Rectal Hyperalgesia (in patients with irritable bowel syndrome and feacal urgency) MedDRA version: 8.1 Level: LLT Classification code 10038072 Term: Rectal pain
Conditions
Interventions
Product Name: SB-705498
Pharmaceutical Form: Film-coated tablet
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Film-coated
Sponsors
GlaxoSmithKline Research & Development
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria for Group 1 (Faecal Urgency) Patients. A subject will be eligible for inclusion in this study only if all of the following criteria apply: • Female or male subjects aged 18 to 65. Women may be of child bearing potential or of non-child bearing potential. Women of child bearing potential must use an effective method of contraception (see below). • Females of non-child bearing potential are defined as: • Post-menopausal females, being amenorrhoeic for at least 2 years with an appropriate clinical profile, e.g., age appropriate, history of vasomotor symptoms. However, if indicated this should be confirmed by oestradiol and FSH levels consistent with menopause (according to local laboratory ranges). • Pre-menopausal females with a documented hysterectomy (medical report verification) and/or bilateral oophorectomy. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment. • Faecal urgency, increased stool frequency, faecal incontinence and rectal hyperalgesia as defined by Chan et al., 2003, with no previous diagnosis of IBS. • Pre-study screening and baseline ECG, which, in the opinion of the Principal Investigator has no abnormalities that will compromise safety in this study. • Clinical laboratory tests at screening showing no clinically significant abnormalities in the opinion of the Principal Investigator. • Signed and dated written informed consent prior to admission to the study. • Able to understand and comply with protocol requirements, instructions and protocol-stated restrictions. • If on anti-diarrhoeal medications for faecal urgency / frequency, these have to be at a stable dose for 2 weeks prior to randomisation. In addition, anti-diarrhoeal medications which are opioids have to be non-systemically absorbed (e.g. loperamide is permitted if on a stable dose for 2 weeks prior to randomisation but not codeine phosphate). Inclusion Criteria for Group 2 (Irritable Bowel Syndrome) Patients A subject will be eligible for inclusion in this study only if all of the following criteria apply: • Female or male subjects aged 18 to 65. Women may be of child bearing potential or of non-child bearing potential (as defined for Group 1). Women of child bearing potential must use an effective method of contraception (see 5.2.3 Exclusion Criteria for Groups 1 and 2). • Has irritable bowel syndrome (IBS) as defined by Rome II criteria [Appendix 3, Drossman, 2000], • Has rectal hyperalgesia as defined by Chan et al., 2003 and determined using the protocol outline in barostat study published by Cremonini et al in 2005. • Pre-study screening and baseline ECG, which, in the opinion of the Principal Investigator has no abnormalities that will compromise safety in this study. • Clinical laboratory tests at screening showing no clinically significant abnormalities in the opinion of the Principal Investigator. • Signed and dated written informed consent prior to admission to the study. • Able to understand and comply with protocol requirements, instructions and protocol-stated restrictions. • If on anti-diarrhoeal medications or laxatives for control of bowel habit, these have to be at a stable dose for 2 weeks prior to randomisation Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) F.1.3.1 Number of subjects for this age
Exclusion criteria
Exclusion criteria: A subject will not be eligible for inclusion in this study if any of the following criteria apply: • Other GI or pain conditions that in the opinion of Investigator may interfere with study procedures or confound data interpretation. • Any clinical or biological abnormality found at screen (other than those related to the disease under investigation) which, in the opinion of the investigator, is clinically significant [e.g., major depression (within the past 3 months)]. • Any concurrent illness or disability that may affect the interpretation of clinical efficacy and/or safety data or otherwise contraindicates participation in this clinical study (i.e., current malignancy, HIV, significant mental illness). • History of alcohol, substance or drug abuse within the last year. • Uncontrolled hypertension at the Screening Visit, defined as persistent (after 3 readings) systolic blood pressure >140mmHg or diastolic blood pressure >90mmHg; measured after 5 min supine rest. A history or presence of multiple cardiovascular risk factors such as, but not limited to family history, myocardial infarction, coronary artery disease, vasospastic angina, heart failure, cardiac arrhythmias or history or presence of cerebrovascular disease, including transient ischemic attack, stroke or peripheral arterial disease. • QTcB > 430 msec for men or > 450 msec for women on screening 12-lead ECG. • Participation in a trial with a new chemical entity within 3 months before the start of the study or participation in any other research trial within 30 days prior to the first dose of current study medication. • A history of drug or other allergy or any other reason that, in the opinion of the physician responsible, contraindicates their participation. • Unable to withdraw from analgesic medications for their rectal hyperalgesia (opioiddependent patients can be included if they are willing to withdraw from their opiate medication with a nineteen day washout period). • Unable / unwilling to refrain from taking the prohibited medications during the study • An unwillingness of male subjects to abstain from sexual intercourse with pregnant or lactating women from the time of the first dose of study medication until five halflives (nineteen days) following administration of the last dose of study medication. • An unwillingness of the male subject to use a condom/spermicide in addition to having their female partner use another form of contraception such as IUD, diaphragm with spermicide, oral contraceptives, injectable progesterone, subdermal implants or a tubal ligation if the woman could become pregnant from the time of the first dose of study medication until 84 days following administration of the last dose of study medication. • Female subjects who are pregnant, breast feeding, or have a positive serum pregnancy test or a positive urine pregnancy test either at screening or pre-dose on each dosing session. • An unwillingness of the female subject to use an appropriate form of contraception. Appropriate forms of contraception are defined as: a. Abstinence – The lifestyle of the female should be such that there is complete abstinence from intercourse from at least the commencement of their last normal period prior to the first dose of study medication and to continue until the first normal period (defined as normal for the woman, both in terms of duration and quantity of menses) after treatment or 15 days after the last dose of medication, whichever is the longest. b.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the effects of a single dose of SB-705498 on rectal pain thresholds and ongoing pain in patients with rectal hypersensitivity associated with faecal urgency (Group 1) and IBS (Group 2);Secondary Objective: To further investigate efficacy and improvements in symptoms and quality of life.;Primary end point(s): VAS Pain score to rectal distensions (at 12, 24, 36 and 48mmHg above baseline operating pressure threshold) pre-dose and 6 hrs post-dose. | — |
Countries
United Kingdom
Outcome results
None listed