Spasticity, Post-Stroke
Conditions
Keywords
GSK1358820, upper limb, spasticity, post-stroke
Brief summary
This trial is a multicenter, open-label study to evaluate the safety and efficacy of GSK1358820 for treatment in post-stroke subjects with focal wrist, finger and in some cases, thumb spasticity. Qualified patients who complete GSK double-blind study 112958 will be enrolled. Subjects will receive a single treatment session of intramuscular GSK1358820 200U or 240U (if thumb spasticity is present). The subjects will be observed until 12 weeks post injection. Outcome measures include changes from baseline at every post injection visit as measured on the Modified Ashworth Scale (MAS), Disability Assessment Scale (DAS) and Global Assessment Scale. Safety parameters will be measured including adverse events, vital signs (pulse and blood pressure) and clinical laboratory tests (haematology, serum chemistry and urinanalysis).
Detailed description
This trial is a multicenter, open-label study to evaluate the safety and efficacy of GSK1358820 for the treatment of patients with focal wrist, finger and in some cases, thumb spasticity post-stroke. Qualified patients will be eligible for enrollment upon completion of double-blind study 112958. Patients will receive a single treatment session with intramuscular injections of GSK1358820 200U or 240U (if thumb spasticity is present).The subjects will be observed for 12 weeks post injection. Each completed subject will attend 4 clinic visits. The maximum study duration is 13 weeks. The study includes a 1 week pretreatment period, during which the screening visit (visit 1 could be the last visit of previous double-blind study 112958 or any time within 3 months after completion of previous study) is to take place. Only one upper limb (meeting inclusion/exclusion criteria) will be evaluated and treated in the study. Subjects will receive a single intramuscular treatment with investigated drug at day 0 (visit 2). There will be two post-injection follow-up visits at week 6 and 12 (visits 3 to 4).
Interventions
DRUGBotulinum toxin type A
Botulinum toxin type A
Sponsors
GlaxoSmithKline
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 76 Years
Healthy volunteers
No
Inclusion criteria
1. Within 3 months after completion of the GSK/Allergan study 112958. 2. Wrist flexor muscle tone of 2 or greater and finger flexor muscle tone of 1 or greater as measured on MAS (0 to 4). 3. At least one functional disability item (i.e., hygiene, dressing, pain, or cosmesis) with a rating of 2 or greater on DAS (0 to 3). 4. If using physical therapy, must be stable for at least 1 month prior to study enrolment in study 112958. 5. \>=40kg in weight. 6. QTc criteria: (either QTcb or QTcf, machine or manual overread, males or females); include the following details as appropriate: QTc\<450 millisecond (msec) or \<480msec for subjects with Bundle Branch Block - values based on either single electrocardiogram (ECG) values or triplicate ECG averaged QTc values obtained over a brief recording period. 7. Liver function tests: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<2xULN; alkaline phosphatase and bilirubin ≤1.5xULN (isolated bilirubin \>1.5ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%). 8. In the opinion of the investigator, subject must clearly understand the intent of the study and be willing and able to comply with study instructions and complete the entire study. 9. Informed consent has been obtained
Exclusion criteria
1. Presence of fixed contracture of the study limb (absence of passive range of motion). 2. Profound atrophy of muscles to be injected (in the investigators opinion). 3. Infection or dermatological condition at the injection sites. 4. Significant inflammation in the study limb limiting joint movement. 5. History of or planned treatment for spasticity with phenol or alcohol block in the study limb. 6. History of or planned surgical intervention for spasticity of the study limb. 7. History (within 3 months of qualification) of or planned (during study period) casting of the study limb. 8. Participation in another clinical study (with the exception of study 112958) , within the 30 days immediately prior to enrolment. 9. Planned or anticipated initiation of new antispasticity medications during the clinical study. 10. Any medical condition that may put the subject at increased risk with exposure to GSK1358820, including diagnosed myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, or any other disorder that might have interfered with neuromuscular function. 11. Concurrent use of aminoglycoside antibiotics or other agents that might interfere with neuromuscular function. A full list of prohibited medications that interfere with neuromuscular transmission is provided as Appendix 1. 12. Current treatment for spasticity with an intrathecal baclofen. 13. Females who are pregnant, nursing, or planning a pregnancy during the study period, or females of childbearing potential, not using a reliable means of contraception. 14. Known allergy or sensitivity to study medication or its components. 15. Bedridden subjects. 16. Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, esophageal or gastric varices or persistent jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). 17. Presence of clinically unstable severe cardiovascular, renal or respiratory disease. 18. Investigator's opinion that the subject has a concurrent condition(s) that may put the subject at significant risk, may confound the study results, or may interfere significantly with the conduct of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline at Week 6 and Week 12 for Wrist Flexor Muscle Tone as Measured on the Modified Ashworth Scale (MAS) | Baseline (Day 0), Week 6, and Week 12 | The investigator or assessor extended the participant's wrist as quickly as possible to grade flexor muscle tone. The MAS wrist score was calculated by using the 6-point MAS (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). Change from Baseline at Week 6 or Week 12 was calculated as the value at Week 6 or Week 12 minus the value at Baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline at Week 6 and Week 12 for Finger Flexor Muscle Tone as Measured on the MAS | Baseline (Day 0), Week 6, and Week 12 | The investigator or assessor extended the participant's finger as quickly as possible to grade the flexor muscle tone. The MAS finger score was calculated by using the 6-point MAS (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). Change from Baseline at Week 6 or Week 12 was calculated as the value at Week 6 or Week 12 minus the value at Baseline. |
| Change From Baseline at Week 6 and Week 12 for Thumb Flexor Muscle Tone as Measured on the MAS | Baseline (Day 0), Week 6, and Week 12 | The investigator or assessor extended the participant's thumb as quickly as possible to grade the flexor muscle tone. The MAS thumb score was calculated by using the 6-point MAS (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). Change from Baseline at Week 6 or Week 12 was calculated as the value at Week 6 or Week 12 minus the value at Baseline. |
| Change From Baseline at Week 6 and Week 12 for the Principal Measure as Assessed on the Disability Assessment Scale (DAS) | Baseline (Day 0), Week 6, and Week 12 | The investigator assessed 4 areas of disability, hygiene, pain, dressing, and limb posture, using the 4-point DAS (0=No functional disability to 3=Severe disability). Prior to the first dose, the investigator, in consultation with the participant, selected 1functional disability item (which had to have a score of 2 or greater as measured on the DAS, indicating moderate to severe disability) from the 4 areas of disability and assessed it as a principal measure. Change from Baseline at Week 6 or Week 12 was calculated as the value at Week 6 or Week 12 minus the value at Baseline. |
| Global Assessment Scale (GAS) Score as Evaluated by the Physician at Week 6 and Week 12 | Week 6 and Week 12 | The physician used the GAS to assess response to treatment at each visit after injection. The assessor was the same throughout the study period. GAS scores were assessed by using the 9-point GAS (-4, -3, -2, -1, -0, +1, +2, +3, +4; -4=very marked worsening, -0=unchanged, +4=very marked improvement) at Week 6 and Week 12. |
| GAS Score as Evaluated by the Care Giver or the Participant at Week 6 and Week 12 | Week 6 and Week 12 | The care giver or participant used the GAS to assess response to treatment at each visit after injection. The assessor was the same throughout the study period. GAS scores were assessed by using the 9-point GAS (-4, -3, -2, -1, -0, +1, +2, +3, +4; -4=very marked worsening, 0=unchanged, +4=very marked improvement) at Week 6 and Week 12. |
| Mean Change From Baseline in Red Blood Cell (RBC) Count at the Exit Visit | Baseline (Day 0) and exit visit (Week 12 or earlier) | Blood samples of participants were collected and evaluated for RBC count at Baseline and at the exit visit. Change from Baseline was calculated as the value at the exit visit (Week 12 or earlier) minus the value at Baseline. |
| Mean Change From Baseline in White Blood Cell (WBC) and Platelet Count at the Exit Visit | Baseline (Day 0) and the exit visit (Week 12 or earlier) | Blood samples of participants were collected and evaluated for WBC count and platelet count at Baseline and at the exit visit. Change from Baseline was calculated as the value at the exit visit (Week 12 or earlier) minus the value at Baseline. |
| Mean Change From Baseline in the Percentage of Neutrophils, the Percentage of Lymphocytes, the Percentage of Monocytes, the Percentage of Eosinophils, and the Percentage of Basophils at the Exit Visit | Baseline (Day 0) and the exit visit (Week 12 or earlier) | Blood samples of participants were collected and evaluated for the percentage of neutrophils, lymphocytes, monocytes, eosinophils, and basophils comprising the total WBC count in the blood at Baseline and at the exit visit. Change from Baseline was calculated as the value at the exit visit (Week 12 or earlier) minus the value at Baseline. |
| Number of Participants Classified as Wrist Treatment Responders at Week 6 and Week 12 | Baseline (Day 0), Week 6, and Week 12 | Wrist treatment responders are defined as participants with a decrease in wrist flexor muscle tone of at least one point on the MAS from Baseline. The MAS wrist score was calculated by using the 6-point MAS (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). |
| Mean Change From Baseline in Hematocrit Value at the Exit Visit | Baseline (Day 0) and the exit visit (Week 12 or earlier) | The hematocrit, also called packed cell volume or erythrocyte volume fraction, is the volume percentage of red blood cells in the blood. Change from Baseline was calculated as the value at the exit visit (Week 12 or earlier) minus the value at Baseline. |
| Mean Change From Baseline in Total Protein and Albumin Values at the Exit Visit | Baseline (Day 0) and the exit visit (Week 12 or earlier) | Blood samples of participants were collected for a biochemical test of total protein and albumin, at Baseline and at the exit visit. Change from Baseline was calculated as the value at the exit visit (Week 12 or earlier) minus the value at Baseline. |
| Mean Change From Baseline in Serum Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase (y-GT), and Alkaline Phosphatase (ALP) Values at the Exit Visit | Baseline (Day 0) and the exit visit (Week 12 or earlier) | Blood samples of participants were collected and evaluated for liver function, including measuring ALT, AST, y-GT, and ALP. Change from Baseline was calculated as the value at the exit visit (Week 12 or earlier) minus the value at Baseline. |
| Mean Change From Baseline in Serum Creatinine, Uric Acid, and Total Bilirubin Values at the Exit Visit | Baseline (Day 0) and the exit visit (Week 12 or earlier) | Blood samples of participants were collected for a biochemical test of creatine, uric acid, and total bilirubin. Creatine and uric acid are evaluated for kidney function. The liver function test includes total bilirubin. Change from Baseline was calculated as the value at the exit visit (Week 12 or earlier) minus the value at Baseline. |
| Mean Change From Baseline in Serum Blood Urea Nitrogen (BUN), Fasting Blood Glucose (FBG), Sodium, Potassium, Chloride, Total Cholesterol, and Triglyceride Values at the Exit Visit | Baseline (Day 0) and the exit visit (Week 12 or earlier) | Blood samples of participants were collected for biochemical tests of BUN, FBG, electrolytes, cholesterol, and triglycerides. The BUN test is primarily used to evaluate kidney function. Electrolytes include sodium, potassium, and chloride. Change from Baseline was calculated as the value at the exit visit minus the value at Baseline. |
| Number of Participants With Clinically Significant Abnormalities of Urinalysis at the Screening and Exit Visits | Screening visit (-Week 1) and the exit visit (Week 12 or earlier) | Urine samples of participants were collected for urinalysis, including measuring protein, blood, leukocyte, glucose, and urobilinogen. All values out of the normal range were evaluated by the investigator. Classification of clinically significant and not clinically significant was based on the investigator's clinical judgment; no specific criteria were used. |
| Mean Change From Baseline in Systolic Blood Pressure (BP) and Diastolic BP at the Exit Visit | Baseline (Day 0) and the exit visit (Week 12 or earlier) | Systolic blood pressure (SBP) and diastolic BP of participants were measured in the sitting position. Change from Baseline was calculated as the value at the exit visit (Week 12 or earlier) minus the value at Baseline. |
| Mean Change From Baseline in Pulse Rate at the Exit Visit | Baseline (Screening) and the exit visit (Week 12 or earlier) | The pulse rate of participants was recorded. Change from Baseline was calculated as the value at the exit visit (Week 12 or earlier) minus the value at Baseline. |
| Mean Change From Baseline in Hemoglobin Content at the Exit Visit | Baseline (Day 0) and the exit visit (Week 12 or earlier) | Blood samples of participants were collected and evaluated for hemoglobin at Baseline and at the exit visit. Change from Baseline was calculated as the value at the exit visit (Week 12 or earlier) minus the value at Baseline. |
Countries
China
Participant flow
Pre-assignment details
Study LOC114609 (NCT01205451) is the open-label (OL) extension of Study 112958 (a double-blind \[DB\] study; NCT01153815). Within 3 months of completion of Study 112958, eligible participants were enrolled in Study 114609.
Participants by arm
| Arm | Count |
|---|---|
| BOTOX in Original DB Study; BOTOX in OL Study Participants who had received Botulinum Toxin Type A (BOTOX or GSK1358820) treatment in the previous double-blind study (Study 112958) received BOTOX 200 Units (U) (4 milliliters \[mL\]) injected into the wrist and finger muscles in this open-label extension study. 40 U (0.8 mL) was injected into the thumb muscles if thumb spasticity was present during the 12-week study (once at Week 0). | 53 |
| Placebo in Original DB Study; BOTOX in OL Study Participants who had received placebo treatment in the previous double-blind study (Study 112958) received BOTOX 200 Units (U) (4 milliliters \[mL\]) injected into the wrist and finger muscles in this open-label extension study. 40 U (0.8 mL) was injected into the thumb muscles if thumb spasticity was present during the 12-week study (once at Week 0). | 53 |
| Total | 106 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Withdrawal by Subject | 5 | 9 |
Baseline characteristics
| Characteristic | BOTOX in Original DB Study; BOTOX in OL Study | Placebo in Original DB Study; BOTOX in OL Study | Total |
|---|---|---|---|
| Age, Continuous | 54.4 Years STANDARD_DEVIATION 10.9 | 55.4 Years STANDARD_DEVIATION 12.53 | 54.9 Years STANDARD_DEVIATION 11.7 |
| Gender Female | 10 Participants | 10 Participants | 20 Participants |
| Gender Male | 43 Participants | 43 Participants | 86 Participants |
| Number of participants with the absence or presence of thumb spasticity Absence | 6 participants | 6 participants | 12 participants |
| Number of participants with the absence or presence of thumb spasticity Presence | 47 participants | 47 participants | 94 participants |
| Race/Ethnicity, Customized Chinese | 53 participants | 53 participants | 106 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 53 | 7 / 56 |
| serious Total, serious adverse events | 1 / 53 | 0 / 56 |
Outcome results
Primary
Change From Baseline at Week 6 and Week 12 for Wrist Flexor Muscle Tone as Measured on the Modified Ashworth Scale (MAS)
The investigator or assessor extended the participant's wrist as quickly as possible to grade flexor muscle tone. The MAS wrist score was calculated by using the 6-point MAS (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). Change from Baseline at Week 6 or Week 12 was calculated as the value at Week 6 or Week 12 minus the value at Baseline.
Time frame: Baseline (Day 0), Week 6, and Week 12
Population: Full Analysis Set (FAS) Population: all randomized and treated participants with at least one post-treatment MAS wrist score. The missing data imputation method was used for analysis. For each participant, missing data points were replaced by the mean of the non-missing scores from both treatment groups for that variable at the specific visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BOTOX in Original DB Study; BOTOX in OL Study | Change From Baseline at Week 6 and Week 12 for Wrist Flexor Muscle Tone as Measured on the Modified Ashworth Scale (MAS) | Week 6 | -1.21 scores on a scale | Standard Deviation 0.616 |
| BOTOX in Original DB Study; BOTOX in OL Study | Change From Baseline at Week 6 and Week 12 for Wrist Flexor Muscle Tone as Measured on the Modified Ashworth Scale (MAS) | Week 12 | -0.88 scores on a scale | Standard Deviation 0.589 |
| Placebo in Original DB Study; BOTOX in OL Study | Change From Baseline at Week 6 and Week 12 for Wrist Flexor Muscle Tone as Measured on the Modified Ashworth Scale (MAS) | Week 6 | -1.33 scores on a scale | Standard Deviation 0.753 |
| Placebo in Original DB Study; BOTOX in OL Study | Change From Baseline at Week 6 and Week 12 for Wrist Flexor Muscle Tone as Measured on the Modified Ashworth Scale (MAS) | Week 12 | -1.12 scores on a scale | Standard Deviation 0.752 |
p-value: <0.000195% CI: [-1.38, -1.04]Wilcoxon signed-rank test
p-value: <0.000195% CI: [-1.54, -1.12]Wilcoxon signed-rank test
p-value: <0.000195% CI: [-1.04, -0.72]Wilcoxon signed-rank test
p-value: <0.000195% CI: [-1.33, -0.91]Wilcoxon signed-rank test
Secondary
Change From Baseline at Week 6 and Week 12 for Finger Flexor Muscle Tone as Measured on the MAS
The investigator or assessor extended the participant's finger as quickly as possible to grade the flexor muscle tone. The MAS finger score was calculated by using the 6-point MAS (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). Change from Baseline at Week 6 or Week 12 was calculated as the value at Week 6 or Week 12 minus the value at Baseline.
Time frame: Baseline (Day 0), Week 6, and Week 12
Population: FAS Population. The missing data imputation method was used for analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BOTOX in Original DB Study; BOTOX in OL Study | Change From Baseline at Week 6 and Week 12 for Finger Flexor Muscle Tone as Measured on the MAS | Week 6 | -1.14 scores on a scale | Standard Deviation 0.716 |
| BOTOX in Original DB Study; BOTOX in OL Study | Change From Baseline at Week 6 and Week 12 for Finger Flexor Muscle Tone as Measured on the MAS | Week 12 | -0.72 scores on a scale | Standard Deviation 0.607 |
| Placebo in Original DB Study; BOTOX in OL Study | Change From Baseline at Week 6 and Week 12 for Finger Flexor Muscle Tone as Measured on the MAS | Week 6 | -1.29 scores on a scale | Standard Deviation 0.769 |
| Placebo in Original DB Study; BOTOX in OL Study | Change From Baseline at Week 6 and Week 12 for Finger Flexor Muscle Tone as Measured on the MAS | Week 12 | -0.96 scores on a scale | Standard Deviation 0.805 |
Secondary
Change From Baseline at Week 6 and Week 12 for the Principal Measure as Assessed on the Disability Assessment Scale (DAS)
The investigator assessed 4 areas of disability, hygiene, pain, dressing, and limb posture, using the 4-point DAS (0=No functional disability to 3=Severe disability). Prior to the first dose, the investigator, in consultation with the participant, selected 1functional disability item (which had to have a score of 2 or greater as measured on the DAS, indicating moderate to severe disability) from the 4 areas of disability and assessed it as a principal measure. Change from Baseline at Week 6 or Week 12 was calculated as the value at Week 6 or Week 12 minus the value at Baseline.
Time frame: Baseline (Day 0), Week 6, and Week 12
Population: FAS Population. The missing data imputation method was used for analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BOTOX in Original DB Study; BOTOX in OL Study | Change From Baseline at Week 6 and Week 12 for the Principal Measure as Assessed on the Disability Assessment Scale (DAS) | Week 6 | -0.64 scores on a scale | Standard Deviation 0.591 |
| BOTOX in Original DB Study; BOTOX in OL Study | Change From Baseline at Week 6 and Week 12 for the Principal Measure as Assessed on the Disability Assessment Scale (DAS) | Week 12 | -0.59 scores on a scale | Standard Deviation 0.57 |
| Placebo in Original DB Study; BOTOX in OL Study | Change From Baseline at Week 6 and Week 12 for the Principal Measure as Assessed on the Disability Assessment Scale (DAS) | Week 6 | -0.72 scores on a scale | Standard Deviation 0.662 |
| Placebo in Original DB Study; BOTOX in OL Study | Change From Baseline at Week 6 and Week 12 for the Principal Measure as Assessed on the Disability Assessment Scale (DAS) | Week 12 | -0.57 scores on a scale | Standard Deviation 0.665 |
Secondary
Change From Baseline at Week 6 and Week 12 for Thumb Flexor Muscle Tone as Measured on the MAS
The investigator or assessor extended the participant's thumb as quickly as possible to grade the flexor muscle tone. The MAS thumb score was calculated by using the 6-point MAS (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). Change from Baseline at Week 6 or Week 12 was calculated as the value at Week 6 or Week 12 minus the value at Baseline.
Time frame: Baseline (Day 0), Week 6, and Week 12
Population: FAS Population. Only those participants who had thumb spasticity were analyzed. The missing data imputation method was used for analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BOTOX in Original DB Study; BOTOX in OL Study | Change From Baseline at Week 6 and Week 12 for Thumb Flexor Muscle Tone as Measured on the MAS | Week 6 | -1.02 scores on a scale | Standard Deviation 0.642 |
| BOTOX in Original DB Study; BOTOX in OL Study | Change From Baseline at Week 6 and Week 12 for Thumb Flexor Muscle Tone as Measured on the MAS | Week 12 | -0.80 scores on a scale | Standard Deviation 0.631 |
| Placebo in Original DB Study; BOTOX in OL Study | Change From Baseline at Week 6 and Week 12 for Thumb Flexor Muscle Tone as Measured on the MAS | Week 6 | -1.22 scores on a scale | Standard Deviation 0.721 |
| Placebo in Original DB Study; BOTOX in OL Study | Change From Baseline at Week 6 and Week 12 for Thumb Flexor Muscle Tone as Measured on the MAS | Week 12 | -0.92 scores on a scale | Standard Deviation 0.716 |
Secondary
GAS Score as Evaluated by the Care Giver or the Participant at Week 6 and Week 12
The care giver or participant used the GAS to assess response to treatment at each visit after injection. The assessor was the same throughout the study period. GAS scores were assessed by using the 9-point GAS (-4, -3, -2, -1, -0, +1, +2, +3, +4; -4=very marked worsening, 0=unchanged, +4=very marked improvement) at Week 6 and Week 12.
Time frame: Week 6 and Week 12
Population: FAS Population. The missing data imputation method was used for analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BOTOX in Original DB Study; BOTOX in OL Study | GAS Score as Evaluated by the Care Giver or the Participant at Week 6 and Week 12 | Week 6 | 1.8 scores on a scale | Standard Deviation 0.91 |
| BOTOX in Original DB Study; BOTOX in OL Study | GAS Score as Evaluated by the Care Giver or the Participant at Week 6 and Week 12 | Week 12 | 1.6 scores on a scale | Standard Deviation 0.81 |
| Placebo in Original DB Study; BOTOX in OL Study | GAS Score as Evaluated by the Care Giver or the Participant at Week 6 and Week 12 | Week 6 | 2.1 scores on a scale | Standard Deviation 0.85 |
| Placebo in Original DB Study; BOTOX in OL Study | GAS Score as Evaluated by the Care Giver or the Participant at Week 6 and Week 12 | Week 12 | 1.7 scores on a scale | Standard Deviation 0.91 |
Secondary
Global Assessment Scale (GAS) Score as Evaluated by the Physician at Week 6 and Week 12
The physician used the GAS to assess response to treatment at each visit after injection. The assessor was the same throughout the study period. GAS scores were assessed by using the 9-point GAS (-4, -3, -2, -1, -0, +1, +2, +3, +4; -4=very marked worsening, -0=unchanged, +4=very marked improvement) at Week 6 and Week 12.
Time frame: Week 6 and Week 12
Population: FAS Population. The missing data imputation method was used for analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BOTOX in Original DB Study; BOTOX in OL Study | Global Assessment Scale (GAS) Score as Evaluated by the Physician at Week 6 and Week 12 | Week 6 | 1.9 scores on a scale | Standard Deviation 0.91 |
| BOTOX in Original DB Study; BOTOX in OL Study | Global Assessment Scale (GAS) Score as Evaluated by the Physician at Week 6 and Week 12 | Week 12 | 1.6 scores on a scale | Standard Deviation 0.82 |
| Placebo in Original DB Study; BOTOX in OL Study | Global Assessment Scale (GAS) Score as Evaluated by the Physician at Week 6 and Week 12 | Week 6 | 2.2 scores on a scale | Standard Deviation 0.84 |
| Placebo in Original DB Study; BOTOX in OL Study | Global Assessment Scale (GAS) Score as Evaluated by the Physician at Week 6 and Week 12 | Week 12 | 1.9 scores on a scale | Standard Deviation 0.93 |
Secondary
Mean Change From Baseline in Hematocrit Value at the Exit Visit
The hematocrit, also called packed cell volume or erythrocyte volume fraction, is the volume percentage of red blood cells in the blood. Change from Baseline was calculated as the value at the exit visit (Week 12 or earlier) minus the value at Baseline.
Time frame: Baseline (Day 0) and the exit visit (Week 12 or earlier)
Population: Safety Set Population. Only those participants for whom data were available for both the Baseline and exit visits were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BOTOX in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in Hematocrit Value at the Exit Visit | -0.003 percentage | Standard Deviation 0.0254 |
| Placebo in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in Hematocrit Value at the Exit Visit | -0.007 percentage | Standard Deviation 0.0257 |
Secondary
Mean Change From Baseline in Hemoglobin Content at the Exit Visit
Blood samples of participants were collected and evaluated for hemoglobin at Baseline and at the exit visit. Change from Baseline was calculated as the value at the exit visit (Week 12 or earlier) minus the value at Baseline.
Time frame: Baseline (Day 0) and the exit visit (Week 12 or earlier)
Population: Safety Set Population. Only those participants for whom data were available for both the Baseline and exit visits were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BOTOX in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in Hemoglobin Content at the Exit Visit | -0.255 Grams per Liter (grams/L) | Standard Deviation 10.9989 |
| Placebo in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in Hemoglobin Content at the Exit Visit | -1.409 Grams per Liter (grams/L) | Standard Deviation 8.7559 |
Secondary
Mean Change From Baseline in Pulse Rate at the Exit Visit
The pulse rate of participants was recorded. Change from Baseline was calculated as the value at the exit visit (Week 12 or earlier) minus the value at Baseline.
Time frame: Baseline (Screening) and the exit visit (Week 12 or earlier)
Population: Safety Set Population. Only those participants for whom data were available for both the Baseline and exit visits were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BOTOX in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in Pulse Rate at the Exit Visit | -3.0 beats per minute | Standard Deviation 9.27 |
| Placebo in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in Pulse Rate at the Exit Visit | 1.0 beats per minute | Standard Deviation 8.49 |
Secondary
Mean Change From Baseline in Red Blood Cell (RBC) Count at the Exit Visit
Blood samples of participants were collected and evaluated for RBC count at Baseline and at the exit visit. Change from Baseline was calculated as the value at the exit visit (Week 12 or earlier) minus the value at Baseline.
Time frame: Baseline (Day 0) and exit visit (Week 12 or earlier)
Population: Safety Set Population: all enrolled and treated participants. Only those participants for whom data were available for both the Baseline and exit visits were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BOTOX in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in Red Blood Cell (RBC) Count at the Exit Visit | -0.050 10^12 cells per Liter | Standard Deviation 0.3682 |
| Placebo in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in Red Blood Cell (RBC) Count at the Exit Visit | -0.039 10^12 cells per Liter | Standard Deviation 0.3087 |
Secondary
Mean Change From Baseline in Serum Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase (y-GT), and Alkaline Phosphatase (ALP) Values at the Exit Visit
Blood samples of participants were collected and evaluated for liver function, including measuring ALT, AST, y-GT, and ALP. Change from Baseline was calculated as the value at the exit visit (Week 12 or earlier) minus the value at Baseline.
Time frame: Baseline (Day 0) and the exit visit (Week 12 or earlier)
Population: Safety Set Population. Only those participants for whom data were available for both the Baseline and exit visits were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BOTOX in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in Serum Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase (y-GT), and Alkaline Phosphatase (ALP) Values at the Exit Visit | ALT, n=47, 44 | -1.100 International Units per Liter (IU/L) | Standard Deviation 10.9938 |
| BOTOX in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in Serum Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase (y-GT), and Alkaline Phosphatase (ALP) Values at the Exit Visit | AST, n=47, 44 | -0.153 International Units per Liter (IU/L) | Standard Deviation 9.3633 |
| BOTOX in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in Serum Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase (y-GT), and Alkaline Phosphatase (ALP) Values at the Exit Visit | y-GT, n=47, 44 | -1.098 International Units per Liter (IU/L) | Standard Deviation 14.0099 |
| BOTOX in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in Serum Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase (y-GT), and Alkaline Phosphatase (ALP) Values at the Exit Visit | ALP, n=46, 44 | -3.087 International Units per Liter (IU/L) | Standard Deviation 10.4821 |
| Placebo in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in Serum Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase (y-GT), and Alkaline Phosphatase (ALP) Values at the Exit Visit | ALP, n=46, 44 | -4.225 International Units per Liter (IU/L) | Standard Deviation 17.2055 |
| Placebo in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in Serum Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase (y-GT), and Alkaline Phosphatase (ALP) Values at the Exit Visit | ALT, n=47, 44 | -0.005 International Units per Liter (IU/L) | Standard Deviation 13.6079 |
| Placebo in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in Serum Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase (y-GT), and Alkaline Phosphatase (ALP) Values at the Exit Visit | y-GT, n=47, 44 | 0.316 International Units per Liter (IU/L) | Standard Deviation 17.4397 |
| Placebo in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in Serum Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase (y-GT), and Alkaline Phosphatase (ALP) Values at the Exit Visit | AST, n=47, 44 | -0.302 International Units per Liter (IU/L) | Standard Deviation 8.2277 |
Secondary
Mean Change From Baseline in Serum Blood Urea Nitrogen (BUN), Fasting Blood Glucose (FBG), Sodium, Potassium, Chloride, Total Cholesterol, and Triglyceride Values at the Exit Visit
Blood samples of participants were collected for biochemical tests of BUN, FBG, electrolytes, cholesterol, and triglycerides. The BUN test is primarily used to evaluate kidney function. Electrolytes include sodium, potassium, and chloride. Change from Baseline was calculated as the value at the exit visit minus the value at Baseline.
Time frame: Baseline (Day 0) and the exit visit (Week 12 or earlier)
Population: Safety Set Population. Only those participants for whom data were available for both the Baseline and exit visits were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BOTOX in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in Serum Blood Urea Nitrogen (BUN), Fasting Blood Glucose (FBG), Sodium, Potassium, Chloride, Total Cholesterol, and Triglyceride Values at the Exit Visit | Sodium, n=47, 44 | 0.423 Millimoles per Liter (mmol/L) | Standard Deviation 3.599 |
| BOTOX in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in Serum Blood Urea Nitrogen (BUN), Fasting Blood Glucose (FBG), Sodium, Potassium, Chloride, Total Cholesterol, and Triglyceride Values at the Exit Visit | Chloride, n=47, 44 | 1.077 Millimoles per Liter (mmol/L) | Standard Deviation 4.0509 |
| BOTOX in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in Serum Blood Urea Nitrogen (BUN), Fasting Blood Glucose (FBG), Sodium, Potassium, Chloride, Total Cholesterol, and Triglyceride Values at the Exit Visit | FBG, n=47, 43 | 0.209 Millimoles per Liter (mmol/L) | Standard Deviation 1.3513 |
| BOTOX in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in Serum Blood Urea Nitrogen (BUN), Fasting Blood Glucose (FBG), Sodium, Potassium, Chloride, Total Cholesterol, and Triglyceride Values at the Exit Visit | Total cholesterol, n=47, 43 | -0.057 Millimoles per Liter (mmol/L) | Standard Deviation 0.841 |
| BOTOX in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in Serum Blood Urea Nitrogen (BUN), Fasting Blood Glucose (FBG), Sodium, Potassium, Chloride, Total Cholesterol, and Triglyceride Values at the Exit Visit | Potassium, n=47, 44 | -0.008 Millimoles per Liter (mmol/L) | Standard Deviation 0.4014 |
| BOTOX in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in Serum Blood Urea Nitrogen (BUN), Fasting Blood Glucose (FBG), Sodium, Potassium, Chloride, Total Cholesterol, and Triglyceride Values at the Exit Visit | Triglycerides, n=47, 43 | -0.039 Millimoles per Liter (mmol/L) | Standard Deviation 0.6525 |
| BOTOX in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in Serum Blood Urea Nitrogen (BUN), Fasting Blood Glucose (FBG), Sodium, Potassium, Chloride, Total Cholesterol, and Triglyceride Values at the Exit Visit | BUN, n=47, 44 | -0.292 Millimoles per Liter (mmol/L) | Standard Deviation 1.1855 |
| Placebo in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in Serum Blood Urea Nitrogen (BUN), Fasting Blood Glucose (FBG), Sodium, Potassium, Chloride, Total Cholesterol, and Triglyceride Values at the Exit Visit | Triglycerides, n=47, 43 | 0.119 Millimoles per Liter (mmol/L) | Standard Deviation 0.5698 |
| Placebo in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in Serum Blood Urea Nitrogen (BUN), Fasting Blood Glucose (FBG), Sodium, Potassium, Chloride, Total Cholesterol, and Triglyceride Values at the Exit Visit | BUN, n=47, 44 | 0.226 Millimoles per Liter (mmol/L) | Standard Deviation 2.9929 |
| Placebo in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in Serum Blood Urea Nitrogen (BUN), Fasting Blood Glucose (FBG), Sodium, Potassium, Chloride, Total Cholesterol, and Triglyceride Values at the Exit Visit | FBG, n=47, 43 | -0.081 Millimoles per Liter (mmol/L) | Standard Deviation 0.8 |
| Placebo in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in Serum Blood Urea Nitrogen (BUN), Fasting Blood Glucose (FBG), Sodium, Potassium, Chloride, Total Cholesterol, and Triglyceride Values at the Exit Visit | Sodium, n=47, 44 | -0.034 Millimoles per Liter (mmol/L) | Standard Deviation 2.7857 |
| Placebo in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in Serum Blood Urea Nitrogen (BUN), Fasting Blood Glucose (FBG), Sodium, Potassium, Chloride, Total Cholesterol, and Triglyceride Values at the Exit Visit | Potassium, n=47, 44 | -0.060 Millimoles per Liter (mmol/L) | Standard Deviation 0.5128 |
| Placebo in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in Serum Blood Urea Nitrogen (BUN), Fasting Blood Glucose (FBG), Sodium, Potassium, Chloride, Total Cholesterol, and Triglyceride Values at the Exit Visit | Chloride, n=47, 44 | -0.143 Millimoles per Liter (mmol/L) | Standard Deviation 3.4336 |
| Placebo in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in Serum Blood Urea Nitrogen (BUN), Fasting Blood Glucose (FBG), Sodium, Potassium, Chloride, Total Cholesterol, and Triglyceride Values at the Exit Visit | Total cholesterol, n=47, 43 | 0.282 Millimoles per Liter (mmol/L) | Standard Deviation 0.9535 |
Secondary
Mean Change From Baseline in Serum Creatinine, Uric Acid, and Total Bilirubin Values at the Exit Visit
Blood samples of participants were collected for a biochemical test of creatine, uric acid, and total bilirubin. Creatine and uric acid are evaluated for kidney function. The liver function test includes total bilirubin. Change from Baseline was calculated as the value at the exit visit (Week 12 or earlier) minus the value at Baseline.
Time frame: Baseline (Day 0) and the exit visit (Week 12 or earlier)
Population: Safety Set Population. Only those participants for whom data were available for both the Baseline and exit visits were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BOTOX in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in Serum Creatinine, Uric Acid, and Total Bilirubin Values at the Exit Visit | Creatinine | -1.509 Micromoles per Liter (μmol/L) | Standard Deviation 9.8783 |
| BOTOX in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in Serum Creatinine, Uric Acid, and Total Bilirubin Values at the Exit Visit | Uric Acid | -3.670 Micromoles per Liter (μmol/L) | Standard Deviation 61.135 |
| BOTOX in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in Serum Creatinine, Uric Acid, and Total Bilirubin Values at the Exit Visit | Total Bilirubin | 0.249 Micromoles per Liter (μmol/L) | Standard Deviation 4.6873 |
| Placebo in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in Serum Creatinine, Uric Acid, and Total Bilirubin Values at the Exit Visit | Creatinine | -0.984 Micromoles per Liter (μmol/L) | Standard Deviation 20.1303 |
| Placebo in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in Serum Creatinine, Uric Acid, and Total Bilirubin Values at the Exit Visit | Uric Acid | -16.198 Micromoles per Liter (μmol/L) | Standard Deviation 67.7636 |
| Placebo in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in Serum Creatinine, Uric Acid, and Total Bilirubin Values at the Exit Visit | Total Bilirubin | -0.293 Micromoles per Liter (μmol/L) | Standard Deviation 3.6399 |
Secondary
Mean Change From Baseline in Systolic Blood Pressure (BP) and Diastolic BP at the Exit Visit
Systolic blood pressure (SBP) and diastolic BP of participants were measured in the sitting position. Change from Baseline was calculated as the value at the exit visit (Week 12 or earlier) minus the value at Baseline.
Time frame: Baseline (Day 0) and the exit visit (Week 12 or earlier)
Population: Safety Set Population. Only those participants for whom data were available for both the Baseline and exit visits were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BOTOX in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in Systolic Blood Pressure (BP) and Diastolic BP at the Exit Visit | Systolic BP | -3.1 Millimeters of mercury (mmHg) | Standard Deviation 8.96 |
| BOTOX in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in Systolic Blood Pressure (BP) and Diastolic BP at the Exit Visit | Diastolic BP | -1.4 Millimeters of mercury (mmHg) | Standard Deviation 6.27 |
| Placebo in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in Systolic Blood Pressure (BP) and Diastolic BP at the Exit Visit | Systolic BP | -2.3 Millimeters of mercury (mmHg) | Standard Deviation 10.02 |
| Placebo in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in Systolic Blood Pressure (BP) and Diastolic BP at the Exit Visit | Diastolic BP | -2.5 Millimeters of mercury (mmHg) | Standard Deviation 7.79 |
Secondary
Mean Change From Baseline in the Percentage of Neutrophils, the Percentage of Lymphocytes, the Percentage of Monocytes, the Percentage of Eosinophils, and the Percentage of Basophils at the Exit Visit
Blood samples of participants were collected and evaluated for the percentage of neutrophils, lymphocytes, monocytes, eosinophils, and basophils comprising the total WBC count in the blood at Baseline and at the exit visit. Change from Baseline was calculated as the value at the exit visit (Week 12 or earlier) minus the value at Baseline.
Time frame: Baseline (Day 0) and the exit visit (Week 12 or earlier)
Population: Safety Set Population. Only those participants for whom data were available for both the Baseline and exit visits were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BOTOX in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in the Percentage of Neutrophils, the Percentage of Lymphocytes, the Percentage of Monocytes, the Percentage of Eosinophils, and the Percentage of Basophils at the Exit Visit | Lymphocytes | 0.118 Percentage of the total WBC | Standard Deviation 6.4613 |
| BOTOX in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in the Percentage of Neutrophils, the Percentage of Lymphocytes, the Percentage of Monocytes, the Percentage of Eosinophils, and the Percentage of Basophils at the Exit Visit | Eosinophils | 0.094 Percentage of the total WBC | Standard Deviation 1.3067 |
| BOTOX in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in the Percentage of Neutrophils, the Percentage of Lymphocytes, the Percentage of Monocytes, the Percentage of Eosinophils, and the Percentage of Basophils at the Exit Visit | Monocytes | -0.217 Percentage of the total WBC | Standard Deviation 1.657 |
| BOTOX in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in the Percentage of Neutrophils, the Percentage of Lymphocytes, the Percentage of Monocytes, the Percentage of Eosinophils, and the Percentage of Basophils at the Exit Visit | Basophils | 0.032 Percentage of the total WBC | Standard Deviation 0.292 |
| BOTOX in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in the Percentage of Neutrophils, the Percentage of Lymphocytes, the Percentage of Monocytes, the Percentage of Eosinophils, and the Percentage of Basophils at the Exit Visit | Neutrophils | -0.009 Percentage of the total WBC | Standard Deviation 6.3905 |
| Placebo in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in the Percentage of Neutrophils, the Percentage of Lymphocytes, the Percentage of Monocytes, the Percentage of Eosinophils, and the Percentage of Basophils at the Exit Visit | Basophils | 0.010 Percentage of the total WBC | Standard Deviation 0.2185 |
| Placebo in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in the Percentage of Neutrophils, the Percentage of Lymphocytes, the Percentage of Monocytes, the Percentage of Eosinophils, and the Percentage of Basophils at the Exit Visit | Neutrophils | -0.757 Percentage of the total WBC | Standard Deviation 7.8585 |
| Placebo in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in the Percentage of Neutrophils, the Percentage of Lymphocytes, the Percentage of Monocytes, the Percentage of Eosinophils, and the Percentage of Basophils at the Exit Visit | Lymphocytes | 0.734 Percentage of the total WBC | Standard Deviation 6.7396 |
| Placebo in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in the Percentage of Neutrophils, the Percentage of Lymphocytes, the Percentage of Monocytes, the Percentage of Eosinophils, and the Percentage of Basophils at the Exit Visit | Monocytes | 0.55 Percentage of the total WBC | Standard Deviation 2.7845 |
| Placebo in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in the Percentage of Neutrophils, the Percentage of Lymphocytes, the Percentage of Monocytes, the Percentage of Eosinophils, and the Percentage of Basophils at the Exit Visit | Eosinophils | 0.49 Percentage of the total WBC | Standard Deviation 2.3799 |
Secondary
Mean Change From Baseline in Total Protein and Albumin Values at the Exit Visit
Blood samples of participants were collected for a biochemical test of total protein and albumin, at Baseline and at the exit visit. Change from Baseline was calculated as the value at the exit visit (Week 12 or earlier) minus the value at Baseline.
Time frame: Baseline (Day 0) and the exit visit (Week 12 or earlier)
Population: Safety Set Population. Only those participants for whom data were available for both the Baseline and exit visits were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BOTOX in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in Total Protein and Albumin Values at the Exit Visit | Total Protein | -0.711 grams/L | Standard Deviation 5.8908 |
| BOTOX in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in Total Protein and Albumin Values at the Exit Visit | Albumin | -0.400 grams/L | Standard Deviation 3.5067 |
| Placebo in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in Total Protein and Albumin Values at the Exit Visit | Total Protein | -1.484 grams/L | Standard Deviation 6.0077 |
| Placebo in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in Total Protein and Albumin Values at the Exit Visit | Albumin | -0.236 grams/L | Standard Deviation 4.4753 |
Secondary
Mean Change From Baseline in White Blood Cell (WBC) and Platelet Count at the Exit Visit
Blood samples of participants were collected and evaluated for WBC count and platelet count at Baseline and at the exit visit. Change from Baseline was calculated as the value at the exit visit (Week 12 or earlier) minus the value at Baseline.
Time frame: Baseline (Day 0) and the exit visit (Week 12 or earlier)
Population: Safety Set Population. Only those participants for whom data were available for both the Baseline and exit visits were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BOTOX in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in White Blood Cell (WBC) and Platelet Count at the Exit Visit | WBCs | 0.111 10^9 cells per Liter | Standard Deviation 1.334 |
| BOTOX in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in White Blood Cell (WBC) and Platelet Count at the Exit Visit | Platelets | -10.660 10^9 cells per Liter | Standard Deviation 38.8734 |
| Placebo in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in White Blood Cell (WBC) and Platelet Count at the Exit Visit | WBCs | -0.273 10^9 cells per Liter | Standard Deviation 2.1714 |
| Placebo in Original DB Study; BOTOX in OL Study | Mean Change From Baseline in White Blood Cell (WBC) and Platelet Count at the Exit Visit | Platelets | -1.386 10^9 cells per Liter | Standard Deviation 41.5828 |
Secondary
Number of Participants Classified as Wrist Treatment Responders at Week 6 and Week 12
Wrist treatment responders are defined as participants with a decrease in wrist flexor muscle tone of at least one point on the MAS from Baseline. The MAS wrist score was calculated by using the 6-point MAS (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).
Time frame: Baseline (Day 0), Week 6, and Week 12
Population: FAS Population. The missing data imputation method was used for analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BOTOX in Original DB Study; BOTOX in OL Study | Number of Participants Classified as Wrist Treatment Responders at Week 6 and Week 12 | Week 6 | 43 participants |
| BOTOX in Original DB Study; BOTOX in OL Study | Number of Participants Classified as Wrist Treatment Responders at Week 6 and Week 12 | Week 12 | 35 participants |
| Placebo in Original DB Study; BOTOX in OL Study | Number of Participants Classified as Wrist Treatment Responders at Week 6 and Week 12 | Week 6 | 42 participants |
| Placebo in Original DB Study; BOTOX in OL Study | Number of Participants Classified as Wrist Treatment Responders at Week 6 and Week 12 | Week 12 | 39 participants |
Secondary
Number of Participants With Clinically Significant Abnormalities of Urinalysis at the Screening and Exit Visits
Urine samples of participants were collected for urinalysis, including measuring protein, blood, leukocyte, glucose, and urobilinogen. All values out of the normal range were evaluated by the investigator. Classification of clinically significant and not clinically significant was based on the investigator's clinical judgment; no specific criteria were used.
Time frame: Screening visit (-Week 1) and the exit visit (Week 12 or earlier)
Population: Safety Set Population. Only those participants for whom data were available for both the Screening and exit visits were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BOTOX in Original DB Study; BOTOX in OL Study | Number of Participants With Clinically Significant Abnormalities of Urinalysis at the Screening and Exit Visits | Urine protein, Screening | 0 participants |
| BOTOX in Original DB Study; BOTOX in OL Study | Number of Participants With Clinically Significant Abnormalities of Urinalysis at the Screening and Exit Visits | Urine protein, Exit visit | 0 participants |
| BOTOX in Original DB Study; BOTOX in OL Study | Number of Participants With Clinically Significant Abnormalities of Urinalysis at the Screening and Exit Visits | Blood, Screening | 0 participants |
| BOTOX in Original DB Study; BOTOX in OL Study | Number of Participants With Clinically Significant Abnormalities of Urinalysis at the Screening and Exit Visits | Blood, Exit visit | 0 participants |
| BOTOX in Original DB Study; BOTOX in OL Study | Number of Participants With Clinically Significant Abnormalities of Urinalysis at the Screening and Exit Visits | Leukocytes, Screening | 1 participants |
| BOTOX in Original DB Study; BOTOX in OL Study | Number of Participants With Clinically Significant Abnormalities of Urinalysis at the Screening and Exit Visits | Leukocytes, Exit visit | 1 participants |
| BOTOX in Original DB Study; BOTOX in OL Study | Number of Participants With Clinically Significant Abnormalities of Urinalysis at the Screening and Exit Visits | Urine glucose, Screeing | 2 participants |
| BOTOX in Original DB Study; BOTOX in OL Study | Number of Participants With Clinically Significant Abnormalities of Urinalysis at the Screening and Exit Visits | Urine glucose, Exit visit | 0 participants |
| BOTOX in Original DB Study; BOTOX in OL Study | Number of Participants With Clinically Significant Abnormalities of Urinalysis at the Screening and Exit Visits | Urobilinogen, Screening | 0 participants |
| BOTOX in Original DB Study; BOTOX in OL Study | Number of Participants With Clinically Significant Abnormalities of Urinalysis at the Screening and Exit Visits | Urobilinogen, Exit visit | 0 participants |
| Placebo in Original DB Study; BOTOX in OL Study | Number of Participants With Clinically Significant Abnormalities of Urinalysis at the Screening and Exit Visits | Urine glucose, Exit visit | 2 participants |
| Placebo in Original DB Study; BOTOX in OL Study | Number of Participants With Clinically Significant Abnormalities of Urinalysis at the Screening and Exit Visits | Urine protein, Screening | 0 participants |
| Placebo in Original DB Study; BOTOX in OL Study | Number of Participants With Clinically Significant Abnormalities of Urinalysis at the Screening and Exit Visits | Leukocytes, Exit visit | 0 participants |
| Placebo in Original DB Study; BOTOX in OL Study | Number of Participants With Clinically Significant Abnormalities of Urinalysis at the Screening and Exit Visits | Urine protein, Exit visit | 0 participants |
| Placebo in Original DB Study; BOTOX in OL Study | Number of Participants With Clinically Significant Abnormalities of Urinalysis at the Screening and Exit Visits | Urobilinogen, Exit visit | 0 participants |
| Placebo in Original DB Study; BOTOX in OL Study | Number of Participants With Clinically Significant Abnormalities of Urinalysis at the Screening and Exit Visits | Blood, Screening | 3 participants |
| Placebo in Original DB Study; BOTOX in OL Study | Number of Participants With Clinically Significant Abnormalities of Urinalysis at the Screening and Exit Visits | Urine glucose, Screeing | 3 participants |
| Placebo in Original DB Study; BOTOX in OL Study | Number of Participants With Clinically Significant Abnormalities of Urinalysis at the Screening and Exit Visits | Blood, Exit visit | 1 participants |
| Placebo in Original DB Study; BOTOX in OL Study | Number of Participants With Clinically Significant Abnormalities of Urinalysis at the Screening and Exit Visits | Urobilinogen, Screening | 0 participants |
| Placebo in Original DB Study; BOTOX in OL Study | Number of Participants With Clinically Significant Abnormalities of Urinalysis at the Screening and Exit Visits | Leukocytes, Screening | 3 participants |