E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Irritable Bowel Syndrome (IBS) |
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MedDRA Classification |
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 test the hypothesis that acute therapeutic effects of GW876008 in IBS patients will reverse stress-induced visceral hypersensitivity as evidenced by changes in RMBF and/or thresholds for perception and pain; thus suggesting a possible mechanism for beneficial therapeutic effects of CRF1 antagonism in irritable bowel syndrome.
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E.2.2 | Secondary objectives of the trial |
To assess the safety and tolerability of GW876008X in adults with irritable bowel syndrome. To assess the effects of GW876008X on thresholds for rectal pain sensitivity in adults with irritable bowel syndrome.
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
A subject will be eligible for inclusion in this study only if all of the following criteria apply: •Subjects are male or female aged 18-65 years, inclusive with irritable bowel syndrome •For the purpose of this study, eligibility will be determined by the clinical diagnosis of IBS guided by Rome II criteria (see Appendix 3). In addition, the subject will complete a daily diary card for a minimum of 14 days. If the subject reports diarrhoea on >70% of the days, the subject will be excluded. •Have completed the screening period (minimum of 14 days) with diarrhoea <70% of the days. •Female subjects of child-bearing potential may be included if using appropriate contraceptive methods including two of the following: 1.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 5 half lives of the study medication, whichever is the longest. 2.Documented tubal ligation 3.Documented placement of an intrauterine device (IUD) or intrauterine system (IUS) provided it is not of the hormonal type. 4.Male partner sterilization (vasectomy) at least 6 months prior to the female subject’s entry into the study and is the sole partner for that female subject. 5.Double barrier method. •Body weight >/= 50 kg (110 lbs) for men and >/= 45 kg (100 lbs) for women and BMI within the range 18.5-29.9 kg/m2 inclusive. •Non-smoker (abstinence from smoking for at least 6 months before the start of the study). •Normal electrocardiogram (subjects must have no clinically significant abnormalities on a 12-lead ECG. •If the subject is < 50 years of age and has not had a colonic examination within 2 years of the Screening Visit, a flexible sigmoidoscopy, flexible sigmoidoscopy plus barium enema, or colonoscopy must be performed. •If the subject is > 50 years of age and has not had a colonic examination within years of the Screening Visit, a colonoscopy or flexible sigmoidoscopy plus barium enema must be performed. •Signed and dated written informed consent prior to admission to the study. •The subject is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions.
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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: •Female subjects who are pregnant or nursing. •Female subjects taking oral contraceptives or other hormonal therapy. •Subjects who have taken any medication for the treatment of IBS within 6 months prior to screening. •Subjects who are taking NSAIDs on a regular basis or within 48 hours of a study day. •As a result of any of the medical interview, physical examination, evaluation of mental state and psychiatric history or screening investigations the physician responsible considers the subject unfit for the study. •The subject has a positive pre-study urine drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines. •A positive pre-study HIV1/2, Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of the start of the study. •The subject has an active psychiatric illness (defined as a HAD score of 7 or more). •The subject has a history of, or active eating disorder. •Any history of suicidal attempts or behaviour. •History of regular alcohol consumption averaging >7 drinks/week for women or 14 drinks/week for men (1 drink (12 g alcohol) = 5 ounces (150 ml) of wine or 12 ounces (360 ml) of beer or 1.5 ounces (45 ml) of 80 proof distilled spirits) within 6 months of screening. •The subject has a screening ECG with a QTc value of >430msec or a PR interval outside the range 120 to 200msec or an ECG that is not suitable for QT measurements (e.g. poorly defined termination of the T-wave) or any other clinically significant ECG finding. •The subject has received an investigational drug or participated in any other research trial within 30 days or 5 half-lives, or twice the duration of the biological effect of any drug (whichever is longer) prior to the first dose of current study medication. •Use of other prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John’s Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and sponsor the medication will not interfere with the study procedures or compromise subject safety. •Consumption of known or suspected inhibitors/inducers of cytochrome P450 CYP1A2 or CYP3A4/5 enzymes is prohibited from 2 weeks prior to the start of the study and until the last study assessment. These include prescription and nonprescription drugs as well as foods such as grapefruit containing foods, Seville orange juice, red wine and other fortified (with dietary supplements, health enhancers etc) foods and drinks (including orange juice), and cruciferous vegetables •History or presence of allergy to the study drug or drugs of this class, or a history of drug or other allergy that, in the opinion of the physician responsible, contraindicates their participation. •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 7 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 an IUD, diaphragm with spermicide, oral contraceptives, injectable progesterone, subdermal implants or a tubal ligation if the women could become pregnant from the time of the first dose of study medication until five half lives or 84 days (whichever is longer) following administration of the last dose of study medication. •Any history of an endocrine disorder including, but not limited to, diabetes or disorders of the hypothalamus, pituitary, adrenal, or thyroid glands, or gonadal disorder or dysfunction of the reproductive organs. •History of renal disease or serum creatinine greater than 1.5 X ULN. •History of hepatic disease, impairment or abnormal liver function test i.e. AST, ALT>3 times upper limit of normal range (ULN), bilirubin>1.5 time ULN. •Any other clinically significant laboratory abnormality. •Less than 10% reduction in RMBF following psychological stress at screening visit 2.
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E.5 End points |
E.5.1 | Primary end point(s) |
•The change in Laser Doppler regional rectal mucosal blood flow (RMBF) measured in response to physiological stress (cold water pressor test). •The change in Laser Doppler regional rectal mucosal blood flow (RMBF) measured in response to psychological stress (dichotomous listening test).
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
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) | No |
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.8.5 | The trial involves multiple Member States | No |
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 | Information not present in EudraCT |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 9 |