Faecal Incontinence
Conditions
Brief summary
The study is being conducted to evaluate the safety and tolerability after single and repeated twice daily intra-anal applications of 1mL NRL001 cream in stepwise increasing concentrations.
Detailed description
Single-centre, randomised, placebo-controlled, double-blind, repeated dose study in healthy male and female volunteers, comprising up to six sequential dose groups receiving 1 mL doses of an investigational cream formulation containing 0.50, 0.75, 1.00, 1.50, 2.00 and 2.50% w/w NRL001. Doses were to be investigated in stepwise increasing fashion. Progression to a higher dose-step required completion of the previous dose-step without safety limiting findings. Each dose-step was to be investigated in 12 subjects; in each dose-group, subjects assigned to active treatment were to be studied in parallel with subjects assigned to placebo in double-blind fashion with random (9:3) treatment assignment. Each subject was to be studied for one study period with double-blind investigational treatment (1 mL of an investigational cream formulation containing NRL001 or matched placebo) twice daily from the morning of D01 to the afternoon of D14; this phase was to be preceded by a single-blind placebo control day (D-1) with administration of placebo in the morning and afternoon.
Interventions
DRUGNRL001 cream 0.5%w/w
DRUGNRL001 cream 0.75%w/w
DRUGNRL001 cream 1.0%w/w
DRUGNRL001 cream 1.5%w/w
DRUGNRL001 cream 2.0%w/w
DRUGNRL001 cream 2.5%w/w
Sponsors
Norgine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
35 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Males or females (only females of non-child-bearing potential or of child-bearing potential while taking medically appropriate contraception) * Caucasian * 35 to 60 years of age (included) * BMI: between 22 and 26 kg.m-2 * BW: between 50 and 100 kg * Willing and able to provide written informed consent
Exclusion criteria
General - all subjects * Previous participation in the trial * Participation in any other trial during the last 90 days * Donation of blood or plasma within the last 90 days before recruitment * History of any clinically relevant allergy * Presence of acute or chronic infection * Presence or history of any relevant medical condition or disease (as evaluated on the basis of medical history, physical examination, recumbent and standing blood pressure, treadmill ergometry, clinical laboratory tests \[haematology, clinical chemistry, urinalysis, serology\]) * Presence or history of migraine, frequent headaches, Raynaud phenomenon, urinary urge, signs and symptoms of prostatism * Presence or history of regular/habitual diarrhoea or constipation; previous anal surgery or trauma, anal fissures, rectal disorders * Resting systolic blood pressure \> 145 or \< 90 mmHg, diastolic blood pressure \> 95 or \< 50 mmHg * Positive treadmill ergometry test * Resting pulse (PR) or electrocardiographic heart rate (HR) \< 55 bpm * ECG: AV-block (AV-block grade I included), QT \> 480 msec, QTc \> 450 msec, sick-sinus syndrome * Positive hepatitis (HBs-Ag or HBc-Ab, HCV-Ab) or HIV serology test * History of alcohol or (social) drug abuse * Positive alcohol or urine drug test * Daily consumption of \> 30 g alcohol * Smoking more than 15 cigarettes/day or equivalent of other tobacco products * Use of prohibited medication * Suspicion or evidence that the subject is not reliable * Suspicion or evidence that the subject is not able to make a free consent or to understand the information detailed in the Subject Information sheet. All females * Positive pregnancy test * Lactating * Premenopausal women : not using contraception which is judged adequate and sufficient in the opinion of the clinical investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recumbent and standing blood pressure and pulse rate | 17 days | BP and pulse taken lying and standing at screening, on control day and profiling days |
| Ambulatory 24 hour BP monitoring | 17 days | Ambulatory 24 hour BP monitoring on control day and profiling days |
| 12-lead digital resting ECG | 17 days | 12-lead digital resting ECG at screening, on control day and profiling days |
| 3-lead ambulatory 24 hour ECG monitoring | 17 days | 24 hour HOLTER monitoring at screening, on control day and profiling days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Well being | 17 days | Any untoward change in health and/or wellbeing |
| Adverse events | 17 days | Any unwanted sign or symptom |
| Plasma concentrations of NRL001 | 17 days | Single and repeat dose pharmacokinetics of NRL001 in plasma |
Outcome results
None listed