Sb-705498 Rectal Pain Study

Irritable Colon Clinical Trial

Official title:

A Double-blind, Randomised, Placebo Controlled, Single Dose, Two-period Crossover Study to Investigate the Therapeutic Potential of the TRPV1 Antagonist SB-705498 in Treatment of Subjects With Rectal Hypersensitivity Including Irritable Bowel Syndrome.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00461682
• Other study ID #: VRA107438
• Status: Terminated
• Phase: Phase 2
• Start date: January 26, 2007
• Est. completion date: September 1, 2007

Study information

• Verified date: July 2018
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

SB-705498 has demonstrated efficacy in several preclinical and human experimental pain models. This study will investigate the efficacy of SB-705498 in patients with rectal pain. This will be a double-blind, placebo-controlled, two-way crossover study. 21 patients with faecal urgency (Group 1), and 21 patients with IBS (Group 2) will complete this study.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: September 1, 2007
• Est. primary completion date: September 1, 2007
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Female/male aged 18-65.

• Women of child bearing potential must use an effective method of contraception

• Faecal urgency as defined by Chan

• ECG, which has no abnormalities

• Normal Clinical labs

• Informed consent and understand protocol requirements

• IBS subjects: Has irritable bowel syndrome (IBS) as defined by Rome II criteria

• Rectal hyperalgesia

Exclusion Criteria:

• Any clinical or biological abnormality found at screen (other than those related to the disease under investigation)

• History of alcohol, substance or drug abuse

• Uncontrolled hypertension

• A history or presence of cardiovascular risk factors

• Participation in a trial within 3 months before the start of the study

• History of allergy

• Unable to withdraw from analgesic medications for their rectal hyperalgesia (opioid-dependent patients can be included if they are willing to withdraw from their opiate medication

Related Conditions & MeSH terms

• Irritable Bowel Syndrome
• Irritable Colon

Intervention

Drug:
• SB-705498

Locations

Country	Name	City	State
United Kingdom	GSK Investigational Site	London

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Visual Analogue Scale (VAS) Pain Score to Rectal Distensions at Pre-dose and up to 6 Hours (h) Post-dose of Each Treatment Period	This analysis was performed at 12, 24, 36 and 48 millimeters of mercury (mmHg) which was above the baseline operating pressure threshold. 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.	Baseline (Pre-dose) and up to 6 hours post-dose of each treatment period
Secondary	Visual Analogue Scores for Rectal Distensions for Gas, Urgency to Defecate and Discomfort at Pre-dose and 6 h Post-dose of Each Treatment Period	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.	Baseline (pre-dose) and up to 6 h post-dose of each treatment period
Secondary	Rectal Sensory Thresholds to Thermal Stimulation (Contact Heat Device, Values Reported as in Study) at Pre-dose and 6h Post-dose of Each Treatment Period	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.	Baseline (pre-dose) and 6h post-dose of each treatment period
Secondary	Peak Pain Intensity Difference (PPID6), as Derived From Maximum Pain Intensity (NRS) Difference From Baseline (Pre-dose on Day 1) by Single Measurement Recorded Over 0-6h of Each Treatment Period	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.	Baseline (pre-dose) and up to 0-6 h of each treatment period
Secondary	Pain Intensity Difference (SPID6), as Derived From Pain Intensity (NRS) Difference From Baseline (Pre-dose on Day 1) by Single Measurement Recorded Over 0-6h Post-dose of Each Treatment Period	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.	Baseline (pre-dose) and up to 0-6 h post-dose of each treatment period
Secondary	Somatic Heat Pain Thresholds (Hand and Foot) Assessed Pre-dose and 6h Post-dose of Each Treatment Period	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 (O) 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.	Baseline (pre-dose) and upto 0-6h post-dose for each treatment period
Secondary	Contact Heat-evoked Potentials (CHEPs) - Optional, Assessed Pre-dose and 6h Post-dose of Each Treatment Period	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.	Baseline (pre-dose) and 6h post-dose of each treatment period
Secondary	Number of Defecations Over 24h and Over 1 Week Following a Dose of SB-705498 (Monitored Using Bristol Stool Scoring Diary Kept 1 Week Pre- and 1 Week Post-dose)	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.	7 days pre-dose and 7 days post-dose of each treatment period
Secondary	Irritable Bowel Syndrome Symptom Severity Score (IBS SSS) Calculated Over Approximately 10 Days Pre- and Post-dose	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.	10 days pre-dose and post-dose of each treatment period
Secondary	Symptom Scoring and Quality of Life Assessments Over Period	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.	Approximately up to 3 months
Secondary	Average Daily Pain Scores at Baseline (Pre-dose), 1, 2, 3, 4, 5 and 6h Post-dose for Each Treatment Period	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.	At Baseline (pre-dose) and each hour post-dose of each treatment period