Post-Stroke Spasticity, Cerebrovascular Accident
Conditions
Keywords
Post-Stroke, Lower Limb, botulinum toxin type A, Spasticity
Brief summary
This is a study to confirm the superior efficacy of GSK1358820 over placebo in patients with equinus deformity associated with post-stroke lower limb spasticity using the Modified Ashworth Scale (MAS) ankle score.
Detailed description
This is a study to confirm the superior efficacy of GSK1358820 over placebo in patients with equinus deformity associated with post-stroke lower limb spasticity using the Modified Ashworth Scale (MAS) ankle score.
Interventions
DRUGGSK1358820
botulinum toxin type A
DRUGPlacebo
Placebo
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Subjects eligible for enrollment in the study must meet all of the following criteria: * Patients with lower limb spasticity who are at least 6 months post-stroke and present with equinus deformity (plantar flexion of the ankle) at the start of double-blind phase (Visit 2). * Patients with MAS ankle score of ≥3 at the start of double-blind phase (Visit 2). * Male or female between 20 and 80 years of age at the time of informed consent. For males, only those who can practice contraception during the study period are eligible. * ≥50kg in weight at the start of double-blind phase (Visit 2). * Inpatient or outpatient; however, the hospitalization status must remain unchanged during the double-blind phase. NOTE: Subjects may be hospitalized for ≤10 days after injection during the treatment period. * Written informed consent from the subject him/herself. If the subject's signature is not legible, the attendance of a witness is required.
Exclusion criteria
* A subject will not be eligible for inclusion in this study if any of the following criteria apply: * Bilateral hemiplegia or quadriplegia. * Presence of fixed contractures of the ankle (absence of range of motion). * Profound atrophy of the muscles to be injected. * Previous surgical intervention, phenol block, ethanol block, or Muscle Afferent Block (MAB) for ankle spasticity. * Casting of the study lower limb within 3 months prior to the start of double-blind phase (Visit 2). * Current treatment with intrathecal baclofen. * Use of peripheral muscle relaxants (dantrolene sodium, suxamethonium chloride, pancuronium bromide, vecuronium bromide, rocuronium bromide). * Concurrent use of antibiotics that interfere with neuromuscular transmission, such as aminoglycoside antibiotics (e.g., streptomycin sulfate, kanamycin sulfate, gentamicin sulfate, neomycin sulphate, spectinomycin hydrochloride), polypeptide antibiotics (e.g., polymixin B sulfate), lincomycin antibiotics (e.g., lincomycin hydrochloride, clindamycin), and enviomycin sulfate. * Previous or current botulinum toxin therapy of any serotype. * Diagnosis of systemic neuromuscular disorders (e.g., myasthenia gravis, Lambert-Eaton syndrome, amyotrophic lateral sclerosis). * Females who are pregnant, nursing, may be pregnant, or planning a pregnancy during the study period. * Known allergy or hypersensitivity to any ingredient of study medication (e.g., human serum albumin). * Presence of psychiatric disorder or impairment of intellectual function that may interfere with the subject's ability to give informed consent or the conduct of the study. * Bedridden patients. * Presence of clinically unstable severe cardiovascular disease. * Presence of clinically significant severe renal or hepatic disease. * Infection or dermatological condition at the proposed injection sites. * Previous or planned participation in another clinical study (including the upper limb spasticity study of GSK1358820) within 6 months prior to the start of double-blind phase (Visit 2). * Others whom the investigator or sub investigator considers not eligible for the study. * Clinically significant severe reduction of muscle strength. * Angle closure glaucoma or its preposition (narrow angle).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve (AUC) for the Change From Baseline in Modified Ashworth Scale (MAS) Ankle Score to the End of the DB Phase (Week 12) | Baseline, Week 12 | Change from baseline in MAS ankle score using a 6-point scale (0, 1, 1+ \[regarded as 1.5\], 2, 3, and 4; 0=no increase in muscle tone; 4=affected part\[s\] rigid in flexion/extension) to each time point in the DB phase was calculated. In the graph plotting time points on the horizontal axis and changes from baseline on the vertical axis, the area surrounded by the MAS ankle score change curve and the horizontal axis was calculated and used as a summary index (AUC) for assessment of the MAS ankle score. Negative changes from baseline indicate improvement, and the AUC has a negative sign. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in the MAS Ankle Score From Baseline to Week 12 of the Double-blind Phase | Baseline; Weeks 1, 4, 6, 8, and 12 | The investigator assessed Modified Ashworth Scale (MAS) ankle score using a 6-point scale (0, 1, 1+, 2, 3, and 4; 0=No increase in muscle tone to 4=Affected part\[s\] rigid in flexion or extension) at each time point in the double-blind phase. The +1 (slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder \[less than half\] of ROM \[range of motion\]) of MAS score is regarded as score 1.5. |
| Mean Change From Baseline in the Physician's Rating Score (PRS) From Baseline to Week 12 of the Double-blind Phase | Baseline; Weeks 1, 4, 6, 8, and 12 | The investigator assessed the PRS of gait pattern consisting of 3 parameters. Affected limb was scored on a scale of -1 (worst) to 9 (best) based on 3 parameters (initial foot contact, foot contact at midstance, gait assistive devices) at each time point in double-blind phase. |
| Mean Change From Baseline in the Time (Seconds) to Walk 10 Meters From Baseline to Week 12 of the Double-blind Phase | Baseline; Weeks 1, 4, 6, 8, and 12 | The time (seconds) required to walk 10 meters was measured at each time point in the double-blind phase. |
| Mean Change From Baseline in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Investigator From Baseline to Week 12 of the Double-blind Phase | Baseline; Weeks 1, 4, 6, 8, and 12 | The CGI of functional disability was assessed at each visit using the 11-point Numeric Rating Scale (NRS) (-5=Worst Possible to 5=Best Possible) at each time point in the double-blind phase. |
| Mean Change From Baseline in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Participant From Baseline to Week 12 of the Double-blind Phase | Baseline; Weeks 1, 4, 6, 8, and 12 | The CGI of functional disability was assessed at each visit using the 11-point Numeric Rating Scale (NRS) (-5=Worst Possible to 5=Best Possible) at each time point in the double-blind phase |
| Mean Change From Baseline in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Physiotherapist/Occupational Therapist From Baseline to Week 12 of the Double-blind Phase | Baseline; Weeks 1, 4, 6, 8, and 12 | The CGI of functional disability was assessed at each visit using the 11-point Numeric Rating Scale (NRS) (-5=Worst Possible to 5=Best Possible) at each time point in the double-blind phase |
| Mean Change From Baseline (at the Start of the Double-blind Phase) in the MAS Ankle Score at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Baseline; Weeks 4, 8, and 12 after each injection (up to Week 48; injections given from Week 12 to Week 36) | The investigator assessed Modified Ashworth Scale (MAS) ankle score using a 6-point scale (0, 1, 1+, 2, 3, and 4; 0=No increase in muscle tone to 4=Affected part\[s\] rigid in flexion or extension) at each time point from baseline (at the start of the double-blind phase) to Week 48. The +1 (slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder \[less than half\] of ROM \[range of motion\]) of MAS score is regarded as score 1.5. |
| Mean Change From Baseline (at the Start of the Double-blind Phase) in the Physician's Rating Score (PRS) at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Baseline; Weeks 4, 8, and 12 after each injection (up to Week 48; injections given from Week 12 to Week 36) | The investigator assessed the PRS of gait pattern consisting of 3 parameters. Affected limb was scored on a scale of -1 (worst) to 9 (best) based on 3 parameters (initial foot contact, foot contact at midstance, gait assistive devices) at each time point from baseline (at the start of the double-blind phase) to Week 48. |
| Mean Change From Baseline (at the Start of the Double-blind Phase) in the Time (Seconds) to Walk 10 Meters at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Baseline; Weeks 4, 8, and 12 after each injection (up to Week 48; injections given from Week 12 to Week 36) | The time (seconds) required to walk 10 meters was measured at each time point from baseline (at the start of the double-blind phase) to Week 48. |
| Mean Change From Baseline (at the Start of the Double-blind Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Investigator at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Baseline; Weeks 4, 8, and 12 after each injection (up to Week 48; injections given from Week 12 to Week 36) | The CGI of functional disability was assessed at each visit using the 11-point Numeric Rating Scale (NRS) (-5=Worst Possible to 5=Best Possible) at each time point from baseline (at the start of the double-blind phase) to Week 48. |
| Mean Change From Baseline (at the Start of the Double-blind Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Participant at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Baseline; Weeks 4, 8, and 12 after each injection (up to Week 48; injections given from Week 12 to Week 36) | The CGI of functional disability was assessed at each visit using the 11-point Numeric Rating Scale (NRS) (-5=Worst Possible to 5=Best Possible) at each time point from baseline (at the start of the double-blind phase) to Week 48. |
| Mean Change From Baseline (at the Start of the DB Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Physiotherapist/Occupational Therapist at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Baseline; Weeks 4, 8, and 12 after each injection (up to Week 48; injections given from Week 12 to Week 36) | The CGI of functional disability was assessed at each visit using the 11-point Numeric Rating Scale (NRS) (-5=Worst Possible to 5=Best Possible) at each time point from baseline (at the start of the double-blind phase) to Week 48. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BTX 300U BTX (GSK1358820) 300U (24 mL) was injected into the lower limb muscles in the 12-week double-blind phase (DB) (once at Week 0) | 58 |
| Placebo Placebo 24 mL was injected into the lower limb muscles in the 12-week double-blind phase (DB) (once at Week 0) | 62 |
| Total | 120 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Double-Blind Phase (12 Weeks) | Adverse Event | 3 | 0 | 0 | 0 |
| Double-Blind Phase (12 Weeks) | Protocol Violation | 0 | 1 | 0 | 0 |
| Double-Blind Phase (12 Weeks) | Withdrawal by Subject | 3 | 0 | 0 | 0 |
| Open-Label Phase (36 Weeks) | Adverse Event | 0 | 0 | 1 | 6 |
| Open-Label Phase (36 Weeks) | Meeting the Exclusion Criteria | 0 | 0 | 0 | 1 |
| Open-Label Phase (36 Weeks) | Withdrawal by Subject | 0 | 0 | 6 | 2 |
Baseline characteristics
| Characteristic | BTX 300U | Placebo | Total |
|---|---|---|---|
| Age Continuous | 62.4 years STANDARD_DEVIATION 8.66 | 62.5 years STANDARD_DEVIATION 9.32 | 62.5 years STANDARD_DEVIATION 8.97 |
| Race/Ethnicity, Customized Asian-Japanese | 58 participants | 62 participants | 120 participants |
| Sex: Female, Male Female | 8 Participants | 16 Participants | 24 Participants |
| Sex: Female, Male Male | 50 Participants | 46 Participants | 96 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 16 / 58 | 16 / 62 | 23 / 50 | 16 / 57 |
| serious Total, serious adverse events | 5 / 58 | 1 / 62 | 3 / 50 | 8 / 57 |
Outcome results
Primary
Area Under the Curve (AUC) for the Change From Baseline in Modified Ashworth Scale (MAS) Ankle Score to the End of the DB Phase (Week 12)
Change from baseline in MAS ankle score using a 6-point scale (0, 1, 1+ \[regarded as 1.5\], 2, 3, and 4; 0=no increase in muscle tone; 4=affected part\[s\] rigid in flexion/extension) to each time point in the DB phase was calculated. In the graph plotting time points on the horizontal axis and changes from baseline on the vertical axis, the area surrounded by the MAS ankle score change curve and the horizontal axis was calculated and used as a summary index (AUC) for assessment of the MAS ankle score. Negative changes from baseline indicate improvement, and the AUC has a negative sign.
Time frame: Baseline, Week 12
Population: Full Analysis Set (FAS): all participants randomized, with the exception of those who did not receive any investigational product and those with no assessment of post-treatment MAS ankle score
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BTX 300U | Area Under the Curve (AUC) for the Change From Baseline in Modified Ashworth Scale (MAS) Ankle Score to the End of the DB Phase (Week 12) | -8.513 Score*week | Standard Deviation 6.6904 |
| Placebo | Area Under the Curve (AUC) for the Change From Baseline in Modified Ashworth Scale (MAS) Ankle Score to the End of the DB Phase (Week 12) | -5.085 Score*week | Standard Deviation 6.6496 |
p-value: 0.00695% CI: [-5.841, -1.016]t-test, 2 sided
Secondary
Mean Change From Baseline (at the Start of the DB Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Physiotherapist/Occupational Therapist at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase
The CGI of functional disability was assessed at each visit using the 11-point Numeric Rating Scale (NRS) (-5=Worst Possible to 5=Best Possible) at each time point from baseline (at the start of the double-blind phase) to Week 48.
Time frame: Baseline; Weeks 4, 8, and 12 after each injection (up to Week 48; injections given from Week 12 to Week 36)
Population: Full Analysis Set (FAS): all participants randomized, with the exception of those who did not receive any investigational product and those with no assessment of post-treatment MAS ankle score
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BTX 300U | Mean Change From Baseline (at the Start of the DB Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Physiotherapist/Occupational Therapist at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 4 after first injection in OL | 1.14 Points on a scale | Standard Deviation 1.708 |
| BTX 300U | Mean Change From Baseline (at the Start of the DB Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Physiotherapist/Occupational Therapist at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 8 after first injection in OL | 1.40 Points on a scale | Standard Deviation 1.814 |
| BTX 300U | Mean Change From Baseline (at the Start of the DB Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Physiotherapist/Occupational Therapist at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 12 after first injection in OL | 1.28 Points on a scale | Standard Deviation 1.919 |
| BTX 300U | Mean Change From Baseline (at the Start of the DB Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Physiotherapist/Occupational Therapist at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 4 after second injection in OL | 1.49 Points on a scale | Standard Deviation 1.882 |
| BTX 300U | Mean Change From Baseline (at the Start of the DB Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Physiotherapist/Occupational Therapist at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 8 after second injection in OL | 1.42 Points on a scale | Standard Deviation 1.88 |
| BTX 300U | Mean Change From Baseline (at the Start of the DB Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Physiotherapist/Occupational Therapist at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 12 after second injection in OL | 1.57 Points on a scale | Standard Deviation 1.965 |
| BTX 300U | Mean Change From Baseline (at the Start of the DB Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Physiotherapist/Occupational Therapist at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 4 after third injection in OL | 1.38 Points on a scale | Standard Deviation 1.84 |
| BTX 300U | Mean Change From Baseline (at the Start of the DB Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Physiotherapist/Occupational Therapist at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 12 after third injection in OL | 1.59 Points on a scale | Standard Deviation 2.438 |
| BTX 300U | Mean Change From Baseline (at the Start of the DB Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Physiotherapist/Occupational Therapist at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 8 after third injection in OL | 1.30 Points on a scale | Standard Deviation 1.918 |
| Placebo | Mean Change From Baseline (at the Start of the DB Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Physiotherapist/Occupational Therapist at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 8 after second injection in OL | 1.76 Points on a scale | Standard Deviation 1.888 |
| Placebo | Mean Change From Baseline (at the Start of the DB Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Physiotherapist/Occupational Therapist at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 4 after first injection in OL | 1.54 Points on a scale | Standard Deviation 1.878 |
| Placebo | Mean Change From Baseline (at the Start of the DB Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Physiotherapist/Occupational Therapist at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 8 after third injection in OL | 1.86 Points on a scale | Standard Deviation 2.155 |
| Placebo | Mean Change From Baseline (at the Start of the DB Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Physiotherapist/Occupational Therapist at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 8 after first injection in OL | 1.54 Points on a scale | Standard Deviation 1.768 |
| Placebo | Mean Change From Baseline (at the Start of the DB Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Physiotherapist/Occupational Therapist at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 12 after second injection in OL | 1.83 Points on a scale | Standard Deviation 1.992 |
| Placebo | Mean Change From Baseline (at the Start of the DB Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Physiotherapist/Occupational Therapist at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 12 after first injection in OL | 1.46 Points on a scale | Standard Deviation 1.702 |
| Placebo | Mean Change From Baseline (at the Start of the DB Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Physiotherapist/Occupational Therapist at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 12 after third injection in OL | 1.50 Points on a scale | Standard Deviation 2.219 |
| Placebo | Mean Change From Baseline (at the Start of the DB Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Physiotherapist/Occupational Therapist at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 4 after second injection in OL | 2.00 Points on a scale | Standard Deviation 1.798 |
| Placebo | Mean Change From Baseline (at the Start of the DB Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Physiotherapist/Occupational Therapist at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 4 after third injection in OL | 1.62 Points on a scale | Standard Deviation 2.145 |
Secondary
Mean Change From Baseline (at the Start of the Double-blind Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Investigator at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase
The CGI of functional disability was assessed at each visit using the 11-point Numeric Rating Scale (NRS) (-5=Worst Possible to 5=Best Possible) at each time point from baseline (at the start of the double-blind phase) to Week 48.
Time frame: Baseline; Weeks 4, 8, and 12 after each injection (up to Week 48; injections given from Week 12 to Week 36)
Population: Full Analysis Set (FAS): all participants randomized, with the exception of those who did not receive any investigational product and those with no assessment of post-treatment MAS ankle score
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BTX 300U | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Investigator at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 8 after first injection in OL | 1.40 Points on a scale | Standard Deviation 1.393 |
| BTX 300U | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Investigator at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 12 after second injection in OL | 1.55 Points on a scale | Standard Deviation 1.611 |
| BTX 300U | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Investigator at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 4 after second injection in OL | 1.93 Points on a scale | Standard Deviation 1.639 |
| BTX 300U | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Investigator at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 4 after third injection in OL | 2.07 Points on a scale | Standard Deviation 1.387 |
| BTX 300U | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Investigator at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 12 after first injection in OL | 1.11 Points on a scale | Standard Deviation 1.387 |
| BTX 300U | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Investigator at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 8 after third injection in OL | 2.04 Points on a scale | Standard Deviation 1.224 |
| BTX 300U | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Investigator at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 8 after second injection in OL | 1.70 Points on a scale | Standard Deviation 1.67 |
| BTX 300U | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Investigator at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 12 after third injection in OL | 2.00 Points on a scale | Standard Deviation 1.177 |
| BTX 300U | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Investigator at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 4 after first injection in OL | 1.43 Points on a scale | Standard Deviation 1.443 |
| Placebo | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Investigator at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 12 after third injection in OL | 1.68 Points on a scale | Standard Deviation 1.416 |
| Placebo | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Investigator at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 4 after first injection in OL | 1.43 Points on a scale | Standard Deviation 1.463 |
| Placebo | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Investigator at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 8 after first injection in OL | 1.54 Points on a scale | Standard Deviation 1.513 |
| Placebo | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Investigator at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 12 after first injection in OL | 1.21 Points on a scale | Standard Deviation 1.589 |
| Placebo | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Investigator at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 4 after second injection in OL | 2.02 Points on a scale | Standard Deviation 1.55 |
| Placebo | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Investigator at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 8 after second injection in OL | 1.89 Points on a scale | Standard Deviation 1.676 |
| Placebo | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Investigator at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 12 after second injection in OL | 1.52 Points on a scale | Standard Deviation 1.683 |
| Placebo | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Investigator at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 4 after third injection in OL | 1.59 Points on a scale | Standard Deviation 1.476 |
| Placebo | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Investigator at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 8 after third injection in OL | 1.82 Points on a scale | Standard Deviation 1.389 |
Secondary
Mean Change From Baseline (at the Start of the Double-blind Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Participant at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase
The CGI of functional disability was assessed at each visit using the 11-point Numeric Rating Scale (NRS) (-5=Worst Possible to 5=Best Possible) at each time point from baseline (at the start of the double-blind phase) to Week 48.
Time frame: Baseline; Weeks 4, 8, and 12 after each injection (up to Week 48; injections given from Week 12 to Week 36)
Population: Full Analysis Set (FAS): all participants randomized, with the exception of those who did not receive any investigational product and those with no assessment of post-treatment MAS ankle score
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BTX 300U | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Participant at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 8 after first injection in OL | 0.98 Points on a scale | Standard Deviation 2.08 |
| BTX 300U | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Participant at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 12 after second injection in OL | 1.19 Points on a scale | Standard Deviation 2.222 |
| BTX 300U | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Participant at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 4 after second injection in OL | 1.26 Points on a scale | Standard Deviation 2.205 |
| BTX 300U | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Participant at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 4 after third injection in OL | 1.62 Points on a scale | Standard Deviation 2.305 |
| BTX 300U | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Participant at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 12 after first injection in OL | 0.66 Points on a scale | Standard Deviation 1.536 |
| BTX 300U | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Participant at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 8 after third injection in OL | 1.56 Points on a scale | Standard Deviation 2.532 |
| BTX 300U | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Participant at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 8 after second injection in OL | 1.37 Points on a scale | Standard Deviation 2.226 |
| BTX 300U | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Participant at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 12 after third injection in OL | 1.33 Points on a scale | Standard Deviation 2.557 |
| BTX 300U | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Participant at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 4 after first injection in OL | 0.92 Points on a scale | Standard Deviation 1.891 |
| Placebo | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Participant at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 12 after third injection in OL | 1.86 Points on a scale | Standard Deviation 2.013 |
| Placebo | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Participant at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 4 after first injection in OL | 1.00 Points on a scale | Standard Deviation 2.149 |
| Placebo | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Participant at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 8 after first injection in OL | 1.04 Points on a scale | Standard Deviation 2.215 |
| Placebo | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Participant at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 12 after first injection in OL | 1.19 Points on a scale | Standard Deviation 2.349 |
| Placebo | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Participant at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 4 after second injection in OL | 1.75 Points on a scale | Standard Deviation 1.973 |
| Placebo | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Participant at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 8 after second injection in OL | 1.67 Points on a scale | Standard Deviation 2.119 |
| Placebo | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Participant at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 12 after second injection in OL | 1.57 Points on a scale | Standard Deviation 2.029 |
| Placebo | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Participant at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 4 after third injection in OL | 1.66 Points on a scale | Standard Deviation 1.396 |
| Placebo | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Participant at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 8 after third injection in OL | 1.86 Points on a scale | Standard Deviation 1.715 |
Secondary
Mean Change From Baseline (at the Start of the Double-blind Phase) in the MAS Ankle Score at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase
The investigator assessed Modified Ashworth Scale (MAS) ankle score using a 6-point scale (0, 1, 1+, 2, 3, and 4; 0=No increase in muscle tone to 4=Affected part\[s\] rigid in flexion or extension) at each time point from baseline (at the start of the double-blind phase) to Week 48. The +1 (slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder \[less than half\] of ROM \[range of motion\]) of MAS score is regarded as score 1.5.
Time frame: Baseline; Weeks 4, 8, and 12 after each injection (up to Week 48; injections given from Week 12 to Week 36)
Population: Full Analysis Set (FAS): all participants randomized, with the exception of those who did not receive any investigational product and those with no assessment of post-treatment MAS ankle score
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BTX 300U | Mean Change From Baseline (at the Start of the Double-blind Phase) in the MAS Ankle Score at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 8 after first injection in OL | -1.29 Points on a scale | Standard Deviation 0.682 |
| BTX 300U | Mean Change From Baseline (at the Start of the Double-blind Phase) in the MAS Ankle Score at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 12 after second injection in OL | -1.19 Points on a scale | Standard Deviation 0.732 |
| BTX 300U | Mean Change From Baseline (at the Start of the Double-blind Phase) in the MAS Ankle Score at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 4 after second injection in OL | -1.55 Points on a scale | Standard Deviation 0.706 |
| BTX 300U | Mean Change From Baseline (at the Start of the Double-blind Phase) in the MAS Ankle Score at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 4 after third injection in OL | -1.48 Points on a scale | Standard Deviation 0.75 |
| BTX 300U | Mean Change From Baseline (at the Start of the Double-blind Phase) in the MAS Ankle Score at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 12 after first injection in OL | -1.03 Points on a scale | Standard Deviation 0.646 |
| BTX 300U | Mean Change From Baseline (at the Start of the Double-blind Phase) in the MAS Ankle Score at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 8 after third injection in OL | -1.41 Points on a scale | Standard Deviation 0.694 |
| BTX 300U | Mean Change From Baseline (at the Start of the Double-blind Phase) in the MAS Ankle Score at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 8 after second injection in OL | -1.36 Points on a scale | Standard Deviation 0.675 |
| BTX 300U | Mean Change From Baseline (at the Start of the Double-blind Phase) in the MAS Ankle Score at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 12 after third injection in OL | -1.44 Points on a scale | Standard Deviation 0.751 |
| BTX 300U | Mean Change From Baseline (at the Start of the Double-blind Phase) in the MAS Ankle Score at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 4 after first injection in OL | -1.37 Points on a scale | Standard Deviation 0.66 |
| Placebo | Mean Change From Baseline (at the Start of the Double-blind Phase) in the MAS Ankle Score at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 12 after third injection in OL | -1.34 Points on a scale | Standard Deviation 0.578 |
| Placebo | Mean Change From Baseline (at the Start of the Double-blind Phase) in the MAS Ankle Score at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 4 after first injection in OL | -1.27 Points on a scale | Standard Deviation 0.653 |
| Placebo | Mean Change From Baseline (at the Start of the Double-blind Phase) in the MAS Ankle Score at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 8 after first injection in OL | -1.33 Points on a scale | Standard Deviation 0.59 |
| Placebo | Mean Change From Baseline (at the Start of the Double-blind Phase) in the MAS Ankle Score at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 12 after first injection in OL | -1.04 Points on a scale | Standard Deviation 0.654 |
| Placebo | Mean Change From Baseline (at the Start of the Double-blind Phase) in the MAS Ankle Score at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 4 after second injection in OL | -1.51 Points on a scale | Standard Deviation 0.64 |
| Placebo | Mean Change From Baseline (at the Start of the Double-blind Phase) in the MAS Ankle Score at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 8 after second injection in OL | -1.43 Points on a scale | Standard Deviation 0.554 |
| Placebo | Mean Change From Baseline (at the Start of the Double-blind Phase) in the MAS Ankle Score at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 12 after second injection in OL | -1.21 Points on a scale | Standard Deviation 0.75 |
| Placebo | Mean Change From Baseline (at the Start of the Double-blind Phase) in the MAS Ankle Score at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 4 after third injection in OL | -1.43 Points on a scale | Standard Deviation 0.764 |
| Placebo | Mean Change From Baseline (at the Start of the Double-blind Phase) in the MAS Ankle Score at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 8 after third injection in OL | -1.43 Points on a scale | Standard Deviation 0.556 |
Secondary
Mean Change From Baseline (at the Start of the Double-blind Phase) in the Physician's Rating Score (PRS) at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase
The investigator assessed the PRS of gait pattern consisting of 3 parameters. Affected limb was scored on a scale of -1 (worst) to 9 (best) based on 3 parameters (initial foot contact, foot contact at midstance, gait assistive devices) at each time point from baseline (at the start of the double-blind phase) to Week 48.
Time frame: Baseline; Weeks 4, 8, and 12 after each injection (up to Week 48; injections given from Week 12 to Week 36)
Population: Full Analysis Set (FAS): all participants randomized, with the exception of those who did not receive any investigational product and those with no assessment of post-treatment MAS ankle score
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BTX 300U | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Physician's Rating Score (PRS) at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 8 after first injection in OL | 1.17 Points on a scale | Standard Deviation 1.494 |
| BTX 300U | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Physician's Rating Score (PRS) at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 12 after second injection in OL | 1.40 Points on a scale | Standard Deviation 1.449 |
| BTX 300U | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Physician's Rating Score (PRS) at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 4 after second injection in OL | 1.30 Points on a scale | Standard Deviation 1.389 |
| BTX 300U | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Physician's Rating Score (PRS) at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 4 after third injection in OL | 1.28 Points on a scale | Standard Deviation 1.461 |
| BTX 300U | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Physician's Rating Score (PRS) at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 12 after first injection in OL | 0.91 Points on a scale | Standard Deviation 1.501 |
| BTX 300U | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Physician's Rating Score (PRS) at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 8 after third injection in OL | 1.33 Points on a scale | Standard Deviation 1.494 |
| BTX 300U | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Physician's Rating Score (PRS) at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 8 after second injection in OL | 1.33 Points on a scale | Standard Deviation 1.569 |
| BTX 300U | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Physician's Rating Score (PRS) at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 12 after third injection in OL | 1.22 Points on a scale | Standard Deviation 1.121 |
| BTX 300U | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Physician's Rating Score (PRS) at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 4 after first injection in OL | 1.10 Points on a scale | Standard Deviation 1.433 |
| Placebo | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Physician's Rating Score (PRS) at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 12 after third injection in OL | 0.96 Points on a scale | Standard Deviation 1.344 |
| Placebo | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Physician's Rating Score (PRS) at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 4 after first injection in OL | 1.35 Points on a scale | Standard Deviation 1.601 |
| Placebo | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Physician's Rating Score (PRS) at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 8 after first injection in OL | 1.46 Points on a scale | Standard Deviation 1.668 |
| Placebo | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Physician's Rating Score (PRS) at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 12 after first injection in OL | 1.15 Points on a scale | Standard Deviation 1.638 |
| Placebo | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Physician's Rating Score (PRS) at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 4 after second injection in OL | 1.48 Points on a scale | Standard Deviation 1.722 |
| Placebo | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Physician's Rating Score (PRS) at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 8 after second injection in OL | 1.47 Points on a scale | Standard Deviation 1.7 |
| Placebo | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Physician's Rating Score (PRS) at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 12 after second injection in OL | 1.29 Points on a scale | Standard Deviation 1.842 |
| Placebo | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Physician's Rating Score (PRS) at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 4 after third injection in OL | 1.04 Points on a scale | Standard Deviation 1.551 |
| Placebo | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Physician's Rating Score (PRS) at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 8 after third injection in OL | 1.15 Points on a scale | Standard Deviation 1.433 |
Secondary
Mean Change From Baseline (at the Start of the Double-blind Phase) in the Time (Seconds) to Walk 10 Meters at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase
The time (seconds) required to walk 10 meters was measured at each time point from baseline (at the start of the double-blind phase) to Week 48.
Time frame: Baseline; Weeks 4, 8, and 12 after each injection (up to Week 48; injections given from Week 12 to Week 36)
Population: Full Analysis Set (FAS): all participants randomized, with the exception of those who did not receive any investigational product and those with no assessment of post-treatment MAS ankle score
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BTX 300U | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Time (Seconds) to Walk 10 Meters at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 8 after first injection in OL | -11.14 seconds | Standard Deviation 27.453 |
| BTX 300U | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Time (Seconds) to Walk 10 Meters at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 12 after second injection in OL | -16.31 seconds | Standard Deviation 32.613 |
| BTX 300U | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Time (Seconds) to Walk 10 Meters at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 4 after second injection in OL | -13.49 seconds | Standard Deviation 29.674 |
| BTX 300U | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Time (Seconds) to Walk 10 Meters at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 4 after third injection in OL | -20.09 seconds | Standard Deviation 42.452 |
| BTX 300U | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Time (Seconds) to Walk 10 Meters at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 12 after first injection in OL | -10.50 seconds | Standard Deviation 27.726 |
| BTX 300U | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Time (Seconds) to Walk 10 Meters at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 8 after third injection in OL | -15.91 seconds | Standard Deviation 43.589 |
| BTX 300U | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Time (Seconds) to Walk 10 Meters at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 8 after second injection in OL | -8.05 seconds | Standard Deviation 45.061 |
| BTX 300U | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Time (Seconds) to Walk 10 Meters at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 12 after third injection in OL | -16.37 seconds | Standard Deviation 51.482 |
| BTX 300U | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Time (Seconds) to Walk 10 Meters at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 4 after first injection in OL | -11.21 seconds | Standard Deviation 25.67 |
| Placebo | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Time (Seconds) to Walk 10 Meters at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 12 after third injection in OL | -13.84 seconds | Standard Deviation 29.241 |
| Placebo | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Time (Seconds) to Walk 10 Meters at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 4 after first injection in OL | -12.09 seconds | Standard Deviation 27.148 |
| Placebo | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Time (Seconds) to Walk 10 Meters at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 8 after first injection in OL | -8.05 seconds | Standard Deviation 22.735 |
| Placebo | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Time (Seconds) to Walk 10 Meters at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 12 after first injection in OL | -9.29 seconds | Standard Deviation 21.851 |
| Placebo | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Time (Seconds) to Walk 10 Meters at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 4 after second injection in OL | -13.05 seconds | Standard Deviation 31.241 |
| Placebo | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Time (Seconds) to Walk 10 Meters at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 8 after second injection in OL | -7.65 seconds | Standard Deviation 22.715 |
| Placebo | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Time (Seconds) to Walk 10 Meters at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 12 after second injection in OL | -13.40 seconds | Standard Deviation 29.508 |
| Placebo | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Time (Seconds) to Walk 10 Meters at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 4 after third injection in OL | -13.42 seconds | Standard Deviation 33.205 |
| Placebo | Mean Change From Baseline (at the Start of the Double-blind Phase) in the Time (Seconds) to Walk 10 Meters at 4, 8, and 12 Weeks After Each Injection in the Open-label Phase | Week 8 after third injection in OL | -12.10 seconds | Standard Deviation 28.24 |
Secondary
Mean Change From Baseline in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Investigator From Baseline to Week 12 of the Double-blind Phase
The CGI of functional disability was assessed at each visit using the 11-point Numeric Rating Scale (NRS) (-5=Worst Possible to 5=Best Possible) at each time point in the double-blind phase.
Time frame: Baseline; Weeks 1, 4, 6, 8, and 12
Population: Full Analysis Set (FAS): all participants randomized, with the exception of those who did not receive any investigational product and those with no assessment of post-treatment MAS ankle score
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BTX 300U | Mean Change From Baseline in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Investigator From Baseline to Week 12 of the Double-blind Phase | Week 4 | 1.09 Points on a scale | Standard Deviation 1.254 |
| BTX 300U | Mean Change From Baseline in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Investigator From Baseline to Week 12 of the Double-blind Phase | Week 8 | 1.13 Points on a scale | Standard Deviation 1.318 |
| BTX 300U | Mean Change From Baseline in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Investigator From Baseline to Week 12 of the Double-blind Phase | Week 6 | 1.21 Points on a scale | Standard Deviation 1.558 |
| BTX 300U | Mean Change From Baseline in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Investigator From Baseline to Week 12 of the Double-blind Phase | Week 12 | 0.81 Points on a scale | Standard Deviation 1.302 |
| BTX 300U | Mean Change From Baseline in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Investigator From Baseline to Week 12 of the Double-blind Phase | Week 1 | 0.82 Points on a scale | Standard Deviation 1.283 |
| Placebo | Mean Change From Baseline in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Investigator From Baseline to Week 12 of the Double-blind Phase | Week 12 | 0.52 Points on a scale | Standard Deviation 1.273 |
| Placebo | Mean Change From Baseline in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Investigator From Baseline to Week 12 of the Double-blind Phase | Week 1 | 0.45 Points on a scale | Standard Deviation 1.082 |
| Placebo | Mean Change From Baseline in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Investigator From Baseline to Week 12 of the Double-blind Phase | Week 4 | 0.64 Points on a scale | Standard Deviation 1.065 |
| Placebo | Mean Change From Baseline in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Investigator From Baseline to Week 12 of the Double-blind Phase | Week 6 | 0.66 Points on a scale | Standard Deviation 1.182 |
| Placebo | Mean Change From Baseline in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Investigator From Baseline to Week 12 of the Double-blind Phase | Week 8 | 0.59 Points on a scale | Standard Deviation 1.23 |
Secondary
Mean Change From Baseline in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Participant From Baseline to Week 12 of the Double-blind Phase
The CGI of functional disability was assessed at each visit using the 11-point Numeric Rating Scale (NRS) (-5=Worst Possible to 5=Best Possible) at each time point in the double-blind phase
Time frame: Baseline; Weeks 1, 4, 6, 8, and 12
Population: Full Analysis Set (FAS): all participants randomized, with the exception of those who did not receive any investigational product and those with no assessment of post-treatment MAS ankle score
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BTX 300U | Mean Change From Baseline in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Participant From Baseline to Week 12 of the Double-blind Phase | Week 4 | 0.75 Points on a scale | Standard Deviation 1.575 |
| BTX 300U | Mean Change From Baseline in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Participant From Baseline to Week 12 of the Double-blind Phase | Week 8 | 1.00 Points on a scale | Standard Deviation 2.028 |
| BTX 300U | Mean Change From Baseline in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Participant From Baseline to Week 12 of the Double-blind Phase | Week 6 | 0.82 Points on a scale | Standard Deviation 1.85 |
| BTX 300U | Mean Change From Baseline in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Participant From Baseline to Week 12 of the Double-blind Phase | Week 12 | 0.49 Points on a scale | Standard Deviation 1.527 |
| BTX 300U | Mean Change From Baseline in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Participant From Baseline to Week 12 of the Double-blind Phase | Week 1 | 0.49 Points on a scale | Standard Deviation 1.477 |
| Placebo | Mean Change From Baseline in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Participant From Baseline to Week 12 of the Double-blind Phase | Week 12 | 0.49 Points on a scale | Standard Deviation 2.18 |
| Placebo | Mean Change From Baseline in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Participant From Baseline to Week 12 of the Double-blind Phase | Week 1 | 0.34 Points on a scale | Standard Deviation 1.47 |
| Placebo | Mean Change From Baseline in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Participant From Baseline to Week 12 of the Double-blind Phase | Week 4 | 0.44 Points on a scale | Standard Deviation 1.756 |
| Placebo | Mean Change From Baseline in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Participant From Baseline to Week 12 of the Double-blind Phase | Week 6 | 0.72 Points on a scale | Standard Deviation 1.976 |
| Placebo | Mean Change From Baseline in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Participant From Baseline to Week 12 of the Double-blind Phase | Week 8 | 0.70 Points on a scale | Standard Deviation 1.978 |
Secondary
Mean Change From Baseline in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Physiotherapist/Occupational Therapist From Baseline to Week 12 of the Double-blind Phase
The CGI of functional disability was assessed at each visit using the 11-point Numeric Rating Scale (NRS) (-5=Worst Possible to 5=Best Possible) at each time point in the double-blind phase
Time frame: Baseline; Weeks 1, 4, 6, 8, and 12
Population: Full Analysis Set (FAS): all participants randomized, with the exception of those who did not receive any investigational product and those with no assessment of post-treatment MAS ankle score
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BTX 300U | Mean Change From Baseline in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Physiotherapist/Occupational Therapist From Baseline to Week 12 of the Double-blind Phase | Week 4 | 0.64 Points on a scale | Standard Deviation 1.271 |
| BTX 300U | Mean Change From Baseline in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Physiotherapist/Occupational Therapist From Baseline to Week 12 of the Double-blind Phase | Week 8 | 1.04 Points on a scale | Standard Deviation 1.78 |
| BTX 300U | Mean Change From Baseline in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Physiotherapist/Occupational Therapist From Baseline to Week 12 of the Double-blind Phase | Week 6 | 0.82 Points on a scale | Standard Deviation 1.55 |
| BTX 300U | Mean Change From Baseline in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Physiotherapist/Occupational Therapist From Baseline to Week 12 of the Double-blind Phase | Week 12 | 1.02 Points on a scale | Standard Deviation 1.337 |
| BTX 300U | Mean Change From Baseline in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Physiotherapist/Occupational Therapist From Baseline to Week 12 of the Double-blind Phase | Week 1 | 0.63 Points on a scale | Standard Deviation 1.19 |
| Placebo | Mean Change From Baseline in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Physiotherapist/Occupational Therapist From Baseline to Week 12 of the Double-blind Phase | Week 12 | 0.97 Points on a scale | Standard Deviation 1.505 |
| Placebo | Mean Change From Baseline in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Physiotherapist/Occupational Therapist From Baseline to Week 12 of the Double-blind Phase | Week 1 | 0.48 Points on a scale | Standard Deviation 1.004 |
| Placebo | Mean Change From Baseline in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Physiotherapist/Occupational Therapist From Baseline to Week 12 of the Double-blind Phase | Week 4 | 1.07 Points on a scale | Standard Deviation 1.377 |
| Placebo | Mean Change From Baseline in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Physiotherapist/Occupational Therapist From Baseline to Week 12 of the Double-blind Phase | Week 6 | 1.03 Points on a scale | Standard Deviation 1.906 |
| Placebo | Mean Change From Baseline in the Clinical Global Impression (CGI) Score of Functional Disability Assessed by the Physiotherapist/Occupational Therapist From Baseline to Week 12 of the Double-blind Phase | Week 8 | 1.00 Points on a scale | Standard Deviation 1.643 |
Secondary
Mean Change From Baseline in the MAS Ankle Score From Baseline to Week 12 of the Double-blind Phase
The investigator assessed Modified Ashworth Scale (MAS) ankle score using a 6-point scale (0, 1, 1+, 2, 3, and 4; 0=No increase in muscle tone to 4=Affected part\[s\] rigid in flexion or extension) at each time point in the double-blind phase. The +1 (slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder \[less than half\] of ROM \[range of motion\]) of MAS score is regarded as score 1.5.
Time frame: Baseline; Weeks 1, 4, 6, 8, and 12
Population: Full Analysis Set (FAS): all participants randomized, with the exception of those who did not receive any investigational product and those with no assessment of post-treatment MAS ankle score
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BTX 300U | Mean Change From Baseline in the MAS Ankle Score From Baseline to Week 12 of the Double-blind Phase | Week 4 | -0.88 Points on a scale | Standard Deviation 0.687 |
| BTX 300U | Mean Change From Baseline in the MAS Ankle Score From Baseline to Week 12 of the Double-blind Phase | Week 8 | -0.82 Points on a scale | Standard Deviation 0.66 |
| BTX 300U | Mean Change From Baseline in the MAS Ankle Score From Baseline to Week 12 of the Double-blind Phase | Week 6 | -0.91 Points on a scale | Standard Deviation 0.733 |
| BTX 300U | Mean Change From Baseline in the MAS Ankle Score From Baseline to Week 12 of the Double-blind Phase | Week 12 | -0.56 Points on a scale | Standard Deviation 0.685 |
| BTX 300U | Mean Change From Baseline in the MAS Ankle Score From Baseline to Week 12 of the Double-blind Phase | Week 1 | -0.61 Points on a scale | Standard Deviation 0.675 |
| Placebo | Mean Change From Baseline in the MAS Ankle Score From Baseline to Week 12 of the Double-blind Phase | Week 12 | -0.40 Points on a scale | Standard Deviation 0.583 |
| Placebo | Mean Change From Baseline in the MAS Ankle Score From Baseline to Week 12 of the Double-blind Phase | Week 1 | -0.52 Points on a scale | Standard Deviation 0.765 |
| Placebo | Mean Change From Baseline in the MAS Ankle Score From Baseline to Week 12 of the Double-blind Phase | Week 4 | -0.43 Points on a scale | Standard Deviation 0.718 |
| Placebo | Mean Change From Baseline in the MAS Ankle Score From Baseline to Week 12 of the Double-blind Phase | Week 6 | -0.47 Points on a scale | Standard Deviation 0.712 |
| Placebo | Mean Change From Baseline in the MAS Ankle Score From Baseline to Week 12 of the Double-blind Phase | Week 8 | -0.43 Points on a scale | Standard Deviation 0.676 |
Secondary
Mean Change From Baseline in the Physician's Rating Score (PRS) From Baseline to Week 12 of the Double-blind Phase
The investigator assessed the PRS of gait pattern consisting of 3 parameters. Affected limb was scored on a scale of -1 (worst) to 9 (best) based on 3 parameters (initial foot contact, foot contact at midstance, gait assistive devices) at each time point in double-blind phase.
Time frame: Baseline; Weeks 1, 4, 6, 8, and 12
Population: Full Analysis Set (FAS): all participants randomized, with the exception of those who did not receive any investigational product and those with no assessment of post-treatment MAS ankle score
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BTX 300U | Mean Change From Baseline in the Physician's Rating Score (PRS) From Baseline to Week 12 of the Double-blind Phase | Week 4 | 0.54 Points on a scale | Standard Deviation 1.224 |
| BTX 300U | Mean Change From Baseline in the Physician's Rating Score (PRS) From Baseline to Week 12 of the Double-blind Phase | Week 8 | 0.61 Points on a scale | Standard Deviation 1.188 |
| BTX 300U | Mean Change From Baseline in the Physician's Rating Score (PRS) From Baseline to Week 12 of the Double-blind Phase | Week 6 | 0.46 Points on a scale | Standard Deviation 1.19 |
| BTX 300U | Mean Change From Baseline in the Physician's Rating Score (PRS) From Baseline to Week 12 of the Double-blind Phase | Week 12 | 0.55 Points on a scale | Standard Deviation 1.264 |
| BTX 300U | Mean Change From Baseline in the Physician's Rating Score (PRS) From Baseline to Week 12 of the Double-blind Phase | Week 1 | 0.40 Points on a scale | Standard Deviation 1.178 |
| Placebo | Mean Change From Baseline in the Physician's Rating Score (PRS) From Baseline to Week 12 of the Double-blind Phase | Week 12 | 0.58 Points on a scale | Standard Deviation 1.565 |
| Placebo | Mean Change From Baseline in the Physician's Rating Score (PRS) From Baseline to Week 12 of the Double-blind Phase | Week 1 | 0.66 Points on a scale | Standard Deviation 1.401 |
| Placebo | Mean Change From Baseline in the Physician's Rating Score (PRS) From Baseline to Week 12 of the Double-blind Phase | Week 4 | 0.63 Points on a scale | Standard Deviation 1.449 |
| Placebo | Mean Change From Baseline in the Physician's Rating Score (PRS) From Baseline to Week 12 of the Double-blind Phase | Week 6 | 0.72 Points on a scale | Standard Deviation 1.474 |
| Placebo | Mean Change From Baseline in the Physician's Rating Score (PRS) From Baseline to Week 12 of the Double-blind Phase | Week 8 | 0.78 Points on a scale | Standard Deviation 1.811 |
Secondary
Mean Change From Baseline in the Time (Seconds) to Walk 10 Meters From Baseline to Week 12 of the Double-blind Phase
The time (seconds) required to walk 10 meters was measured at each time point in the double-blind phase.
Time frame: Baseline; Weeks 1, 4, 6, 8, and 12
Population: Full Analysis Set (FAS): all participants randomized, with the exception of those who did not receive any investigational product and those with no assessment of post-treatment MAS ankle score
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BTX 300U | Mean Change From Baseline in the Time (Seconds) to Walk 10 Meters From Baseline to Week 12 of the Double-blind Phase | Week 4 | -6.10 seconds | Standard Deviation 22.852 |
| BTX 300U | Mean Change From Baseline in the Time (Seconds) to Walk 10 Meters From Baseline to Week 12 of the Double-blind Phase | Week 8 | -3.14 seconds | Standard Deviation 35.78 |
| BTX 300U | Mean Change From Baseline in the Time (Seconds) to Walk 10 Meters From Baseline to Week 12 of the Double-blind Phase | Week 6 | -7.80 seconds | Standard Deviation 20.568 |
| BTX 300U | Mean Change From Baseline in the Time (Seconds) to Walk 10 Meters From Baseline to Week 12 of the Double-blind Phase | Week 12 | -10.14 seconds | Standard Deviation 26.93 |
| BTX 300U | Mean Change From Baseline in the Time (Seconds) to Walk 10 Meters From Baseline to Week 12 of the Double-blind Phase | Week 1 | 2.14 seconds | Standard Deviation 34.828 |
| Placebo | Mean Change From Baseline in the Time (Seconds) to Walk 10 Meters From Baseline to Week 12 of the Double-blind Phase | Week 12 | -8.53 seconds | Standard Deviation 24.71 |
| Placebo | Mean Change From Baseline in the Time (Seconds) to Walk 10 Meters From Baseline to Week 12 of the Double-blind Phase | Week 1 | -5.02 seconds | Standard Deviation 11.436 |
| Placebo | Mean Change From Baseline in the Time (Seconds) to Walk 10 Meters From Baseline to Week 12 of the Double-blind Phase | Week 4 | -7.37 seconds | Standard Deviation 20.782 |
| Placebo | Mean Change From Baseline in the Time (Seconds) to Walk 10 Meters From Baseline to Week 12 of the Double-blind Phase | Week 6 | -8.48 seconds | Standard Deviation 18.075 |
| Placebo | Mean Change From Baseline in the Time (Seconds) to Walk 10 Meters From Baseline to Week 12 of the Double-blind Phase | Week 8 | -8.19 seconds | Standard Deviation 18.633 |