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

NCT00857467 | Completed Phase 1

• 1 other identifier: NRL001-01/2008 (SUM)
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Fecal Incontinence

Outcome Measures

Primary Outcomes (1)

• Change in MARP after a single dose

  6 hours

Secondary Outcomes (3)

• Pharmacokinetic plasma assessment to determine systemic uptake

  6 hours

• Adverse events

  6 hours

• Cardiovascular parameters; heart rate and blood pressure

  6 hours

Study Arms (2)

1 g suppository

EXPERIMENTAL

Subjects receive 5 mg NRL001, 10 mg NRL001 and placebo in a 1g rectal suppository

Drug: NRL001

2 g suppository

EXPERIMENTAL

Subjects receive 5 mg NRL001, 10 mg NRL001 and placebo in a 2 g rectal suppository.

Drug: NRL001

Interventions

NRL001 DRUG

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.

1 g suppository

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• No previous history of ano-rectal conditions or diseases
• No history of cardiovascular disease
• to 60 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)

You may not qualify if:

• 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
• Use of monoamine oxidase inhibitors presently or within the last 2 weeks before study participation
• Use of any medication in the last 30 days applied to the anus and/or via the rectum
• 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.
• 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 160 mmHg or diastolic blood pressure greater than 90 mmHg; 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 or lactating females
• History of any clinically relevant allergy
• 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 comply with the requirements of the trial
• Volunteers who have been exposed to more than 5 mSv of ionising radiation in the last 12 months.

Sponsors & Collaborators

• Norgine: lead

Study Sites (1)

Department of GI Surgery, Nottingham University Hospital

Nottingham, NG7 2UH, United Kingdom

Location

Related Publications (1)

• Simpson JA, Bush D, Gruss HJ, Jacobs A, Pediconi C, Scholefield JH. A randomised, controlled, crossover study to investigate the safety and response of 1R,2S-methoxamine hydrochloride (NRL001) on anal function in healthy volunteers. Colorectal Dis. 2014 Mar;16 Suppl 1:5-15. doi: 10.1111/codi.12541.

  PMID: 24499492 DERIVED

MeSH Terms

Conditions

Fecal Incontinence

Condition Hierarchy (Ancestors)

Rectal Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Study Officials

• Hans-Jürgen Gruss, MD

  Norgine

  STUDY DIRECTOR

• John H Scholefield, MD

  Nottingham University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: March 5, 2009
• First Posted: March 6, 2009
• Study Start: February 1, 2009
• Primary Completion: December 1, 2009
• Last Updated: December 23, 2009

Record last verified: 2009-12

Locations

GB (1)