Efficacy Study in Lumbosacral Radiculopathy

A minimum of 500,000 samples were run and the number of times the treatment difference estimated as greater than 0 was recorded. Non-informative prior distributions were applied for each of the weeks' treatment difference. For each weekly pain score calculation, a minimum of 4 days or more was required. If less than 4 average daily pain scores were recorded for any given week; then, that week's pain score was considered as missing and was excluded from the statistical analysis. Reduction in pain intensity was calculated from pain intensity score at indicated week minus the baseline pain intensity score. The scores were analyzed based on the 11 point Pain Intensity Numerical Rating Scale (PI-NRS) with 0 score indicating no pain and score of 10 indicating maximum pain. Arithmetic mean values have been presented; however, statistical analysis has been presented for least square (LS) means.

Pain intensities were produced for each of the 15 questions on the SF-MPQ, split by treatment group, dimension and date of assessment. The total number of missing responses were recorded. The Short Form McGill Pain Questionnaire has 15 questions with the first 11 questions representing the sensory dimensions and questions 12 onwards representing the affective dimensions. The total score will be derived as the sum of all 15 questions with sub-group scores calculated for each of the 2 different dimensions. Change from Baseline is the value at indicated time point minus the Baseline value.

The Short Form McGill Pain Questionnaire (SF-MPQ) has 15 questions with the first 11 questions representing the sensory dimensions and questions 12 onwards representing the affective dimensions. The total score was derived as the sum of all 15 questions with sub-group scores calculated for each of the 2 different dimensions. Data for few participants was not available (considered as missing). Based on intensity types of pain, participants with mild, moderate, severe and missing were considered.

For the Galer neuropathic pain scale, the total score was calculated excluding question 8 with the maximum total score being 100. Higher scores indicated Worsening of pain. Supplementary to this, a sub score for non-allodynic pain was calculated from summing 8 items of the Galer Neuropathic Pain Score. The two items excluded from the sub score were those questioning sensitivity and surface pain, questions 6 and 10. Change from Baseline is the value at indicated time point minus the Baseline value. Arithmetic means have been presented; however, statistical analysis has been based on adjusted (LS) means.

The scores were analyzed based on the 11 point Pain Intensity Numerical Rating Scale (PI-NRS) with 0 score indicating no pain and score of 10 indicating maximum pain. The number of participants showing 30 percent and 50 percent reduction in average daily pain scores were recorded at Baseline (7 days prior to Day 1) on every Week up to 5 weeks. Change from Baseline is the value at indicated time point minus the Baseline value.

The PGIC and CGIC are numeric scale and was meant to measure neuropathic pain that was measured on Days 8, 21 and 35 of treatment and the follow-up visit. The scale ranges from 0 to 7 with Very Much Improved=1, Much Improved=2, Minimally Improved=3, No Change=4, Minimally Worse=5, Much Worse=6, Very Much Worse=7. Lower scores indicated improvement and higher scores indicated worsening. PGIC scale was rated by participants and CGIC by respective clinicians. Change from Baseline is the value at indicated time point minus the Baseline value. The PGIC analysis was performed for low back pain.

The Oswestry Disability Index consists of ten questions, each with a possible six answers. Each question was ranked from zero to five, with zero being showing no symptoms and five being the most severe case. The total score was derived for analysis by summing the individual responses from the ten questions, and dividing through by the total number of possible answers to the number of questions answered multiplied by 100. Change from Baseline is the value at indicated time point minus the Baseline value. Values were available only for Week 4 visit (Day 28).

Mean dose of rescue medication used to relieve pain was monitored over 5 weeks.

Profile of Mood States (POMS) questionnaire was used to assess a participant's mood over the previous week. It consists of 65 items, each with a score of 0 (not at all), 1 (a little), 2 (moderately), 3 (quite a bit), and 4 (extremely). The item scores were summarized as a total score and also into 6 mood domain scores at each time-point. A higher score indicated a more negative mood state except for vigour which is weighted negatively and so a lower score indicates a more negative mood. The sum of each item in a domain was added together to get the overall domain score. The Mood Disturbance Total Score was obtained by summing up all 6 domains with the Vigour-Activity domain weighted negatively. If more than 2 scores are missing then the domain score was set to missing and for more than 4 items, the total score was not calculated. Change from baseline is the value at indicated time point minus the Baseline value.

Sleep interference score analysis was performed over 5 weeks. Change from Baseline is the value at indicated time point minus the Baseline value. Baseline was considered as 7 days prior to Day 1.

The score from each question on the SF-36 was calculated by adding together each of the sub-questions. The overall total score was calculated as the sum over each of the 11 questions; however, for this study only questions 3 to 8 was completed and so the total score was based only on these questions. The different domains of SF-36 component have been described in the category titles. Change from Baseline is the value at indicated time point minus the Baseline value. Observed case (OC) data for only Week 4 was available and has been presented. Adjusted means have been presented as LS means.

Participants were asked to walk for 20 meters at a pace they feel comfortable. When they had finished walking, they were instructed to record the intensity of their neuropathic pain again. The distance they had walked and the time taken was recorded. The change in intensity of pain after walking from before walking was defined as the walking-associated pain. Change from Baseline is the value at indicated time point minus the Baseline value. Median time required has been presented; however, the statistical analysis is based on the adjusted mean (LS mean) values. Data for only Week 4 is available and has been presented.

Participants were asked to walk for 20 meters at a pace they feel comfortable. When they had finished walking, they were instructed to record the intensity of their neuropathic pain again. The change in intensity of pain after walking from before walking was defined as the walking-associated pain. Change from Baseline is the value at indicated time point minus the Baseline value. Median time required has been presented; however, the statistical analysis is based on the adjusted mean (LS mean) values. Data for only Week 4 is available and has been presented.

Adverse event (AE) is an unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain time period after the study has ended. This change may or may not be caused by the intervention being studied. Serious adverse event (SAE) is an adverse event that results in death, is life-threatening, requires inpatient hospitalization or extends a current hospital stay, results in an ongoing or significant incapacity or interferes substantially with normal life functions, or causes a congenital anomaly or birth defect. Medical events that do not result in death, are not life-threatening, or do not require hospitalization may be considered serious adverse events if they put the participant in danger or require medical or surgical intervention to prevent one of the results listed above.

Vital signs analyzed included diastolic blood pressure (DBP) , systolic blood pressure (SBP) ,and heart rate (HR). DBP more than (>) 100 millimeters of mercury (mm Hg) and <45 mm Hg was considered as of potentially clinical importance (PCI). SBP of >160 mm Hg and <85 mm Hg and HR of >110 beats per minute (bpm) and <40 bpm were considered of PCI.

Abnormal ECG values were recorded and were classified as abnormal and clinically significant (CS) and abnormal and not clinically /clinically insignificant (CI). The participants were analyzed over 5 weeks.

Participants were analyzed for abnormality in clinical chemistry , hematological and urinalysis parameters over 5 weeks. Values were recorded abnormal as high (H) or low (L).