Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Double-Blind, Placebo-Controlled Trial to Evaluate the Safety and Tolerability of Oral Once-Daily Prucalopride (R108512) Solution in Constipated Elderly Subjects Living in a Nursing Facility
Brief Summary: The purpose of this study is to determine whether prucalopride is safe and effective in the treatment of constipation in elderly subjects living in a nursing facility.

Hypothesis:

Prucalopride up to a dose of 4 mg once daily is safe and well tolerated in in elderly subjects living in a nursing facility.


Options:
A: INCLUSION CRITERIA

1. Females aged 18 to 65 years old inclusive
2. A diagnosis of functional constipation as defined by two or more of the following:

   1. fewer than three spontaneous complete bowel movements per week
   2. hard or lumpy stools more than 25 % of the time
   3. straining during a bowel movement more than 25 % of the time
3. A normal rectal exam result on file within the past 2 years or performed at screen to exclude the possibility of an evacuation disorder. Examination must exclude findings suggestive of an evacuation disorder such as high sphincter tone at rest, failure of perineal descent and spasm, tenderness or paradoxical contraction of the puborectalis muscles.
4. Females of child-bearing potential (those who have not experienced a bilateral tubal ligation, hysterectomy or menopause) must use an acceptable method of contraception during the study. Acceptable methods are surgical sterilization, hormonal methods such as oral contraceptives, Norplant and Depo-Provera, double barrier method such as a condom and spermicide, and an IUD.

   Abstinent females may participate if they agree to use the double barrier method should they become sexually active during the study.
5. Able to provide written informed consent prior to any study procedures being performed

EXCLUSION CRITERIA

1. Female patients who are pregnant or breast feeding
2. Structural or metabolic diseases/conditions that affect the gastrointestinal system or functional gastrointestinal disorders other than constipation. The long version BDQ will be used to confirm patients have constipation.
3. Unable to withdraw all medications 48 hours prior to Visit 1; any medication that alters GI transit including but not limited to laxatives, magnesium or aluminum-containing antacids. prokinetics, erythromycin, narcotics, anticholinergics, tricyclic antidepressants and SNRIs; analgesic drugs including opiates, NSAIDs, and COX-2 inhibitors (Note: Tylenol is permitted), GABAergic agents and benzodiazepines.

   Note: All other concomitant medications will be reviewed on a case by case basis by the study physicians.
4. Clinical evidence (including but not limited to a clinically significant abnormal physical exam, ECG or laboratory test result in the past medical record) or current clinically significant abnormal physical exam or laboratory test result that could indicate significant cardiovascular, respiratory, renal, hepatic, gastrointestinal, hematological, neurological, psychiatric or other diseases that interfere with the objectives of the study. If a laboratory test result is abnormal and clinically significant, it may be repeated once at the discretion of the PI. If the laboratory test result remains abnormal and clinically significant, the patient will be discontinued from the study and referred to a primary care physician for further evaluation.
5. Patients who are considered by the PI to be alcoholics not in remission or known substance abusers.
6. Patients who have participated in another clinical study in the past 30 days.
B: Inclusion Criteria:

1. Male and female patients at least 65 years of age (no upper age limit).
2. History of constipation. i.e., the patient should have received any treatment for constipation at any time during the 4 weeks (28 days) preceding entry into the study, including fibre/bulk forming supplements.
3. The patient had to live in a nursing facility.
4. The patient had to be clinically stable.
5. The patient had to be able to take oral medications.
6. The patient had to be continent of bowels the majority of time.
7. The patient had to be able to reliably communicate AEs.
8. The patient had to provide informed consent, signed by the patient or legally acceptable representative and by the investigator.

Exclusion Criteria:

1. Patients who were known to be HIV positive or who had AIDS.
2. Patients who were being actively treated with Propulsid (cisapride) or cancer chemotherapy other than hormonal agents.
3. Patients with significantly impaired renal function, i.e., creatinine clearance \<30 mL/min using the Cockcroft and Gault formula:

   Males: CLCR = \[(140-age) x (weight in kg)\] / 72 x (SCR).

   Females: CLCR = male value x 0.85

   Because the calculated value for creatinine clearance could be artificially high when serum creatinine concentrations were very low, patients with a serum creatinine \<0.5 mg/dL were excluded from the study.
4. Patients who received an investigational drug in the 30 days preceding the study.
5. Patients who had previously received either R093877 or R108512.
C: Inclusion Criteria:

* Patient is 18 years of age or older
* Patient meets colonoscopy requirements according to the American Gastroenterological Association
* Patient meets criteria for chronic constipation including weekly bowel movement frequency requirements and reports one or more symptoms of constipation according to protocol requirements
* Patient has successfully completed study requirements with no clinically-significant findings: physical exam, ECG, clinical laboratory tests
* Patient is fluent in English

Exclusion Criteria:

* Patient reports loose or watery stools
* Patient meets criteria for IBS including protocol-defined abdominal discomfort or pain
* Patient may not take prohibited medications per protocol
* Medical diagnoses, medical conditions, or family history that would not make the patient a good candidate for the study or limit the patient's ability to complete the clinical study
D: Inclusion Criteria:

* 1. Male and non-pregnant, non breast-feeding female outpatients at least 18 years of age (no upper age limit).
* 2. History of constipation; the subject reports, on average, two or fewer spontaneous bowel movements per week that result in a feeling of complete evacuation and or one or more of the following for at least 6 months before the selection visit:

  1. very hard (little balls) and/or hard stools at least a quarter of the stools
  2. sensation of incomplete evacuation following at least a quarter of the stools
  3. straining at defecation at least a quarter of the time. 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.

Subjects who never have spontaneous bowel movements are considered to be constipated and are eligible for the trial.

Exclusion Criteria:

* 1. Subjects in whom constipation is thought to be drug-induced, or subjects using any disallowed medication.
* 2. Subjects suffering from endocrine disorders, metabolic disorders or neurologic disorders.
* 3. Subjects with a megacolon/megarectum or a diagnosis of pseudo-obstruction.
* 4. Constipation as a result of surgery.
* 5. Known or suspected organic disorders of the large bowel, i.e. obstruction, carcinoma, or inflammatory bowel disease.
* 6. Subjects with severe and clinically uncontrolled cardiovascular, liver, or lung disease, neurologic or psychiatric disorders (including active alcohol or drug abuse), cancer or AIDS, and other gastrointestinal or endocrine disorders.
* 7. Subjects with impaired renal function.
* 8. Subjects with clinically significant abnormalities of haematology, urinalysis, or blood chemistry.
* 9. Females of child-bearing potential without adequate contraceptive protection during the trial.

Answer: B