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.
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 1
- 试验地点
- 2
- 主要终点
- Visual Analogue Scale (VAS) Pain Score to Rectal Distensions at Pre-dose and up to 6 Hours (h) Post-dose of Each Treatment Period
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Female/male aged 18-
- •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
排除标准
- •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
结局指标
主要结局
Visual Analogue Scale (VAS) Pain Score to Rectal Distensions at Pre-dose and up to 6 Hours (h) Post-dose of Each Treatment Period
时间窗: Baseline (Pre-dose) and up to 6 hours 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.
次要结局
- 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(Baseline (pre-dose) and 6h post-dose of each treatment period)
- Symptom Scoring and Quality of Life Assessments Over Period(Approximately up to 3 months)
- 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(Baseline (pre-dose) and up to 0-6 h of each treatment period)
- 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(Baseline (pre-dose) and up to 6 h post-dose of each treatment period)
- 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(Baseline (pre-dose) and up to 0-6 h post-dose of each treatment period)
- Somatic Heat Pain Thresholds (Hand and Foot) Assessed Pre-dose and 6h Post-dose of Each Treatment Period(Baseline (pre-dose) and upto 0-6h post-dose for each treatment period)
- Contact Heat-evoked Potentials (CHEPs) - Optional, Assessed Pre-dose and 6h Post-dose of Each Treatment Period(Baseline (pre-dose) and 6h post-dose of each treatment period)
- 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)(7 days pre-dose and 7 days post-dose of each treatment period)
- Irritable Bowel Syndrome Symptom Severity Score (IBS SSS) Calculated Over Approximately 10 Days Pre- and Post-dose(10 days pre-dose and post-dose of each treatment period)
- Average Daily Pain Scores at Baseline (Pre-dose), 1, 2, 3, 4, 5 and 6h Post-dose for Each Treatment Period(At Baseline (pre-dose) and each hour post-dose of each treatment period)