A Phase III Study to Evaluate the Efficacy and Safety of GSK1358820 in Subjects With Post-stroke Upper Limb Spasticity

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.