A Multi-centre, Phase II, Double-blind, Randomised, Placebo-controlled, Parallel Group, Dose-ranging Study in Patients With Faecal Incontinence; to Evaluate the Efficacy, Safety and Tolerability of Locally Applied NRL001 Over an 8 Week Treatment Period

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2013 by Norgine
Sponsor:
Information provided by (Responsible Party):
Norgine
ClinicalTrials.gov Identifier:
NCT01656720
First received: August 1, 2012
Last updated: July 25, 2013
Last verified: July 2013
  Purpose

The purpose of this study is to evaluate the safety, tolerability and efficacy of NRL001 in the treatment of faecal incontinence, compared against placebo


Condition Intervention Phase
Faecal Incontinence
Drug: 1R, 2S-methoxamine hydrochloride
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Multi-centre, Phase II, Double-blind, Randomised, Placebo-controlled, Parallel Group, Dose-ranging Study in Patients With Faecal Incontinence; to Evaluate the Efficacy, Safety and Tolerability of Locally Applied NRL001 Over an 8 Week Treatment Period

Resource links provided by NLM:


Further study details as provided by Norgine:

Primary Outcome Measures:
  • Evaluate the efficacy of NRL001 in faecal incontinence by assessing the improvement of the incontinence status after 4 weeks of treatment compared to baseline by means of the Wexner score [ Time Frame: Up to 8 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To provide data on the efficacy of NRL001 in patients with faecal incontinence over an 8 week treatment period [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • To provide preliminary data on the safety and tolerability of NRL001 (5mg, 7.5mg and 10mg) over an 8 week treatment period compared to placebo [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • To evaluate the population pharmacokinetics and to establish any pharmacokinetic/pharmacodynamic relationship with adverse events [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • To evaluate the dose-response relationship in order to identify the appropriate dose(s) of NRL001 for future studies [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • To evaluate the effect of treatment according to the patient's Faecal Incontinence Quality of Life questionnaire at 4 and 8 weeks [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • To evaluate the effect of treatment according to the Vaizey score at 4 and 8 weeks [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 580
Study Start Date: February 2012
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Placebo 2g Suppository
Drug: Placebo
Active Comparator: NRL001 5mg
5mg NRL001 in a 2g suppository
Drug: 1R, 2S-methoxamine hydrochloride
Other Name: NRL001
Active Comparator: NRL001 7.5mg
7.5mg NRL001 in a 2g suppository
Drug: 1R, 2S-methoxamine hydrochloride
Other Name: NRL001
Active Comparator: NRL001 10mg
10mg NRL001 in a 2g suppository
Drug: 1R, 2S-methoxamine hydrochloride
Other Name: NRL001

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • An ultrasound assessment of the internal anal sphincter within the previous 12 months confirming an intact circular internal sphincter with minimal scars (maximum 60 degrees scarring circumferentially).
  • Diagnosis of faecal incontinence with a Wexner score of 8 - 20 inclusive at Visit 1 - Screening Visit.
  • Historical clinical evidence (past 6 months prior to Visit 1 - Screening Visit) of faecal incontinence episodes (solids, liquid, gas or mucus).
  • Greater than or equal to two faecal incontinence episodes (solids, liquid, gas or mucus) per week during the 4 week historical period prior to Visit 1 - Screening Visit.
  • Able and willing to receive rectal examinations and treatments.
  • Patients must be aged >18 without significant acute or uncontrolled chronic disease.
  • Patients must understand the purpose and risks of the study and be able to provide written informed consent and willing, able and competent to complete the entire study and comply with study instructions as defined in the protocol.
  • Female patients must be postmenopausal (for at least one year and confirmed by serum FSH at screening), or surgically sterile, practicing true sexual abstinence, or using Investigator-approved methods of contraception throughout the study until after the post study physical examination and have a negative pregnancy test at screening.
  • Sexually active male patients must use condoms with their partners throughout the study and for 90 days after completion of the study in addition to their partner's normal mode of contraception.
  • Male patients must not donate sperm during the study and for 90 days after the completion of the study.
  • Patients taking any continuous medication need to have been on a stable regimen for at least 1 month prior to Visit 1 - Screening Visit.

Exclusion Criteria:

  • External anal sphincter disruption related to faecal incontinence caused by trauma.
  • Patients with complicating gastrointestinal (GI) disease including those with inflammatory bowel diseases, patients that have received radiotherapy or surgery for anal cancer, patients with rectal prolapse, transanal surgery.
  • Relevant history of or presence of any significant or uncontrolled cardiovascular risk including:

    1. Systolic > 160mmHg or Diastolic > 100mmHg. Patients on a stable regimen for > 3 months with controlled hypertension prior to Visit 1 - Screening Visit (Systolic < 140mmHg or Diastolic < 90mmHg) can be included.
    2. Abnormal 24 hour Screening Holter: corrected QT interval (QTcf) prolongation with cut-off values of >460 ms for females and >430 ms for males, acute arrhythmia, nocturnal bradycardia with heart rate (HR) < 40bpm, atrial fibrillation, AV block Type II and III, Sick Sinus Syndrome, vasovagal syncope.
    3. Fixed cardiac output states (severe aortic stenosis (AS), hypertrophic obstructive cardiomyopathy (HOCM).
    4. Significant mitral regurgitation (MR).
    5. Cardiac failure (New York Heart Association (NYHA) stage II-IV).
  • Severe or uncontrolled asthma or chronic obstructive pulmonary disease determined by clinical history, physical examination, lung function tests or exercise tolerance
  • Chronic liver disease (e.g. liver cirrhosis, chronic hepatitis, severe hepatic insufficiency).
  • Vascular claudication after <50 metres walking distance.
  • Severe renal impairment defined as glomerular filtration rate (GFR) ≤ 30 ml/min, uncontrolled and reno-vascular end stage renal disease.
  • Patients with diabetic polyneuropathies.
  • Any type of chronic diarrhoea or frequent diarrhoea (defined as >5 loose stools per day).
  • Faecal impaction and overflow diarrhoea.
  • Male patients with clinically diagnosed prostatic hyperplasia.
  • Clinically significant electrolyte abnormalities, e.g. clinically significant low/high potassium and low sodium.
  • Presence of clinical symptomatic haemorrhoids (grade III and IV), anal fissures or anorectal fistulas.
  • Less than 2 episodes of faecal incontinence (solids, liquid, gas or mucus) per week during the 4 week historical period prior to Visit 1 - Screening Visit.
  • Participation in a clinical drug study during the 90 days preceding the initial dose in this study.
  • Known history of allergy to methoxamine or any other ingredients of the Investigational Medicinal Product.
  • Patients who, in the opinion of the Investigator, are unsuitable for participation in the study due to any dependencies, general medical conditions or significant illness within two weeks prior to randomisation.
  • Use of any disallowed concomitant medication or other medication that the Investigator believes may affect the study including over-the-counter (OTC) products within 30 days prior to the Investigational Medicinal Product administration.
  • A personal or family history of QTcf prolongation or sudden death.
  • Patients taking Loperamide (2mg) >8 tablets per day for faecal incontinence either alone or in combination with codeine phosphate and/or paracetamol (8/500mg).
  • Patients using any device for the treatment of faecal incontinence.
  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: NCT01656720

Contacts
Contact: Deborah J Jones, BSc(Hons) +44189582 ext 6636 djones3@norgine.com
Contact: Richard Ng Kwet Shing, MD +44189545 ext 3584 rng@norgine.com

  Show 51 Study Locations
Sponsors and Collaborators
Norgine
Investigators
Principal Investigator: Laurent Siproudhis, MD Hopital Pontchaillou
  More Information

No publications provided

Responsible Party: Norgine
ClinicalTrials.gov Identifier: NCT01656720     History of Changes
Other Study ID Numbers: NRL001-01/2011 (SEFI)
Study First Received: August 1, 2012
Last Updated: July 25, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Norgine:
Faecal Incontinence
Suppository
Wexner score

Additional relevant MeSH terms:
Fecal Incontinence
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Methoxamine
Adrenergic Agents
Adrenergic Agonists
Adrenergic alpha-1 Receptor Agonists
Adrenergic alpha-Agonists
Autonomic Agents
Cardiovascular Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sympathomimetics
Therapeutic Uses
Vasoconstrictor Agents

ClinicalTrials.gov processed this record on October 21, 2014