Safety and Tolerability of a Single Intra-anal Dose of NRL001 in Healthy Volunteers

Study Overview
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Brief Summary
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This study is conducted to explore the safety and tolerability and plasma pharmacokinetics of NRL001 after single intra-anal dose of 1mL cream at increasing concentrations.

Official Title
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A Randomised, Placebo-controlled, Double-blind, Cross-over Study in Healthy Men and Women to Evaluate the Safety, Tolerability and Pharmacokinetics of Single Intra-anal Doses of NRL001 for Three Doses Using a Cream Formulation Relative to a Matched Placebo Formulation for Reference

Conditions
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Fecal Incontinence

Intervention / Treatment
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* Drug: Placebo control
* Drug: NRL001 cream


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: IN.1) sex: male and female (non-child-bearing potential or using medically adequate contraception IN.2) race: Caucasian IN.3) BW: 50 - 100 kg IN.4) BMI: 20 - 28 kg.m-2 IN.5) age: 21 - 50 years IN.6) type: healthy on the basis of specified criteria evaluated at the screening visit IN.7) willing and able to provide informed consent Exclusion Criteria: General EX.1) Previous participation in the trial EX.2) Participant in any other trial during the last 90 days EX.3) Donation of blood during the last 60 days or a history of blood loss exceeding 300 mL within the last 3 months EX.4) History of any clinically relevant allergy (including hypersensitivity to the trial medications) EX.5) Presence of acute or chronic infection EX.6) Presence or history of any relevant co-morbidity EX.7) Resting systolic blood pressure > 140 or < 90 mmHg, diastolic blood pressure > 95 or < 50 mmHg EX.8) Clinically relevant ECG-abnormalities, prolonged QTc with > 450 msec in males and > 460 msec in females in particular EX.9) Presence of any relevant abnormality in the laboratory safety tests, especially low haemoglobin, increased liver enzymes EX.10) Positive serology for HBsAg, anti HBc and anti HCV EX.11) Positive HIV test EX.12) Positive alcohol or urine drug test on recruitment (and upon admission) EX.13) History of alcohol and/or drug abuse and/or daily use of > 30 gr alcohol EX.14) Smoking more than 15 cigarettes/day or equivalent of other tobacco products EX.15) Use of prohibited medication EX.16) Suspicion or evidence that the subject is not trustworthy and reliable EX.17) Suspicion or evidence that the subject is not able to make a free consent or to understand the information in this regard General - all females EX.18) Positive pregnancy test EX.19) Lactating EX.20) Not using appropriate contraception in pre-menopausal women (note: under the conditions of the present study, women using hormonal contraceptives will be informed that this method is not sufficient during the study and that further i.e. mechanical methods [condom, diaphragm with spermicidal gel] should be used in addition).

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control<br>Placebo control | Drug: Placebo control<br>* Placebo cream<br>|
| Experimental: Low dose NRL001<br>0.5% NRL001 cream | Drug: NRL001 cream<br>* Cream for single-dose intra-anal application<br>|
| Experimental: Intermediate dose NRL001<br>0.75% NRL001 cream | Drug: NRL001 cream<br>* Cream for single-dose intra-anal application<br>|
| Experimental: High dose NRL001<br>1.0% NRL001 cream | Drug: NRL001 cream<br>* Cream for single-dose intra-anal application<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax of NRL001 |  | 30 mins, 1, 2, 3, 4, 5, 6, 8 and 12 hours after dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC of NRL001 |  | 30 mins, 1, 2, 3, 4, 5, 6, 8 and 12 hours after dosing | 
| Tolerability of NRL001 | Spontaneously reported adverse events will be recorded | Up to 12 hours post-dosing |