PK, PD and Safety Comparative Trial of Isosorbide Mononitrate Gel in Healthy Participants and With Anal Fissure

Pharmacokinetics, Pharmacodynamics and Safety Comparative Trial of Isosorbide Mononitrate Gel in Participants With Anal Fissure and Healthy Volunteers.

This is a Phase I trial to evaluate Pharmacokinetics, Pharmacodynamics and Safety of Isosorbide Mononitrate gel for usage in participants with anal fissure and healthy volunteers. Three doses will be used in patients with anal fissure (0.5%, 1.0% or 2.0%) and healthy volunteers will receive 2.0% dose. All treatment will last 7 days.

Study Overview

• Status: Withdrawn
• Conditions: Anal Fissure
• Intervention / Treatment: Drug: Isosorbide Mononitrate

Detailed Description

This is a Phase I, open-label, parallel trial to evaluate Pharmacokinetics, Pharmacodynamics and Safety of Isosorbide Mononitrate gel for usage in participants with anal fissure and healthy volunteers.

Investigational product will be randomly assigned as follows:

• healthy volunteers will receive 2g (2.0%) of investigational product at a single dose, and will undergo a washout period of 7 days; subsequently, they will receive 2g of investigational product once daily, for 7 consecutive days;
• participants with anal fissure will receive 2g of investigational product, either at 0.5%, 1.0% or 2.0%, at a single dose, and will undergo a washout period of 7 days; subsequently, they will receive 2g of investigational product, either at 0.5%, 1.0% or 2.0%, once daily, for 7 consecutive days.

• Study Type: Interventional
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female subjects aged ≥ 18 years-old;
• Body mass index (BMI) ≥ 19 Kg/m2 and ≤ 35 Kg/m2;
• For healthy volunteers: good health conditions or without significant diseases, according to best medical judgement, according to protocol requirements and study evaluations: medical history, blood pressure and heart rate measurements, physical examination, electrocardiogram (ECG) and screening laboratory tests;
• For participants with the condition under study: anal fissure;
• Ability to understand the nature and objectives of the trial, including risks and adverse events; willingness to cooperate with the researcher and proceed according to all study requirements, which shall be confirmed by Informed Consent Form signature.

Exclusion Criteria:

• Known hypersensitivity to the investigational products (naproxen or rebamipide) or chemically related compounds; history of serious adverse reactions or hypersensitivity to any drug;
• Chronic therapy with any drugs, except oral contraceptives and medication authorized by principal investigator (each case to be individually evaluated);
• History of hepatic, kidney, lungs, gastrointestinal, epileptic, hematologic or psychiatric disease; hypotension or hypertension, or any other co-morbidity that requires priority immediate treatment ot that, at principal investigator discretion, might interfere with study participation or expose study participant to risks other than predicted;
• Deviations on screening laboratory results that are considered as clinically relevant by the principal investigator;
• Smoking;
• History of drugs and alcohol addiction or excessive alcohol consumption (> 35 g/ day);
• Use of regular medications within 2 weeks prior study enrollment or use of any medications within one week prior to study enrollment, except oral contraceptives or cases which, based on drug's or metabolite's half-life, complete elimination can be assumed;
• Treatment, within 6 months before the trial, with any drugs known to have a well established toxic potential to major organs;
• Participation in any other experimental research or administration of any experimental drug within six months before this trial;
• Donation or loss of 450 mL of blood (or more) within 3 months before the trial, or 4 donations within 12 months before the trial;
• Any condition, according to investigator's best judgement, that prevents the subject to participate in the trial;
• Pregnancy, labor or miscarriage with 12 weeks before admission predicted date.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Isosorbide Mononitrate 2.0% healthy; Isosorbide Mononitrate gel 2.0% - 2g Anorectal usage Once daily Healthy volunteers	Drug: Isosorbide Mononitrate; Healthy volunteers will receive 2g (2.0%) of investigational product at a single dose, and will undergo a washout period of 7 days; subsequently, they will receive 2g of investigational product once daily, for 7 consecutive days. Participants with anal fissure will receive 2g of investigational product, either at 0.5%, 1.0% or 2.0%, at a single dose, and will undergo a washout period of 7 days; subsequently, they will receive 2g of investigational product, either at 0.5%, 1.0% or 2.0%, once daily, for 7 consecutive days.
Experimental: Isosorbide Mononitrate 0.5% anal fissure; Isosorbide Mononitrate gel 0.5% - 2g Anorectal usage Once daily Participants with anal fissure	Drug: Isosorbide Mononitrate; Healthy volunteers will receive 2g (2.0%) of investigational product at a single dose, and will undergo a washout period of 7 days; subsequently, they will receive 2g of investigational product once daily, for 7 consecutive days. Participants with anal fissure will receive 2g of investigational product, either at 0.5%, 1.0% or 2.0%, at a single dose, and will undergo a washout period of 7 days; subsequently, they will receive 2g of investigational product, either at 0.5%, 1.0% or 2.0%, once daily, for 7 consecutive days.
Experimental: Isosorbide Mononitrate 1.0% anal fissure; Isosorbide Mononitrate gel 1.0% - 2g Anorectal usage Once daily Participants with anal fissure	Drug: Isosorbide Mononitrate; Healthy volunteers will receive 2g (2.0%) of investigational product at a single dose, and will undergo a washout period of 7 days; subsequently, they will receive 2g of investigational product once daily, for 7 consecutive days. Participants with anal fissure will receive 2g of investigational product, either at 0.5%, 1.0% or 2.0%, at a single dose, and will undergo a washout period of 7 days; subsequently, they will receive 2g of investigational product, either at 0.5%, 1.0% or 2.0%, once daily, for 7 consecutive days.
Experimental: Isosorbide Mononitrate 2.0% anal fissure; Isosorbide Mononitrate gel 2.0% - 2g Anorectal usage Once daily Participants with anal fissure	Drug: Isosorbide Mononitrate; Healthy volunteers will receive 2g (2.0%) of investigational product at a single dose, and will undergo a washout period of 7 days; subsequently, they will receive 2g of investigational product once daily, for 7 consecutive days. Participants with anal fissure will receive 2g of investigational product, either at 0.5%, 1.0% or 2.0%, at a single dose, and will undergo a washout period of 7 days; subsequently, they will receive 2g of investigational product, either at 0.5%, 1.0% or 2.0%, once daily, for 7 consecutive days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics, area under the curve time zero - last (AUC t0-last)	7 days
Pharmacokinetics, area under the curve time zero - infinite (AUC t0-inf)	7 days
Pharmacokinetics, constant of elimination (Ke)	7 days
Pharmacokinetics, half-life (t1/2)	7 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety, by number of adverse events	7 days
Safety, by blood pressure measurement	7 days
Anorectal muscle contractility, by anorectal manometry	7 days

Collaborators and Investigators

• Sponsor: Biolab Sanus Farmaceutica
• Investigators: Principal Investigator: Gilberto De Nucci, PhD, Galeno Desenvolvimento de Pesquisas

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2017
• Primary Completion (Anticipated): October 1, 2017
• Study Completion (Anticipated): November 1, 2017

Study Registration Dates

• First Submitted: January 26, 2016
• First Submitted That Met QC Criteria: January 26, 2016
• First Posted (Estimate): January 29, 2016

Study Record Updates

• Last Update Posted (Actual): July 17, 2017
• Last Update Submitted That Met QC Criteria: July 13, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases; Anus Diseases; Fissure in Ano; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Natriuretic Agents; Diuretics, Osmotic; Diuretics; Nitric Oxide Donors; Isosorbide; Isosorbide Dinitrate; Isosorbide-5-mononitrate
• Other Study ID Numbers: GDN 001/16

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No