular injection distributed between 4 injection points in the 4 targeted muscles of the study foot. Following the double-blind treatment period, all participants who met retreatment criteria were treated during the open-label period with Dysport 300 U on Cycle 2 Day 1 and either Dysport 300 U or 500 U on Cycle 3 Day 1. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.	Dysport 300 U On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of Dysport 300 U intramuscular injection distributed between 4 injection points (75 U each) in the 4 targeted muscles of the study foot. Following the double-blind treatment period, all participants who met retreatment criteria were treated during the open-label period with Dysport 300 U on Cycle 2 Day 1 and either Dysport 300 U or 500 U on Cycle 3 Day 1. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.	Dysport 500 U On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of Dysport 500 U intramuscular injection distributed between 4 injection points (125 U each) in the 4 targeted muscles of the study foot. Following the double-blind treatment period, all participants who met retreatment criteria were treated during the open-label period with Dysport 300 U on Cycle 2 Day 1 and either Dysport 300 U or 500 U on Cycle 3 Day 1. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.
Double-Blind Treatment Cycle 1 Withdrawal by Subject	5	2	5
Double-Blind Treatment Cycle 1 Study terminated by sponsor	0	6	3
Double-Blind Treatment Cycle 1 Lost to Follow-up	1	1	0
Double-Blind Treatment Cycle 1 Technical problems	0	0	2
Double-Blind Treatment Cycle 1 Physician Decision	1	0	0
Double-Blind Treatment Cycle 1 Protocol deviation	0	1	0
Double-Blind Treatment Cycle 1 Other	1	0	1
Open-Label Treatment Cycle 2 Study terminated by sponsor	0	21	0
Open-Label Treatment Cycle 2 Withdrawal by Subject	0	11	0
Open-Label Treatment Cycle 2 Lost to Follow-up	0	3	0
Open-Label Treatment Cycle 3 Withdrawal by Subject	0	0	4
Open-Label Treatment Cycle 3 Study terminated by sponsor	0	1	1
Open-Label Treatment Cycle 3 Lost to Follow-up	0	0	1

Baseline Characteristics

Dysport in Hallux Abducto Valgus (HAV) Phase IIa

Baseline characteristics by cohort

Measure	Placebo n=63 Participants On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of placebo (matching with Dysport) intramuscular injection distributed between 4 injection points in the 4 targeted muscles of the study foot. Following the double-blind treatment period, all participants who met retreatment criteria were treated during the open-label period with Dysport 300 U on Cycle 2 Day 1 and either Dysport 300 U or 500 U on Cycle 3 Day 1. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.	Dysport 300 U n=63 Participants On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of Dysport 300 U intramuscular injection distributed between 4 injection points (75 U each) in the 4 targeted muscles of the study foot. Following the double-blind treatment period, all participants who met retreatment criteria were treated during the open-label period with Dysport 300 U on Cycle 2 Day 1 and either Dysport 300 U or 500 U on Cycle 3 Day 1. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.	Dysport 500 U n=60 Participants On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of Dysport 500 U intramuscular injection distributed between 4 injection points (125 U each) in the 4 targeted muscles of the study foot. Following the double-blind treatment period, all participants who met retreatment criteria were treated during the open-label period with Dysport 300 U on Cycle 2 Day 1 and either Dysport 300 U or 500 U on Cycle 3 Day 1. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.	Total n=186 Participants Total of all reporting groups
Age, Continuous	48.3 years STANDARD_DEVIATION 13.18 • n=5 Participants	48.4 years STANDARD_DEVIATION 14.04 • n=7 Participants	48.0 years STANDARD_DEVIATION 12.24 • n=5 Participants	48.2 years STANDARD_DEVIATION 13.12 • n=4 Participants
Age, Customized <65 years	56 Participants n=5 Participants	58 Participants n=7 Participants	57 Participants n=5 Participants	171 Participants n=4 Participants
Age, Customized >=65 and <85 years	7 Participants n=5 Participants	5 Participants n=7 Participants	3 Participants n=5 Participants	15 Participants n=4 Participants
Age, Customized >=85 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Sex: Female, Male Female	55 Participants n=5 Participants	60 Participants n=7 Participants	56 Participants n=5 Participants	171 Participants n=4 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants	15 Participants n=4 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants
Race/Ethnicity, Customized Asian	1 participants n=5 Participants	5 participants n=7 Participants	6 participants n=5 Participants	12 participants n=4 Participants
Race/Ethnicity, Customized Black or African American	10 participants n=5 Participants	4 participants n=7 Participants	9 participants n=5 Participants	23 participants n=4 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants
Race/Ethnicity, Customized White	49 participants n=5 Participants	54 participants n=7 Participants	43 participants n=5 Participants	146 participants n=4 Participants
Race/Ethnicity, Customized Other	3 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants	5 participants n=4 Participants
Race/Ethnicity, Customized Hispanic or Latino	16 participants n=5 Participants	10 participants n=7 Participants	16 participants n=5 Participants	42 participants n=4 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	47 participants n=5 Participants	53 participants n=7 Participants	44 participants n=5 Participants	144 participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline and Week 8 in the double-blind treatment period

Population: The ITT analysis set included all randomized participants. For participants without any available post-Baseline NPRS average scores, the Week 8 average pain score was imputed.

The NPRS is a widely used and validated unidimensional measure of pain intensity in adults. Participants were asked to rate the intensity of their foot pain during physical activity (example, walking, standing or running) based on an 11-point scale ranging from 0 to 10, where 0 represents "no pain" and 10 represents "worst possible pain". Higher scores indicate a worse outcome. Daily pain intensities were recorded by the participant using an electronic diary (eDiary) for 7 consecutive days prior to each study visit. Baseline was defined as the daily NPRS score averaged over the 7 consecutive days prior to the Baseline visit (Day 1).

Outcome measures

Measure	Placebo n=63 Participants On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of placebo (matching with Dysport) intramuscular injection distributed between 4 injection points in the 4 targeted muscles of the study foot. Following the double-blind treatment period, all participants who met retreatment criteria were treated during the open-label period with Dysport 300 U on Cycle 2 Day 1 and either Dysport 300 U or 500 U on Cycle 3 Day 1. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.	Dysport 300 U n=63 Participants On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of Dysport 300 U intramuscular injection distributed between 4 injection points (75 U each) in the 4 targeted muscles of the study foot. Following the double-blind treatment period, all participants who met retreatment criteria were treated during the open-label period with Dysport 300 U on Cycle 2 Day 1 and either Dysport 300 U or 500 U on Cycle 3 Day 1. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.	Dysport 500 U n=60 Participants On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of Dysport 500 U intramuscular injection distributed between 4 injection points (125 U each) in the 4 targeted muscles of the study foot. Following the double-blind treatment period, all participants who met retreatment criteria were treated during the open-label period with Dysport 300 U on Cycle 2 Day 1 and either Dysport 300 U or 500 U on Cycle 3 Day 1. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.
Least Square (LS) Mean Change From Baseline in the Daily Numeric Pain Rating Scale (NPRS) Score at Week 8	-2.04 units on a scale Interval -2.66 to -1.41	-1.71 units on a scale Interval -2.33 to -1.1	-2.40 units on a scale Interval -3.03 to -1.77

SECONDARY outcome

Timeframe: Baseline and Weeks 4 and 12 in the double-blind treatment period

Population: The ITT analysis set included all randomized participants. For participants without any available post-Baseline NPRS average scores, the Weeks 4 and 12 average pain scores were imputed.

The NPRS is a widely used and validated unidimensional measure of pain intensity in adults. Participants were asked to rate the intensity of their foot pain during physical activity (example, walking, standing or running) based on an 11-point scale ranging from 0 to 10, where 0 represents "no pain" and 10 represents "worst possible pain". Higher scores indicate a worse outcome. Daily pain intensities were recorded by the participant using an eDiary for 7 consecutive days prior to each study visit. Baseline was defined as the daily NPRS score averaged over the 7 consecutive days prior to the Baseline visit (Day 1).

Outcome measures

Measure	Placebo n=63 Participants On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of placebo (matching with Dysport) intramuscular injection distributed between 4 injection points in the 4 targeted muscles of the study foot. Following the double-blind treatment period, all participants who met retreatment criteria were treated during the open-label period with Dysport 300 U on Cycle 2 Day 1 and either Dysport 300 U or 500 U on Cycle 3 Day 1. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.	Dysport 300 U n=63 Participants On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of Dysport 300 U intramuscular injection distributed between 4 injection points (75 U each) in the 4 targeted muscles of the study foot. Following the double-blind treatment period, all participants who met retreatment criteria were treated during the open-label period with Dysport 300 U on Cycle 2 Day 1 and either Dysport 300 U or 500 U on Cycle 3 Day 1. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.	Dysport 500 U n=60 Participants On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of Dysport 500 U intramuscular injection distributed between 4 injection points (125 U each) in the 4 targeted muscles of the study foot. Following the double-blind treatment period, all participants who met retreatment criteria were treated during the open-label period with Dysport 300 U on Cycle 2 Day 1 and either Dysport 300 U or 500 U on Cycle 3 Day 1. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.
LS Mean Change From Baseline in the Daily NPRS Score at Weeks 4 and 12 Week 4	-1.68 units on a scale Interval -2.26 to -1.11	-1.36 units on a scale Interval -1.94 to -0.78	-1.85 units on a scale Interval -2.45 to -1.25
LS Mean Change From Baseline in the Daily NPRS Score at Weeks 4 and 12 Week 12	-1.72 units on a scale Interval -2.35 to -1.09	-1.61 units on a scale Interval -2.23 to -1.0	-2.42 units on a scale Interval -3.06 to -1.78

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8 and 12 in the double-blind treatment period

Population: The ITT analysis set included all randomized participants. The results are presented for the participants with data available at Baseline and specific time points.

The foot function index (FFI) was developed to assess foot-related pain, disability and activity limitations and later revised to include foot-related health and quality of life. A modified version of FFI specific to this study was used. The mFFI consists of a total of 21 items grouped into 3 subscales: pain (7 questions), disability (9 questions) and activity limitation (5 questions). The mFFI disability subscale is rated using numeric rating scale ranging from 0 to 10, where 0 represents "no difficulty" and 10 represents "so difficult unable to do". For each item, the participant was asked to record the number value which best corresponded to effect of the foot complaints. To obtain a subscale score, the item scores for a given subscale (i.e., pain, disability or activity limitation subscales) were totaled and divided by maximum total possible and then multiplied by 100. Each subscale score, as well as the total score, ranged from 0 to 100. Higher scores indicate a worse outcome.

Outcome measures

Measure	Placebo n=52 Participants On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of placebo (matching with Dysport) intramuscular injection distributed between 4 injection points in the 4 targeted muscles of the study foot. Following the double-blind treatment period, all participants who met retreatment criteria were treated during the open-label period with Dysport 300 U on Cycle 2 Day 1 and either Dysport 300 U or 500 U on Cycle 3 Day 1. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.	Dysport 300 U n=53 Participants On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of Dysport 300 U intramuscular injection distributed between 4 injection points (75 U each) in the 4 targeted muscles of the study foot. Following the double-blind treatment period, all participants who met retreatment criteria were treated during the open-label period with Dysport 300 U on Cycle 2 Day 1 and either Dysport 300 U or 500 U on Cycle 3 Day 1. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.	Dysport 500 U n=47 Participants On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of Dysport 500 U intramuscular injection distributed between 4 injection points (125 U each) in the 4 targeted muscles of the study foot. Following the double-blind treatment period, all participants who met retreatment criteria were treated during the open-label period with Dysport 300 U on Cycle 2 Day 1 and either Dysport 300 U or 500 U on Cycle 3 Day 1. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.
LS Mean Change From Baseline in the Daily Modified Foot Function Index (mFFI) Disability Subscale Score at Weeks 4, 8 and 12 Week 4	-17.95 units on a scale Interval -23.06 to -12.84	-15.29 units on a scale Interval -20.47 to -10.12	-16.87 units on a scale Interval -22.27 to -11.48
LS Mean Change From Baseline in the Daily Modified Foot Function Index (mFFI) Disability Subscale Score at Weeks 4, 8 and 12 Week 8	-22.44 units on a scale Interval -28.0 to -16.87	-18.68 units on a scale Interval -24.19 to -13.17	-21.26 units on a scale Interval -27.05 to -15.48
LS Mean Change From Baseline in the Daily Modified Foot Function Index (mFFI) Disability Subscale Score at Weeks 4, 8 and 12 Week 12	-17.21 units on a scale Interval -23.11 to -11.31	-21.04 units on a scale Interval -26.8 to -15.27	-21.50 units on a scale Interval -27.61 to -15.39

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8 and 12 in the double-blind treatment period

Population: The ITT analysis set included all randomized participants. The results are presented for the participants with data available at Baseline and specific time points.

The FFI was developed to assess foot-related pain, disability and activity limitations and later revised to include foot-related health and quality of life. A modified version of the FFI specific to this study was used. The mFFI consists of a total of 21 items grouped into 3 subscales: pain (7 questions), disability (9 questions) and activity limitation (5 questions). The mFFI pain subscale is rated using numeric rating scale ranging from 0 to 10, where 0 represents "no pain" and 10 represents "worst pain imaginable". For each item, the participant was asked to record the number value which best corresponded to the effect of the foot complaints. To obtain a subscale score, the item scores for a given subscale (i.e., pain, disability or activity limitation subscales) were totaled and divided by the maximum total possible and then multiplied by 100. Each subscale score, as well as the total score, ranged from 0 to 100. Higher scores indicate a worse outcome.

Outcome measures

Measure	Placebo n=52 Participants On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of placebo (matching with Dysport) intramuscular injection distributed between 4 injection points in the 4 targeted muscles of the study foot. Following the double-blind treatment period, all participants who met retreatment criteria were treated during the open-label period with Dysport 300 U on Cycle 2 Day 1 and either Dysport 300 U or 500 U on Cycle 3 Day 1. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.	Dysport 300 U n=53 Participants On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of Dysport 300 U intramuscular injection distributed between 4 injection points (75 U each) in the 4 targeted muscles of the study foot. Following the double-blind treatment period, all participants who met retreatment criteria were treated during the open-label period with Dysport 300 U on Cycle 2 Day 1 and either Dysport 300 U or 500 U on Cycle 3 Day 1. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.	Dysport 500 U n=48 Participants On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of Dysport 500 U intramuscular injection distributed between 4 injection points (125 U each) in the 4 targeted muscles of the study foot. Following the double-blind treatment period, all participants who met retreatment criteria were treated during the open-label period with Dysport 300 U on Cycle 2 Day 1 and either Dysport 300 U or 500 U on Cycle 3 Day 1. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.
LS Mean Change From Baseline in the Daily mFFI Pain Subscale Score at Weeks 4, 8 and 12 Week 4	-17.97 units on a scale Interval -23.23 to -12.7	-15.67 units on a scale Interval -21.0 to -10.33	-19.30 units on a scale Interval -24.86 to -13.73
LS Mean Change From Baseline in the Daily mFFI Pain Subscale Score at Weeks 4, 8 and 12 Week 8	-22.30 units on a scale Interval -28.15 to -16.45	-20.69 units on a scale Interval -26.5 to -14.88	-24.58 units on a scale Interval -30.67 to -18.49
LS Mean Change From Baseline in the Daily mFFI Pain Subscale Score at Weeks 4, 8 and 12 Week 12	-18.94 units on a scale Interval -25.05 to -12.83	-21.74 units on a scale Interval -27.72 to -15.76	-24.30 units on a scale Interval -30.64 to -17.96

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8 and 12 in the double-blind treatment period

Population: The ITT analysis set included all randomized participants. The results are presented for the participants with data available at Baseline and specific time points.

The FFI was developed to assess foot-related pain, disability and activity limitations and later revised to include foot-related health and quality of life. A modified version of the FFI specific to this study was used. The mFFI consists of a total of 21 items grouped into three subscales: pain (7 questions), disability (9 questions) and activity limitation (5 questions). The mFFI items are rated using numeric rating scales ranging from 0 to 10, where 0 represents "no pain/no difficulty/none of the time" and 10 represents "worst pain imaginable/so difficult unable to do/all of the time" for pain, disability and activity limitation subscales, respectively. For each item, the participant was asked to record the number value which best corresponded to the effect of the foot complaints. To obtain a total score, the scores of all 3 subscales were totaled and divided by 3. Each subscale score, as well as the total score, ranged from 0 to 100. Higher scores indicate a worse outcome.

Outcome measures

Measure	Placebo n=52 Participants On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of placebo (matching with Dysport) intramuscular injection distributed between 4 injection points in the 4 targeted muscles of the study foot. Following the double-blind treatment period, all participants who met retreatment criteria were treated during the open-label period with Dysport 300 U on Cycle 2 Day 1 and either Dysport 300 U or 500 U on Cycle 3 Day 1. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.	Dysport 300 U n=53 Participants On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of Dysport 300 U intramuscular injection distributed between 4 injection points (75 U each) in the 4 targeted muscles of the study foot. Following the double-blind treatment period, all participants who met retreatment criteria were treated during the open-label period with Dysport 300 U on Cycle 2 Day 1 and either Dysport 300 U or 500 U on Cycle 3 Day 1. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.	Dysport 500 U n=47 Participants On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of Dysport 500 U intramuscular injection distributed between 4 injection points (125 U each) in the 4 targeted muscles of the study foot. Following the double-blind treatment period, all participants who met retreatment criteria were treated during the open-label period with Dysport 300 U on Cycle 2 Day 1 and either Dysport 300 U or 500 U on Cycle 3 Day 1. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.
LS Mean Change From Baseline in the Daily mFFI Total Score at Weeks 4, 8 and 12 Week 4	-14.87 units on a scale Interval -18.98 to -10.75	-12.80 units on a scale Interval -16.96 to -8.64	-15.10 units on a scale Interval -19.45 to -10.76
LS Mean Change From Baseline in the Daily mFFI Total Score at Weeks 4, 8 and 12 Week 8	-18.82 units on a scale Interval -23.32 to -14.32	-16.16 units on a scale Interval -20.62 to -11.69	-18.79 units on a scale Interval -23.48 to -14.11
LS Mean Change From Baseline in the Daily mFFI Total Score at Weeks 4, 8 and 12 Week 12	-15.65 units on a scale Interval -20.48 to -10.82	-17.45 units on a scale Interval -22.18 to -12.72	-18.89 units on a scale Interval -23.9 to -13.88

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8 and 12 in the double-blind treatment period

Population: The ITT analysis set included all randomized participants. The results are presented for the participants with data available at Baseline and specific time points.

The FFI was developed to assess foot-related pain, disability and activity limitations and later revised to include foot-related health and quality of life. A modified version of the FFI specific to this study was used. The mFFI consists of a total of 21 items grouped into 3 subscales: pain (7 questions), disability (9 questions) and activity limitation (5 questions). The mFFI activity limitation subscale is rated using numeric rating scale ranging from 0 to 10, where 0 represents "none of the time" and 10 represents "all of the time". For each item, the participant was asked to record the number value which best corresponded to the effect of the foot complaints. To obtain a subscale score, the item scores for a given subscale (i.e., pain, disability or activity limitation subscales) were totaled and divided by the maximum total possible and then multiplied by 100. Each subscale score, as well as the total score, ranged from 0 to 100. Higher scores indicate a worse outcome.

Outcome measures

Measure	Placebo n=52 Participants On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of placebo (matching with Dysport) intramuscular injection distributed between 4 injection points in the 4 targeted muscles of the study foot. Following the double-blind treatment period, all participants who met retreatment criteria were treated during the open-label period with Dysport 300 U on Cycle 2 Day 1 and either Dysport 300 U or 500 U on Cycle 3 Day 1. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.	Dysport 300 U n=53 Participants On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of Dysport 300 U intramuscular injection distributed between 4 injection points (75 U each) in the 4 targeted muscles of the study foot. Following the double-blind treatment period, all participants who met retreatment criteria were treated during the open-label period with Dysport 300 U on Cycle 2 Day 1 and either Dysport 300 U or 500 U on Cycle 3 Day 1. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.	Dysport 500 U n=48 Participants On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of Dysport 500 U intramuscular injection distributed between 4 injection points (125 U each) in the 4 targeted muscles of the study foot. Following the double-blind treatment period, all participants who met retreatment criteria were treated during the open-label period with Dysport 300 U on Cycle 2 Day 1 and either Dysport 300 U or 500 U on Cycle 3 Day 1. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.
LS Mean Change From Baseline in the Daily mFFI Activity Limitation Subscale Score at Weeks 4, 8 and 12 Week 4	-9.02 units on a scale Interval -12.08 to -5.96	-7.00 units on a scale Interval -10.08 to -3.91	-9.03 units on a scale Interval -12.28 to -5.79
LS Mean Change From Baseline in the Daily mFFI Activity Limitation Subscale Score at Weeks 4, 8 and 12 Week 8	-12.12 units on a scale Interval -15.52 to -8.71	-8.81 units on a scale Interval -12.17 to -5.45	-10.62 units on a scale Interval -14.17 to -7.07
LS Mean Change From Baseline in the Daily mFFI Activity Limitation Subscale Score at Weeks 4, 8 and 12 Week 12	-11.09 units on a scale Interval -14.79 to -7.4	-9.25 units on a scale Interval -12.87 to -5.63	-10.84 units on a scale Interval -14.69 to -6.99

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8 and 12 in the double-blind treatment period

Population: The ITT analysis set included all randomized participants. The results are presented for the participants with data available at Baseline and specific time points.

The HV angle was measured directly on weight-bearing anteriorposterior radiographs, in which the X-ray beam was angled 15° towards the heel centered on the second tarsometatarsal joint with a source to image-receptor distance of 100 centimeters (cm).

Outcome measures

Measure	Placebo n=59 Participants On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of placebo (matching with Dysport) intramuscular injection distributed between 4 injection points in the 4 targeted muscles of the study foot. Following the double-blind treatment period, all participants who met retreatment criteria were treated during the open-label period with Dysport 300 U on Cycle 2 Day 1 and either Dysport 300 U or 500 U on Cycle 3 Day 1. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.	Dysport 300 U n=62 Participants On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of Dysport 300 U intramuscular injection distributed between 4 injection points (75 U each) in the 4 targeted muscles of the study foot. Following the double-blind treatment period, all participants who met retreatment criteria were treated during the open-label period with Dysport 300 U on Cycle 2 Day 1 and either Dysport 300 U or 500 U on Cycle 3 Day 1. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.	Dysport 500 U n=54 Participants On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of Dysport 500 U intramuscular injection distributed between 4 injection points (125 U each) in the 4 targeted muscles of the study foot. Following the double-blind treatment period, all participants who met retreatment criteria were treated during the open-label period with Dysport 300 U on Cycle 2 Day 1 and either Dysport 300 U or 500 U on Cycle 3 Day 1. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.
LS Mean Change From Baseline in HV Angle at Weeks 4, 8 and 12 Week 4	-0.31 degrees Interval -1.06 to 0.45	-0.25 degrees Interval -0.99 to 0.49	-0.92 degrees Interval -1.71 to -0.13
LS Mean Change From Baseline in HV Angle at Weeks 4, 8 and 12 Week 8	-0.43 degrees Interval -1.17 to 0.3	-0.67 degrees Interval -1.4 to 0.05	-0.80 degrees Interval -1.57 to -0.04
LS Mean Change From Baseline in HV Angle at Weeks 4, 8 and 12 Week 12	0.30 degrees Interval -0.44 to 1.05	-0.68 degrees Interval -1.41 to 0.04	-0.45 degrees Interval -1.22 to 0.33

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8 and 12 in the double-blind treatment period

Population: The ITT analysis set included all randomized participants. The results are presented for the participants with data available at Baseline and specific time points.

The intermetatarsal angle was measured directly on weight-bearing anteriorposterior radiographs, in which the X-ray beam was angled 15° towards the heel centered on the second tarsometatarsal joint with a source to image-receptor distance of 100 cm.

Outcome measures

Measure	Placebo n=59 Participants On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of placebo (matching with Dysport) intramuscular injection distributed between 4 injection points in the 4 targeted muscles of the study foot. Following the double-blind treatment period, all participants who met retreatment criteria were treated during the open-label period with Dysport 300 U on Cycle 2 Day 1 and either Dysport 300 U or 500 U on Cycle 3 Day 1. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.	Dysport 300 U n=62 Participants On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of Dysport 300 U intramuscular injection distributed between 4 injection points (75 U each) in the 4 targeted muscles of the study foot. Following the double-blind treatment period, all participants who met retreatment criteria were treated during the open-label period with Dysport 300 U on Cycle 2 Day 1 and either Dysport 300 U or 500 U on Cycle 3 Day 1. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.	Dysport 500 U n=54 Participants On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of Dysport 500 U intramuscular injection distributed between 4 injection points (125 U each) in the 4 targeted muscles of the study foot. Following the double-blind treatment period, all participants who met retreatment criteria were treated during the open-label period with Dysport 300 U on Cycle 2 Day 1 and either Dysport 300 U or 500 U on Cycle 3 Day 1. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.
LS Mean Change From Baseline in Intermetatarsal Angle at Weeks 4, 8 and 12 Week 4	0.06 degrees Interval -0.34 to 0.46	0.40 degrees Interval 0.01 to 0.79	0.16 degrees Interval -0.25 to 0.58
LS Mean Change From Baseline in Intermetatarsal Angle at Weeks 4, 8 and 12 Week 8	-0.02 degrees Interval -0.41 to 0.36	0.49 degrees Interval 0.11 to 0.87	0.45 degrees Interval 0.05 to 0.85
LS Mean Change From Baseline in Intermetatarsal Angle at Weeks 4, 8 and 12 Week 12	0.42 degrees Interval 0.01 to 0.83	0.19 degrees Interval -0.21 to 0.59	0.04 degrees Interval -0.38 to 0.47

SECONDARY outcome

Timeframe: Up to 24 weeks in the double-blind treatment period

Population: The safety population included all participants who received at least one dose of study drug administration (including only partial administration). Participants who were not retreated were considered censored at the date of their last visit and not included in the summary but included in the analysis.

Time to retreatment was calculated as ([Date of retreatment - previous injection date] + 1) / 7 (week). Time to retreatment was calculated for each cycle and the data presented here for the double-blind treatment period.

Outcome measures

Measure	Placebo n=61 Participants On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of placebo (matching with Dysport) intramuscular injection distributed between 4 injection points in the 4 targeted muscles of the study foot. Following the double-blind treatment period, all participants who met retreatment criteria were treated during the open-label period with Dysport 300 U on Cycle 2 Day 1 and either Dysport 300 U or 500 U on Cycle 3 Day 1. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.	Dysport 300 U n=63 Participants On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of Dysport 300 U intramuscular injection distributed between 4 injection points (75 U each) in the 4 targeted muscles of the study foot. Following the double-blind treatment period, all participants who met retreatment criteria were treated during the open-label period with Dysport 300 U on Cycle 2 Day 1 and either Dysport 300 U or 500 U on Cycle 3 Day 1. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.	Dysport 500 U n=56 Participants On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of Dysport 500 U intramuscular injection distributed between 4 injection points (125 U each) in the 4 targeted muscles of the study foot. Following the double-blind treatment period, all participants who met retreatment criteria were treated during the open-label period with Dysport 300 U on Cycle 2 Day 1 and either Dysport 300 U or 500 U on Cycle 3 Day 1. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.
Median Time to Retreatment	12.6 weeks Interval 12.0 to 13.0	13.1 weeks Interval 13.0 to 16.0	13.1 weeks Interval 13.0 to 15.0

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8 and 12 in the double-blind treatment period

Population: The ITT analysis set included all randomized participants. The results are presented for the participants with data available at Baseline and specific time points.

An assessment of PGI-S of foot pain was conducted by the participant using a 4-point Likert scale ranging from 0= no pain to 3= severe pain. Higher scores indicate a worse outcome. The PGI-S was assessed by the participant by answering the following question: "How severe was your foot pain while performing physical activities (example, standing, walking or running) over the past week?" (0=no pain; 1=mild pain; 2=moderate pain; 3=severe pain).

Outcome measures

Measure	Placebo n=50 Participants On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of placebo (matching with Dysport) intramuscular injection distributed between 4 injection points in the 4 targeted muscles of the study foot. Following the double-blind treatment period, all participants who met retreatment criteria were treated during the open-label period with Dysport 300 U on Cycle 2 Day 1 and either Dysport 300 U or 500 U on Cycle 3 Day 1. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.	Dysport 300 U n=53 Participants On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of Dysport 300 U intramuscular injection distributed between 4 injection points (75 U each) in the 4 targeted muscles of the study foot. Following the double-blind treatment period, all participants who met retreatment criteria were treated during the open-label period with Dysport 300 U on Cycle 2 Day 1 and either Dysport 300 U or 500 U on Cycle 3 Day 1. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.	Dysport 500 U n=46 Participants On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of Dysport 500 U intramuscular injection distributed between 4 injection points (125 U each) in the 4 targeted muscles of the study foot. Following the double-blind treatment period, all participants who met retreatment criteria were treated during the open-label period with Dysport 300 U on Cycle 2 Day 1 and either Dysport 300 U or 500 U on Cycle 3 Day 1. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.
LS Mean Change From Baseline in Patient Global Impression of Severity (PGI-S) of Foot Pain Score at Weeks 4, 8 and 12 Week 4	-0.76 units on a scale Interval -0.99 to -0.54	-0.56 units on a scale Interval -0.8 to -0.32	-0.46 units on a scale Interval -0.71 to -0.22
LS Mean Change From Baseline in Patient Global Impression of Severity (PGI-S) of Foot Pain Score at Weeks 4, 8 and 12 Week 8	-0.74 units on a scale Interval -0.97 to -0.51	-0.64 units on a scale Interval -0.88 to -0.39	-0.79 units on a scale Interval -1.03 to -0.56
LS Mean Change From Baseline in Patient Global Impression of Severity (PGI-S) of Foot Pain Score at Weeks 4, 8 and 12 Week 12	-0.58 units on a scale Interval -0.82 to -0.35	-0.59 units on a scale Interval -0.82 to -0.36	-0.60 units on a scale Interval -0.85 to -0.35

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8 and 12 in the double-blind treatment period

Population: The ITT analysis set included all randomized participants. The results are presented for the participants with data available at Baseline and specific time points.

An assessment of PGI-S of disability was conducted by the participant using a 4-point Likert scale ranging from 0= no disability to 3= severe disability. Higher scores indicate a worse outcome. The PGI-S was assessed by the participant by answering the following question: "How severe was your disability while performing physical activities (example, standing, walking or running) over the past week?" (0=no disability; 1=mild disability; 2=moderate disability; 3=severe disability).

Outcome measures

Measure	Placebo n=50 Participants On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of placebo (matching with Dysport) intramuscular injection distributed between 4 injection points in the 4 targeted muscles of the study foot. Following the double-blind treatment period, all participants who met retreatment criteria were treated during the open-label period with Dysport 300 U on Cycle 2 Day 1 and either Dysport 300 U or 500 U on Cycle 3 Day 1. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.	Dysport 300 U n=53 Participants On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of Dysport 300 U intramuscular injection distributed between 4 injection points (75 U each) in the 4 targeted muscles of the study foot. Following the double-blind treatment period, all participants who met retreatment criteria were treated during the open-label period with Dysport 300 U on Cycle 2 Day 1 and either Dysport 300 U or 500 U on Cycle 3 Day 1. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.	Dysport 500 U n=46 Participants On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of Dysport 500 U intramuscular injection distributed between 4 injection points (125 U each) in the 4 targeted muscles of the study foot. Following the double-blind treatment period, all participants who met retreatment criteria were treated during the open-label period with Dysport 300 U on Cycle 2 Day 1 and either Dysport 300 U or 500 U on Cycle 3 Day 1. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.
LS Mean Change From Baseline in PGI-S of Disability Score at Weeks 4, 8 and 12 Week 8	-0.54 units on a scale Interval -0.8 to -0.28	-0.66 units on a scale Interval -0.93 to -0.38	-0.68 units on a scale Interval -0.94 to -0.42
LS Mean Change From Baseline in PGI-S of Disability Score at Weeks 4, 8 and 12 Week 12	-0.55 units on a scale Interval -0.8 to -0.31	-0.63 units on a scale Interval -0.87 to -0.38	-0.67 units on a scale Interval -0.93 to -0.4
LS Mean Change From Baseline in PGI-S of Disability Score at Weeks 4, 8 and 12 Week 4	-0.47 units on a scale Interval -0.7 to -0.25	-0.57 units on a scale Interval -0.82 to -0.32	-0.42 units on a scale Interval -0.68 to -0.16

SECONDARY outcome

Timeframe: Weeks 4, 8 and 12 in the double-blind treatment period

Population: The ITT analysis set included all randomized participants. The results are presented for the participants with data available at specific time points.

An assessment of PGI-I of foot pain was conducted by the participant using a 7-point Likert scale ranging from -3= very much worse to +3= very much improved. Higher scores indicate a better outcome. The PGI-I was assessed by the participant answering the following question: "Compared to your foot pain prior to the study treatment initiation, your foot pain while performing physical activities (example, standing, walking or running) now is: +3=very much improved; +2=much improved; +1=minimally improved; 0=no change; -1=minimally worse; -2=much worse; -3=very much worse".

Outcome measures

Measure	Placebo n=51 Participants On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of placebo (matching with Dysport) intramuscular injection distributed between 4 injection points in the 4 targeted muscles of the study foot. Following the double-blind treatment period, all participants who met retreatment criteria were treated during the open-label period with Dysport 300 U on Cycle 2 Day 1 and either Dysport 300 U or 500 U on Cycle 3 Day 1. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.	Dysport 300 U n=53 Participants On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of Dysport 300 U intramuscular injection distributed between 4 injection points (75 U each) in the 4 targeted muscles of the study foot. Following the double-blind treatment period, all participants who met retreatment criteria were treated during the open-label period with Dysport 300 U on Cycle 2 Day 1 and either Dysport 300 U or 500 U on Cycle 3 Day 1. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.	Dysport 500 U n=46 Participants On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of Dysport 500 U intramuscular injection distributed between 4 injection points (125 U each) in the 4 targeted muscles of the study foot. Following the double-blind treatment period, all participants who met retreatment criteria were treated during the open-label period with Dysport 300 U on Cycle 2 Day 1 and either Dysport 300 U or 500 U on Cycle 3 Day 1. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.
LS Mean Patient Global Impression of Improvement (PGI-I) of Foot Pain Score at Weeks 4, 8 and 12 Week 4	1.32 units on a scale Interval 0.98 to 1.65	1.32 units on a scale Interval 0.98 to 1.66	1.53 units on a scale Interval 1.17 to 1.9
LS Mean Patient Global Impression of Improvement (PGI-I) of Foot Pain Score at Weeks 4, 8 and 12 Week 8	1.30 units on a scale Interval 0.94 to 1.67	1.36 units on a scale Interval 1.0 to 1.73	1.32 units on a scale Interval 0.96 to 1.69
LS Mean Patient Global Impression of Improvement (PGI-I) of Foot Pain Score at Weeks 4, 8 and 12 Week 12	1.28 units on a scale Interval 0.93 to 1.63	1.40 units on a scale Interval 1.07 to 1.74	1.21 units on a scale Interval 0.83 to 1.59

SECONDARY outcome

Timeframe: Weeks 4, 8 and 12 in the double-blind treatment period

Population: The ITT analysis set included all randomized participants. The results are presented for the participants with data available at specific time points.

An assessment of PGI-I of the participant's disability was conducted by the participant using a 7-point Likert scale ranging from -3= very much worse to +3= very much improved. Higher scores indicate a better outcome. The PGI-I was assessed by the participant answering the following question: "Compared to your disability prior to the study treatment initiation, your disability while performing physical activities (example, standing, walking or running) now is: +3=very much improved; +2=much improved; +1=minimally improved; 0=no change; -1=minimally worse; -2=much worse; -3=very much worse".

Outcome measures

Measure	Placebo n=51 Participants On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of placebo (matching with Dysport) intramuscular injection distributed between 4 injection points in the 4 targeted muscles of the study foot. Following the double-blind treatment period, all participants who met retreatment criteria were treated during the open-label period with Dysport 300 U on Cycle 2 Day 1 and either Dysport 300 U or 500 U on Cycle 3 Day 1. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.	Dysport 300 U n=53 Participants On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of Dysport 300 U intramuscular injection distributed between 4 injection points (75 U each) in the 4 targeted muscles of the study foot. Following the double-blind treatment period, all participants who met retreatment criteria were treated during the open-label period with Dysport 300 U on Cycle 2 Day 1 and either Dysport 300 U or 500 U on Cycle 3 Day 1. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.	Dysport 500 U n=46 Participants On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of Dysport 500 U intramuscular injection distributed between 4 injection points (125 U each) in the 4 targeted muscles of the study foot. Following the double-blind treatment period, all participants who met retreatment criteria were treated during the open-label period with Dysport 300 U on Cycle 2 Day 1 and either Dysport 300 U or 500 U on Cycle 3 Day 1. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.
LS Mean PGI-I of Disability Score at Weeks 4, 8 and 12 Week 4	1.15 units on a scale Interval 0.83 to 1.47	1.16 units on a scale Interval 0.83 to 1.48	1.31 units on a scale Interval 0.95 to 1.66
LS Mean PGI-I of Disability Score at Weeks 4, 8 and 12 Week 8	1.19 units on a scale Interval 0.85 to 1.53	1.23 units on a scale Interval 0.88 to 1.57	1.41 units on a scale Interval 1.06 to 1.75
LS Mean PGI-I of Disability Score at Weeks 4, 8 and 12 Week 12	1.15 units on a scale Interval 0.81 to 1.48	1.21 units on a scale Interval 0.89 to 1.52	1.28 units on a scale Interval 0.92 to 1.64

SECONDARY outcome

Timeframe: Baseline and Weeks 8 and 12 in the double-blind treatment period

Population: The ITT analysis set included all randomized participants. The results are presented for the participants with data available at Baseline and specific time points.

The SF-36 is a 36-item questionnaire which measures the extent to which physical health impacts an individual's functional ability and perceived wellbeing in mental, social, and physical aspects of life. The SF-36 has 8 subscales: physical function, role physical, bodily pain, global health, vitality, social function, role emotional and mental health. Each scale ranges from 0-100, where 0= lowest level of health and 100= highest level of health. Scores on these subscales can be aggregated into the physical component summary (physical function, role physical, bodily pain and global health) and mental component summary (mental health, vitality, social function and role emotional). Physical component summary score ranges from 0.65 to 80.73 and mental component summary score ranges from -8.81 to 81.65, where low score indicates lowest level of health and high score indicates highest level of health. Positive change from Baseline indicates an improvement in quality of life.

Outcome measures

Measure	Placebo n=58 Participants On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of placebo (matching with Dysport) intramuscular injection distributed between 4 injection points in the 4 targeted muscles of the study foot. Following the double-blind treatment period, all participants who met retreatment criteria were treated during the open-label period with Dysport 300 U on Cycle 2 Day 1 and either Dysport 300 U or 500 U on Cycle 3 Day 1. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.	Dysport 300 U n=59 Participants On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of Dysport 300 U intramuscular injection distributed between 4 injection points (75 U each) in the 4 targeted muscles of the study foot. Following the double-blind treatment period, all participants who met retreatment criteria were treated during the open-label period with Dysport 300 U on Cycle 2 Day 1 and either Dysport 300 U or 500 U on Cycle 3 Day 1. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.	Dysport 500 U n=53 Participants On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of Dysport 500 U intramuscular injection distributed between 4 injection points (125 U each) in the 4 targeted muscles of the study foot. Following the double-blind treatment period, all participants who met retreatment criteria were treated during the open-label period with Dysport 300 U on Cycle 2 Day 1 and either Dysport 300 U or 500 U on Cycle 3 Day 1. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.
Mean Change From Baseline in 36-Item Short Form Health Survey (SF-36) Score at Weeks 8 and 12 Week 8: SF-36 - Physical component summary score	3.08 units on a scale Standard Deviation 7.815	3.19 units on a scale Standard Deviation 6.013	3.30 units on a scale Standard Deviation 7.127
Mean Change From Baseline in 36-Item Short Form Health Survey (SF-36) Score at Weeks 8 and 12 Week 12: SF-36 - Physical component summary score	3.19 units on a scale Standard Deviation 7.776	5.04 units on a scale Standard Deviation 7.430	2.51 units on a scale Standard Deviation 7.133
Mean Change From Baseline in 36-Item Short Form Health Survey (SF-36) Score at Weeks 8 and 12 Week 8: SF-36 - Mental component summary score	-0.66 units on a scale Standard Deviation 7.299	-0.30 units on a scale Standard Deviation 6.419	-0.84 units on a scale Standard Deviation 6.022
Mean Change From Baseline in 36-Item Short Form Health Survey (SF-36) Score at Weeks 8 and 12 Week 12: SF-36 - Mental component summary score	-0.43 units on a scale Standard Deviation 5.587	-0.28 units on a scale Standard Deviation 7.821	-0.22 units on a scale Standard Deviation 6.970

Adverse Events

Double-Blind Treatment Period (Cycle 1): Placebo

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Double-Blind Treatment Period (Cycle 1): Dysport 300 U

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Double-Blind Treatment Period (Cycle 1): Dysport 500 U

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Open-Label Treatment Period (Cycle 2): Dysport 300 U

Serious events: 1 serious events

Other events: 11 other events

Deaths: 0 deaths

Open-Label Treatment Period (Cycle 3): Dysport 300 U

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Open-Label Treatment Period (Cycle 3): Dysport 500 U

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Measure	Double-Blind Treatment Period (Cycle 1): Placebo n=61 participants at risk On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of placebo (matching with Dysport) intramuscular injection distributed between 4 injection points in the 4 targeted muscles of the study foot. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.	Double-Blind Treatment Period (Cycle 1): Dysport 300 U n=63 participants at risk On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of Dysport 300 U intramuscular injection distributed between 4 injection points (75 U each) in the 4 targeted muscles of the study foot. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.	Double-Blind Treatment Period (Cycle 1): Dysport 500 U n=56 participants at risk On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of Dysport 500 U intramuscular injection distributed between 4 injection points (125 U each) in the 4 targeted muscles of the study foot. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.	Open-Label Treatment Period (Cycle 2): Dysport 300 U n=146 participants at risk On Cycle 2 Day 1 in the open-label treatment period, all participants who met retreatment criteria received a single dose of Dysport 300 U intramuscular injection distributed between 4 injection points (75 U each) in the 4 targeted muscles of the study foot. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.	Open-Label Treatment Period (Cycle 3): Dysport 300 U n=8 participants at risk On Cycle 3 Day 1 in the open-label treatment period, all participants who met retreatment criteria received a single dose of Dysport 300 U intramuscular injection distributed between 4 injection points (75 U each) in the 4 targeted muscles of the study foot. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.	Open-Label Treatment Period (Cycle 3): Dysport 500 U n=56 participants at risk On Cycle 3 Day 1 in the open-label treatment period, all participants who met retreatment criteria received a single dose of Dysport 500 U intramuscular injection distributed between 4 injection points (125 U each) in the 4 targeted muscles of the study foot. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chronic myeloid leukaemia	0.00% 0/61 • From first administration of study drug (Cycle 1 Day 1) up to end of the study, approximately 36 weeks. The safety population included all participants who received at least one dose of study drug administration (including only partial administration).	0.00% 0/63 • From first administration of study drug (Cycle 1 Day 1) up to end of the study, approximately 36 weeks. The safety population included all participants who received at least one dose of study drug administration (including only partial administration).	1.8% 1/56 • Number of events 1 • From first administration of study drug (Cycle 1 Day 1) up to end of the study, approximately 36 weeks. The safety population included all participants who received at least one dose of study drug administration (including only partial administration).	0.00% 0/146 • From first administration of study drug (Cycle 1 Day 1) up to end of the study, approximately 36 weeks. The safety population included all participants who received at least one dose of study drug administration (including only partial administration).	0.00% 0/8 • From first administration of study drug (Cycle 1 Day 1) up to end of the study, approximately 36 weeks. The safety population included all participants who received at least one dose of study drug administration (including only partial administration).	0.00% 0/56 • From first administration of study drug (Cycle 1 Day 1) up to end of the study, approximately 36 weeks. The safety population included all participants who received at least one dose of study drug administration (including only partial administration).
Nervous system disorders Aphasia	0.00% 0/61 • From first administration of study drug (Cycle 1 Day 1) up to end of the study, approximately 36 weeks. The safety population included all participants who received at least one dose of study drug administration (including only partial administration).	0.00% 0/63 • From first administration of study drug (Cycle 1 Day 1) up to end of the study, approximately 36 weeks. The safety population included all participants who received at least one dose of study drug administration (including only partial administration).	0.00% 0/56 • From first administration of study drug (Cycle 1 Day 1) up to end of the study, approximately 36 weeks. The safety population included all participants who received at least one dose of study drug administration (including only partial administration).	0.00% 0/146 • From first administration of study drug (Cycle 1 Day 1) up to end of the study, approximately 36 weeks. The safety population included all participants who received at least one dose of study drug administration (including only partial administration).	0.00% 0/8 • From first administration of study drug (Cycle 1 Day 1) up to end of the study, approximately 36 weeks. The safety population included all participants who received at least one dose of study drug administration (including only partial administration).	1.8% 1/56 • Number of events 1 • From first administration of study drug (Cycle 1 Day 1) up to end of the study, approximately 36 weeks. The safety population included all participants who received at least one dose of study drug administration (including only partial administration).
Gastrointestinal disorders Abdominal pain	0.00% 0/61 • From first administration of study drug (Cycle 1 Day 1) up to end of the study, approximately 36 weeks. The safety population included all participants who received at least one dose of study drug administration (including only partial administration).	0.00% 0/63 • From first administration of study drug (Cycle 1 Day 1) up to end of the study, approximately 36 weeks. The safety population included all participants who received at least one dose of study drug administration (including only partial administration).	0.00% 0/56 • From first administration of study drug (Cycle 1 Day 1) up to end of the study, approximately 36 weeks. The safety population included all participants who received at least one dose of study drug administration (including only partial administration).	0.68% 1/146 • Number of events 1 • From first administration of study drug (Cycle 1 Day 1) up to end of the study, approximately 36 weeks. The safety population included all participants who received at least one dose of study drug administration (including only partial administration).	0.00% 0/8 • From first administration of study drug (Cycle 1 Day 1) up to end of the study, approximately 36 weeks. The safety population included all participants who received at least one dose of study drug administration (including only partial administration).	0.00% 0/56 • From first administration of study drug (Cycle 1 Day 1) up to end of the study, approximately 36 weeks. The safety population included all participants who received at least one dose of study drug administration (including only partial administration).
Gastrointestinal disorders Constipation	0.00% 0/61 • From first administration of study drug (Cycle 1 Day 1) up to end of the study, approximately 36 weeks. The safety population included all participants who received at least one dose of study drug administration (including only partial administration).	0.00% 0/63 • From first administration of study drug (Cycle 1 Day 1) up to end of the study, approximately 36 weeks. The safety population included all participants who received at least one dose of study drug administration (including only partial administration).	0.00% 0/56 • From first administration of study drug (Cycle 1 Day 1) up to end of the study, approximately 36 weeks. The safety population included all participants who received at least one dose of study drug administration (including only partial administration).	0.68% 1/146 • Number of events 1 • From first administration of study drug (Cycle 1 Day 1) up to end of the study, approximately 36 weeks. The safety population included all participants who received at least one dose of study drug administration (including only partial administration).	0.00% 0/8 • From first administration of study drug (Cycle 1 Day 1) up to end of the study, approximately 36 weeks. The safety population included all participants who received at least one dose of study drug administration (including only partial administration).	0.00% 0/56 • From first administration of study drug (Cycle 1 Day 1) up to end of the study, approximately 36 weeks. The safety population included all participants who received at least one dose of study drug administration (including only partial administration).
Gastrointestinal disorders Colitis ischaemic	0.00% 0/61 • From first administration of study drug (Cycle 1 Day 1) up to end of the study, approximately 36 weeks. The safety population included all participants who received at least one dose of study drug administration (including only partial administration).	0.00% 0/63 • From first administration of study drug (Cycle 1 Day 1) up to end of the study, approximately 36 weeks. The safety population included all participants who received at least one dose of study drug administration (including only partial administration).	0.00% 0/56 • From first administration of study drug (Cycle 1 Day 1) up to end of the study, approximately 36 weeks. The safety population included all participants who received at least one dose of study drug administration (including only partial administration).	0.68% 1/146 • Number of events 1 • From first administration of study drug (Cycle 1 Day 1) up to end of the study, approximately 36 weeks. The safety population included all participants who received at least one dose of study drug administration (including only partial administration).	0.00% 0/8 • From first administration of study drug (Cycle 1 Day 1) up to end of the study, approximately 36 weeks. The safety population included all participants who received at least one dose of study drug administration (including only partial administration).	0.00% 0/56 • From first administration of study drug (Cycle 1 Day 1) up to end of the study, approximately 36 weeks. The safety population included all participants who received at least one dose of study drug administration (including only partial administration).

Other adverse events

Measure	Double-Blind Treatment Period (Cycle 1): Placebo n=61 participants at risk On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of placebo (matching with Dysport) intramuscular injection distributed between 4 injection points in the 4 targeted muscles of the study foot. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.	Double-Blind Treatment Period (Cycle 1): Dysport 300 U n=63 participants at risk On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of Dysport 300 U intramuscular injection distributed between 4 injection points (75 U each) in the 4 targeted muscles of the study foot. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.	Double-Blind Treatment Period (Cycle 1): Dysport 500 U n=56 participants at risk On Cycle 1 Day 1 in the double-blind treatment period, participants received a single dose of Dysport 500 U intramuscular injection distributed between 4 injection points (125 U each) in the 4 targeted muscles of the study foot. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.	Open-Label Treatment Period (Cycle 2): Dysport 300 U n=146 participants at risk On Cycle 2 Day 1 in the open-label treatment period, all participants who met retreatment criteria received a single dose of Dysport 300 U intramuscular injection distributed between 4 injection points (75 U each) in the 4 targeted muscles of the study foot. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.	Open-Label Treatment Period (Cycle 3): Dysport 300 U n=8 participants at risk On Cycle 3 Day 1 in the open-label treatment period, all participants who met retreatment criteria received a single dose of Dysport 300 U intramuscular injection distributed between 4 injection points (75 U each) in the 4 targeted muscles of the study foot. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.	Open-Label Treatment Period (Cycle 3): Dysport 500 U n=56 participants at risk On Cycle 3 Day 1 in the open-label treatment period, all participants who met retreatment criteria received a single dose of Dysport 500 U intramuscular injection distributed between 4 injection points (125 U each) in the 4 targeted muscles of the study foot. The 4 targeted muscles of the study foot were the oblique head of the adductor hallucis muscle, the transverse head of the adductor hallucis muscle, the flexor hallucis brevis muscle and the extensor hallucis brevis muscle.
General disorders Injection site pain	1.6% 1/61 • Number of events 1 • From first administration of study drug (Cycle 1 Day 1) up to end of the study, approximately 36 weeks. The safety population included all participants who received at least one dose of study drug administration (including only partial administration).	3.2% 2/63 • Number of events 2 • From first administration of study drug (Cycle 1 Day 1) up to end of the study, approximately 36 weeks. The safety population included all participants who received at least one dose of study drug administration (including only partial administration).	5.4% 3/56 • Number of events 3 • From first administration of study drug (Cycle 1 Day 1) up to end of the study, approximately 36 weeks. The safety population included all participants who received at least one dose of study drug administration (including only partial administration).	2.1% 3/146 • Number of events 4 • From first administration of study drug (Cycle 1 Day 1) up to end of the study, approximately 36 weeks. The safety population included all participants who received at least one dose of study drug administration (including only partial administration).	0.00% 0/8 • From first administration of study drug (Cycle 1 Day 1) up to end of the study, approximately 36 weeks. The safety population included all participants who received at least one dose of study drug administration (including only partial administration).	5.4% 3/56 • Number of events 3 • From first administration of study drug (Cycle 1 Day 1) up to end of the study, approximately 36 weeks. The safety population included all participants who received at least one dose of study drug administration (including only partial administration).
Musculoskeletal and connective tissue disorders Pain in extremity	4.9% 3/61 • Number of events 3 • From first administration of study drug (Cycle 1 Day 1) up to end of the study, approximately 36 weeks. The safety population included all participants who received at least one dose of study drug administration (including only partial administration).	3.2% 2/63 • Number of events 3 • From first administration of study drug (Cycle 1 Day 1) up to end of the study, approximately 36 weeks. The safety population included all participants who received at least one dose of study drug administration (including only partial administration).	5.4% 3/56 • Number of events 5 • From first administration of study drug (Cycle 1 Day 1) up to end of the study, approximately 36 weeks. The safety population included all participants who received at least one dose of study drug administration (including only partial administration).	4.1% 6/146 • Number of events 6 • From first administration of study drug (Cycle 1 Day 1) up to end of the study, approximately 36 weeks. The safety population included all participants who received at least one dose of study drug administration (including only partial administration).	0.00% 0/8 • From first administration of study drug (Cycle 1 Day 1) up to end of the study, approximately 36 weeks. The safety population included all participants who received at least one dose of study drug administration (including only partial administration).	1.8% 1/56 • Number of events 1 • From first administration of study drug (Cycle 1 Day 1) up to end of the study, approximately 36 weeks. The safety population included all participants who received at least one dose of study drug administration (including only partial administration).
Skin and subcutaneous tissue disorders Hyperkeratosis	3.3% 2/61 • Number of events 2 • From first administration of study drug (Cycle 1 Day 1) up to end of the study, approximately 36 weeks. The safety population included all participants who received at least one dose of study drug administration (including only partial administration).	7.9% 5/63 • Number of events 5 • From first administration of study drug (Cycle 1 Day 1) up to end of the study, approximately 36 weeks. The safety population included all participants who received at least one dose of study drug administration (including only partial administration).	1.8% 1/56 • Number of events 1 • From first administration of study drug (Cycle 1 Day 1) up to end of the study, approximately 36 weeks. The safety population included all participants who received at least one dose of study drug administration (including only partial administration).	2.1% 3/146 • Number of events 3 • From first administration of study drug (Cycle 1 Day 1) up to end of the study, approximately 36 weeks. The safety population included all participants who received at least one dose of study drug administration (including only partial administration).	0.00% 0/8 • From first administration of study drug (Cycle 1 Day 1) up to end of the study, approximately 36 weeks. The safety population included all participants who received at least one dose of study drug administration (including only partial administration).	0.00% 0/56 • From first administration of study drug (Cycle 1 Day 1) up to end of the study, approximately 36 weeks. The safety population included all participants who received at least one dose of study drug administration (including only partial administration).

Additional Information

Medical Director

Ipsen Pharma

Phone: see email

Email: clinical.trials@ipsen.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place