Effects of Oral PEG 3350 on Electrolyte Balance

Inclusion criteria

• The subjects written informed consent must be obtained prior to inclusion.
• Male and female patients between 18 and 70 years of age with confirmed chronic constipation after the run-in period; this is defined as patients who have recorded in their diaries less than 3 bowel motions/week plus one of the following symptoms:

Straining during at least 25% of defecations Lumpy or hard stools with at least 25% of defecations Sense of incomplete evacuation with at least 25% of defecation Sensation of ano-rectal blockage with at least 25% of defecation Manula manoeuvres of facilitate at least 25% of defecation

• Willing and able to follow the entire procedure and to comply with the study instructions.
• For the subgroup of patient volunteers taking ACE-inhibitors (36 subjects): A history of hypertension, with blood pressure controlled to acceptable levels by a stable regimen of ACE-inhibitors.

Exclusion criteria

• Participation in a clinical research study involving investigational drugs or dosage forms within the previous 3 months.
• Subjects who have previously been enrolled in this study.
• Subjects who are currently or have a history of abuse of alcohol, non-medical drugs, medicinal drugs or other substance abuse eg solvents.
• Major surgery in within the last 12 months.
• Malignant tumors within the last 5 years.
• Uncontrolled blood pressure or terminal cardiac, liver and/or kidney diseases.
• Clinical relevant acute gastrointestinal tract disease, including evidence of intestinal perforation or obstruction, paralytic ileus, toxic megacolon, severe inflammatory conditions.
• Acute urinary tract conditions, including cystitis.
• Patients with diagnosis or evidence of the following diseases: Hypothyroidism, diabetes mellitus, porphyria, pituitary gland insufficiency, pheochromocytoma, glucagonoma, neurological diseases (eg Hirschprung disease, neurofibromatosis, Chagas disease, stroke, autonomous neuropathy, intestinal pseudoobstruction, Multiple sclerosis, medullar injury, Parkinson disease, Shy-Drager syndrome), collagenosis, vasculitis, myopathy (e.g. sclerodermatitis, amyloidosis, dermatomyositis), intoxication with heavy metals (e.g. Pb, As, Hg)
• Concomitant medication:

• Use of any oral purgatives/laxatives and prokinetics within the last 14 days prior to dosing.
• Use of any opioids, anti-cholinergics, tricyclic anti-depressants, MAOIs, Fe preparations, within the 4 weeks prior to dosing.
• Use of any Ca-antagonists, Beta-blockers or diuretics within the last 4 weeks prior to dosing.
• other medication which in the opinion of the Investigator could interfere with the principal function of the GI tract.
• Subject unable to provide written consent.
• Failure to satisfy the Investigator of fitness to participate for any other reason, including suspected non-compliance.
• Women of childbearing potential, who are not using and not willing to use medically reliable methods of contraception for the entire study duration, unless they are surgically sterilised/hysterectomised or any other criteria considered sufficiently reliable by the Investigator in individual cases.
• Patients with electrolytes disturbances or clinical signs of dehydration.
• Positive test at screening for HIV or hepatitis.
• Any clinically significant abnormal test results.