Safety, Tolerability and Pharmacokinetic Study of MB12066 in Healthy Volunteers

Study Overview
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Brief Summary
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The purpose of this study is to investigate the safety and tolerability of MB12066 after a single or multiple oral dose and to investigate the pharmacokinetic characteristics of MB12066 after a single or multiple oral dose.

Detailed Description
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Safety/ Tolerability evaluation Adverse events, Physical examinations, Vital signs, ECG (including continuous ECG monitoring), Laboratory tests (including hematology, chemistry, coagulation, PBS, NAD(P)+/NAD(P)H ratio, urinalysis), CIC Pharmacokinetic Evaluation(single) Serial blood samples and urine collections for pharmacokinetic evaluations will be conducted between 0 (pre-dose) and 96 hours after a single oral dose. Blood sampling time pre-dose, 0.5, 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 72h post-dose Urine collection time 0h - 6h, 6h - 12h, 12h - 24h, 24h - 48h, 48h - 72h Evaluation parameters AUClast, AUCinf, Cmax, Tmax, t1/2, Vd/F, CL/F, Ae, fe, CLR Pharmacokinetic Evaluation(multiple) Serial blood samples and urine collections for pharmacokinetic evaluations will be conducted after a single oral dose and Steady state. Blood sampling time Day 1 pre-dose, 0.5h, 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, Day3-6 Pre-dose, Day7 Pre-dose, 0.5h, 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 72h, 96h post-dose Urine collection time Day 1 Pre-dose, 0h - 6h, 6h - 12h, 12h - 24h, Day 7 Pre-dose, 0h - 6h, 6h - 12h, 12h - 24h Evaluation parameters Cmax,ss, Cmin,ss, Cav,ss, AUCτ, Tmax,ss, t1/2, PTF(peak to trough fluctuation ratio), fe, CLss/F, CLR

Official Title
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A Dose Block-randomized, Double-blind, Placebo-controlled, Single or Multiple Dosing, Dose-escalation Clinical Trial to Investigate the Safety, Tolerability and Pharmacokinetic Characteristics of MB12066 in Healthy Male Subjects

Conditions
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Metabolic Syndrome, Obesity

Intervention / Treatment
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* Drug: MB12066
* Drug: MB12066
* Drug: MB12066
* Drug: MB12066
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is informed of the investigational nature of this study and voluntarily agrees to participate in this study and signs an Institutional Review Board (IRB) - approved informed consent prior to performing any of the screening procedures Healthy Korean male volunteers, age ranged 20 to 45 years (both inclusive) A subject with body weight between 60 kg (inclusive) and 90 kg (exclusive) and body mass index (BMI) between 18.5 (inclusive) and 25 (exclusive). ☞ BMI (kg/m2) = weight (kg) / {height (m)}2 Findings within the range of clinical acceptability in medical history and physical examination, and laboratory results within the laboratory reference ranges for the relevant laboratory tests (unless the investigator considers the deviation to be irrelevant for the purpose of the study) Exclusion Criteria: A subject with history of allergies including drug allergies (aspirin, antibiotics, etc.), or history of clinically significant allergies A subject with clinical evidence or history of hepatic (including carrier of hepatitis virus), renal, respiratory, endocrine, neurologic, immunologic, hematologic, oncologic, psychiatric, or cardiovascular disease A subject with history of gastrointestinal disease or surgery (except simple appendectomy or repair of hernia), which can influence the absorption of the study drug A subject whose hemoglobin(Hb) level < 12 g/dL A subject with fasting plasma glucose (FPG) level ≤ 70 mg/dL or ≥ 126 mg/dL A subject with HbA1c level ≥ 7.0 % A subject whose systolic blood pressure (SBP) ≤ 90 mmHg or ≥ 140 mmHg, diastolic blood pressure (DBP) ≤ 40 mmHg or ≥ 90 mmHg or pulse rate (PR) ≥ 100 /min after at least 5 min sitting A subject with history of drug abuse or positive urine drug screening test A subject who has taken any prescribed medication or herbal compounds within 14 days prior to the study drug administration. In addition, a subject who has taken any over-the-counter drug or vitamin supplements within 7 days prior to the study drug administration (However, investigators can judge the subject, who has taken the medications during those periods above, eligible for the trial if all other conditions are satisfied.) A subject who has participated in any other clinical trial either for investigational or marketed drugs within 8 weeks before the study drug administration A subject who has donated or had loss of ≥ 400 mL of blood within 8 weeks prior to start of administration of study drug A subject who consumes more than 21 units of alcohol per week or unable to stop drinking throughout the study period. A smoker (except for whom quitted smoking prior to the drug administration for at least 3 months) A subject who heavily takes caffeine or caffeine-containing products, grapefruit, grapefruit juice, grapefruit-containing products A subject with unusual dietary habit A subject who was previously assigned to treatment during this study The investigator judges the subject not eligible for the study after reviewing clinical laboratory results or other reasons.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MB12066 300mg<br>single dose | Drug: MB12066<br>* MB12066 300mg<br>* Other names: beta-lapachone;|
| Active Comparator: MB12066 400mg<br>single dose | Drug: MB12066<br>* MB12066 400mg<br>* Other names: beta-lapachone;|
| Active Comparator: MB12066 100mg<br>multiple dose | Drug: MB12066<br>* MB12066 100mg<br>* Other names: beta-lapachone;|
| Active Comparator: MB12066 200mg<br>multiple dose | Drug: MB12066<br>* MB12066 200mg<br>* Other names: beta-lapachone;|
| Placebo Comparator: Placebo<br>Placebo 300mg(single dose), 400mg (single dose), 100mg (multiple dose), 200mg (multiple dose) | Drug: Placebo<br>* Placebo 300mg (single dose), 400mg (single dose), 100mg (multiple dose), 200mg (multiple dose)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events (single dose) | Adverse events | Single dose: from day-1 to day8-10 | 
| Number of Patients with with Adverse Events (Multiple Dose) | Adverse Events | Multiple dose: from day-1 to day15-17 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of Pharmacokinetic Evaluation (single dose) | Single oral dose Blood sampling time pre-dose, 0.5h, 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 72h post-dose Urine collection time 0h - 6h, 6h - 12h, 12h - 24h, 24h - 48h, 48h - 72h Evaluation parameters Cmax,ss, Cmin,ss, Cav,ss, AUCτ, Tmax,ss, t1/2, PTF(peak to trough fluctuation ratio), fe, CLss/F, CLR | between 0 (pre-dose) and 72 hours after a single oral dose. | 
| Composite of Pharmacokinetic Evaluation (multiple dose) | Multiple oral dose Blood sampling time Day 1 pre-dose, 0.5h, 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h post-dose Day 3-6 pre-dose Day 7 pre-dose, 0.5h, 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 72h, 96h post-dose Urine collection time Day 1 0h - 6h, 6h - 12h, 12h - 24h Day 7 0h - 6h, 6h - 12h, 12h - 24h Evaluation parameters Cmax,ss, Cmin,ss, Cav,ss, AUCτ, Tmax,ss, t1/2, PTF(peak to trough fluctuation ratio), fe, CLss/F, CLR | between 0 (pre-dose) and 24 hours and between 7day and 11 day after a multiple oral dose. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Safety, Tolerability, Pharmacokinetic