A Phase 3 interventional study of Botulinum toxin A (GSK1358820) and Placebo in Spasticity, Post-Stroke, sponsored by GlaxoSmithKline. Completed at 38 sites in Japan. Open to participants aged 20 Years to 80 Years. Per ClinicalTrials.gov, last updated 2020-06-02.
Sponsored by GlaxoSmithKline · Phase 3, Interventional, and Treatment
Botulinum toxin A (GSK1358820) is a sterile, purified type A botulinum neurotoxin complex. In Japan, 240 units of botulinum toxin A are approved as a maximum dose per administration for upper limb spasticity. This study is planned to evaluate the effectiveness and safety of 400 units of botulinum toxin A which can help to increase the maximum dose per administration to 400 units from 240 units as the treatment with 240 units is considered insufficient in subjects with post-stroke upper limb spasticity. Approximately 120 subjects will be randomized to receive either 400 or 240 units of botulinum toxin A in double blind phase followed by open-label phase in which 400 units of the study treatment will be injected in both the groups. The study period will be up to 52 weeks, consisting of a screening phase up to 4 weeks, minimum 12-week double blind phase (Part 1), maximum 36- week open-label phase (12 weeks per cycle with 3 treatment phases: Part 2, Part 3 and Part 4).
Exclusion Criteria:
Subjects will receive a total dose of 400 units of botulinum toxin A of which 240 units will be injected into the muscles that act on finger (including thumb flexors) and wrist flexors, and a total of 160 units will be injected into the muscles that act on the elbow flexors.
Drug: Botulinum toxin A (GSK1358820)
Subjects will receive 240 units of botulinum toxin A injected into the muscles that act on the finger (including thumb flexors) and wrist flexors. Placebo will be injected into the muscles that act on the elbow flexors.
Drug: Botulinum toxin A (GSK1358820) · Drug: Placebo
Subjects will receive botulinum toxin A with a dose of 400 units injected in a divided doses.
Drug: Botulinum toxin A (GSK1358820)
GSK1358820 is sterile, purified type A botulinum neurotoxin complex. GSK1358820 injection will contain botulinum toxin A (100 units), sodium chloride (0.9 milligrams \[mg\]), and human serum albumin (0.5 mg). It will be available with doses of 400 units and 240 units.
Placebo injection will contain sodium chloride (0.9 mg).
Percentage of Participants Who Had Modified Ashworth Scale (MAS) Score Reduced at Least 1 From Baseline in the Elbow Flexors at Week 6
MAS was used to measure the level of spasticity. The test was performed in a sitting position throughout the study. The affected parts were extended as fast as possible to grade the flexor muscle tones. It was scored on a scale of 0 to 4 as: 0=No increase in muscle tone, 1=Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion (ROM) when the affected part(s) is moved in flexion or extension, 1+= Slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half of ROM, 2 =More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved, 3= Considerable increase in muscle tone, passive movement difficult and 4= Affected part(s) rigid in flexion or extension. Higher scores= Worst outcome while lower scores= Better outcome.
Time frame: Week 6
Percentage of Participants Who Had MAS Score Reduction in Elbow, Wrist, Finger and Thumb Flexors up to Week 12
MAS was used to measure the level of spasticity. The test was performed in a sitting position throughout the study. The affected parts were extended as fast as possible to grade the flexor muscle tones. It was scored on a scale of 0 to 4 as: 0=No increase in muscle tone, 1=Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion (ROM) when the affected part(s) is moved in flexion or extension, 1+=Slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM, 2=More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved, 3=Considerable increase in muscle tone, passive movement difficult and 4=Affected part(s) rigid in flexion or extension. Higher scores=worst outcome while lower scores=better outcome.
Time frame: Week 2, Week 4, Week 6 and Week 12
Change From Baseline in MAS Scores in Elbow, Wrist, Finger and Thumb Flexors up to Week 12 (Mixed Model Repeated Measures [MMRM])
The affected parts were extended as fast as possible to grade the flexor muscle tones. It was scored on a scale of 0 to 4 as: 0=No increase in muscle tone, 1=Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion (ROM) when the affected part(s) is moved in flexion/extension, 1+=Slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM, 2=More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved, 3=Considerable increase in muscle tone, passive movement difficult and 4=Affected part(s) rigid in flexion/extension. Higher scores=worst outcome while lower scores=better outcome. Baseline was defined as the latest pre-first dose assessment with a non-missing value. Change from Baseline was calculated as the post-dose visit value minus the Baseline value.
Time frame: Baseline (Day 1), Week 2, Week 4, Week 6 and Week 12
Change From Baseline in Principal Therapeutic Target of Disability Assessment Scale (DAS) - MMRM up to Week 12
The investigator assessed 4 areas of disability namely hygiene, pain, dressing and limb posture and was graded using the 4-point DAS scale where (0=No functional disability, 1: Mild disability, 2: Moderate disability and 3=Severe disability). The investigator, in consultation with the participant, selected 1 functional disability item from the 4 areas of disability and assessed it as a principal therapeutic target. The maximum possible score was 3 where higher scores indicate severe disability and lowers scores indicate sound functional ability. Baseline value was defined as the latest pre-first dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as the post-dose visit value minus the Baseline value.
Time frame: Baseline (Day 1), Week 2, Week 4, Week 6 and Week 12
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) After 84 Days of First Treatment
An AE is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment was categorized as SAE. Data for number of participants with any AE and any SAE is presented.
Time frame: Up to 84 days post first treatment
Number of Participants With AEs and SAEs-Overall Study Period
An AE is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment was categorized as SAE. Data for number of participants with any AE and any SAE is presented.
Time frame: Up to Week 48
Number of Participants With Abnormal Findings After Physical Examinations
Physical examinations included assessment of lungs, cardiovascular system, and abdominal region (liver and spleen). This analysis was not planned and data was not collected and captured in the database.
Time frame: Up to Week 48
Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline
Hematology parameters along with their normal ranges included: basophils (0 to 2 percent), eosinophils (0 to 8 percent), hemoglobin (135 to 175 grams/liter), hematocrit (0.397 to 0.524 proportion of red blood cells in blood), lymphocytes (18 to 49 percent), monocytes (2 to 10 percent), total neutrophils (40 to 75 percent), platelet count (140 to 340 giga cells/liter), red blood cell count (4.3 to 5.7 trillion cells/liter), white blood cell count (3.3 to 9 giga cells/liter), mean corpuscular volume (85 to 102 femtoliters), mean corpuscular hemoglobin (28 to 34 picograms) and reticulocyte count (0.004 to 0.019 percent/ratio). Shift in values relative to normal range as high and low have been presented for categories having non-zero values.
Time frame: Up to Week 48
Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline
Clinical chemistry parameters assessed were alkaline phosphatase (100 to 325 international units/liter), alanine amino transferase (5 to 45 international units/liter), aspartate amino transferase (10 to 40 international units/liter), direct bilirubin (0 to 3.42 micromoles/liter), total bilirubin (3.42 to 20.52 micromoles/liter), calcium (2.0958 - 2.5948 millimoles/liter), creatinine (53.924 - 91.936 micromoles/liter), potassium (3.5 - 5 millimoles/liter), sodium (137 - 147 millimoles/liter), total protein (67 - 83 grams/liter), urea/blood urea nitrogen (BUN) \[2.856 - 7.14 millimoles/liter\]. Shift in values relative to normal range as high and low have been presented for categories having non-zero values.
Time frame: Up to Week 48
Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Analysis
Urinalysis parameters assessed were urine occult blood, urine protein . In this dipstick test, occult blood and protein in urine samples were recorded as negative trace, 1+, 2+, and 3+ (the plus sign increases with occult blood or proteins in the urine: 1+=slightly positive, 2+=positive, 3+=high positive etc). Number of participants with worst-case urinalysis results post-Baseline relative to Baseline by dipstick analysis have been presented.
Time frame: Up to Week 48
Change From Baseline in Vital Sign Parameters Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 12 and Week 48
Vital sign parameters SBP and DBP were measured in a semi-recumbent position after a 5-minute rest. If measurement in a semi-recumbent position was difficult, measurement in another position (e.g., sitting) was acceptable. The measurement was performed always in the same position during the study period. SBP and DBP were measured using an automated device. Baseline value was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post-dose visit value minus the Baseline value.
Time frame: Baseline (Day 1), Week 12 and Week 48
Change From Baseline in Vital Sign Parameter Heart Rate at Week 12 and Week 48
Vital sign parameter heart rate was measured in a semi-recumbent position after a 5-minute rest. If measurement in a semi-recumbent position was difficult, measurement in another position (e.g., sitting) was acceptable. The measurement was performed always in the same position during the study period. Heart rate was measured using an automated device. Baseline value was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post-dose visit value minus the Baseline value.
Time frame: Baseline (Day 1), Week 12 and Week 48
Change From Baseline in Vital Sign Parameter Temperature at Week 12 and Week 48
Vital sign parameter temperature was measured orally, intra-aurally, or axillary fossa, the participant was instructed to refrain from eating food or drinking beverage within 5 minutes before the measurement. The method for the measurement of body temperature was same throughout the study. Baseline value was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post-dose visit value minus the Baseline value.
Time frame: Baseline (Day 1), Week 12 and Week 48
This was a multicenter study conducted at 40 study centers in Japan, of which 38 centers enrolled participants.
| Milestone | GSK1358820 240 U | GSK1358820 400 U |
|---|---|---|
| Started | 63 | 61 |
| Completed | 60 | 57 |
| Not completed | 3 | 4 |
| Withdrew: Adverse event | 0 | 3 |
| Withdrew: Withdrawal by subject | 3 | 1 |
| Milestone | GSK1358820 240 U | GSK1358820 400 U |
|---|---|---|
| Started | 60 | 57 |
| Completed | 58 | 57 |
| Not completed | 2 | 0 |
| Withdrew: Protocol defined stopping criteria | 1 | 0 |
| Withdrew: Withdrawal by subject | 1 | 0 |
| Milestone | GSK1358820 240 U | GSK1358820 400 U |
|---|---|---|
| Started | 55 | 56 |
| Completed | 54 | 55 |
| Not completed | 1 | 1 |
| Withdrew: Withdrawal by subject | 1 | 1 |
| Milestone | GSK1358820 240 U | GSK1358820 400 U |
|---|---|---|
| Started | 43 | 40 |
| Completed | 43 | 40 |
| Not completed | 0 | 0 |
MAS was used to measure the level of spasticity. The test was performed in a sitting position throughout the study. The affected parts were extended as fast as possible to grade the flexor muscle tones. It was scored on a scale of 0 to 4 as: 0=No increase in muscle tone, 1=Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion (ROM) when the affected part(s) is moved in flexion or extension, 1+= Slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half of ROM, 2 =More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved, 3= Considerable increase in muscle tone, passive movement difficult and 4= Affected part(s) rigid in flexion or extension. Higher scores= Worst outcome while lower scores= Better outcome.
| Percentage of participants | GSK1358820 240 U | GSK1358820 400 U |
|---|---|---|
| Percentage of Participants Who Had Modified Ashworth Scale (MAS) Score Reduced at Least 1 From Baseline in the Elbow Flexors at Week 6 | 50.8 | 68.9 |
MAS was used to measure the level of spasticity. The test was performed in a sitting position throughout the study. The affected parts were extended as fast as possible to grade the flexor muscle tones. It was scored on a scale of 0 to 4 as: 0=No increase in muscle tone, 1=Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion (ROM) when the affected part(s) is moved in flexion or extension, 1+=Slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM, 2=More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved, 3=Considerable increase in muscle tone, passive movement difficult and 4=Affected part(s) rigid in flexion or extension. Higher scores=worst outcome while lower scores=better outcome.
| Percentage of participants | GSK1358820 240 U | GSK1358820 400 U |
|---|---|---|
| Elbow Flexion, Week 2, n=63,61 | 44.4 | 77.0 |
| Elbow Flexion, Week 4, n=63,61 | 52.4 | 73.8 |
| Elbow Flexion, Week 6, n=63,61 | 50.8 | 68.9 |
| Elbow Flexion, Week 12, n=63,61 | 33.3 | 45.9 |
| Wrist Flexion, Week 2, n=63,61 | 77.8 | 72.1 |
| Wrist Flexion, Week 4, n=63,61 | 82.5 | 73.8 |
| Wrist Flexion, Week 6, n=63,61 | 81.0 | 68.9 |
| Wrist flexion, Week 12, n=63,61 | 54.0 | 44.3 |
| Finger Flexion, Week 2, n=63,61 | 87.3 | 78.7 |
| Finger Flexion, Week 4, n=63,61 | 85.7 | 75.4 |
| Finger Flexion, Week 6, n=63,61 | 81.0 | 72.1 |
| Finger Flexion, Week 12, n =63,61 | 46.0 | 45.9 |
| Thumb Flexion, Week 2, n=60,54 | 75.0 | 64.8 |
| Thumb Flexion, Week 4, n=60,54 | 71.7 | 64.8 |
| Thumb Flexion, Week 6, n=60,54 | 68.3 | 66.7 |
| Thumb flexion, Week 12,n=60,54 | 46.7 | 46.3 |
The affected parts were extended as fast as possible to grade the flexor muscle tones. It was scored on a scale of 0 to 4 as: 0=No increase in muscle tone, 1=Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion (ROM) when the affected part(s) is moved in flexion/extension, 1+=Slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM, 2=More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved, 3=Considerable increase in muscle tone, passive movement difficult and 4=Affected part(s) rigid in flexion/extension. Higher scores=worst outcome while lower scores=better outcome. Baseline was defined as the latest pre-first dose assessment with a non-missing value. Change from Baseline was calculated as the post-dose visit value minus the Baseline value.
| Scores on a scale | GSK1358820 240 U | GSK1358820 400 U |
|---|---|---|
| Elbow Flexion, Week 2, n=63,60 | -0.59 ± 0.089 | -1.07 ± 0.102 |
| Elbow Flexion, Week 4, n=63,59 | -0.7 ± 0.097 | -1.12 ± 0.110 |
| Elbow Flexion, Week 6, n=63,59 | -0.71 ± 0.107 | -1.09 ± 0.128 |
| Elbow Flexion, Week 12, n=60,57 | -0.35 ± 0.072 | -0.61 ± 0.101 |
| Wrist Flexion, Week 2, n=63,60 | -1.29 ± 0.120 | -1.21 ± 0.126 |
| Wrist Flexion, Week 4, n=63,59 | -1.45 ± 0.122 | -1.35 ± 0.132 |
| Wrist Flexion, Week 6, n=63,59 | -1.29 ± 0.115 | -1.31 ± 0.136 |
| Wrist flexion, Week 12, n=60,57 | -0.69 ± 0.097 | -0.59 ± 0.107 |
| Finger Flexion, Week 2, n=63,60 | -1.38 ± 0.113 | -1.28 ± 0.121 |
| Finger Flexion, Week 4, n=63,59 | -1.49 ± 0.117 | -1.32 ± 0.130 |
| Finger Flexion, Week 6, n=63,59 | -1.36 ± 0.118 | -1.22 ± 0.123 |
| Finger Flexion, Week 12, n=60,57 | -0.63 ± 0.116 | -0.59 ± 0.097 |
| Thumb Flexion, Week 2, n=60,53 | -1.24 ± 0.123 | -0.96 ± 0.130 |
| Thumb Flexion, Week 4, n=60,53 | -1.29 ± 0.127 | -1.15 ± 0.138 |
| Thumb Flexion, Week 6, n=60,53 | -1.12 ± 0.119 | -1.10 ± 0.132 |
| Thumb flexion, Week 12, n=57,51 | -0.69 ± 0.133 | -0.61 ± 0.144 |
The investigator assessed 4 areas of disability namely hygiene, pain, dressing and limb posture and was graded using the 4-point DAS scale where (0=No functional disability, 1: Mild disability, 2: Moderate disability and 3=Severe disability). The investigator, in consultation with the participant, selected 1 functional disability item from the 4 areas of disability and assessed it as a principal therapeutic target. The maximum possible score was 3 where higher scores indicate severe disability and lowers scores indicate sound functional ability. Baseline value was defined as the latest pre-first dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as the post-dose visit value minus the Baseline value.
| Scores on scale | GSK1358820 240 U | GSK1358820 400 U |
|---|---|---|
| Week 2, n=63,60 | -0.34 ± 0.087 | -0.59 ± 0.085 |
| Week 4, n=63,59 | -0.46 ± 0.096 | -0.62 ± 0.086 |
| Week 6, n=63,59 | -0.52 ± 0.081 | -0.67 ± 0.078 |
| Week 12, n=60,57 | -0.35 ± 0.082 | -0.63 ± 0.092 |
An AE is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment was categorized as SAE. Data for number of participants with any AE and any SAE is presented.
| Participants | GSK1358820 240 U | GSK1358820 400 U |
|---|---|---|
| Any AE | 29 | 31 |
| Any SAE | 4 | 5 |
An AE is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment was categorized as SAE. Data for number of participants with any AE and any SAE is presented.
| Participants | GSK1358820 240 U | GSK1358820 400 U |
|---|---|---|
| Any AE | 52 | 49 |
| Any SAE | 6 | 8 |
Physical examinations included assessment of lungs, cardiovascular system, and abdominal region (liver and spleen). This analysis was not planned and data was not collected and captured in the database.
No measurements were reported for this outcome.
Hematology parameters along with their normal ranges included: basophils (0 to 2 percent), eosinophils (0 to 8 percent), hemoglobin (135 to 175 grams/liter), hematocrit (0.397 to 0.524 proportion of red blood cells in blood), lymphocytes (18 to 49 percent), monocytes (2 to 10 percent), total neutrophils (40 to 75 percent), platelet count (140 to 340 giga cells/liter), red blood cell count (4.3 to 5.7 trillion cells/liter), white blood cell count (3.3 to 9 giga cells/liter), mean corpuscular volume (85 to 102 femtoliters), mean corpuscular hemoglobin (28 to 34 picograms) and reticulocyte count (0.004 to 0.019 percent/ratio). Shift in values relative to normal range as high and low have been presented for categories having non-zero values.
| Participants | GSK1358820 240 U | GSK1358820 400 U |
|---|---|---|
| Eosinophils, To high | 7 | 3 |
| Hemoglobin, To low | 5 | 5 |
| Hemoglobin, To high | 1 | 5 |
| Hematocrit, To low | 5 | 5 |
| Hematocrit, To high | 4 | 6 |
| Lymphocytes, To low | 11 | 11 |
| Lymphocytes, To high | 0 | 1 |
| Mean corpuscle hemoglobin, To low | 2 | 1 |
| Mean corpuscle hemoglobin, To high | 1 | 3 |
| Mean corpuscle volume, To low | 3 | 0 |
| Mean corpuscle volume, To high | 1 | 2 |
| Monocytes, To high | 0 | 4 |
| Total neutrophils, To low | 0 | 1 |
| Total neutrophils, To high | 6 | 11 |
| Platelet count, To low | 2 | 1 |
| Platelet count, To high | 7 | 4 |
| Red blood cell count, To low | 2 | 2 |
| Red blood cell count, To high | 2 | 7 |
| Reticulocytes, To high | 4 | 5 |
| White blood cell count, To low | 0 | 1 |
| White blood cell count, To high | 3 | 3 |
Clinical chemistry parameters assessed were alkaline phosphatase (100 to 325 international units/liter), alanine amino transferase (5 to 45 international units/liter), aspartate amino transferase (10 to 40 international units/liter), direct bilirubin (0 to 3.42 micromoles/liter), total bilirubin (3.42 to 20.52 micromoles/liter), calcium (2.0958 - 2.5948 millimoles/liter), creatinine (53.924 - 91.936 micromoles/liter), potassium (3.5 - 5 millimoles/liter), sodium (137 - 147 millimoles/liter), total protein (67 - 83 grams/liter), urea/blood urea nitrogen (BUN) \[2.856 - 7.14 millimoles/liter\]. Shift in values relative to normal range as high and low have been presented for categories having non-zero values.
| Participants | GSK1358820 240 U | GSK1358820 400 U |
|---|---|---|
| Alkaline Phosphatase, High | 5 | 6 |
| Alanine amino transferase, High | 8 | 6 |
| Aspartate amino transferase, High | 3 | 2 |
| Direct bilirubin, High | 1 | 2 |
| Total bilirubin, High | 0 | 2 |
| Calcium, Low | 0 | 1 |
| Creatinine, Low | 5 | 1 |
| Creatinine, High | 3 | 2 |
| Potassium, Low | 1 | 1 |
| Potassium, High | 1 | 1 |
| Sodium, Low | 5 | 2 |
| Sodium, High | 1 | 0 |
| Total protein, Low | 11 | 14 |
| Total protein, High | 1 | 1 |
| Urea/BUN, Low | 2 | 3 |
| Urea/BUN, High | 7 | 5 |
Urinalysis parameters assessed were urine occult blood, urine protein . In this dipstick test, occult blood and protein in urine samples were recorded as negative trace, 1+, 2+, and 3+ (the plus sign increases with occult blood or proteins in the urine: 1+=slightly positive, 2+=positive, 3+=high positive etc). Number of participants with worst-case urinalysis results post-Baseline relative to Baseline by dipstick analysis have been presented.
| Participants | GSK1358820 240 U | GSK1358820 400 U |
|---|---|---|
| Occult blood, Any increase | 11 | 11 |
| Occult blood, Increase to trace | 4 | 2 |
| Occult blood, Increase to 1+ | 2 | 7 |
| Occult blood, Increase to 2+ | 1 | 2 |
| Occult blood, Increase to 3+ | 4 | 0 |
| Protein, Any increase | 9 | 14 |
| Protein, Increase to trace | 4 | 11 |
| Protein, Increase to 1+ | 4 | 2 |
| Protein, Increase to 2+ | 1 | 0 |
| Protein, Increase to 3+ | 0 | 1 |
| Protein, Increase to 4+ | 0 | 0 |
Vital sign parameters SBP and DBP were measured in a semi-recumbent position after a 5-minute rest. If measurement in a semi-recumbent position was difficult, measurement in another position (e.g., sitting) was acceptable. The measurement was performed always in the same position during the study period. SBP and DBP were measured using an automated device. Baseline value was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post-dose visit value minus the Baseline value.
| Millimeters of mercury | GSK1358820 240 U | GSK1358820 400 U |
|---|---|---|
| SBP, Week 12; n=60, 57 | 0.8 ± 11.29 | 1.3 ± 11.19 |
| DBP, Week 12; n=60, 57 | 0.5 ± 8.01 | 0.1 ± 10.39 |
| SBP, Week 48; n=57, 56 | -1.6 ± 13.85 | -1.7 ± 14.60 |
| DBP, Week 48; n=57, 56 | -1.8 ± 10.01 | -1.2 ± 11.42 |
Vital sign parameter heart rate was measured in a semi-recumbent position after a 5-minute rest. If measurement in a semi-recumbent position was difficult, measurement in another position (e.g., sitting) was acceptable. The measurement was performed always in the same position during the study period. Heart rate was measured using an automated device. Baseline value was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post-dose visit value minus the Baseline value.
| Beats per minute | GSK1358820 240 U | GSK1358820 400 U |
|---|---|---|
| Week 12; n=60, 57 | 0.2 ± 9.95 | 2.6 ± 8.20 |
| Week 48; n=57, 56 | 0.5 ± 10.05 | -0.1 ± 9.01 |
Vital sign parameter temperature was measured orally, intra-aurally, or axillary fossa, the participant was instructed to refrain from eating food or drinking beverage within 5 minutes before the measurement. The method for the measurement of body temperature was same throughout the study. Baseline value was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post-dose visit value minus the Baseline value.
| Degree Celsius | GSK1358820 240 U | GSK1358820 400 U |
|---|---|---|
| Week 12; n=59, 56 | -0.03 ± 0.428 | -0.08 ± 0.466 |
| Week 48; n=57, 56 | 0.00 ± 0.505 | -0.06 ± 0.461 |
Collected over Non-serious AE and SAE were collected from start of the study drug until Week 48 in double blind-phase (Treatment cycle1) and from day of injection in Treatment cycles 2, 3 and 4 until Week 48 (48 weeks after first treatment) for participants in the respective treatment cycles in Open-label phase.. Non-serious events are listed at a 3% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| GSK1358820 240 U (Double Blind-Treatment Cycle 1) | 0/63 (0%) | 4/63 (6.3%) | 19/63 (30.2%) |
| GSK1358820 400 U (Double Blind-Treatment Cycle 1) | 1/61 (1.6%) | 5/61 (8.2%) | 24/61 (39.3%) |
| GSK1358820 240 U (Open Label-Treatment Cycle 2) | 0/60 (0%) | 1/60 (1.7%) | 7/60 (11.7%) |
| GSK1358820 400 U (Open labelTreatment Cycle 2) | 0/57 (0%) | 2/57 (3.5%) | 11/57 (19.3%) |
| GSK1358820 240 U (Open Label-Treatment Cycle 3) | 0/55 (0%) | 2/55 (3.6%) | 12/55 (21.8%) |
| GSK1358820 400 U (Open Label-Treatment Cycle 3) | 0/56 (0%) | 1/56 (1.8%) | 6/56 (10.7%) |
| GSK1358820 240 U (Open Label-Treatment Cycle 4) | 0/43 (0%) | 0/43 (0%) | 7/43 (16.3%) |
| GSK1358820 400 U (Open Label-Treatment Cycle 4) | 0/40 (0%) | 2/40 (5%) | 13/40 (32.5%) |
| Event | GSK1358820 240 U (Double Blind-Treatment Cycle 1) | GSK1358820 400 U (Double Blind-Treatment Cycle 1) | GSK1358820 240 U (Open Label-Treatment Cycle 2) | GSK1358820 400 U (Open labelTreatment Cycle 2) | GSK1358820 240 U (Open Label-Treatment Cycle 3) | GSK1358820 400 U (Open Label-Treatment Cycle 3) | GSK1358820 240 U (Open Label-Treatment Cycle 4) | GSK1358820 400 U (Open Label-Treatment Cycle 4) |
|---|---|---|---|---|---|---|---|---|
| PneumoniaInfections and infestations | 1/63 | 1/61 | 0/60 | 0/57 | 0/55 | 1/56 | 0/43 | 1/40 |
| Cerebral haemorrhageNervous system disorders | 0/63 | 1/61 | 0/60 | 0/57 | 0/55 | 0/56 | 0/43 | 1/40 |
| CellulitisInfections and infestations | 0/63 | 0/61 | 0/60 | 0/57 | 1/55 | 0/56 | 0/43 | 0/40 |
| Prostate cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 0/63 | 0/61 | 0/60 | 0/57 | 1/55 | 0/56 | 0/43 | 0/40 |
| PyelonephritisInfections and infestations | 0/63 | 0/61 | 0/60 | 1/57 | 0/55 | 0/56 | 0/43 | 0/40 |
| Decreased activityGeneral disorders | 1/63 | 1/61 | 0/60 | 1/57 | 0/55 | 0/56 | 0/43 | 0/40 |
| Lung infectionInfections and infestations | 0/63 | 0/61 | 1/60 | 0/57 | 0/55 | 0/56 | 0/43 | 0/40 |
| Pelvic fractureInjury, poisoning and procedural complications | 0/63 | 1/61 | 0/60 | 0/57 | 0/55 | 0/56 | 0/43 | 0/40 |
| Spinal compression fractureInjury, poisoning and procedural complications | 0/63 | 1/61 | 0/60 | 0/57 | 0/55 | 0/56 | 0/43 | 0/40 |
| DeliriumPsychiatric disorders | 0/63 | 1/61 | 0/60 | 0/57 | 0/55 | 0/56 | 0/43 | 0/40 |
| Event | GSK1358820 240 U (Double Blind-Treatment Cycle 1) | GSK1358820 400 U (Double Blind-Treatment Cycle 1) | GSK1358820 240 U (Open Label-Treatment Cycle 2) | GSK1358820 400 U (Open labelTreatment Cycle 2) | GSK1358820 240 U (Open Label-Treatment Cycle 3) | GSK1358820 400 U (Open Label-Treatment Cycle 3) | GSK1358820 240 U (Open Label-Treatment Cycle 4) | GSK1358820 400 U (Open Label-Treatment Cycle 4) |
|---|---|---|---|---|---|---|---|---|
| NasopharyngitisInfections and infestations | 11/63 | 7/61 | 2/60 | 1/57 | 4/55 | 0/56 | 2/43 | 3/40 |
| FallInjury, poisoning and procedural complications | 3/63 | 7/61 | 4/60 | 5/57 | 3/55 | 3/56 | 2/43 | 0/40 |
| ContusionInjury, poisoning and procedural complications | 1/63 | 4/61 | 3/60 | 3/57 | 1/55 | 2/56 | 0/43 | 0/40 |
| InsomniaPsychiatric disorders | 1/63 | 3/61 | 0/60 | 0/57 | 0/55 | 0/56 | 0/43 | 0/40 |
| Oxygen saturation decreasedInvestigations | 2/63 | 3/61 | 0/60 | 0/57 | 2/55 | 0/56 | 0/43 | 0/40 |
| ArthralgiaMusculoskeletal and connective tissue disorders | 0/63 | 3/61 | 0/60 | 0/57 | 0/55 | 0/56 | 0/43 | 0/40 |
| ConstipationGastrointestinal disorders | 0/63 | 3/61 | 0/60 | 0/57 | 0/55 | 0/56 | 0/43 | 0/40 |
| InfluenzaInfections and infestations | 3/63 | 2/61 | 0/60 | 0/57 | 0/55 | 0/56 | 0/43 | 0/40 |
| Ligament sprainInjury, poisoning and procedural complications | 0/63 | 0/61 | 0/60 | 0/57 | 0/55 | 0/56 | 2/43 | 0/40 |
| HypertensionVascular disorders | 2/63 | 1/61 | 0/60 | 0/57 | 0/55 | 0/56 | 2/43 | 0/40 |
| Age, Continuous(Years) | GSK1358820 240 U | GSK1358820 400 U | Total |
|---|---|---|---|
| Mean | 57.3 ± 10.98 | 57.1 ± 9.90 | 57.2 ± 10.42 |
| Sex: Female, Male(Participants) | GSK1358820 240 U | GSK1358820 400 U | Total |
|---|---|---|---|
| Female | 10 | 15 | 25 |
| Male | 53 | 46 | 99 |
| Race/Ethnicity, Customized(Participants) | GSK1358820 240 U | GSK1358820 400 U | Total |
|---|---|---|---|
| Japanese/East Asian Heritage (AH)/South East AH | 63 | 60 | 123 |
| Asian & Native Hawaiian or other Pacific Islander | 0 | 1 | 1 |
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Plan to share: Yes — IPD for this study will be made available via the Clinical Study Data Request site.
Supporting information: Study protocol, Sap, Icf, Csr
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