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

NCT01656720 | Completed Phase 2

• 1 other identifier: NRL001-01/2011 (SEFI)
• Study Type: interventional
• Target: 417
• Locations: 9 countries
• Sites: 51

Brief Summary

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

Conditions

Faecal Incontinence

Keywords

Faecal Incontinence; Suppository; Wexner score

Outcome Measures

Primary Outcomes (1)

• 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

  Up to 8 weeks

Secondary Outcomes (6)

• To provide data on the efficacy of NRL001 in patients with faecal incontinence over an 8 week treatment period

  8 weeks

• 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

  8 weeks

• To evaluate the population pharmacokinetics and to establish any pharmacokinetic/pharmacodynamic relationship with adverse events

  8 weeks

• To evaluate the dose-response relationship in order to identify the appropriate dose(s) of NRL001 for future studies

  8 weeks

• To evaluate the effect of treatment according to the patient's Faecal Incontinence Quality of Life questionnaire at 4 and 8 weeks

  8 weeks

Study Arms (4)

Placebo

PLACEBO COMPARATOR

Placebo 2g Suppository

Drug: Placebo

NRL001 5mg

ACTIVE COMPARATOR

5mg NRL001 in a 2g suppository

Drug: 1R, 2S-methoxamine hydrochloride

NRL001 7.5mg

ACTIVE COMPARATOR

7.5mg NRL001 in a 2g suppository

Drug: 1R, 2S-methoxamine hydrochloride

NRL001 10mg

ACTIVE COMPARATOR

10mg NRL001 in a 2g suppository

Drug: 1R, 2S-methoxamine hydrochloride

Interventions

1R, 2S-methoxamine hydrochloride DRUG

Also known as: NRL001

NRL001 10mg; NRL001 5mg; NRL001 7.5mg

Placebo DRUG

Placebo

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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:
• 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.
• 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.
• Fixed cardiac output states (severe aortic stenosis (AS), hypertrophic obstructive cardiomyopathy (HOCM).
• Significant mitral regurgitation (MR).
• 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.

Sponsors & Collaborators

• Norgine: lead

Study Sites (51)

Fakultni Nemocnice BRNO

Brno, 620 00, Czechia

Location

Gastroenterologie S R O

Hradec Králové, 500 02, Czechia

Location

Krajska Nemocnice Liberec

Liberec, 130 00, Czechia

Location

Fakulni Nemocnice Kralovske

Prague, 100 34, Czechia

Location

Egk S.R.O Sanatoriu< Sv

Prague, 130 00, Czechia

Location

GEP Clinic S.R.O

Prague, 130 00, Czechia

Location

Fakultni Nemocnice V Motole

Prague, 150 06, Czechia

Location

Fakultni Nemocnice Na Bulovce, Gynekologicko-Porodnicka Klinika

Prague, 180 00, Czechia

Location

Chu Bordeaux - Hopital St Andre

Bordeaux, 33000, France

Location

Chu Lyon Groupement Hospitalier Edouard Herriot

Lyon, 69003, France

Location

Chu Nantes - Hotel Dieu - Institut Des Maladies De L'Appareil Digestif (IMAD)

Nantes, 44093, France

Location

Dr Laurent Siproudhis

Rennes, France

Location

Chu Rouen - Hopital De Charles Nicolle

Rouen, 76031, France

Location

Zentrum Fur Darm-Und Beckenchirurgie

Berlin, 14163, Germany

Location

Martin-Luther-Krankenhaus

Berlin, 14193, Germany

Location

Universitats-Frauenklink

Heidelberg, 69115, Germany

Location

PMC Pannon Medical Center

Budapest, H-1136, Hungary

Location

Polyclinic for Outpatients, Szakrendelo Intezet

Budapest, H-1183, Hungary

Location

University of Debrecen, Medical and Health Science Center

Debrecen, 4032, Hungary

Location

University of Szeged, Albert Szent-Gyorgyi Clinical Center, Faculty of Medicine

Szeged, 6720, Hungary

Location

Javorszky Odon Hopsital

Vac Argenti, H-2600, Hungary

Location

Csolnoky Ferenc Veszprem

Veszprém, H-8200, Hungary

Location

Chirurgia Gastroenterologica

Milan, 20132, Italy

Location

Casa Di Cura San Pio X

Milan, 20159, Italy

Location

Seconda Unita Operativa Di Chirurgia Generale

Pordenone, 33170, Italy

Location

Dipartimento Emergenza Urgenza

Rome, 00161, Italy

Location

Unita Operativa Complessa Gastroenteroloogia A

Rome, 00161, Italy

Location

Unita Operativa Complessa Patologia Chirurgica A Indirizzo Gastroenterologico

Rome, Italy

Location

Nzoz Vitamed

Bydgoszcz, 85-079, Poland

Location

General And Proctology Surgeon

Gdów, 32-420, Poland

Location

Centrum Medyczne, Wyzszej Szkoly Informatycznej

Głowno, 95-015, Poland

Location

Nzoz Mekmed S.C. Przychondnia Lekarska

Katowice, 40-079, Poland

Location

Nzoz Mikomed

Lodz, 94-238, Poland

Location

Osrodek Badawczo - Leczniczy Zbigniew Zegota

Ostróda, 14-100, Poland

Location

Endoskopia

Sopot, 81-756, Poland

Location

Lubelskie Centrum Diagnostyczne

Świdnik, 21-040, Poland

Location

Lecznica Prosen SMO Private Medical Health Care Centre

Warsaw, 01-231, Poland

Location

Ars Medica SC

Wroclaw, 53-333, Poland

Location

Hospital Valle De Hebron

Barcelona, 08035, Spain

Location

Hospital Clinic De Barcelona

Barcelona, 08036, Spain

Location

Hospital De Mataro

Mataró, 08304, Spain

Location

USP, Hospital De Marbella

Málaga, 29603, Spain

Location

Hospital Clinico Universtiaria Lozana Blesa

Zaragoza, 50009, Spain

Location

Pelvic Floor Centre

Malmo, 205 02, Sweden

Location

Kirurgiska Kliniken Universitetssjukhuset

Örebro, 70362, Sweden

Location

Enheten For Nedre Abdominell Kirurgi

Stockholm, 141 86, Sweden

Location

Institute of Surgical Sciences

Uppsala, 75185, Sweden

Location

St Mark's Hospital

London, HA1 3UJ, United Kingdom

Location

University College Hospital

London, NW1 2BU, United Kingdom

Location

Queens Medical Centre

Nottingham, NG7 2UH, United Kingdom

Location

Nothern General Hopsital

Sheffield, S5 7AU, United Kingdom

Location

MeSH Terms

Conditions

Encopresis

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Behavioral Symptoms; Behavior; Elimination Disorders; Mental Disorders

Study Officials

• Laurent Siproudhis, MD

  Hopital Pontchaillou

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 1, 2012
• First Posted: August 3, 2012
• Study Start: February 1, 2012
• Primary Completion: December 1, 2013
• Study Completion: September 1, 2014
• Last Updated: June 9, 2015

Record last verified: 2015-06

Locations

HU (6); PL (10); GB (4); CZ (8); IT (6); ES (5); DE (3); SE (4); FR (5)