Effect of High- and Low-sodium Intake on the Pharmacokinetics and Pharmacodynamic Effects of Fimasartan

NCT02147704 | Completed Phase 4

• 1 other identifier: DUMC-FMS-NA
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

It has been known that the blood pressure lowering effect of angiotensin receptor antagonists (ARBs) and angiotensin converting enzyme (ACE) inhibitors is impaired in patients on high sodium intake. There was an enhanced blood pressure lowering effect of ACE inhibitor when sodium intake was restricted or diuretics were added. The reason is partially explained by sodium sensitivity or low rennin activity in high sodium intake. However, the exact mechanism of sodium intake dependency is not clearly understood. In a recent study, an ARB, candesartan was revealed to have sodium intake dependency, showing lower plasma concentration when subjects were on high sodium intake compared to on low sodium intake. However, plasma concentration of another ARB, valsartan and an ACE inhibitor ramipril was not changed depending on the sodium intake. The strongly suggested mechanism is the involvement of transporter P-glycoprotein (Pg-P). the function and expression of Pg-P are modified by genetic polymorphism of multidrug resistance 1 gene. Although the transport mechanism of Fimasartan from gut is not fully understood, it has been known that the multidrug resistance 1 is not involved. Thus, the pharmacokinetic and pharmacodynamic property of fimasartan is expected not to be affected by the status of sodium intake. The present study is designed to investigate whether the pharmacokinetic and pharmacodynamic property of fimasartan is changed depending on the sodium intake.

Conditions

Hypertension

Outcome Measures

Primary Outcomes (1)

• Area under the curve from time 0 to 24 hr (AUC0-24h) and area under the curve form time 0 to infinite (AUC0-inf) of the study drug in each diet period

  Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hr after dose

Secondary Outcomes (1)

• Cmax of the study drug in each diet period

  Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hr after dose

Other Outcomes (2)

• Change of plasma renin activity and plasma aldosterone level from the baseline in each diet period

  -24, -22, -20, -18, -16, and -12 hr before dose and predose, 2, 4, 6, 8, 12, and 24 h after dose

• Tmax and half-life of the study drug in each diet period

  Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hr after dose

Study Arms (2)

Goup I

OTHER

Group I: Fimasartan 60 mg in a low-sodium intake period --\> Fimasartan 60 mg in a high-sodium intake period

Dietary Supplement: High-sodium diet; Dietary Supplement: low-sodium diet

Group II

OTHER

Group II: Fimasartan 60 mg in a high-sodium intake period --\> Fimasartan 60 mg in a low-sodium intake period

Dietary Supplement: High-sodium diet; Dietary Supplement: low-sodium diet

Interventions

High-sodium diet DIETARY_SUPPLEMENT

1. One of high- or low sodium intake for 7 days during each period 2. High sodium intake: 50 mmol/day by diet + 250 mmol/day by salt tablets

Goup I; Group II

low-sodium diet DIETARY_SUPPLEMENT

1. One of high- or low sodium intake for 7 days during each period 2. Low sodium intake : 50 mmol/day by diet

Goup I; Group II

Eligibility Criteria

• Age: 20 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• The subject who has a body weight of 50 to 90 kg and has a body mass index (BMI) of 18.5 to 29.9 kg/m2.
• The subject who voluntarily agrees to participate in the study by written informed consent.

You may not qualify if:

• The subject who has a history of hypersensitivity reaction to fimasartan or other drugs.
• The subject who has galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption.
• The subject who has a history of any history or evidence of any clinically significant hepatic, urologic, gastrointestinal, neurologic, pulmonary, endocrinologic, musculoskeletal, hematologic, oncologic, psychiatric, cardiovascular disease.
• The subject who has a history of gastrointestinal disease (Crohn's disease, ulcer, acute or chronic pancreatitis and etc.) or surgery (except simple appendectomy or hernia repair) which can significantly affect the absorption of the study drug.
• The subject who has a systolic blood pressure (SBP) =\<90 or \>=160 mmHg, diastolic blood pressure (DBP) =\<60 or \>=90 mmHg, and/or pulse rate (PR) \>=100.
• The subject who has alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) \>1.5 x upper limit of normal.
• The subject who has a history of drug abuse.
• The subject who has participated in any interventional clinical study within 60 days prior to the study drug administration.
• The subject who has used any prescribed or traditional oriental drugs within 2 weeks, or nonprescribed drugs within 1 week prior to the study administration.
• The subject who has donated 1 unit (450 mL) of blood or more within 60 days, or received a transfusion of any blood or blood products or donated plasma within 60 days prior to the study administration.
• The subject who has eaten unusual diet which can affect the absorption, distribution, metabolism, elimination processes of the study drug.
• The subject who is a heavy smoker (\>10 cigarettes per day) within 3 months prior to Screening and unable to quit smoking during study period.
• The subject who consumes more than 21 unit/week of alcohols or unable to stop drinking during study period.
• The subjects who consumes excessive amount of grapefruit containing beverage of food and unable to quit eating or drinking them.
• The subjects who consumes excessive amount of caffeine containing beverage of food and unable to quit eating or drinking them.

Sponsors & Collaborators

• DongGuk University: lead
• Boryung Pharmaceutical Co., Ltd: collaborator

Study Sites (1)

Clinical Trial Center, Dongguk University Ilsan Hospital

Goyang-si, Gyeonggi-do, 440-710, South Korea

Location

MeSH Terms

Conditions

Hypertension

Interventions

Diet, Sodium-Restricted

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Officials

• Moo-Yong Rhee, MD, PhD

  Clinical Trial Center, Dongguk University Ilsan Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, MD, PhD, Director of Clinical Trial Center

Study Record Dates

• First Submitted: May 21, 2014
• First Posted: May 28, 2014
• Study Start: May 1, 2014
• Primary Completion: July 1, 2014
• Study Completion: September 1, 2014
• Last Updated: July 1, 2016

Record last verified: 2016-06

Locations

KR (1)