Safety, Tolerability and Pharmacokinetic Study of MB12066 in Healthy Volunteers

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

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.

Study Overview

• Status: Completed
• Conditions: Obesity; Metabolic Syndrome
• Intervention / Treatment: Drug: MB12066; Drug: MB12066; Drug: MB12066; Drug: MB12066; Drug: Placebo

Detailed Description

• 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

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Daehang-ro, Jongno-Gu
    • Seoul, Daehang-ro, Jongno-Gu, Korea, Republic of, 110-774
      • Clinical Research Institute of Seoul National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. 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
2. Healthy Korean male volunteers, age ranged 20 to 45 years (both inclusive)
3. 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
4. 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:

1. A subject with history of allergies including drug allergies (aspirin, antibiotics, etc.), or history of clinically significant allergies
2. 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
3. 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
4. A subject whose hemoglobin(Hb) level < 12 g/dL
5. A subject with fasting plasma glucose (FPG) level ≤ 70 mg/dL or ≥ 126 mg/dL
6. A subject with HbA1c level ≥ 7.0 %
7. 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
8. A subject with history of drug abuse or positive urine drug screening test
9. 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.)
10. A subject who has participated in any other clinical trial either for investigational or marketed drugs within 8 weeks before the study drug administration
11. A subject who has donated or had loss of ≥ 400 mL of blood within 8 weeks prior to start of administration of study drug
12. A subject who consumes more than 21 units of alcohol per week or unable to stop drinking throughout the study period.
13. A smoker (except for whom quitted smoking prior to the drug administration for at least 3 months)
14. A subject who heavily takes caffeine or caffeine-containing products, grapefruit, grapefruit juice, grapefruit-containing products
15. A subject with unusual dietary habit
16. A subject who was previously assigned to treatment during this study
17. The investigator judges the subject not eligible for the study after reviewing clinical laboratory results or other reasons.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

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

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Yungjin Pharm. Co., Ltd.
• Collaborators: KT&G Corporation
• Investigators: Principal Investigator: Kyung-Sang Yu, Professor, Clinical Research Institute of Seoul National University Hospital

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): April 1, 2012
• Study Completion (Actual): April 1, 2012

Study Registration Dates

• First Submitted: September 21, 2011
• First Submitted That Met QC Criteria: September 30, 2011
• First Posted (Estimate): October 3, 2011

Study Record Updates

• Last Update Posted (Actual): December 21, 2017
• Last Update Submitted That Met QC Criteria: December 19, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: Safety; Tolerability; Pharmacokinetic
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Insulin Resistance; Hyperinsulinism; Metabolic Syndrome; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Beta-lapachone
• Other Study ID Numbers: MB12066_002