This study is being done to evaluate the effect of fesoterodine 4 mg and 8 mg as compared to
placebo on the speed at which food travels through the stomach, intestines and colon.
Sustained release fesoterodine and solifenacin are both FDA-approved for the treatment of
overactive bladder.
However, the effects of fesoterodine on GI transit are unknown. Since chronic constipation
is a common symptoms, can significantly impair quality of life, and is associated with
urinary urgency, it is important to understand the effects of anticholinergic agents on
gastrointestinal transit in healthy subjects.
Inclusion Criteria:
1. Healthy female subjects, between the ages of 18 and 55 years, inclusive (Healthy is
defined as no clinically relevant abnormalities identified by a detailed medical
history, full physical examination, including blood pressure and pulse rate
measurement, 12-lead ECG and clinical laboratory tests).
2. Body Mass Index (BMI) of 17. 5 to 30. 5 kg/m2, and a total body weight of >50 kg (110
lbs).
3. An informed consent document signed and dated by the subject or a legally acceptable
representative.
4. Subjects who are willing and able to comply with scheduled visits, treatment plan,
laboratory tests, and other study procedures.
5. Females of childbearing potential who are currently taking oral contraceptives may be
enrolled but must have a negative pregnancy test prior to enrollment. In the event of
a positive pregnancy test during the study conduct period, the Investigator must
ensure that the appropriate procedures and actions are undertaken and documentation
prepared.
Exclusion Criteria:
Subjects presenting with any of the following will not be included in the study:
1. Functional gastrointestinal disorders as characterized by a symptom questionnaire.
2. Significant anxiety or depression characterized by the hospital anxiety and
depression questionnaire.
3. Evidence or history of uncontrolled narrow angle glaucoma or clinically significant
hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular,
hepatic, psychiatric, neurologic, or allergic disease. Subjects with drug allergies
which are relevant to the study will be excluded but other drug allergies or
untreated, asymptomatic, seasonal allergies at time of dosing do not render a subject
ineligible.
4. Subjects with evidence or history of clinically significant urologic diseases
(urinary retention, obstructive disturbance of bladder emptying, micturition
disturbance, nocturia or pollakisuria, e. g. prostatic hyperplasia, urethral
stricture.
5. History of gastrointestinal surgeries except for appendectomy or abdominal wall
hernia repair, cholecystectomy, or hysterectomy performed more than 3 months before
study participation.
6. History of febrile illness within 5 days prior to first dose.
7. A positive urine drug screen.
8. History of regular alcohol consumption exceeding 7 drinks/ week (1 drink = 5 ounces
(150 mL) of wine or 12 ounces (360) mL of beer or 1. 5 ounces (45 mL) of hard liquor)
within 6 months of screening.
9. Use of tobacco- or nicotine containing products in excess of the equivalent of 5
cigarettes per day.
10. Currently consuming more than 5 caffeinated beverages per day.
11. Treatment with an investigational drug within 30 days (or as determined by the local
requirement, whichever is longer) or 5 half-lives preceding the first dose of study
medication.
12. 12-lead ECG demonstrating QTc > 470 msec at screening. If QTc exceeds 450 msec, the
ECG should be repeated two more times and the average of the three QTc values should
be used to determine the subject's eligibility.
13. Use of prescription or nonprescription drugs and (herbal or dietary) supplements
within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study
medication. Limited use of non-prescription medications that are not believed to
affect subject safety or the overall results of the study may be permitted on a
case-by-case basis following approval by the sponsor. As an additional exception,
acetaminophen/paracetamol may be used at doses of < or = 1 g/day.
14. Use of the following medication for specified duration prior to enrollment:
- Anticholinergics or antispasmodic drugs (such as solifenacin, oxybutynin,
tolterodine, hyoscyamine, propantheline, trospium or flavoxate) within one month
prior to enrollment.
- Drugs with significant anticholinergic effects such as tricyclic antidepressants
(eg, amitriptyline, nortriptyline) within one month prior to enrollment.
- Selective serotonin reuptake inhibitors (eg, fluoxetine, paroxetine) within six
weeks prior to enrollment.
d. Opiates (eg, oxycodone) or medication containing morphine or codeine within
one month prior to enrollment.
- Calcium channel blockers that modify gastrointestinal motility (verapamil,
diltiazem, nifedipine) within one month prior to enrollment.
- Potent inhibitors of CYP3A4 such as macrolide antibiotics (erythromycin and
clarithromycin), antifungal agents (ketoconazole and itraconazole), cimetidine,
MAOIs, and protease inhibitors within one month (or 5 half-lives, whichever is
longer) prior to enrollment.
- Drugs and/or herbal preparations capable of inducing hepatic enzyme metabolism
(eg, barbiturates, rifampin, carbamazepine, phenytoin, primidone or St. John's
Wort) within one month (or 5 half-lives, whichever is longer) prior to
enrollment.
15. Consumption of grapefruit or grapefruit containing products within 7 days prior to
the first dose of study medication.
16. Blood donation of approximately 1 pint (500 mL) within 56 days prior to dosing.
17. History of hypersensitivity to fesoterodine or solifenacin or any components of its
formulation, or to peanut or soya.
18. Unwilling or unable to comply with the Lifestyle guidelines described in this
protocol.
19. Subject is the investigator or a sub-Investigator, research assistant, pharmacist,
study coordinator, other staff, or study personnel directly involved with the conduct
of the study.
20. Other severe acute or chronic medical or psychiatric condition or laboratory
abnormality that may increase the risk associated with study participation or
investigational product administration or may interfere with the interpretation of
study results and, in the judgement of the investigator, would make the subject
inappropriate for entry into this study.
