Bioequivalence Study of Oral Suspension and Intravenous Formulation of Edaravone in Healthy Adult Subjects

Healthy Adult Subjects Clinical Trial

Official title:

Bioequivalence Study of Oral Suspension and Intravenous Formulation of Edaravone in Healthy Adult Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04493281
• Other study ID #: MT-1186-J03
• Status: Completed
• Phase: Phase 1
• Start date: March 22, 2019
• Est. completion date: May 9, 2019

Study information

• Verified date: January 2024
• Source: Mitsubishi Tanabe Pharma Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To evaluate the single-dose bioequivalence of oral suspension and intravenous (IV) formulation of edaravone in the fasting state in healthy adult subjects

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: May 9, 2019
• Est. primary completion date: April 21, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 20 Years to 45 Years

Eligibility

Inclusion Criteria:

• Healthy adult male or female volunteers
• Japanese
• Subjects aged between 20 and 45 years at the time of informed consent
• Subjects who have thoroughly understood the contents of the study and voluntarily provided written informed consent to participate in the study

Exclusion Criteria: Additional screening criteria check may apply for qualification:

• Subjects with a current or previous history of cardiac, hepatic, renal, gastrointestinal, respiratory, psychiatric/nervous, hematopoietic, or endocrine diseases, and those whom the investigator (or subinvestigator) deems unsuitable for the study
• Body mass index (BMI) of <18.0 or >30.0, or body weight of <50 kg (BMI formula: body weight [kg]/height [m]2, rounded to one decimal place)
• Subjects who have undergone any surgery known to affect the gastrointestinal absorption of drugs
• Female subjects who do not agree to use an effective method of contraception from screening or 2 weeks before the start of investigational product administration, whichever comes earlier, to 14 days after the completion (or discontinuation) of investigational product administration. Male subjects who do not agree to use an effective method of contraception from the start of investigational product administration to 14 days after the completion (or discontinuation) of investigational product administration
• Subjects who have previously received edaravone
• Subjects who have participated in another clinical study and received an investigational product within 12 weeks before providing informed consent

Related Conditions & MeSH terms

• Healthy Adult Subjects

Intervention

Drug:
• MT-1186
Oral suspension
• MCI-186
Intravenous formulation

Locations

Country	Name	City	State
Japan	Investigational site	Tokyo

Sponsors (1)

Lead Sponsor	Collaborator
Mitsubishi Tanabe Pharma Corporation

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area Under the Plasma Concentration Versus Time Curve From Time Zero up to the Last Quantifiable Concentration Time-point (AUC0-t) of Unchanged Edaravone After Oral and Intravenous Administration		The date of dosing is defined as Day 1. PO: Day 1 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12 hrs; IV: Day 1 at pre-dose, 0.25, 0.5, 1, 1.083, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12 hrs; Both groups: Day 2 at 24, 36 hrs; Day 3 at 48 hrs.
Primary	Area Under the Plasma Concentration Versus Time Curve From Time Zero up to Infinity With Extrapolation of the Terminal Phase (AUC0-inf) of Unchanged Edaravone After Oral and Intravenous Administration		The date of dosing is defined as Day 1. PO: Day 1 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12 hrs; IV: Day 1 at pre-dose, 0.25, 0.5, 1, 1.083, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12 hrs; Both groups: Day 2 at 24, 36 hrs; Day 3 at 48 hrs.
Primary	Maximum Plasma Concentration (Cmax) of Unchanged Edaravone After Oral and Intravenous Administration		The date of dosing is defined as Day 1. PO: Day 1 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12 hrs; IV: Day 1 at pre-dose, 0.25, 0.5, 1, 1.083, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12 hrs; Both groups: Day 2 at 24, 36 hrs; Day 3 at 48 hrs.
Secondary	Time to Reach Maximum Plasma Concentration (Tmax)		The date of dosing is defined as Day 1. PO: Day 1 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12 hrs; IV: Day 1 at pre-dose, 0.25, 0.5, 1, 1.083, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12 hrs; Both groups: Day 2 at 24, 36 hrs; Day 3 at 48 hrs.
Secondary	Area Under the Plasma Concentration Versus Time Curve From Time Zero up to 24 Hours (AUC0-24)		The date of dosing is defined as Day 1. PO: Day 1 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12 hrs; Day 2 at 24 hrs ; IV: Day 1 at pre-dose, 0.25, 0.5, 1, 1.083, 1.25, 1.5, 1.75,2, 3, 4, 6, 8, 12 hrs; Day 2 at 24 hrs.
Secondary	Area Under the Plasma Concentration Versus Time Curve From Time Zero up to the Last Sampling Time-point (for All Time-points) (AUC0-all)		The date of dosing is defined as Day 1. PO: Day 1 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12 hrs; IV: Day 1 at pre-dose, 0.25, 0.5, 1, 1.083, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12 hrs; Both groups: Day 2 at 24, 36 hrs; Day 3 at 48 hrs.
Secondary	Terminal Elimination Half-life (t1/2)		The date of dosing is defined as Day 1. PO: Day 1 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12 hrs; IV: Day 1 at pre-dose, 0.25, 0.5, 1, 1.083, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12 hrs; Both groups: Day 2 at 24, 36 hrs; Day 3 at 48 hrs.
Secondary	Elimination Rate Constant From the Central Compartment (Kel)		The date of dosing is defined as Day 1. PO: Day 1 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12 hrs; IV: Day 1 at pre-dose, 0.25, 0.5, 1, 1.083, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12 hrs; Both groups: Day 2 at 24, 36 hrs; Day 3 at 48 hrs.
Secondary	Mean Residence Time From Time Zero up to Infinity With Extrapolation of the Terminal Phase (MRT0-inf) of Unchanged Edaravone		The date of dosing is defined as Day 1. PO: Day 1 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12 hrs; IV: Day 1 at pre-dose, 0.25, 0.5, 1, 1.083, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12 hrs; Both groups: Day 2 at 24, 36 hrs; Day 3 at 48 hrs.
Secondary	Total Clearance (CL) of Unchanged Edaravone After Intravenous Administration		The date of dosing is defined as Day 1. Day 1 at pre-dose, 0.25, 0.5, 1, 1.083, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12 hrs; Day 2 at 24, 36 hrs; Day 3 at 48 hrs.
Secondary	Volume of Distribution During Terminal Phase (Vz) of Unchanged Edaravone After Intravenous Administration		The date of dosing is defined as Day 1. Day 1 at pre-dose, 0.25, 0.5, 1, 1.083, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12 hrs; Day 2 at 24, 36 hrs; Day 3 at 48 hrs.
Secondary	Volume of Distribution at Steady State (Vss) of Unchanged Edaravone After Intravenous Administration		The date of dosing is defined as Day 1. Day 1 at pre-dose, 0.25, 0.5, 1, 1.083, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12 hrs; Day 2 at 24, 36 hrs; Day 3 at 48 hrs.
Secondary	Apparent Total Clearance (CL/F) of Unchanged Edaravone After Oral Administration		The date of dosing is defined as Day 1. Day 1 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12 hrs; Day 2 at 24, 36 hrs; Day 3 at 48 hrs.
Secondary	Apparent Volume of Distribution During Terminal Phase (Vz/F) of Unchanged Edaravone After Oral Administration		The date of dosing is defined as Day 1. Day 1 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12 hrs; Day 2 at 24, 36 hrs; Day 3 at 48 hrs.
Secondary	Apparent Volume of Distribution at Steady State (Vss/F) of Unchanged Edaravone After Oral Administration		The date of dosing is defined as Day 1. Day 1 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12 hrs; Day 2 at 24, 36 hrs; Day 3 at 48 hrs.
Secondary	Cumulative Amount of Drug Excreted in Urine From Time Zero up to 48 Hours (Ae0-48)		Urine samples are collected: Day1 to 6.
Secondary	Cumulative Percentage of Drug Excreted in Urine From Time Zero up to 48 Hours (Ae0-48)		Urine samples are collected: Day1 to 6.
Secondary	Renal Clearance (CLr) of Unchanged Edaravone		Urine samples are collected: Day1 to 6.
Secondary	Bioavailability (F) of Unchanged Edaravone After Oral Administration	Bioavailability was calculated from ratio of AUC0-inf of unchanged edaravone after oral and intravenous administration.	PO: Day 1 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 12 hrs; Day 2 at 24 and 36 hrs; Day 3 at 48 hrs. IV: Day 1 at pre-dose, 0.25, 0.5, 1, 1.083, 1.25, 1.5, 1.75,2, 3, 4, 6, 8, 12 hrs; Day 2 at 24 and 36 hrs; Day 3 at 48hrs.
Secondary	AUC0-t of Sulfate and Glucuronide Conjugates After Oral and Intravenous Administration		The date of dosing is defined as Day 1. PO: Day 1 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12 hrs; IV: Day 1 at pre-dose, 0.25, 0.5, 1, 1.083, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12 hrs; Both groups: Day 2 at 24, 36 hrs; Day 3 at 48 hrs.
Secondary	AUC0-inf of Sulfate and Glucuronide Conjugates After Oral and Intravenous Administration		The date of dosing is defined as Day 1. PO: Day 1 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12 hrs; IV: Day 1 at pre-dose, 0.25, 0.5, 1, 1.083, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12 hrs; Both groups: Day 2 at 24, 36 hrs; Day 3 at 48 hrs.
Secondary	Cmax of Sulfate and Glucuronide Conjugates After Oral and Intravenous Administration		The date of dosing is defined as Day 1. PO: Day 1 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12 hrs; IV: Day 1 at pre-dose, 0.25, 0.5, 1, 1.083, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12 hrs; Both groups: Day 2 at 24, 36 hrs; Day 3 at 48 hrs.
Secondary	Number of Participants With Adverse Events and Adverse Drug Reactions		Day 1 to 11