Sb-705498 Rectal Pain Study

The VAS scores for assessment of rectal sensation for pain, gas, urgency and discomfort were analyzed separately. Participants assessed the cough severity and urge to cough using VAS immediately prior to capsaicin challenge. No results were reported since the study objectives were not met due to the early study termination and withdrawal of participant. Average of Day -1 and pre-dose was planned as Baseline for VAs assessment. The VAS score was planned to be analyzed on Day-1, Day 1, 2 hours, and 24 hours. Average daily pain scores as captured in participant diary cards were planned to be summarized descriptively and planned to be analyzed. The 11 point pain intensity numerical rating scale ranging from 0 to 10, where 0 represents "No pain" and 10 represents "Worst pain imaginable" was planned to be used for the subjective assessment of the pain. No results were reported since the study objectives were not met due to the early study termination and withdrawal of participant.

Visceral hypersensitivity is defined as reduced pain and discomfort threshold to rectal stimuli. Rectal hypersensitivity was correlated with the degree of rectal hypersensitivity (up-regulation of TRPV-1 receptors) as measured by rectal thermal stimulation. Ongoing rectal pain intensity scale is 11-point numeric rating scale, where 0=Unnoticeable/No Pain, 10=Unbearable/Worst Pain. An average of daily scores over 1 week pre-dose and 1 week post-dose was recorded. Single measurements pre-dose and at hourly intervals within 6 hours post-dose were also recorded. Participants were planned to stay in the hospital for 6h post-dose and were planned to be discharged when physician was satisfied with their medical condition. No results were reported since the study objectives were not met due to the early study termination and withdrawal of participant. Participants assessed the cough severity and urge to cough using VAS immediately prior to capsaicin challenge.

No results were reported since the study objectives were not met due to the early study termination and withdrawal of participant. Change from Baseline (pre-dose) is the value at indicated time-point minus the Baseline value. Average daily pain scores as captured in participant diary cards were planned to be summarized descriptively and planned to be analyzed. The 11 point pain intensity numerical rating scale ranging from 0 to 10, where 0 represents "No pain" and 10 represents "Worst pain imaginable" was planned to be used for the subjective assessment of the pain.

Change from Baseline (pre-dose0 is the value at indicated time point minus the Baseline value. Average daily pain scores as captured in participant diary cards were planned to be summarized descriptively and planned to be analyzed. The 11 point pain intensity numerical rating scale ranging from 0 to 10, where 0 represents "No pain" and 10 represents "Worst pain imaginable" was planned to be used for the subjective assessment of the pain. No results were reported since the study objectives were not met due to the early study termination and withdrawal of participant.

Evoked potentials were to be recorded from midline electrodes by placing a ground electrode on temporal lobe region. A low cut off filter with a time constant of 1.06103 and a frequency of 0.15 hertz (Hz) and a high cut off filter of 100Hz was to be applied. The impedance from all electrodes was maintained below 5 ohms (Ω) and the electroencephalogram (EEG) was recorded, digitized at a sampling rate of 500 Hz. Responses from ten stimuli were to be recorded from each participant with the thermode placed over foot and one hand (non-dominant side). The thermode heating rate was set at 70 degree Celsius per second (°C/s) and the cooling rate at 40°C/s. The baseline temperature was 32 °C, destination temperature 51 °C, and stimulus interval approximately of 7 seconds. The participants were allowed to withdraw any time. No results were reported since the study objectives were not met due to the early study termination and withdrawal of participant.

For heat pain threshold measurement, temperature of the thermode was gradually increased from the baseline (32°C) at a rate of 1°C/s. The ramp was stopped and the temperature of the thermode was returned to the Baseline. This was repeated three times. The threshold temperatures and the average value were recorded by the computer. If the thermode temperature reached 50°C without the participant responding, the ramp was stopped and the temperature was returned to baseline automatically to prevent skin injury. This test was performed within two minutes. The respective cut-off temperature is then recorded for that trial. No results were reported since the study objectives were not met due to the early study termination and withdrawal of participant.

Onset associated with change in the frequency and change in the appearance of stools, abnormal stool frequency (>3/day or < 3/week); abnormal stool form (lumpy/hard or loose/watery stool), abnormal stool passage (straining, urgency, or feeling of incomplete evacuation); passage of mucus, and bloating were analyzed over period. No results were reported since the study objectives were not met due to the early study termination and withdrawal of participant.

Participants were rated on a scale based on following parameters - Onset associated with change in the frequency and change in the appearance of stools, abnormal stool frequency (>3/day or < 3/week); abnormal stool form (lumpy/hard or loose/watery stool), abnormal stool passage (straining, urgency, or feeling of incomplete evacuation); passage of mucus, and bloating were analyzed over period. No results were reported since the study objectives were not met due to the early study termination and withdrawal of participant.

Different scales used in this study included HAD, BDI, SF36, Bristol Stool Scoring, IBS QOL and SSS that were used to rate different scores on respective scales. Untreated pain leads to a decrease in daily function capability, social stresses, loss of work, an overall poor quality of life and a burden on healthcare resources. No results were reported since the study objectives were not met due to the early study termination and withdrawal of participant.

Individual pain scores were collected at screening and pre and post dose during the anorectal physiological assessments. Average daily pain scores as captured in participants' diary cards were summarized descriptively and analyzed. The 11 point pain intensity numerical rating scale ranges from 0 to 10, where 0 represents "No pain" and 10 represents "Worst pain imaginable". This was used for the subjective assessment of the pain over period. No results were reported since the study objectives were not met due to the early study termination and withdrawal of participant.