Drug-drug Interaction Study(Lobeglitazone, Warfarin)

Open Label, Randomized, Crossover Study to Evaluate a Pharmacokinetic Drug Interaction Between Lobeglitazone and Warfarin in Healthy Subjects

The purpose of this study is to evaluate a pharmacokinetic drug interaction between lobeglitazone and warfarin in healthy subjects.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Warfarin; Drug: Lobeglitazone

Detailed Description

From day 1 to day 12, lobeglitazone 0.5mg is administered daily to Group 1 subjects during period 1. Then on day 5,warfarin 25mg is co-administered Group 1 subjects at period 1. After 10 day-break, warfarin 25mg is administered Group 1 subjects at period 2. On period 2, lobeglitazone is not administered.

Group 2 is administered in reverse order.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Samsung Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• A healthy male volunteer between 19 and 55 years old.
• BMI between 19 and 27.
• Signed the informed consent form prior to study participation.
• Able to participate in the entire trial

Exclusion Criteria:

• Clinically significant hepatic, renal, digestive system, respiratory system, endocrine system, nervous system, hematologic, cardiovascular system, tumor or have history of tumor
• Clinically significant hemorrhagic disease
• Genetic problems such as galactose intolerance, Lapp lactase deficiency, glucose-galactose malabsorption
• Have hypersensitivity reactions history for lobeglitazone, warfarin, excipient of IP or aspirin, antibiotics
• Medication which might significantly alter the absorption, distribution, metabolism, or excretion of investigational products within 30 days prior to screening
• Participated in the other clinical trials and administrated IP within 60 days prior to screening
• Subject takes ethical drug or herbal medicine within 14 days, OTC within 7 days before screening
• Previously donate whole blood within 60 days or component blood within 30 days
• sit SBP < 90mmHg or sit SBP ≥ 140mmHg or sit DBP < 60mmHg or sit DBP ≥ 90mmHg
• A heavy alcohol consumer (alcohol > 140 g/week) or cannot stop drinking
• A heavy smoker (cigarette > 10 cigarettes per day) or cannot stop smoking
• A heavy caffeine consumer (more than 4cups per a day) or A heavy grapefruit consumer (more than 1cup per a day) or cannot stop having
• Positive for the Triage TOX drug on urine
• Positive for HIV antibody, HBsAg, HCV antibody test
• AST, ALT or Total bilirubin > UNL * 1.5
• Estimated GFR < normal limit
• INR, aPTT over the normal limit
• Clinically significant laboratory test result
• Clinically significant ECG
• An impossible one who participates in clinical trial by investigator's decision including other reason

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Lobeglitazone; Subjects received Lobeglitazone 0.5 mg daily for 12 days in one period and in the other period, Subjects don't receive Lobeglitazone.	Drug: Lobeglitazone
EXPERIMENTAL: Warfarin; Subjects received Warfarin 25 mg once at period 1 and 2.	Drug: Warfarin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Assess AUC of lobeglitazone	0, 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24h
Assess Cmax of lobeglitazone	0, 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24h
Assess AUC of S-warfarin	0, 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168h
Assess Cmax of S-warfarin	0, 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168h
Assess AUC of R-warfarin	0, 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168h
Assess Cmax of R-warfarin	0, 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168h

Secondary Outcome Measures

Outcome Measure	Time Frame
Assess tmax of lobeglitazone	0, 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24h
Assess t1/2 of lobeglitazone	0, 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24h
Assess CL/F of lobeglitazone	0, 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24h
Assess Vd/F of lobeglitazone	0, 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24h
Assess tmax of S-warfarin	0, 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168h
Assess t1/2 of S-warfarin	0, 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168h
Assess CL/F of S-warfarin	0, 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168h
Assess Vd/F of S-warfarin	0, 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168h
Assess tmax of R-warfarin	0, 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168h
Assess t1/2 of R-warfarin	0, 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168h
Assess CL/F of R-warfarin	0, 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168h
Assess Vd/F of R-warfarin	0, 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168h

Collaborators and Investigators

• Sponsor: Chong Kun Dang Pharmaceutical
• Investigators: Principal Investigator: Jae Wook Ko, Ph.D, Samsung Medical Center

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (ACTUAL): February 1, 2014
• Study Completion (ACTUAL): May 1, 2014

Study Registration Dates

• First Submitted: November 25, 2013
• First Submitted That Met QC Criteria: December 1, 2013
• First Posted (ESTIMATE): December 6, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): July 3, 2014
• Last Update Submitted That Met QC Criteria: July 1, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: Phase 1; Warfarin; Type 2 Diabetes Mellitus; Drug-Drug interaction; Lobeglitazone
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Anticoagulants; Warfarin
• Other Study ID Numbers: 19DDI13016