E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Irritable Bowel Syndrome (IBS) |
|
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 determine whether there is a difference in colonic mucosal blood flow determined by Laser Doppler Flowmetry (LDF) in subjects who have taken 6 days BID dosing of 1mg alosetron vs. placebo.
|
|
E.2.2 | Secondary objectives of the trial |
To determine there is a difference in colonic mucosal blood flow determined by Laser Doppler Flowmetry (LDF) between female healthy volunteers and female d-IBS patients.
|
|
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: 1. The subject signs and dates a written informed consent form prior to the initiation of any study-related activities. 2. The subject is between 18 and 65 years of age at the time of the Screening Visit. 3. The subject is female and either: • A healthy subject. Healthy subjects are defined as individuals who are free from clinically significant illness or disease as determined by their medical history (including family), physical examination, laboratory studies, and other tests. OR • A d-IBS patient per the Rome II criteria that has a normal result from a flexible sigmoidoscopy or colonoscopy, or flexible sigmoidoscopy plus barium enema, according to subject’s age, within 2 years of the Screening visit. • If the subject is <50 years of age, normal result from a flexible sigmoidoscopy or colonoscopy, or flexible sigmoidoscopy plus barium enema. • If the subject is ≥50 years of age, normal result from a colonoscopy or flexible sigmoidoscopy plus barium enema. 4. The subject demonstrates a negative urine pregnancy test result prior to investigational product administration and be either: • Of non-childbearing potential (i.e., physiologically incapable of becoming pregnant) • post-menopausal define as one year without menses in the absence of hormone replacement therapy. • sterilization (via hysterectomy or bilateral tubal ligation) • Of childbearing potential and agrees to one of the following acceptable non-hormonal contraceptive methods consistently and in accordance with both the product label and the instructions of a physician. Subjects will use effective contraceptive methods for at least one month prior to Screening and should continue to use the same contraceptive method throughout the study (Follow-up Visit). • Complete abstinence from intercourse • an intra-uterine device (IUD) inserted by a qualified physician, provided the IUD is not of the hormonal type and it has published data showing that the highest expected failure rate is less than 1% per year (not all IUDs meet this criterion) • double barrier method if comprised of a spermicide with either a condom or diaphragm • sterilization of partner 5. The subject is ambulatory (defined as not depending exclusively on a wheelchair for mobility).
|
|
E.4 | Principal exclusion criteria |
A subject will not be eligible for inclusion in this study if any of the following criteria apply: 1. The subject is taking oral contraceptive or other hormonal therapy. 2. The subject has a concurrent illness or disability that may affect the interpretation of clinical data, or otherwise contraindicates participation in this clinical study (e.g., an unstable cardiovascular, autoimmune, renal, hepatic, pulmonary, endocrine, metabolic, gastrointestinal, hematologic, or neurological condition). 3. The subject has constipation-predominant IBS (c-IBS) or alternating IBS per the ROME II criteria. 4. The subject has current evidence of or history of chronic or severe constipation, or a history of sequelae from constipation. 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) • 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 • gastrointestinal adhesions • ischemic colitis • toxic megacolon • impaired intestinal circulation • gastrointestinal perforation • thrombophlebitis or hypercoagulable state • gastrointestinal obstruction and/or stricture • coronary artery disease (CAD) • significant atherosclerosis. • Current evidence of (within the past 6 months): • diverticulitis • ileus • symptomatic cholelithiasis • proctitis. • Current evidence of: • Hemoccult (+) stool. 6. The subject has a BMI of ≥27. 7. Mental impairment or inability or refusal to follow directions. 8. The subject has current evidence of, or has been treated for a malignancy within the past five years (other than localized basal cell, squamous cell skin cancer or cancer in situ that has been resected). 9. The subject exhibits evidence of hepatic dysfunction, viral hepatitis, or exhibits serum ALT (SGPT), AST (SGOT) values >2.5 times the upper limit of normal or alkaline phosphatase or bilirubin values >2.0 times the upper limit of normal. 10. The subject displays renal impairment as evidenced by a serum creatinine value >2.0 mg/dl. 11. The subject has used any medication within the seven days prior to dosing, unless approved by the investigator and GSK personnel. Section 9.1. 12. The subject has used an investigational drug, or participated in an investigational study, within 30 days of the Screening Visit. 13. The subject has a history of drug allergies (including but not limited to hypersensitivity responses to alosetron which, in the opinion of the investigator, contraindicates the subject's participation in this study. 14. Subjects who have made a blood donation (>450mL) within 6 weeks prior to screening. 15. The subject has a history of alcohol and/or substance abuse within the past two years. 16. The subject is pregnant. 17. The subject is breastfeeding.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
- Left colon mucosal blood flow determined by LDF. - Rectal mucosal blood flow determined by LDF. - Incidence of adverse events grouped by body system.
|
|
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 | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.8.5 | The trial involves multiple Member States | Information not present in EudraCT |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Information not present in EudraCT |
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
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 2 |