Study to Investigate Safety and Response to 1 or 2 g Rectal Suppositories Containing 5 or 10 mg NRL001.

Fecal Incontinence Clinical Trial

Official title:

Randomised, Double-blind, Single Dose, Three-way, Cross-over Study to Investigate the Safety and Response to 1g or 2g Rectal Suppositories Containing 5 mg or 10 mg 1R,2S-methoxamine Hydrochloride [NRL001] or Matching Placebo

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00857467
• Other study ID #: NRL001-01/2008 (SUM)
• Status: Completed
• Phase: Phase 1
• First received: March 5, 2009
• Last updated: December 21, 2009
• Start date: February 2009

Study information

• Verified date: December 2009
• Source: Norgine
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

This is a healthy volunteer three-way crossover study. A total of 12 subjects will receive three single administrations of 1 g rectal suppositories (containing either 5 mg NRL001, 10 mg NRL001 or matching placebo), with a washout period of at least 7 days between dosings. A further 12 subjects will receive three single administrations of 2 g rectal suppositories (containing either 5 mg NRL001, 10 mg NRL001 or matching placebo), again with a 7 day washout period between dosings. The pharmacodynamic response, pharmacokinetics and safety profile will be determined.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. primary completion date: December 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

1. No previous history of ano-rectal conditions or diseases

2. No history of cardiovascular disease

3. 18 to 60 years of age

4. 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:

1. Use of medication in the last 30 days with a vasodilatory activity, or use of any medication currently or within the last 30 days which the Investigator believes may affect the study participation or results

2. Use of monoamine oxidase inhibitors presently or within the last 2 weeks before study participation

3. Use of any medication in the last 30 days applied to the anus and/or via the rectum

4. Application of any unlicensed medication within the previous 3 months or participation in any other research study in the last three months which involved being paid a disturbance allowance; having an invasive procedure (e.g. venepuncture >50ml, endoscopy) or exposure to ionising radiation.

5. Regular intake of more than 21 units of alcohol per week

6. History or any evidence of cardiovascular disease including ischaemic heart disease and hypertension (defined on examination: systolic blood pressure greater than 160 mmHg or diastolic blood pressure greater than 90 mmHg; based on at least two separate readings), peripheral vascular disease or Raynaud's syndrome

7. Presence of diabetes mellitus

8. History or symptoms of thyroid diseases, including hypo- or hyperthyroidism

9. Pregnant or lactating females

10. History of any clinically relevant allergy

11. 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

12. Volunteers whom the Investigator feels would not comply with the requirements of the trial

13. Volunteers who have been exposed to more than 5 mSv of ionising radiation in the last 12 months.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fecal Incontinence

Intervention

Drug:
• NRL001
Subjects receive single doses of 5 mg NRL001, 10 mg NRL001 and placebo in a 1 g rectal suppository, with a 7-day washout period between dosing.
• NRL001
Subjects receive single doses of 5 mg NRL001, 10 mg NRL001 and placebo in a 2 g rectal suppository, with a 7-day washout period between dosing.

Locations

Country	Name	City	State
United Kingdom	Department of GI Surgery, Nottingham University Hospital	Nottingham

Sponsors (1)

Lead Sponsor	Collaborator
Norgine

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in MARP after a single dose		6 hours	No
Secondary	Pharmacokinetic plasma assessment to determine systemic uptake		6 hours	No
Secondary	Adverse events		6 hours	Yes
Secondary	Cardiovascular parameters; heart rate and blood pressure		6 hours	Yes