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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Norgine
ClinicalTrials.gov Identifier:
NCT01175941
First received: August 4, 2010
Last updated: November 2, 2012
Last verified: November 2012
  Purpose

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.


Condition Intervention Phase
Fecal Incontinence
Drug: NRL001
Drug: Placebo control
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-blind, Randomized, Placebo-controlled, Cross Over Study in Patient Volunteers With Faecal Incontinence to Evaluate the Effect on Rectal Compliance, Rectal Sensitivity, Recto-anal Inhibitory Reflex, Sphincter Pressures, Safety and Tolerability of a Daily Rectal Application of a 10 mg NRL001 Suppository for Seven Consecutive Days

Resource links provided by NLM:


Further study details as provided by Norgine:

Primary Outcome Measures:
  • Mean anal resting pressure and rectal compliance [ Time Frame: 7 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Rectal sensitivity [ Time Frame: 7 days ] [ Designated as safety issue: No ]
  • Adverse events [ Time Frame: 7 days ] [ Designated as safety issue: No ]
  • Plasma concentration over time [ Time Frame: 7 days ] [ Designated as safety issue: No ]

Enrollment: 14
Study Start Date: August 2010
Study Completion Date: December 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: NRL001
10 mg NRL001 in a 2 g suppository
Drug: NRL001
10 mg NRL001 in a 2 g suppository, administered once daily for 7 days
Placebo Comparator: Placebo
Matched placebo control
Drug: Placebo control
Matched placebo - administered as a 2 g suppository, once daily for 7 days

  Eligibility

Ages Eligible for Study:   40 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01175941

Locations
United Kingdom
Queens Medical Centre
Nottingham, Nottinghamshire, United Kingdom, NG7 2UH
Sponsors and Collaborators
Norgine
Investigators
Principal Investigator: Jonathan A Simpson, MD Nottingham University Hospital
  More Information

No publications provided

Responsible Party: Norgine
ClinicalTrials.gov Identifier: NCT01175941     History of Changes
Other Study ID Numbers: NRL001-01/2010 (MANO)
Study First Received: August 4, 2010
Last Updated: November 2, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Fecal Incontinence
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases

ClinicalTrials.gov processed this record on October 21, 2014