| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10023003 |
| E.1.2 | Term | Irritable bowel syndrome |
|
| 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 determine the pharmacodynamic effect of single doses of GSK561679 and GW876008 on meal induced cortisol responses in patients with IBS. |
|
| E.2.2 | Secondary objectives of the trial |
To compare the safety and effect on cytokines of single doses of GSK561679 and GW876008 in patients with IBS.
To characterize the safety and tolerability of single doses of GSK561679 and GW876008 in patients with IBS.
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
A subject will be eligible for inclusion in this study only if all of the following criteria apply:
1. Female or male subjects aged 18 and < 65 at the time of the screening visit.
1. Has irritable bowel syndrome (IBS) as defined by Rome II criteria (Appendix 12)
2. Pre-study screening and baseline ECG, which, in the opinion of the Principal Investigator has no abnormalities that will compromise safety in this study.
3. Clinical laboratory tests at screening showing no clinically significant abnormalities in the opinion of the Principal Investigator.
4. Signed and dated written informed consent prior to admission to the study.
5. Able to understand and comply with protocol requirements, instructions and protocol-stated restrictions.
6. Female subject is currently either of:
• non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post-menopausal or any female who is surgically sterilized (via documented hysterectomy or bilateral tubal ligation).
(For purposes of this study, postmenopausal is defined as one year without menses)
OR
• child bearing potential, the subject is eligible to enter and participate in this study if she is not lactating and has a negative pregnancy test both at screening (serum -HCG negative) and baseline (urine) prior to investigational product administration at visits 2, 3 and 4 and follow-up on visit 5. The subject must also agree to one of the following methods of contraception:
i. Complete abstinence from intercourse two weeks prior to administration of study drug, throughout the clinical trial, until the completion of follow-up procedures or for two weeks following discontinuation of the study medication in cases where subject discontinues the study prematurely. (Subjects utilizing this method must agree to use an alternate method of contraception if they should become sexually active and will be queried on whether they have been abstinent in the preceding 2 weeks when they present to the clinic for the Final Visit.) or,
ii. has a male sexual partner who is surgically sterilized prior to the Screen Visit and is the only male sexual partner for that subject or,
iii. sexual partner(s) is/are exclusively female or,
iv. Oral contraceptives (either combined or progestogen only) with double-barrier method of contraception consisting of spermicide with either condom or diaphragm. (Women of child-bearing potential using an oral contraceptive in combination with a double-barrier method of contraception are required to continue to use this form of contraception for 1 week following discontinuation of study medication).
v. Use of double-barrier contraception, specifically, a spermicide plus a mechanical barrier (e.g. male condom, female diaphragm). The subject must be using this method for at least 1 week following the end of the study or,
vi. Use of any intrauterine device (IUD) with published data showing that the highest expected failure rate is less than 1% per year. The subject must have the device inserted at least 2 weeks prior to the first Screen Visit, throughout the study, and 2 weeks following the end of the study.
8. Non-tobacco user (abstinence from tobacco use for at least 1 month before the start of the study).
9. Agree to remain in the clinic for the time defined in the protocol.
|
|
| E.4 | Principal exclusion criteria |
1. 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.
2. Subject has any of the following exclusionary psychiatric conditions (Note: current
diagnoses are to be based on the M.I.N.I administered at screening).
• A current DSM-IV Axis I disorder such as Dysthmia, Phobia, Major Depression,
Obsessive Compulsive Disorder, Body Dysmorphic disorder, or Panic Disorder
as a primary diagnosis currently or within 6 months prior to the screening visit.
• A current DSM-IV-TR diagnosis of Antisocial or Borderline Personality
Disorder, Dementia, or another current DSM-IV-TR Axis II diagnosis that
would suggest non-responsiveness to pharmacotherapy or non-compliance with
the protocol; or
• A current (within six months prior to Screening Visit) diagnosis of anorexia
nervosa or bulimia; or
• A history of Schizophrenia, Schizoaffective Disorder, or a Bipolar Disorder; or
• Is currently being treated by medication for any of the above psychiatric
disorders. Psychiatric medications would include, but not limited to,
antidepressants (e.g. SSRIs, SNRIs, TCAs) anxiolytics, antipsychotics.
3. Subjects who, in the investigator’s judgement, pose a current, serious or suicidal or
homicidal risk or have made a suicide attempt within the past 6 months or have ever
been homicidal.
4. Subjects who are pregnant or nursing.
5. Evidence of a biochemical or structural abnormality of the digestive tract.
These conditions include (but not limited to):
Current evidence, or history of (at any time in the past);
• inflammatory bowel disease (Crohn's disease or ulcerative colitis)
• functional dyspepsia
• Lactose intolerance, not on a stable diet
• Celiac Disease
• laxative abuse (in the clinical judgement of the physician)
• gastrointestinal surgery (exceptions include 6 months post-surgery
appendectomy, cholecystectomy, fundoplication without gas bloat, or
hiatal hernia repair; 3 months post-surgery herniorrhaphy without bowel
resection)
• gastroparesis
• GI malignancy
• carcinoid syndrome
• amyloidosis
• chronic pancreatitis
• symptomatic gastrointestinal adhesions
• toxic megacolon
• gastrointestinal perforation
• gastrointestinal obstruction and/or stricture.
6. Current evidence of or within the past 6 months:
• diverticulitis
• ileus
• symptomatic cholelithiasis
• proctitis.
7. Current evidence of Haemoccult (+) stool of unknown aetiology.
8. Subjects who have taken any medication for the treatment of IBS within 1 month
prior to screening except for anti-diarrhoeal medications or laxatives for control of
bowel habit which is allowed if at a stable dose for 2 weeks prior to randomisation.
9. Subject is currently taking any prohibited medication.
10. Subjects who are taking NSAIDs including aspirin on a regular basis or within 48
hours of a study day. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| • Serum cortisol / ACTH and DHEA levels taken at 20-minute intervals over the study period. |
|
| 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 | Yes |
| 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 | Yes |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | Yes |
| E.6.13 | Others | Information not present in EudraCT |
| 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 | 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
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | 71 |
| E.8.9.2 | In all countries concerned by the trial days | 71 |
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