Study to Assess the Effect Of Alosetron On Mucosal Blood Flow
Condition: Irritable Colon
MeSH terms: Irritable Bowel Syndrome
Intervention: alosetron
Intervention MeSH terms: Alosetron
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double
Enrollment: 49.0
Sex: Female
Minimum age: 18 Years
Maximum age: 49 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: mucosal blood flow d-IBS

Summary:

      This study will look at colonic mucosal blood flow in subjects who have taken alosetron vs
      placebo and healthy volunteers vs diarrhea-predominant Irritable Bowel Syndrome (d-IBS)
      patients.
    

Eligibility criteria:

        Inclusion criteria:

          -  The subject signs and dates a written informed consent form prior to the initiation of
             any study-related activities.

          -  The subject is between 18 and 49 years of age at the time of the Screening Visit.

          -  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 who has a normal result from a flexible
             sigmoidoscopy or colonoscopy, or flexible sigmoidoscopy plus barium enema, within 2
             years of the Screening visit.

               -  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 The subject is ambulatory (defined as not depending
             exclusively on a wheelchair for mobility).

        Exclusion criteria:

          -  The subject is taking oral contraceptive or other hormonal therapy.

          -  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).

          -  The subject has constipation-predominant IBS (c-IBS) or alternating IBS per the ROME
             II criteria.

          -  The subject has current evidence of or history of chronic or severe constipation, or a
             history of sequelae from constipation.

          -  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):

               -  GI/Bowel conditions:

               -  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

               -  gastrointestinal adhesions

               -  ischemic colitis

               -  toxic megacolon

               -  impaired intestinal circulation

               -  gastrointestinal perforation

               -  gastrointestinal obstruction and/or stricture

               -  Ischemic cardiovascular conditions:

               -  coronary artery disease (CAD)

               -  significant atherosclerosis

               -  chronic pancreatitis

               -  diabetes

               -  thrombophlebitis or hypercoagulable state.

               -  Current evidence of (within the past 6 months):

               -  diverticulitis

               -  ileus

               -  symptomatic cholelithiasis

               -  proctitis.

               -  Current evidence of:

               -  Hemoccult (+) stool.

          -  The subject has a BMI of ≥27.

          -  Mental impairment or inability or refusal to follow directions.

          -  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).

          -  The subject exhibits evidence of hepatic dysfunction, viral hepatitis, or exhibits
             serum ALT (alanine aminotransferase) (SGPT), AST (aspartate aminotransferase) (SGOT)
             values >2.5 times the upper limit of normal or alkaline phosphatase or bilirubin
             values >2.0 times the upper limit of normal.

          -  The subject displays renal impairment as evidenced by a serum creatinine value >2.0
             mg/dl.

          -  The subject has used any medication within the seven days prior to dosing, unless
             approved by the investigator and GlaxoSmithKline (GSK) personnel. Section 9.1.

          -  The subject has used an investigational drug, or participated in an investigational
             study, within 30 days of the Screening Visit.

          -  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.

          -  Subjects who have made a blood donation (>450mL) within 6 weeks prior to screening.

          -  The subject has a history of alcohol and/or substance abuse within the past two years.

          -  The subject is pregnant. The subject is breastfeeding.