Phase 2 Study of MD-1100 Acetate Administered for 14 Days to Patients Meeting Criteria for Chronic Constipation

A Randomized, Multicenter, Double-Blind, Parallel-Design, Phase 2 Trial of Oral MD-1100 Acetate Administered for 14 Days Once Daily at 100 ug, 300 ug, 1000 ug, or Placebo to Patients With Chronic Constipation

The purpose of this study is to determine the safety and gastrointestinal pharmacodynamics (stool frequency, stool consistency, stool ease of passage, stool completeness of evacuation) of MD-1100 acetate administered daily for 14 days.

Inclusion Criteria:

• Male or non-pregnant, non-breastfeeding female, age 18-70 years old at the time of first dose;
• Sexually active patients of childbearing potential agree to use double-barrier birth control;
• Females of childbearing potential must complete negative pregnancy tests prior to first dose;
• Negative colonoscopy within 10 years or completion of negative flexible sigmoidoscopy if under the age of 50 provided there is no history of rectal bleeding, weight loss, or anemia;
• BMI must be greater than/equal to 18.5 and less than 35.0;
• Successful completion of physical exam, 12-lead ECG, clinical laboratory tests prior to first dose of study medication;
• Vital signs must not have clinically-significant findings within 4 hours of first dose of study medication;
• Patient reports 3 or less spontaneous bowel movements (SBMs) per week and meets 1 or more of the following criteria for constipation for 12 weeks in the previous 12 months: straining at least 25% bowel movements (BMs), lumpy or hard stools at least 25% of BMs, or sensation of incomplete evacuation at least 25% of BMs;
• Patient reports 3 or less SBMs during the 7-day Pre-treatment Period;
• Patient is compliant with IVRS for at least 6 days in the 7-day Pre-treatment Period.

Exclusion Criteria:

• Use of investigational drug within 30 days;
• Laxative/enema-induced diarrhea within 60 days;
• Patient meets ROME II criteria for functional diarrhea;
• Most bothersome symptom is moderate or severe abdominal pain or abdominal discomfort;
• History of cancer, inflammatory bowel disease, ischemic colitis, bowel resection, colostomy, or fecal impaction;
• Diagnosis of cathartic colon or laxative/enema abuse, pelvic floor dysfunction, evacuation disorder, bulimia, anorexia, or neurological disorders;
• Surgery within 30 days or GI surgery within 6 months of first dose of study medication. Cholecystectomy and/or appendectomy are acceptable if completed more than 60 days prior to first dose of study medication;
• Patient may not use any disallowed medications (prescription and/or over-the-counter treatments for chronic constipation or C-IBS, drugs that target 5-HT4, 5-HT2b, or 5-HT3 receptors, narcotics, anti-cholinergic agents, GI preparations, etc.) during the 7-day Pre-treatment Period or during the study. Stable, continuous (30 days or more) use of dietary fiber is acceptable.
• Any acute or chronic condition that would limit the patient's ability to complete and/or participate in the study.