E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Rectal Hyperalgesia (in patients with irritable bowel syndrome and feacal urgency) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10038072 |
E.1.2 | Term | Rectal pain |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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) |
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E.2.2 | Secondary objectives of the trial |
To further investigate efficacy and improvements in symptoms and quality of life. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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
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E.4 | Principal 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. One of the following methods is acceptable as the sole method of contraception if there is indisputable data that it is >99% effective otherwise it should be used with a barrier method (condom or occlusive cap {diaphragm or cervical/vault caps} used with spermicidal foam/gel/film/cream/suppository): • Established use of oral, injected or implanted hormonal methods of contraception from at least the commencement of their last normal period prior to the first dose of study medication. Subjects using hormonal contraception should use a barrier method in addition from the first dose of study medication until their next normal period following the end of the study. • Documented tubal ligation. • Documented placement of an intrauterine device (IUD) or intrauterine system (IUS). • Male partner sterilisation (vasectomy) prior to the female subject's entry into the study and is the sole partner for that female subject. • condom and occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream. |
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E.5 End points |
E.5.1 | 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. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 1 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |