Pharmacokinetics/Pharmacodynamics (PK/PD) Characteristics of Tolvaptan Tablet in Korean Healthy Male

A Dose Block-randomized, Double-blind, Placebo-controlled, Single Dose, Dose-escalation Study to Investigate the Safety, Tolerance, Pharmacokinetics and Pharmacodynamics of Tolvaptan in Healthy Korean Male Subjects Bipolar Disorder

To investigate the safety, tolerance, pharmacokinetics and pharmacodynamics of tolvaptan 15, 30 and 60 mg after single oral administration in healthy Korean male subjects.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Tolvaptan 15mg or 30mg or 60mg or Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 46
• 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 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Healthy Korean male subjects between 20 and 45 years of age, inclusive.
2. Body Mass Index (BMI) of 20 to 26 kg/m2, body,weight ≥ 50kg BMI = weight (kg)/height2(m)
3. Informed consent from the subjects

Exclusion Criteria:

1. Clinically significant abnormality of respiratory, cardiovascular, hepatic, neurologic, endocrine, hematologic, urinary, psychiatric.
2. History of gastrointestinal disease or surgery which can affect intestinal absorption of the study drug.
3. History of any significant drug allergy or hypersensitivity.
4. AST or ALT > 1.25 times upper normal limit at screening clinical laboratory test
5. Supine blood pressure after resting for ≥ 3 minutes, higher than 140/90 mmHg or lower than 100/50 mmHg, Supine pulse, after resting for ≥ 3 minutes, outside the range of 40 to 90 beats/minute.
6. Subjects who had history of drug abuse or alcohol addiction
7. Subjects who used of any prescription drug or herbal medication within 2 weeks prior to the first dosing of the study drug, or any over-the-counter or vitamin supplements within 1 week prior to the first dosing (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)
8. 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: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; Single dose, Tolvaptan 15mg or Placebo/day	Drug: Tolvaptan 15mg or 30mg or 60mg or Placebo; Single dose of Tolvaptan 15mg or 30mg or 60mg or Placebo per day
Experimental: Arm 2; Single dose, Tolvaptan 30mg or Placebo/day	Drug: Tolvaptan 15mg or 30mg or 60mg or Placebo; Single dose of Tolvaptan 15mg or 30mg or 60mg or Placebo per day
Experimental: Arm 3; Single dose, Tolvaptan 60mg or Placebo/day	Drug: Tolvaptan 15mg or 30mg or 60mg or Placebo; Single dose of Tolvaptan 15mg or 30mg or 60mg or Placebo per day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
PK parameters: AUC, Cmax, Tmax	1 day
PD parameters: 24 hour fluid balance	1 day
Safety: adverse event, body weight, physical examination, vital sign, ECG, clinical laboratory test	4 days

Collaborators and Investigators

• Sponsor: Korea Otsuka Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Kyung-sang Yu, MD, Seoul National University Hospital

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): March 1, 2010

Study Registration Dates

• First Submitted: November 3, 2009
• First Submitted That Met QC Criteria: November 15, 2009
• First Posted (Estimate): November 17, 2009

Study Record Updates

• Last Update Posted (Estimate): March 11, 2010
• Last Update Submitted That Met QC Criteria: March 10, 2010
• Last Verified: March 1, 2010

More Information

Terms related to this study

• Keywords: Healthy Korean male
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Natriuretic Agents; Antidiuretic Hormone Receptor Antagonists; Tolvaptan
• Other Study ID Numbers: 156-KOA-0801