Study of MN-166 (Ibudilast) Extended Release Tablet Formulations Compared With Capsules in Healthy Volunteers

Bioequivalence Study of Two MN-166 (Ibudilast) 50 mg Extended Release Tablet Formulations Compared With MN-166 (Ibudilast) 10mg Capsules in Healthy Volunteers

To compare the bioavailability and pharmacokinetic profiles of two different formulations MN-166 50mg, extended release (ER) tablets with MN-166 10mg capsules in a single-dose regimen in healthy volunteers

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: MN-166

Detailed Description

Part 1:

To compare the bioavailability and pharmacokinetic profiles of two different formulations MN-166 50mg, extended release (ER) tablets with MN-166 10mg capsules in a single-dose regimen in healthy volunteers; and To choose one of the two MN-166 50mg ER tablet formulations for evaluation in Part 2.

Secondary: To determine the safety and tolerability of the two formulations of MN-166 ER tablets in a single-dose regimen in healthy volunteers.

Part 2:

To compare the bioavailability and steady-state pharmacokinetic profile of MN-166 50mg ER tablet with MN-166 10mg capsules in a multiple-dose regimen in healthy volunteers; and

Secondary: To determine the safety and tolerability of MN-166 ER tablets in a multiple-dose regimen in healthy volunteers

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Cypress, California, United States, 90630
      • WCCT Global, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Able to provide written informed consent.
2. Healthy non-smoking male and female subjects aged 18 to 65 years, inclusive.
3. No clinical abnormalities in laboratory and urine analyses.
4. Normal renal function (GFR > 90mL/min).
5. Liver enzymes should be less than twice the upper limit of normal (ULN).
6. Screening electrocardiogram (ECG) with QT interval adjusted for heart rate within normal limits.
7. Agree to use barrier contraceptive methods during the course of the study (hormonal contraceptive alone is not acceptable).
8. Females of child-bearing potential must have a negative pregnancy test on Study Day 1.

Exclusion Criteria:

1. Known hypersensitivity to Pinatos® or its components.
2. Condition(s) which might affect drug absorption, metabolism or excretion.
3. Untreated mental illness, current drug addiction or abuse or alcoholism.
4. Donated blood in the past 90 days or have poor peripheral venous access.
5. Platelets < l00,000/mm3, history of thrombocytopenia.
6. Confirmed diagnosis of chronic liver disease, e.g., chronic Hep. B, Hep. C infection, auto-immune, alcoholic or neoplastic liver disease.
7. Positive serostatus for HIV.
8. Currently pregnant or nursing.
9. History of clinically significant cardiovascular, pulmonary, endocrine, neurological, metabolic, or psychiatric diseases.
10. Received an investigational drug in the past 30 days.
11. Unable to swallow tablets.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Extended-release formulation 1 (ER1); 50mg MN-166 tablet. This formulation is intended for once-a-day dosing, hence, the label of extended-release.	Drug: MN-166; an orally available small molecule drug approved in Japan and Korea for asthma and post-stroke complications and has been prescribed for these indications for more than 25 years; Other Names: ibudilast; Pinatos® capsule
Experimental: Extended-release formulation 2 (ER2); 50mg MN-166 tablet. This formulation is intended for once-a-day dosing, hence, the label of extended-release.	Drug: MN-166; an orally available small molecule drug approved in Japan and Korea for asthma and post-stroke complications and has been prescribed for these indications for more than 25 years; Other Names: ibudilast; Pinatos® capsule
Active Comparator: Intermediate-release formulation (IR); 10mg MN-166 capsule. This formulation is typically given two or three times daily, hence, the label of intermediate-release.	Drug: MN-166; an orally available small molecule drug approved in Japan and Korea for asthma and post-stroke complications and has been prescribed for these indications for more than 25 years; Other Names: ibudilast; Pinatos® capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare the PK Profile of two new formulations in Single-day dose of MN-166	Compare the maximum plasma concentrations [Cmax] of MN-166 of two different formulations MN-166 50mg, extended release (ER) tablets with MN-166 10mg capsules in a single-dose regimen in healthy volunteers.	5 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare the incidence of treatment-emergent adverse events of two new formulations in Single-day dose of MN-166	Compare the number and frequency of treatment-emergent adverse events (serious and non-serious) profiles of two different formulations MN-166 50mg, extended release (ER) tablets with MN-166 10mg capsules in a single-dose regimen in healthy volunteers.	5 weeks
Compare the PK Profile of two new formulations in Multi-day dose of MN-166	Compare the maximum plasma concentrations [Cmax] of MN-166 of two different formula in a multiple-dose regimen.	3 weeks
Compare the incidence of treatment-emergent adverse events of two new formulations in Multi-day dose of MN-166	Compare the number and frequency of treatment-emergent adverse events (serious and non-serious) of MN-166 (pharmacokinetic profiles) of two different formula in a multiple-dose regimen.	3 weeks

Collaborators and Investigators

• Sponsor: MediciNova
• Investigators: Principal Investigator: Robina Smith, MD, WCCT Global, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 11, 2018
• Primary Completion (Actual): July 6, 2018
• Study Completion (Actual): September 30, 2018

Study Registration Dates

• First Submitted: April 18, 2018
• First Submitted That Met QC Criteria: May 10, 2018
• First Posted (Actual): May 23, 2018

Study Record Updates

• Last Update Posted (Actual): May 31, 2019
• Last Update Submitted That Met QC Criteria: May 29, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Phosphodiesterase Inhibitors; Ibudilast
• Other Study ID Numbers: MN-166-HDT-001

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