Effect of 7 Days of Dosing With a 10 mg Rectal Suppository of NRL001in Patients With Faecal Incontinence

NCT01175941 | Completed Phase 1

• 1 other identifier: NRL001-01/2010 (MANO)
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

This is a study to examine the effect of alpha adrenergic stimulation of the anal canal and rectum on parameters affecting the control of defecation in subjects with faecal incontinence. The study will investigate the effects of rectal suppositories containing 10 mg NRL001 given for seven days, once daily. Rectal compliance and median anal resting pressure will be considered the primary objective of the study. A pharmacokinetic evaluation plus safety and tolerability assessment including monitoring of electrocardiograms (ECGs), blood pressure and heart rate will also be evaluated as secondary objectives.

Conditions

Fecal Incontinence

Outcome Measures

Primary Outcomes (1)

• Mean anal resting pressure and rectal compliance

  7 days

Secondary Outcomes (3)

• Rectal sensitivity

  7 days

• Adverse events

  7 days

• Plasma concentration over time

  7 days

Study Arms (2)

NRL001

EXPERIMENTAL

10 mg NRL001 in a 2 g suppository

Drug: NRL001

Placebo

PLACEBO COMPARATOR

Matched placebo control

Drug: Placebo control

Interventions

NRL001 DRUG

10 mg NRL001 in a 2 g suppository, administered once daily for 7 days

NRL001

Placebo control DRUG

Matched placebo - administered as a 2 g suppository, once daily for 7 days

Placebo

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patient volunteers aged 40 to 85 years without clinically significant or uncontrolled cardiovascular, renal or hepatic disease (as determined by medical history, physical examination, laboratory test values, vital signs, and electrocardiograms \[ECGs\] at screening)
• Patients with mild/moderate passive faecal incontinence based on clinical symptomology and demonstrating the following criteria:
• ARP ≥20mmHg and ≤80mmHg
• Intact IAS as demonstrated by endoanal ultrasound
• Rectal capacity ≥150ml
• Cleveland Clinic Score ≥6 and ≤ 15
• Body mass index (BMI) ≥ 16 and ≤ 32
• Able and willing to receive rectal treatments
• Able to voluntarily provide written informed consent to participate in the study
• Must understand the purposes and risks of the study and agree to follow the restrictions and schedule of procedures as defined in the protocol
• Female volunteers must be either postmenopausal (for at least one year and confirmed by serum FSH at screening), or surgically sterile, practising true sexual abstinence, or using Investigator-approved methods of contraception throughout the study until after post study physical examination and have a negative pregnancy test at screening
• Must be willing to consent to have data entered into The Over-Volunteering Prevention System

You may not qualify if:

• Patients with FI related to anatomical and/or traumatic sphincter defects
• Presence of any significant or uncontrolled cardiovascular, pulmonary, hepatic, renal, immunologic, neurological or psychiatric disease
• Concomitant ano-rectal conditions or diseases assessed as potentially interfering with the study medication by the Investigator (e.g. concomitant haemorrhoids, anal fissures). Conditions considered not interfering with the study medication are allowed
• Clinically relevant ECG-abnormalities with evident QTc prolongation and/or acute arrhythmia
• Current or history of drug or alcohol abuse
• Use of any disallowed concomitant medication, including over-the-counter items within 30 days prior to study drug administration until the end of the study
• Use of any medication in the last 30 days applied via the rectum
• Use of any medication currently or within the last 30 days which the investigator believes may affect the study participation or results
• Unstable regimen of any statin, hypertensive or diuretic medication (patient volunteers must be on a stable regimen for at least 2 months)
• Participation in a clinical drug study during the 90 days preceding the initial dose in this study
• History of any allergy to nifedipine or any alpha-adrenoceptor antagonist or latex
• Consumption of alcoholic beverages within 24 hours prior to each dosing
• Patient volunteers who are considered not competent to consent to the trial or score less than 25 on the MMSE®
• Volunteers who, in the opinion of the Investigator, are unsuitable for participation in the study

Sponsors & Collaborators

• Norgine: lead

Study Sites (1)

Queens Medical Centre

Nottingham, Nottinghamshire, NG7 2UH, United Kingdom

Location

MeSH Terms

Conditions

Fecal Incontinence

Condition Hierarchy (Ancestors)

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

Study Officials

• Jonathan A Simpson, 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
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2010
• First Posted: August 5, 2010
• Study Start: August 1, 2010
• Primary Completion: November 1, 2011
• Study Completion: December 1, 2011
• Last Updated: November 5, 2012

Record last verified: 2012-11

Locations

GB (1)