A Randomized, Double-blind, Placebo-controlled Multicenter Study to Assess the Efficacy, Safety and Tolerability of Tegaserod 2 mg Bid vs Placebo in Patients With Chronic Constipation

This is an interventional treatment trial for Constipation focused on measuring Chronic constipation Read More

Inclusion Criteria for entry into the study (Performed at screening):

• Male and females of at least 18 years of age (no upper limit).

• History of constipation for at least 12 months before screening. Constipation is defined as follows: less than three spontaneous bowel movements per week that result in a feeling of complete evacuation, and one or more of the following:

  • At least 25% of the stools are very hard and/or hard stools (Type 1 and/or 2 on the Bristol Stool Form scale)14,
  • Sensation of incomplete evacuation following at least 25% of the bowel movements
  • Straining on at least 25% of the defecations The above criteria are only applicable for spontaneous bowel movements, i.e. not preceded within a period of 24 hours by the intake of a laxative agent or by the use of an enema. Patients who never have spontaneous bowel movements (that is, all bowel movements are preceded by laxatives) are considered constipated and eligible for the study.
• Patients who are able to communicate well with the investigator and to comply with the requirements for the entire study, including the withdrawal period.
• Patients who provide written informed consent before participating in the study after being given a full description of the study.

Exclusion Criteria for entry into the study (Performed at screening):

Patients meeting one or more of the following criteria should not be included in the study

• Use of herbs before 2 weeks of study
• Planned use of disallowed medication.
• With evidence of cathartic colon or a history of laxative abuse
• With a history of fecal impaction which necessitated surgical intervention
• Whose chronic constipation, according to the investigator's clinical judgment, is thought to be a result of: bowel surgery, gynecological surgery, neurologic disorders (e.g. aganglionosis, hypoganglionosis, autonomic neuropathy, Parkinson's disease, spinal cord injury or tumor, cerebrovascular accidents, multiple sclerosis), systemic sclerosis, myloidosis, scleroderma, myotonic dystrophy
• With a diagnosis of megarectum or colon, intestinal pseudo-obstruction, mechanical outlet obstruction, congenital anorectal malformation, rectocele, intestinal carcinoma, inlammatory bowel disease.
• An endoscopic/radiologic bowel evaluation (colonoscopic examination and/or a sigmoidoscopy + barium enema) is required in order to rule out cancer, inflammatory bowel disease or other structural disease. This evaluation must have been performed within the past 5 years. In addition, there should not be history or evidence of weight loss, anemia or rectal bleeding since the evaluation was performed.
• Existence of surgical or medical conditions which interfere with the absorption, distribution, metabolism and excretion of the study medication.
• With hypo or hyper thyroidism (clinically significant abnormal TSH level at screening)
• With clinical evidence (including physical exam, vital signs, ECG, laboratory tests) of significant cardiovascular, respiratory, renal, hepatic, gastrointestinal, hematology, endocrine or metabolic disorders, neurologic disease, or of any disease that may interfere with the patient successfully completing the study . Patient with insulin-dependent diabetes are excluded from the study.
• With psychosis, schizophrenia, mania or major psychiatric illness needing pharmacological treatment. A well-compensated depression does not exclude a potential patient.
• With symptoms of a significant clinical illness in the two weeks preceding baseline.
• With other relevant intercurrent medical condition that may interfere with the objectives of the study.
• Women who are pregnant or breast-feeding.
• Fertile women who are not currently using or complying with a medically approved method of contraception such as, but not exclusively, one of the following:Oral birth control pills administered for at least 1 full monthly cycle prior to study medication administration, Progesterone implanted rods inserted for at least 1 month prior to study medication administration, Intra-uterine device (IUD), Medroxyprogesterone acetate administered for a minimum of 1 month prior to study medication administration and continued until 1 month following the last dose of study medication, Double barrier methods (such as condoms and spermicide), Abstinence, when in the opinion of the investigator, their occupation or life style gives sufficient evidence that abstinence will be maintained throughout the study and for 1 month thereafter. In the case of abstinence, it should be recorded in the source documents that the patient was appropriately counseled.

Fertile woman is defined as a woman who is not surgically sterile (i.e. hysterectomy, bilateral oophorectomy or bilateral tubal ligation), or is not post-menopausal (a post-menopausal patient is defined as a patient who has not menstruated for 12 months or more).

• With evidence or history of drug or alcohol abuse within the past 12 months.
• Who received another investigational drug within the 30 days prior to entry in the study.
• Who participated in a prior tegaserod study.

Exclusion criteria for randomization (Performed at Day 1):

Patients to be excluded from entry into the double-blind period of the study are those:

• Whose constipation, as defined in Inclusion Criteria No. 2, was not confirmed by the diary data of the baseline period (average of the last two weeks of baseline).
• With loose or watery stools (Type 6 or 7 stool form according to the Bristol stool form scale) occurring in more than 3 days during the baseline period.
• In whom exclusion criteria, listed for the baseline period, are identified prior to the start of the treatment period.
• Who did not comply with completing the daily diary assessments. To be randomized, a patient must have at least 11 days of complete daily diary data during the last 14 days of the baseline period.
• Who did not comply with completing the weekly diary assessments. To be randomized, a patient must have completed at least 1 complete weekly diary assessment during the last 14 days of the baseline period.
• Who deviated from the guidelines regarding prohibited medications (see section 3.4.4) more than two days (more than 3 days) during baseline.