Duration of P-glycoprotein Inhibition After Oral Administration of HM30181AK Tablet (PGP inhibitor)

Clinical Trial to Investigate the Duration of P-glycoprotein Inhibition After Oral Administration of HM30181AK Tablet in Healthy Male Subjects : An Open, Parallel Dose Group Design

The purposes of this study are to investigate the duration of P-glycoprotein inhibition after oral administration of HM30181AK tablet in healthy male subject and proper dose of HM30181AK tablet.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: HM30181AK 1mg; Drug: Loperamide 2mg; Drug: HM30181AK 5mg; Drug: HM30181AK 15mg; Drug: HM30181AK 60mg

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Seoul National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Healthy male volunteers aged 20 to 50 years at screening

2. Subjects whose weights are heavier than or equal to 50 kg and ±20% of ideal body weight

   • Ideal body weight = (height cm - 100) x 0.9
3. Subjects who provided written, voluntary informed consent to participate in this clinical trial and to comply the directions including contraception after being fully informed of and understand this trial

Exclusion Criteria:

1. Subjects who have the clinically significant diseases or history in liver, kidney, nervous system, respiratory system, endocrine system, blood tumor and cardiovascular system.
2. History of the gastrointestinal diseases which may affect the absorption of oral drugs (e.g., Crohn's disease) or gastrointestinal operations (excluding simple typhlotomy and hernia repair).

3. The following results in laboratory test

   • AST, ALT > 1.25 x upper limits of normal
4. Systolic blood pressure below 100 mmHg or above 150 mmHg or diastolic blood pressure below 65 mmHg or above 95 mmHg in vital signs
5. History of drug allergy or other allergies which are clinically significant
6. History of drug abuse or positive reaction for drug abuse in urine screening test
7. Subjects who took prescription drugs or herbal medicines within 2 weeks prior to the first day of drug administration or OTC or vitamin preparations within 1 week prior to the first day of drug administration If the subjects meet other criteria, they could participate in the trial in the judgement of investigator.)
8. Subjects who have participated in other clinical trial within 2 months prior to the first day of drug administration
9. Whole blood donation within 2 months prior to the first day of drug administration or apheresis donation within 2 weeks prior to the first day of drug administration
10. Subject who are continuously drinking alcohol (over 21 units/week) or who cannot quit drinking during clinical trial period
11. Subject who are smoking over 10 cigar/day
12. Subjects who eat food containing caffeine or grapefruit or drink alcohol in prohibited period
13. Subjects who are inappropriate in the judgement of the investigator due to the reasons including clinical laboratory test results

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1mg group; Administration of HM30181AK 1mg on day 4 and Loperamide 16mg (Loperamide 2mg x 8cap) on day 1,4,8,11,15	Drug: HM30181AK 1mg; HM30181AK 1mg tablet; Drug: Loperamide 2mg; Loperamide 2mg capsule
Experimental: 5mg group; Administration of HM30181AK 5mg on day 4 and Loperamide 16mg(Loperamide 2mg x 8cap) on day 1,4,8,11,15	Drug: Loperamide 2mg; Loperamide 2mg capsule; Drug: HM30181AK 5mg; HM30181AK 5mg tablet
Experimental: 10mg group; Administration of HM30181AK 10mg(HM30181AK 5mg x 2tab)on day 4 and Loperamide 16mg (Loperamide 2mg x 8cap) on day 1,4,8,11,15	Drug: Loperamide 2mg; Loperamide 2mg capsule; Drug: HM30181AK 5mg; HM30181AK 5mg tablet
Experimental: 15mg group; Administration of HM30181AK 15mg on day 4 and Loperamide 16mg (Loperamide 2mg x 8cap) on day 1,4,8,11,15	Drug: Loperamide 2mg; Loperamide 2mg capsule; Drug: HM30181AK 15mg; HM30181AK 15mg tablet
Experimental: 60mg group; Administration of HM30181AK 60mg on day 4 and Loperamide 16mg (Loperamide 2mg x 8cap) on day 1,4,8,11,15	Drug: Loperamide 2mg; Loperamide 2mg capsule; Drug: HM30181AK 60mg; HM30181AK 60mg tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Evaluate the duration of P-glycoprotein inhibition of HM30181AK by the Loperamide AUC measurement.	Day 1~Day 18

Secondary Outcome Measures

Outcome Measure	Time Frame
Evaluate the PK parameters (Cmax, AUClast, AUCinf, Tmax, T1/2, CL/F etc) of HM30181AK by measuring the blood concentration of HM30181AK	Day 4

Collaborators and Investigators

• Sponsor: Hanmi Pharmaceutical Company Limited
• Investigators: Principal Investigator: Kyung-Sang Yu, MD., Ph.D, Seoul National University Hospital

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (Actual): August 1, 2009
• Study Completion (Actual): September 1, 2009

Study Registration Dates

• First Submitted: August 6, 2009
• First Submitted That Met QC Criteria: August 6, 2009
• First Posted (Estimate): August 7, 2009

Study Record Updates

• Last Update Posted (Estimate): September 13, 2010
• Last Update Submitted That Met QC Criteria: September 10, 2010
• Last Verified: September 1, 2010

More Information

Terms related to this study

• Keywords: Pgp inhibitor; P-glycoprotein inhibitor
• Additional Relevant MeSH Terms: Gastrointestinal Agents; Loperamide; Antidiarrheals
• Other Study ID Numbers: HM-OXL-104