Effect of Single Doses of 10 mg NRL001 Applied as a Suppository to the Anal Canal or Rectum

Study Overview
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Brief Summary
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Study to assess the effects of 10mg NRL001 on mean anal resting pressure (MARP) when administered as a slow release suppository applied to the anal canal or rectum. In addition, the pharmacokinetics of NRL001 in plasma, adverse events, and any changes in heart rate or blood pressure were to be assessed.

Official Title
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Proof of Concept Study in Healthy Volunteers to Investigate the Safety and Response to a Single Dose of 10mg Methoxamine (NRL001) Applied Locally Using a Suppository to the Anal Canal or Rectum

Conditions
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Fecal Incontinence

Intervention / Treatment
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* Drug: NRL001


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: No previous history of ano-rectal conditions/ diseases No history of cardiovascular disease 18 to 75 years of age Males and females (pre-menopausal females of child-bearing potential must be using adequate contraceptive methods and have a negative pregnancy test before the start of the study) Exclusion Criteria: Use of medication in the last 30 days with a vasodilatory activity Use of monoamine oxidase inhibitors (MAOI) presently or within the last two weeks before study participation Use of any medication in the last 30 days applied to the anus and/or via the rectum (exception: participation in NRL001-01/2006 (SUPP) for previous dosing into the anal canal) Application of any unlicensed medication within the previous 3 months (exception: participation in NRL001-01/2006 (SUPP)) Regular intake of more than 21 units of alcohol per week History or any evidence of cardiovascular disease including ischaemic heart disease and hypertension (defined on examination: systolic blood pressure greater than 160mmHg or diastolic blood pressure greater than 90mmHg; based on at least two separate readings), peripheral vascular disease or Raynaud's syndrome Presence of diabetes mellitus History or symptoms of thyroid diseases, including hypo- or hyperthyroidism Pregnant females Breast feeding mothers Presence of concomitant gastrointestinal diseases or disorders, such as significant abdominal symptoms and haemorrhoids but also any significant organ (e.g. renal, hepatic or cardiac) dysfunction Volunteers whom the investigator feels would not be compliant with the requirements of the trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intra-anal<br>The first 12 subjects were administered 10mg NRL001 as a slow release suppository into the anal canal. | Drug: NRL001<br>* 10mg NRL001 was administered as a slow release suppository<br>* Other names: Methoxamine Hydochloride;|
| Experimental: Rectal<br>The second 12 subjects were administered 10mg NRL001 as a slow release rectal suppository. | Drug: NRL001<br>* 10mg NRL001 was administered as a slow release suppository<br>* Other names: Methoxamine Hydochloride;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in mean anal resting pressure (MARP) |  | Up to 6 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of NRL001 in plasma |  | Up to 6 hours post-dose | 
| Monitoring of blood pressure and heart rate |  | Up to 6 hours post-dose |