The Safety and Dose Response to Single Anal Doses of NRL001

Phase 1

Completed

• Conditions: Faecal Incontinence
• Interventions: Drug: Perianal NRL001 Gel 3 strengths; Drug: Intraanal NRL001 Gel 2 strengths; Drug: Intrarectal NRL001 Gel

• Registration Number: NCT06593743
• Lead Sponsor: Norgine

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Study Start: 2002-12
• Primary Completion: 2004-07
• Study Completion: 2013-11-12
• Study First Submitted: 2015-06-09
• Status Verified: 2024-09
• Study First Submitted QC: 2024-09-10
• Last Update Submitted: 2024-09-10
• Study First Posted: 2024-09-12
• Last Update Posted: 2024-09-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 44

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Perianal NRL001 Gel 3 strengths	Perianal NRL001 Gel 3 strengths	A single peri-anal application of NRL001 0.3%, 1%, 3% gel in stepwise dose ascending fashion.
Intraanal NRL001 Gel 2 strengths	Intraanal NRL001 Gel 2 strengths	A single intra-anal application of 3% or 1% NRL001 gel.
Intrarectal NRL001 Gel	Intrarectal NRL001 Gel	A single intra-rectal application of 1% NRL001 gel.

Primary Outcome Measures

Name	Time	Method
Mean anal resting pressure	Six hours at visit 2	Mean anal resting pressure (MARP) was recorded using anal manometric catheter

Secondary Outcome Measures

Name	Time	Method
Blood pressure (mmHg)	Six hours at visit 2	Blood pressure was measured before the application of the trial medication and then every 30 minutes for the first 2 hours after application, plus 2 hourly for the remaining follow-up period.
Pulse rate (beats per minute)	Six hours at visit 2	Pulse rate was measured before the application of the trial medication and then every 30 minutes for the first 2 hours after application, plus 2 hourly for the remaining follow-up period.

Trial Locations

Locations (1)

University Hospital - Queens Medical Centre; 🇬🇧 Nottingham, United Kingdom