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

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

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.

Study Overview

• Status: Completed
• Conditions: Fecal Incontinence
• Intervention / Treatment: Drug: Placebo control; Drug: NRL001 cream

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Bulgaria
  • Sofia, Bulgaria
    • University Hospital MHAPT Zaritza Johanna

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Control; Placebo control	Drug: Placebo control; Placebo cream
EXPERIMENTAL: Low dose NRL001; 0.5% NRL001 cream	Drug: NRL001 cream; Cream for single-dose intra-anal application
EXPERIMENTAL: Intermediate dose NRL001; 0.75% NRL001 cream	Drug: NRL001 cream; Cream for single-dose intra-anal application
EXPERIMENTAL: High dose NRL001; 1.0% NRL001 cream	Drug: NRL001 cream; Cream for single-dose intra-anal application

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Norgine
• Investigators: Study Director: Hans Gruss, MD PhD, Norgine

Study record dates

Study Major Dates

• Study Start: April 1, 2007
• Primary Completion (ACTUAL): May 1, 2007
• Study Completion (ACTUAL): June 1, 2007

Study Registration Dates

• First Submitted: July 29, 2011
• First Submitted That Met QC Criteria: July 29, 2011
• First Posted (ESTIMATE): August 1, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): August 1, 2011
• Last Update Submitted That Met QC Criteria: July 29, 2011
• Last Verified: July 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases; Fecal Incontinence
• Other Study ID Numbers: NRL001-02/2006(SD)