| 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.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 7.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10023003 |
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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 |
| The primary objective is to determine whether talnetant provides adequate relief of IBS pain and discomfort in any dose group compared to placebo and to determine the safety and tolerability in IBS subjects. |
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| E.2.2 | Secondary objectives of the trial |
1. Explore differentiation in response among subgroups of IBS patients (e.g., bowel subgroup, or gender subgroup).
2. Obtain dose-response information for design of subsequent studies.
3. Evaluate for positive treatment effects within bowel subgroups for secondary symptoms:
a urgency
b stool frequency
c stool consistency
d bloating (encompasses abdominal fullness or swelling)
e a feeling of incomplete evacuation
f straining during a bowel movement.
4. Compare treatment groups for global improvement of IBS symptoms.
5. Compare treatment groups for improvement of IBS pain or discomfort.
6. Compare treatment groups for changes in bowel pattern.
7. Provide data on the effect of talnetant on subjects’ quality of life.
8. To estimate the plasma concentrations of talnetant in IBS patients and to characterize the relationship between plasma concentrations and response (adequate relief).
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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:
1. The subject signs and dates a written informed consent form prior to the initiation of any study-related activities, including discontinuation of any prohibited medications. (see Section 8.2 of the protocol)
2. The subject must be a male or female at least 18 years of age at the time of the Screening Visit.
If female; the subject must have a negative serum pregnancy test result prior to investigational product administration and is eligible to participate if one of the followinhg criteria apply:
a Is of non-childbearing potential (i.e., physiologically incapable of becoming pregnant)
post-menopausal defined as one year without menses in the absence of hormone replacement therapy.
sterilization (via hysterectomy or bilateral tubal ligation)
b Is of child-bearing potential and agrees to commit to one of the protocol-approved contraceptive methods (below) consistently and in accordance with both the product label and the instructions of a physician. Subjects will use one of the following GSK acceptable contraceptive methods for at least one month prior to Screening, and should continue to use the same contraceptive method throughout the study (Week 12).
oral birth control pills administered for at least one monthly cycle prior to investigational product administration and continue throughout the 8-week treatment phase and the 4-week follow-up phase
Progesterone implanted rods (NORPLANT†) inserted for at least one month prior to the investigational product administration but not beyond the third successive year following insertion.
an IUD, inserted by a qualified clinician, with published data showing that the highest expected failure rate is less than 1% per year (not all IUDs meet this criterion)
medroxyprogesterone acetate (DEPO-PROVERA†) administered for a minimum of one month prior to the investigational product administration and administered for one month following study completion
complete abstinence from intercourse for two weeks prior to the investigational product administration, throughout the 8-week treatment phase, and the 4-week follow-up phase
double barrier method comprised of a spermicide with either a condom or diaphragm.
has a male partner who is sterile to female subject's entry into the study and is the sole sexual partner for that female subject.
3. The subject has normal results from a flexible sigmoidoscopy or colonoscopy, or a flexible sigmoidoscopy plus barium enema, according to subject's age, within 2 years of randomization. Otherwise, the appropriate procedure(s) must be performed and normal results obtained during the 7-day procedure window (prior to randomization):
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 2 years of the Screening Visit, a colonoscopy or flexible sigmoidoscopy plus barium enema must be performed.
Colonic procedure results must be known prior to dispensing study medication.
4. The subject has been diagnosed with IBS consistent with the Rome II Criteria as adapted in Appendix 3.
5. During the two-week screening phase, the subject must have documented an average IBS pain or discomfort score >1.5 (on a 5 point scale where 0=none, 1=mild, 2=moderate, 3=severe, 4=very severe).
6. During the two-week screening phase, the subject must have conducted self-assessments on at least 12 days using the telephone data entry system.
7. The subject is ambulatory (defined as not depending exclusively on a wheelchair for mobility).
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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:
1. Subject reported no stool for 7 consecutive days during the two-week screening phase.
2. 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)
laxative abuse (in the clinical judgement of the physician)
gastrointestinal surgery (exceptions include greater than or equal to 6 months post-surgery appendectomy, cholecystectomy, fundoplication without gas bloat, or hiatal hernia repair; greater then or equal to 3 months post-surgery herniorrhaphy without bowel resection)
gastroparesis
GI malignancy
carcinoid syndrome
amyloidosis
chronic pancreatitis
gastrointestinal adhesions
toxic megacolon
gastrointestinal perforation
gastrointestinal obstruction and/or stricture.
Current evidence of or within the past 6 months:
diverticulitis
ileus
symptomatic cholelithiasis
proctitis.
Current evidence of:
Hemoccult (+) stool of unknown etiology.
3. 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).
4. Mental impairment or inability or refusal to follow directions, inability to understand how to use the touch-tone telephone system, or inability or refusal to complete any of the study questionnaires.
5. 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).
6. Exhibits evidence of hepatic dysfunction, viral hepatitis, or exhibits serum ALT (SGPT), AST (SGOT), alkaline phosphatase or bilirubin values >2.0 times the upper limit of normal.
7. Renal impairment as evidenced by a serum creatinine value >2.0 mg/dl.
8. Strongly or mildly positive (>20 units) TTG IgA test for celiac sprue prior to randomization.
9. Exhibits an abnormal creatine kinase value of greater than or equal to 5.0 times the upper limit of normal.
10. Male subjects exhibit a total testosterone value of <7nmol/L (<200ng/dL)
11. Exhibits an abnormal serum thyroid-stimulating hormone (TSH) value (If TSH has not been measured within the past three years, it must be assayed prior to randomization).
12. Failure to discontinue of one (or more) prohibited concomitant medication(s) within 7 days prior to the Screening Visit as described in Section 8.2.
13. Failure to remain on a stable dose of one (or more) permitted medication(s) for at least 30 days prior to the Screening Visit as detailed in Section 8.1.
14. Use of an investigational drug, or participated in an investigational study within 30 days of the Screening Visit.
15. History of hypersensitivity to quinolone antibiotics or quinolone derivatives.
16. Diagnoses of a psychiatric disorder (DSM-IV) within the past two years that required hospitalization and/or involved a suicide attempt (e.g., major depression). Subjects diagnosed with a psychiatric disorder that did not require hospitalization or involve a suicide attempt must have remained on a stable dose of medication for at least six months prior to the Screening Visit.
17. History of alcohol and/or substance abuse within the past two years.
18. The subject is pregnant.
19. The subject is breastfeeding.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| The proportion of subjects with adequate relief of IBS pain and discomfort on all 4 of the last 4 weeks of the treatment phase. |
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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 | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Information not present in EudraCT |
| E.6.8 | Bioequivalence | Information not present in EudraCT |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Yes |
| 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) | 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
| E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
| 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 | Information not present in EudraCT |
| 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 | Yes |
| E.8.2.3 | Other | Information not present in EudraCT |
| E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.5 | The trial involves multiple Member States | Yes |
| 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 | |
| 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 months | 9 |
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