Relative Bioavailability of MN-166 (Ibudilast) in Extended Release Tablet vs. Intermediate-release Capsule in Healthy Volunteers
Relative Bioavailability of MN-166 (Ibudilast) in Extended Release Tablet vs. Intermediate-release Capsule in Healthy Volunteers
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.
This is a Phase 1, open-label, single-center study in at least 12 healthy volunteers or
 participants.

 Participants (at least n=2/sequence) meeting study eligibility and providing informed consent
 will be randomized to one of six treatment sequences. The three treatments of each sequence
 will be administered in a crossover fashion, separated by one week apart. Thus, participation
 in the study is 3 weeks long per participant.

 During each single-dose treatment, participants will check in the study facility the night
 before dosing and remain at the facility until 32 hours after dosing. For example, the
 participant would arrive at the study facility at 8:00 PM Sunday night, receive a single dose
 at 8:00 AM Monday morning, and blood samples will be taken prior to dosing and 30 minutes, 1,
 2 4, 6, 8, 10, 12, 24, and 32 hours after dosing. After the 32-hour sample collection,
 participants may leave the study facility. Participants will return to the study facility for
 outpatient visits at each remaining PK sampling day (48, 72, and 96 hours after dosing) and
 after last treatment in each sequence. Participants will be discharged from the study after
 the last treatment.
Inclusion Criteria:

 1. Able to provide written informed consent.

 2. 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.

 3. A body mass index (BMI) of 18 kg/m2 or greater, but less than 36 kg/m2.

 4. Agree to use barrier contraceptive methods during the course of the study (hormonal
 contraceptive alone is not acceptable).

 5. 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.

 Exclusion Criteria:

 1. History of clinically significant drug allergy or anaphylaxis, including known
 hypersensitivity to Pinatos® or its components.

 2. History of any condition(s) which might affect drug absorption, metabolism or
 excretion.

 3. Clinical evidence or a history of clinically significant cardiovascular, respiratory,
 renal, hepatic, gastrointestinal, hematological, neurologic, or other chronic disease
 as judged by the Investigator.

 4. 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.

 5. 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.

 6. Estimated creatinine clearance outside the normal range (</= 80 mL/min) at screening.

 7. 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.

 8. Evidence of alcohol and/or drug abuse within one year of screening.

 9. Positive results on screen for drugs of abuse or alcohol at screening visit or Day 0.

 10. 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).

 11. Donated blood in the past 90 days or have poor peripheral venous access.

 12. Platelets < 100,000/mm3, history of thrombocytopenia.

 13. Confirmed diagnosis of chronic liver disease, for example, chronic Hepatitis B,
 Hepatitis C infection, auto-immune, alcoholic or neoplastic liver disease.

 14. Positive serostatus for HIV, HCV, or HBV.

 15. Currently pregnant or nursing.

 16. Male partners of females who are pregnant.

 17. History of clinically significant cardiovascular, pulmonary, endocrine, neurological,
 metabolic, or psychiatric disease.

 18. Participation in a clinical study with an investigational drug, biologic, or device
 within 3 months before receiving study drug.

 19. Used any systemic medications, including vitamins and over-the-counter items, during
 the 14 days (or five times the elimination half-life of the medication, whichever is
 longer) before receiving study drug or will require their use during the study.
 Metabolic inducers and herbal preparations, which have been shown to produce metabolic
 enzyme induction or inhibition, whether as teas or formulations, are prohibited 28
 days before dosing. Paracetamol 3000 mg/day will be allowed up to 2 consecutive days
 before dosing and during the outpatient phase of the study, as needed.

 20. Unable to swallow large tablets.