Relative Bioavailability of MN-166 (Ibudilast) in Extended Release Tablet vs. Intermediate-release Capsule in Healthy Volunteers

NCT04054206 | Completed Phase 1 FDA Drug

• 1 other identifier: MN-166-HDT-002
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This study will investigate the PK, relative bioavailability, safety, and tolerability of the extended release (ER) 50 mg MN-166 (ibudilast) tablet formulation as compared to the intermediate-release (IR) capsule formulation of MN-166 (ibudilast) and to examine the effect of food on the pharmacokinetics of the ER formulation.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (2)

• Compare the pharmacokinetic profile of ER and IR formulations in single-dose administration of MN-166 (ibudilast)

  Compare the maximum plasma concentrations (Cmax) of MN-166 (ibudilast) of ER 50 mg tablet and IR 10 mg capsule (5 capsules) formulations, in a single-dose regimen in healthy volunteers.

  From the time of pre-dose (immediately prior to taking the assigned MN-166/ibudilast formulation) to 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 32, 48, 72, 96, and 168 hours post-single treatment dose.

• Compare the pharmacokinetic profile of ER and IR formulations in single-dose administration of MN-166 (ibudilast) under fed or fasting states

  Cmax of MN-166 (ibudilast) of ER 50 mg tablet and IR 10 mg capsule (5 capsules) formulations, in a single-dose regimen in healthy volunteers fed a high-fat meal 1 hour prior to dosing or fasted 8 hours prior to dosing.

  From the time of pre-dose (immediately prior to taking the assigned MN-166/ibudilast formulation under either feeding or fasting conditions) to 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 32, 48, 72, 96, and 168 hours post-single treatment dose.

Secondary Outcomes (3)

• Number of healthy volunteers with treatment-related adverse events as assessed by CTCAE v.4.0

  From the time of pre-dose (immediately prior to taking the assigned MN-166/ibudilast formulation under either feeding or fasting conditions) to 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 32, 48, 72, 96, and 168 hours post-single treatment dose.

• Changes in physical exam results

  From the night before single-dose treatment to 168 hours post-dose under fed and fasted conditions.

• Number of participants with clinically significant abnormal laboratory results

  From the night before single-dose treatment to 168 hours post-dose under fed and fasted conditions.

Study Arms (6)

Sequence 1

ACTIVE COMPARATOR

Two participants will be randomly assigned to sequence 1 comprising 3 treatments (ER fasted, ER fed, and IR fasted) in a crossover design, administered one week apart: Day 1-7: ER fasted; Day 8-15: ER fed Day 15-22: IR fasted

Drug: MN-166

Sequence 2

ACTIVE COMPARATOR

Two participants will be randomly assigned to sequence 2 comprising 3 treatments in a crossover design, administered one week apart: Day 1-7: ER fed; Day 8-15: IR fasted; Day 15-22: ER fasted

Drug: MN-166

Sequence 3

ACTIVE COMPARATOR

Two participants will be randomly assigned to sequence 3 comprising 3 treatments in a crossover design, administered one week apart: Day 1-7: IR fasted; Day 8-15: ER fasted; Day 15-22: ER fed

Drug: MN-166

Sequence 4

ACTIVE COMPARATOR

Two participants will be randomly assigned to sequence 4 comprising 3 treatments in a crossover design, administered one week apart: Day 1-7: IR fasted; Day 8-15: ER fed; Day 15-22: ER fasted

Drug: MN-166

Sequence 5

ACTIVE COMPARATOR

Two participants will be randomly assigned to sequence 5 comprising 3 treatments in a crossover design, administered one week apart: Day 1-7: ER fasted; Day 8-15: IR fasted; Day 15-22: ER fed

Drug: MN-166

Sequence 6

ACTIVE COMPARATOR

Two participants will be randomly assigned to sequence 6 comprising 3 treatments in a crossover design, administered one week apart: Day 1-7: ER fed; Day 8-15: ER fasted; Day 15-22: IR fasted

Drug: MN-166

Interventions

MN-166 DRUG

MN-166 (ibudilast) is an orally available small molecule drug currently being investigated for human treatment in multiple sclerosis, amyotrophic lateral sclerosis, glioblastoma, and alcohol and drug use disorders.

Also known as: ibudilast, Pinatos capsule

Sequence 1; Sequence 2; Sequence 3; Sequence 4; Sequence 5; Sequence 6

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Able to provide written informed consent.
• Healthy non-smoking male and female subjects aged 18 to 45 years, inclusive. Health status is determined by physical examination, medical history, no clinical abnormalities in laboratory and urine analyses, normal renal function, liver enzymes less than twice the upper limit of normal (ULN), and electrocardiogram (ECG) with QT interval adjusted for heart rate within normal limits at the screening visit.
• A body mass index (BMI) of 18 kg/m2 or greater, but less than 36 kg/m2.
• Agree to use barrier contraceptive methods during the course of the study (hormonal contraceptive alone is not acceptable).
• Females of child-bearing potential must have a negative urine pregnancy test on Day 1. If post-menopausal female, follicle stimulating hormone (FSH) level \> 40 IU/L.

You may not qualify if:

• History of clinically significant drug allergy or anaphylaxis, including known hypersensitivity to Pinatos® or its components.
• History of any condition(s) which might affect drug absorption, metabolism or excretion.
• Clinical evidence or a history of clinically significant cardiovascular, respiratory, renal, hepatic, gastrointestinal, hematological, neurologic, or other chronic disease as judged by the Investigator.
• History of severe psychiatric disease, especially major depression. Severe psychiatric disease is defined as treatment with an antidepressant medication or a major tranquilizer at therapeutic doses for major depression or psychosis, respectively, for at least 3 months at any previous time or any history of the following: a suicidal attempt, hospitalization for psychiatric disease, or a period of disability due to a psychiatric disease.
• History of severe cardiac disease \[e.g., New York Heart Association (NYHA) Functional Class III or IV\], myocardial infarction within 6 months, ventricular tachyarrhythmias requiring ongoing treatment, unstable angina or other significant cardiovascular diseases.
• Estimated creatinine clearance outside the normal range (\</= 80 mL/min) at screening.
• History or other evidence of severe illness or any other conditions which would make the subject, in the opinion of the investigator, unsuitable for the study.
• Evidence of alcohol and/or drug abuse within one year of screening.
• Positive results on screen for drugs of abuse or alcohol at screening visit or Day 0.
• History within 1 year of screening visit, or current habit, of smoking more than 10 cigarettes per day or equivalent (\>3 cigars or \>3 pipes-full).
• Donated blood in the past 90 days or have poor peripheral venous access.
• Platelets \< 100,000/mm3, history of thrombocytopenia.
• Confirmed diagnosis of chronic liver disease, for example, chronic Hepatitis B, Hepatitis C infection, auto-immune, alcoholic or neoplastic liver disease.
• Positive serostatus for HIV, HCV, or HBV.
• Currently pregnant or nursing.

Sponsors & Collaborators

• MediciNova: lead

Study Sites (1)

Collaborative Neuroscience Network

Garden Grove, California, 92845, United States

Location

MeSH Terms

Interventions

ibudilast

Study Officials

• David P Walling, PhD

  Collaborative Neuroscience Network, LLC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 12 healthy male and female participants (enrollment is 6 female and 6 male participants). Each enrolled/consented participant will be randomly assigned to 1 of 6 treatment sequences which consists of 3 treatments (ER fasted, ER fed, and IR fasted) in a crossover design, administered one week apart.

Study Record Dates

• First Submitted: August 6, 2019
• First Posted: August 13, 2019
• Study Start: June 24, 2019
• Primary Completion: July 17, 2019
• Study Completion: May 31, 2020
• Last Updated: July 15, 2020

Record last verified: 2020-07

Locations

US (1)