Faecal IncontinencePhase 2NCT01656720
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
A Phase 2 study testing 1R, 2S-methoxamine hydrochloride in people with Faecal Incontinence, run by Norgine at 51 sites in 9 countries.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Faecal Incontinence
- What is being tested?
- 1R, 2S-methoxamine hydrochloride
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 417 participants
- Where
- 51 sitesin 9 countries
- Study dates
- Feb 2012to Sep 2014
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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).
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- 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.
- 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.
Trial locations and contacts
51 sites in 9 countries.
51 sites in 9 countries
Poland10 sites
Nzoz Vitamed
Bydgoszcz, 85-079
General And Proctology Surgeon
Gdów, 32-420
Centrum Medyczne, Wyzszej Szkoly Informatycznej
Głowno, 95-015
Nzoz Mekmed S.C. Przychondnia Lekarska
Katowice, 40-079
Nzoz Mikomed
Lodz, 94-238
Osrodek Badawczo - Leczniczy Zbigniew Zegota
Ostróda, 14-100
Endoskopia
Sopot, 81-756
Lubelskie Centrum Diagnostyczne
Świdnik, 21-040
Lecznica Prosen SMO Private Medical Health Care Centre
Warsaw, 01-231
Ars Medica SC
Wroclaw, 53-333
Czechia8 sites
Fakultni Nemocnice BRNO
Brno, 620 00
Gastroenterologie S R O
Hradec Králové, 500 02
Krajska Nemocnice Liberec
Liberec, 130 00
Fakulni Nemocnice Kralovske
Prague, 100 34
Egk S.R.O Sanatoriu< Sv
Prague, 130 00
GEP Clinic S.R.O
Prague, 130 00
Fakultni Nemocnice V Motole
Prague, 150 06
Fakultni Nemocnice Na Bulovce, Gynekologicko-Porodnicka Klinika
Prague, 180 00
Hungary6 sites
PMC Pannon Medical Center
Budapest, H-1136
Polyclinic for Outpatients, Szakrendelo Intezet
Budapest, H-1183
University of Debrecen, Medical and Health Science Center
Debrecen, 4032
University of Szeged, Albert Szent-Gyorgyi Clinical Center, Faculty of Medicine
Szeged, 6720
Javorszky Odon Hopsital
Vac Argenti, H-2600
Csolnoky Ferenc Veszprem
Veszprém, H-8200
Italy6 sites
Chirurgia Gastroenterologica
Milan, 20132
Casa Di Cura San Pio X
Milan, 20159
Seconda Unita Operativa Di Chirurgia Generale
Pordenone, 33170
Dipartimento Emergenza Urgenza
Rome, 00161
Unita Operativa Complessa Gastroenteroloogia A
Rome, 00161
Unita Operativa Complessa Patologia Chirurgica A Indirizzo Gastroenterologico
Rome
France5 sites
Chu Bordeaux - Hopital St Andre
Bordeaux, 33000
Chu Lyon Groupement Hospitalier Edouard Herriot
Lyon, 69003
Chu Nantes - Hotel Dieu - Institut Des Maladies De L'Appareil Digestif (IMAD)
Nantes, 44093
Dr Laurent Siproudhis
Rennes
Chu Rouen - Hopital De Charles Nicolle
Rouen, 76031
Spain5 sites
Hospital Valle De Hebron
Barcelona, 08035
Hospital Clinic De Barcelona
Barcelona, 08036
USP, Hospital De Marbella
Málaga, 29603
Hospital De Mataro
Mataró, 08304
Hospital Clinico Universtiaria Lozana Blesa
Zaragoza, 50009
Sweden4 sites
Pelvic Floor Centre
Malmö, 205 02
Kirurgiska Kliniken Universitetssjukhuset
Örebro, 70362
Enheten For Nedre Abdominell Kirurgi
Stockholm, 141 86
Institute of Surgical Sciences
Uppsala, 75185
United Kingdom4 sites
St Mark's Hospital
London, HA1 3UJ
University College Hospital
London, NW1 2BU
Queens Medical Centre
Nottingham, NG7 2UH
Nothern General Hopsital
Sheffield, S5 7AU
Germany3 sites
Zentrum Fur Darm-Und Beckenchirurgie
Berlin, 14163
Martin-Luther-Krankenhaus
Berlin, 14193
Universitats-Frauenklink
Heidelberg, 69115
About this study
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
- Being tested
- 1R, 2S-methoxamine hydrochloride, Placebo
- Keywords
- Faecal Incontinence, Suppository, Wexner score
- Medical subject headings
- Encopresis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
1R, 2S-methoxamine hydrochlorideDrug
Also called NRL001
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Placebo 2g Suppository Receives: Drug: Placebo |
| NRL001 5mg | Active comparator | 5mg NRL001 in a 2g suppository Receives: Drug: 1R, 2S-methoxamine hydrochloride |
| NRL001 7.5mg | Active comparator | 7.5mg NRL001 in a 2g suppository Receives: Drug: 1R, 2S-methoxamine hydrochloride |
| NRL001 10mg | Active comparator | 10mg NRL001 in a 2g suppository Receives: Drug: 1R, 2S-methoxamine hydrochloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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
Measured: 8 weeks
To evaluate the population pharmacokinetics and to establish any pharmacokinetic/pharmacodynamic relationship with adverse events
Measured: 8 weeks
To evaluate the dose-response relationship in order to identify the appropriate dose(s) of NRL001 for future studies
Measured: 8 weeks
To evaluate the effect of treatment according to the patient's Faecal Incontinence Quality of Life questionnaire at 4 and 8 weeks
Measured: 8 weeks
To evaluate the effect of treatment according to the Vaizey score at 4 and 8 weeks
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2012 (estimated)
- Study startFeb 2012
- Primary completionDec 2013
- Study completionSep 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Faecal IncontinenceStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 417 participants (actual)
Sponsor and investigators
- Lead sponsor
- Norgine
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Laurent Siproudhis, MD, Principal investigator, Hopital Pontchaillou
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01656720
- Sponsor's protocol ID
- NRL001-01/2011 (SEFI)
- Status last verified
- Jun 2015
- First submitted
- 1 Aug 2012
- Last updated
- 9 Jun 2015
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01656720
- Acronym / sponsor ID
- NRL001-01/2011 (SEFI)
- Conditions
- Faecal Incontinence
- Keywords
- Faecal Incontinence, Suppository, Wexner score
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 417 participants (actual)
- Lead sponsor
- NorgineIndustry (pharma, biotech, devices)
- Study start
- Feb 2012
- Primary completion
- Dec 2013 (actual)
- Study completion
- Sep 2014 (actual)
- First posted
- 3 Aug 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the safety, tolerability and efficacy of NRL001 in the treatment of faecal incontinence, compared against placebo
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboPlacebo 2g Suppository |
| NRL001 5mg | Active comparator | Drug: 1R, 2S-methoxamine hydrochloride5mg NRL001 in a 2g suppository |
| NRL001 7.5mg | Active comparator | Drug: 1R, 2S-methoxamine hydrochloride7.5mg NRL001 in a 2g suppository |
| NRL001 10mg | Active comparator | Drug: 1R, 2S-methoxamine hydrochloride10mg NRL001 in a 2g suppository |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (26 listed)
- 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:
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 1R, 2S-methoxamine hydrochlorideAlso: NRL001 | Drug | NRL001 10mg, NRL001 5mg, NRL001 7.5mg |
| Placebo | Drug | Placebo |
Primary outcome
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
6 secondary outcomes
To provide data on the efficacy of NRL001 in patients with faecal incontinence over an 8 week treatment period
Time frame: 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
Time frame: 8 weeks
To evaluate the population pharmacokinetics and to establish any pharmacokinetic/pharmacodynamic relationship with adverse events
Time frame: 8 weeks
To evaluate the dose-response relationship in order to identify the appropriate dose(s) of NRL001 for future studies
Time frame: 8 weeks
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
To evaluate the effect of treatment according to the Vaizey score at 4 and 8 weeks
Time frame: 8 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2015.
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Iltamiocel Compared to Placebo for Chronic Fecal Incontinence in Females With Obstetric Injury
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Laurent Siproudhis, MD principal investigator
Hopital Pontchaillou
51 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 1R, 2S-methoxamine hydrochloride in people with Faecal Incontinence, run by Norgine at 51 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 51 sites in Poland, Czechia, Hungary, Italy, France and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jun 2015.