Clinical trial NCT06593730: Safety and Tolerability of the Twice Daily Intra-anal Application of NRL001 Cream for 14 Days
Official title: Double-blind, Placebo-controlled, Randomised, Parallel-group Study in Healthy Volunteers to Evaluate the Safety, Tolerability, Pharmacodynamic Effects and Pharmacokinetics of Twice Daily Intra-anal Application of NRL001-cream for 14 Days.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Faecal Incontinence
Lead sponsor: Norgine
Sponsor class: INDUSTRY
First posted: 2024-09-19
Enrollment: 72
Sex: ALL
Minimum age (years): 35
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

Primary outcomes:
measure: Recumbent and standing blood pressure and pulse rate
timeFrame: 17 days
measure: Ambulatory 24 hour BP monitoring
timeFrame: 17 days
measure: 12-lead digital resting ECG
timeFrame: 17 days
measure: 3-lead ambulatory 24 hour ECG monitoring
timeFrame: 17 days
Secondary outcomes:
measure: Plasma concentrations of NRL001
timeFrame: 17 days
measure: Well being
timeFrame: 17 days
measure: Adverse events
timeFrame: 17 days
Other outcomes:
Locations:
Study officials:
References: