An Study to Examine the Effect of Coated Suppositories on Anal Pressure in Healthy Subjects

Study Overview
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Brief Summary
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This is an open label, dose-finding, 2-parts study. Approximately 6 subjects will be participating in this study. This study is composed of 2 parts: Part 1 is a dose finding study. Part 2 is a pharmacodynamic and pharmacokinetic study of an elected dose. A screening will be used to determine patients' suitability for inclusion in the trial. Within one week after the screening visit, subjects who meet all inclusion criteria and none of the exclusion criteria will enter part 1 of the study, one day of dose escalation. During this part, patients will undergo rectal manometry to determine anal pressure at baseline. Afterwards coated suppositories at various drug concentrations will be inserted and follow up manometries will be performed to determine response. Patients that presented with an increase in rectal resting pressure without adverse events will enter the second part of the study. In this part, patients will be administered with a coated suppository, at a dose found at part 1 of the study to cause significant anal contraction. Manometry studies will be performed before insertion (baseline) and at 1, 3 and 5 hours after insertion. Blood levels for drug concentrations will be taken at times 0, 30, 60, 120, 180, 300 minutes after administration and rectal manometries will be done at times 0, 1, 3 and 5 hours after administration.

Official Title
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An Open Label Study to Examine the Effect of Coated Suppositories on Anal Pressure in Healthy Subjects

Conditions
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Fecal Incontinence

Intervention / Treatment
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* Drug: coated suppository


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed written informed consent. Male or female subjects 18 to 55 years of age; Exclusion Criteria: Known allergy to the active drug or excipients. Pregnancy or lactation. Active cardiovascular or cerebrovascular disease including unstable angina, myocardial infarction, transient ischemic attacks/stroke, clinically significant arrhythmia, congestive heart failure, or cardiac valve abnormalities; Type 1 diabetes mellitus; Insulin treated type 2 diabetes mellitus; Renal insufficiency. Liver insufficiency. Malignant disease within 5 years of screening; History of rectal surgery. History of HIV, hepatitis B, hepatitis C. Has upon physical examination a rectal deformation or signs of rectal disease such as fissure, bleeding hemorrhoids, fistula, infection or space occupying lesion. Chronic use of medications with the exception of birth control pills.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: treatment<br> | Drug: coated suppository<br>* Dose escalating study<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in resting anal pressure | The primary outcome is the change in resting anal pressure as measured 90 minutes after insertion of coated suppository and in comparison to baseline measurement taken before intervention. | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Drug absorption | Blood samples for determining drug absorption be taken at times 0, 30, 60, 120, 180, 300 minutes after administration | 1 day |