The Safety and Dose Response to Single Anal Doses of NRL001

Proof of Concept Study in Healthy Volunteers to Investigate the Safety and Dose Response to a Single Dose (0.3%,1% or 3%) of Methoxamine (NRL001)applied to the Anus

Single centre dose-finding and proof-of-concept study in healthy volunteers to assess the effects of single doses of NRL001 on the mean anal resting pressure (MARP). In addition, the pharmacokinetics of NRL001 and subject safety are also examined.

This is a single centre dose-finding and proof-of-concept study in healthy volunteers to assess the effects of single doses of NRL001 on the mean anal resting pressure (MARP). In addition, the pharmacokinetics of NRL001 and subject safety are also examined.

The study consists of four parts, which evaluate different NRL001 concentrations and sites of application. Treatments consist of a single local application of either 0.3%, 1% or 3% w/w NRL001 gel applied peri-anally, of either 1% or 3% w/w NRL001 gel applied intra-anally, or 1% w/w NRL001 administered rectally. In addition, a 10 mg NRL001-containing suppository applied to the rectum is assessed.

Inclusion Criteria:

• No previous history of ano-rectal conditions/diseases.
• No history of heart disease.
• 18 to 75 years of age.
• Males and females but 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 vasodilatory activity.
• Use of any medication in the last 30 days applied to the anus and/or via the rectum (exception: participation in Part A, Part B or Part C of NRL001-01/2002(HV)
• Regular intake of more than 21 units of alcohol per week.
• 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.