Pharmacokinetics Trial of Isosorbide Mononitrate 0.5% Gel for Intra Anal Application in Healthy Subjects

Phase I Clinical Trial to Evaluate the Pharmacokinetic Profile of a Formulation With Isosorbide Mononitrate 0.5% Gel - Manufactured by Sanus Pharmaceutical Ltda, to Intra Anal Application in Healthy Males and Females' Subjects

This is a Phase I trial to evaluate pharmacokinetics and safety of Isosorbide Mononitrate gel for intra anal administration in healthy subjects.

Study Overview

• Status: Withdrawn
• Conditions: Healthy Subjects; Pharmacokinetics
• Intervention / Treatment: Drug: Isosorbide mononitrate

Detailed Description

This is a Phase I trial to evaluate the pharmacokinetics and safety of Isosorbide Mononitrate gel for intra anal administration. For the current study 2g of a 0,5% gel will be used (as part of a safety investigational profile with doses up to 2% in other studies).

The investigational product will be administered to the participants by the study physician as a single dose. Blood samples will be collected prior dose and up to 36:00 hours to characterize the pharmacokinetic profile.

Safety parameters, including adverse events, will be monitored by the study team during confinement (up to 24 hours post dose), at the 36 hour sample collection (ambulatory basis) and as reported by the subjects or verified at the discharge visit, up to 15 days after dosing.

• Study Type: Interventional
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female subjects aged from 18 to 50 years-old;
• Good health conditions or without significant diseases, according to medical judgement, according to protocol requirements and study evaluations: medical history, blood pressure and heart rate measurements, physical examination, electrocardiogram (ECG) and screening laboratory test;
• Ability to understand the nature and objectives of the trial, including risks and adverse events;
• Willingness to proceed according to all study requirements, which shall be confirmed by Informed Consent Form signature;
• Agree to use safe contraceptive method.

Exclusion Criteria:

• Known to have hypersensitivity reaction to the studied drug or to chemically related compounds;
• History or presence of chronic gastrointestinal diseases or other condition that may interfere with drug absorption, distribution, metabolism or excretion;
• Maintenance therapy with any drug known to interact with the investigational drug, except contraceptives;
• History of liver, kidney, lung, gastrointestinal, epileptic, haematological or psychiatric disease; hypertension of any etiology; history of myocardial infarction, angina and / or heart failure or malignant neoplasms. Have any current disease, acute or chronic, in follow-up or treatment;
• Have active orificial pathology, such as hemorrhoidal thrombosis, acute or chronic anal fissures, as assessed by the study physician within 15 days from confinement;
• Electrocardiographic findings not recommended at the physician's discretion to participate in the study;
• History of cardiac (any), renal (renal exeresis or agenesis), gastrointestinal (partial or total removal of the esophagus, stomach, duodenum, jejunum, ileum, ascending colon, transverse colon, descending colon, sigmoid or rectum), liver or pancreas surgery;
• Screening laboratory test results outside normal ranges set by the clinical analysis laboratory, unless considered non-clinically significant by the Principal Investigator / Physician;
• Smoker (more than five cigarettes / day);
• Eating foods containing xanthine, including more than five cups of coffee or tea per day;
• Unusual eating habits, eg vegetarians;
• History of excessive alcohol consumption (drinking 4 or more alcoholic beverages in one day or 8 or more alcoholic beverages per week for women and 5 or more alcoholic beverages in one day or 15 or more alcoholic beverages per week for men);
• History of drug use;
• Use of regular medication within two weeks prior to initiation of treatment and the date of pre-confinement clinical assessment;
• Use of medication containing sildenafil, vardenafil or riociguate, up to 03 days before confinement;
• Use medication containing tadalafil up to 08 days before confinement;
• Use of any medication, except contraceptives or cases where, based on the half-life of the drug and / or active metabolites, complete elimination may be assumed;
• Hospitalization due to any reason up to eight weeks before the start of the trial treatment;
• Treatment with any drug known to have well established toxic potential in the large organs, within three months prior to the study;
• Participation in any other experimental research or administration of any experimental drug within six months prior to the commencement of this trial;
• Pregnancy or breastfeeding or wish to become pregnant during the trial period;
• Donation or loss of 450 mL or more of blood within the three months prior to the trial or donation of more than 1500 mL within the twelve months preceding the trial;
• Any condition that, according to the investigator's best judgement, precludes participation in this trial;
• Inability to lie down, preferably on the side, for 1 hour or as long as necessary at the doctor's discretion;
• Positive test for pregnancy;
• Breathalyzer test result greater than zero;
• Positive result for drug of abuse testing;
• Unavailability for registration on the National Register for Bioequivalence Studies (CNVB)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Test Drug; Isosorbide 0.5% gel	Drug: Isosorbide mononitrate; Intra-anal application performed by the study physician of 2 g of the study drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the plasma concentration versus time curve from time zero to last (AUC 0-last)		36 hours
Area under the plasma concentration versus time curve from time zero to infinite (AUC 0-inf)		36 hours
Maximum (peak) plasma concentration (Cmax)		36 hours
Time to reach maximum (peak) plasma concentration (Tmax)	Time frame from drug administration to sampling time of maximum plasma concentration	36 hours
Elimination rate constant (Ke)		36 hours
Half life (t1/2)		36 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of adverse events		15 days
Blood Pressure	Blood pressure (Systolic and Diastolic Blood Pressure) pre-dose, at each hour until 12 hours after dose and 24 hours after dose	1 day
Pulse	Pulse pre-dose, at each hour until 12 hours after dose and 24 hours after dose	1 day

Collaborators and Investigators

• Sponsor: Biolab Sanus Farmaceutica
• Investigators: Principal Investigator: José Pedrazzoli Jr., MD, CAEP - Centro Avancado de Estudos e Pesquisas Ltda.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 20, 2020
• Primary Completion (ACTUAL): December 20, 2020
• Study Completion (ACTUAL): December 20, 2020

Study Registration Dates

• First Submitted: January 25, 2021
• First Submitted That Met QC Criteria: January 27, 2021
• First Posted (ACTUAL): January 28, 2021

Study Record Updates

• Last Update Posted (ACTUAL): February 1, 2021
• Last Update Submitted That Met QC Criteria: January 28, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Healthy volunteers; Pharmacokinetics; Anal Fissure; Isosorbide Mononitrate; Intra anal application
• Additional Relevant MeSH Terms: 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: CAEP 56.003.19PC

Drug and device information, study documents

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