Evaluation of the Bioavailability of Methylprednisolone

Sponsor

Edda Sciutto Conde (Other)

Overall Status

Completed

CT.gov ID

NCT05649878

Collaborator

(none)

Enrollment

Location

Arms

Actual Duration (Days)

34.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is aimed to evaluate the bioavailability of methylprednisolone in healthy subjects of both genders, with administration intranasally versus intravenous

Condition or Disease	Intervention/Treatment	Phase
Methylprednisone Administration Intranasal Administration Intravenous Administration Healthy Subjects	Drug: Evaluation of bioavailability of methylprednisolone succinate administered intravenously Drug: Evaluation of bioavailability of methylprednisolone succinate administered intranasally	N/A

Detailed Description

The most important property of a drug dosage is its ability to deliver the active ingredient to the site of action in a quantity sufficient to exert the expected pharmacological effect. This ability is known as bioavailability. Methylprednisolone is a drug with wide clinical use in patients with inflammatory pathologies (infectious or non-infectious). The main routes of administration are oral and intravenous. The intranasal route could be one more effective, less invasive that would allow to obtain a faster therapeutic concentration and in greater concentration in the lungs and in the central nervous system than the intravenous route, maintaining very similar systemic concentrations to those achieved intravenously. For these reasons, it is important to know the bioavailability of methylprednisolone administered by this route in order to establish the best dosing regimen. The pilot study is of an exploratory nature (descriptive, comparative or informative), whose objective is to know the pharmacokinetic characteristics of a new route of administration of a drug in the study population to establish the pharmacokinetic parameters, and the comparison between the intranasal bioavailability against the intravenous administration by determining confidence intervals and calculating one-sided double t of Scuirmann.

Objetive: To evaluate the bioavailability of methylprednisolone in healthy subjects of both genders, with administration intranasally versus intravenous dose of 1 ml of methylprednisolone sodium succinate equivalent to 62.5 mg of methylprednisolone.

Study Design

Study Type:

Interventional

Actual Enrollment :

8 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

A single dose design was used, with 8 subjects under fasting conditions, two periods, two sequences, open, crossed with blocks scheme A-B and B-A, randomized, longitudinal, comparative and prospective, with a washout period of seven days between the two study sessions. The treatment groups were balanced, having an equal number of subjects who were randomly assigned to the administration sequences of the drug under study. MEP sodium succinate was administered intravenously (1 mL, equivalent to 62.5 mg of Methylprednisolone) or the same dose intranasally by 2 using a Mucosal Atomization Device (MAD Nasal). The nominal doses were similar, allowing direct pharmacokinetic comparison without dose normalization. Venous blood samples were obtained via an indwelling catheter before administration at different times. Plasma was separated and frozen at -70 °C for further analysis.A single dose design was used, with 8 subjects under fasting conditions, two periods, two sequences, open, crossed with blocks scheme A-B and B-A, randomized, longitudinal, comparative and prospective, with a washout period of seven days between the two study sessions. The treatment groups were balanced, having an equal number of subjects who were randomly assigned to the administration sequences of the drug under study. MEP sodium succinate was administered intravenously (1 mL, equivalent to 62.5 mg of Methylprednisolone) or the same dose intranasally by 2 using a Mucosal Atomization Device (MAD Nasal). The nominal doses were similar, allowing direct pharmacokinetic comparison without dose normalization. Venous blood samples were obtained via an indwelling catheter before administration at different times. Plasma was separated and frozen at -70 °C for further analysis.

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

Evaluation of the Bioavailability of Methylprednisolone Succinate Administered Intranasally

Actual Study Start Date :

Nov 5, 2021

Actual Primary Completion Date :

Nov 10, 2021

Actual Study Completion Date :

Nov 12, 2021

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Intravenously MEP Single dose of MEP sodium succinate intravenously administered. MEP (equivalent to 62.5 mg of Methylprednisolone). Samples were obtained at 0.333, 0.50, 0.667, 0.833, 1, 1.0, 2, 3, 4, 6, 8, 10, 12 and 24 h after MEP administration.	Drug: Evaluation of bioavailability of methylprednisolone succinate administered intravenously Bioavailability of methylprednisolone in healthy subjects of both genders, when administered intravenously. The nominal doses were similar, volunteers were randomly assigned to receive a single dose of MEP by IV bolus of 1.5 mL. Venous blood samples were obtained via an indwelling catheter before administration and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 8, 12 and 24 h for DXM. Plasma was separated and frozen at -70 °C for further analysis.
Active Comparator: Intranasally MEP Volunteers were randomly assigned to receive a single dose of MEP intranasally administered (equivalent to 62.5 mg of Methylprednisolone), using a Mucosal Atomization Device (MAD Nasal). Samples were obtained at 0.333, 0.50, 0.667, 0.833, 1, 1.0, 2, 3, 4, 6, 8, 10, 12 and 24 h after MEP administration.	Drug: Evaluation of bioavailability of methylprednisolone succinate administered intranasally Bioavailability of methylprednisolone in healthy subjects of both genders, when administered intranasally. Volunteers were randomly assigned to receive a single dose of MEP intranasally by using a Mucosal Atomization Device (MAD Nasal). allowing direct pharmacokinetic comparison without dose normalization. Venous blood samples were obtained via an indwelling catheter before administration and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 8, 12 and 24 h for DXM. Plasma was separated and frozen at -70 °C for further analysis.

Arm

Intervention/Treatment

Active Comparator: Intravenously MEP

Single dose of MEP sodium succinate intravenously administered. MEP (equivalent to 62.5 mg of Methylprednisolone). Samples were obtained at 0.333, 0.50, 0.667, 0.833, 1, 1.0, 2, 3, 4, 6, 8, 10, 12 and 24 h after MEP administration.

Drug: Evaluation of bioavailability of methylprednisolone succinate administered intravenously

Bioavailability of methylprednisolone in healthy subjects of both genders, when administered intravenously. The nominal doses were similar, volunteers were randomly assigned to receive a single dose of MEP by IV bolus of 1.5 mL. Venous blood samples were obtained via an indwelling catheter before administration and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 8, 12 and 24 h for DXM. Plasma was separated and frozen at -70 °C for further analysis.

Active Comparator: Intranasally MEP

Volunteers were randomly assigned to receive a single dose of MEP intranasally administered (equivalent to 62.5 mg of Methylprednisolone), using a Mucosal Atomization Device (MAD Nasal). Samples were obtained at 0.333, 0.50, 0.667, 0.833, 1, 1.0, 2, 3, 4, 6, 8, 10, 12 and 24 h after MEP administration.

Drug: Evaluation of bioavailability of methylprednisolone succinate administered intranasally

Bioavailability of methylprednisolone in healthy subjects of both genders, when administered intranasally. Volunteers were randomly assigned to receive a single dose of MEP intranasally by using a Mucosal Atomization Device (MAD Nasal). allowing direct pharmacokinetic comparison without dose normalization. Venous blood samples were obtained via an indwelling catheter before administration and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 8, 12 and 24 h for DXM. Plasma was separated and frozen at -70 °C for further analysis.

Outcome Measures

Primary Outcome Measures

Absolute Bioavailability of Methylprednisolone, Intranasal Route vs. Intravenous Route [2 weeks]
The sample size used for this exploratory study (descriptive, comparative or informative) made it possible to determine the absolute bioavailability (with informative value), for which the bioavailability was compared in the 2 types of administration: Intranasal vs. Intravenous with a sample size of 8 research subjects, even though the ANADEVA is informative, the requirements regarding type I error (alpha), type II error (beta) and a minimum difference to detect between the 2 routes of administration: intranasal vs. IV. The realization of the present study allowed to know the pharmacokinetic and safety parameters of the drug MEP administered by 2 different routes, as well as to determine the CVintra%

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Age between 18 and 55 years. Clinically healthy. Body mass index between 18.0 and 27.0 Kg/m2. Negative results to detect the presence of human immunodeficiency virus [HIV], Hepatitis B [HBV], Hepatitis C [HCV) and test for detection of Syphilis (VDRL).

Subjects with negative results in tests for the detection of drugs of abuse such as:

amphetamines, benzodiazepines, cocaine, methamphetamines, morphine and tetrahydro-cannabinoids.

Negative (qualitative) pregnancy test.

Exclusion Criteria:

Subjects with any condition or alteration of the nose or nasal mucosa. Subjects with a history of hypersensitivity to the study drug. Subjects with a history of cardiovascular, renal, hepatic, metabolic, gastrointestinal, neurological, endocrine, hematopoietic disorders (any type of anemia), mental illness or other organic abnormalities that could affect the pharmacokinetic study of the product under study.

Subjects who require any medication during the course of the study. Principal Investigator will not include the subject in the study. Subjects who have been hospitalized for any reason within the sixty days prior to the start of the study or who have been seriously ill within the thirty days prior to the start of the study.

Subjects who have received an investigational drug within ninety days prior to the start of the study.

Subjects who have donated or lost 450 ml or more of blood within the ninety days prior to the start of the study.

Subjects who have smoked tobacco, ingested alcohol, consumed beverages or foods containing xanthines.

Positive (qualitative) pregnancy test.