HypertensionPhase 4NCT02147704
Effect of High- and Low-sodium Intake on the Pharmacokinetics and Pharmacodynamic Effects of Fimasartan
A Phase 4 study testing High-sodium diet and low-sodium diet in people with Hypertension, run by DongGuk University at 1 site in South Korea.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 to 45 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Hypertension
- What is being tested?
- High-sodium diet and low-sodium diet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteSouth Korea
- Study dates
- May 2014to Sep 2014
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 45 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
- The subject who has a positive result for hepatitis C antibodies, hepatitis B surface antigen,
- The subject who are unable to perform the present clinical study, judged by investigators.
Trial locations and contacts
1 site in 1 country.
South Korea1 site
Clinical Trial Center, Dongguk University Ilsan Hospital
Goyang-si, Gyeonggi-do, 440-710
About this study
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.
Read more
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.
Read the detailed description
The study design is a two-diet, two-period, two-sequence, randomized, open label and cross-over with 1-week diet-washout and 2-weeks drug-washout interval. The participants (n=16) are randomly assigned to either of 7 days of low sodium (50 mmol/day) or high sodium diet (300 mol) after hospitalization. After completion of 7-days of first period, all participants are discharge and recommended to eat usual diet. After 1-week of diet washout, all participants are hospitalized for second period. The compliance of diet is determined by measurement of 24-hour urine sodium excretion. The 24-hour urine sodium excretion should be < 100 mmol/24-hour in the low sodium diet period and > 200 mmol/24-hour in high sodium diet period.
On the morning of 7th day of each period (high sodium or low sodium diet period), all participants receive 60 mg of fimasartan in the fasting state. Blood samples for pharmacokinetic and pharmacodynamic study are drawn for 24-hour.
The detailed measures are as followings:
- High- and low-sodium intake
- One of high- or low sodium intake for 7 days during each period
- Low sodium intake : 50 mmol/day by diet
- High sodium intake: 50 mmol/day by diet + 250 mmol/day by salt tablets
- 24 hour excreted amount of sodium in urine to determine the compliance for the high- and low-sodium intake
- 24 hour excreted amount of sodium in urine for low sodium intake < 100 mmol
- 24 hour excreted amount of sodium in urine for high sodium intake > 200 mmol
- Vital signs
- Systolic and diastolic blood pressures and pulse rate in sitting position and body temperature
- Blood chemistry and complete blood count
- Measure at the morning of first day after overnight fasting
- white blood cell count, red blood count, hemoglobin, hematocrit, platelet, Calcium, sodium, potassium, glucose, blood urea nitrogen, creatinine, uric acid, cholesterol, albumin, total bilirubin, AST, ALT, blood urea nitrogen
- Urinalysis
- potential of hydrogen, protein, bilirubin, glucose, urobilinogen, ketone, nitrite, blood
- Pharmacokinetic blood sampling
- Plasma samples for fimasartan concentration
- Pharmacodynamic blood sampling
- Plasma samples for renin activity
- Serum samples for aldosterone concentration
- Conditions
- Hypertension
- Being tested
- High-sodium diet, low-sodium diet
- Medical subject headings
- Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High-sodium dietDietary supplement
- One of high- or low sodium intake for 7 days during each period
- High sodium intake: 50 mmol/day by diet + 250 mmol/day by salt tablets
low-sodium dietDietary supplement
- One of high- or low sodium intake for 7 days during each period
- Low sodium intake : 50 mmol/day by diet
| Study group | Role | What they receive |
|---|---|---|
| Goup I | Other | Group I: Fimasartan 60 mg in a low-sodium intake period --> Fimasartan 60 mg in a high-sodium intake period Receives: 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 Receives: Dietary Supplement: High-sodium diet; Dietary Supplement: low-sodium diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hr after dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 May 2014 (estimated)
- Study startMay 2014
- Primary completionJul 2014
- Study completionSep 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- DongGuk University
- Sponsor type
- University, hospital or other
- Collaborators
- Boryung Pharmaceutical Co., Ltd
- Responsible party
- Principal investigator, Moo-Yong Rhee, DongGuk University
- Investigators
- Moo-Yong Rhee, MD, PhD, Principal investigator, Clinical Trial Center, Dongguk University Ilsan Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02147704
- Sponsor's protocol ID
- DUMC-FMS-NA
- Status last verified
- Jun 2016
- First submitted
- 21 May 2014
- Last updated
- 1 Jul 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of High- and Low-sodium Intake on the Pharmacokinetics and Pharmacodynamic Effects of Fimasartan
- ClinicalTrials.gov ID
- NCT02147704
- Acronym / sponsor ID
- DUMC-FMS-NA
- Conditions
- Hypertension
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- DongGuk UniversityUniversity, hospital or other
- Collaborators
- Boryung Pharmaceutical Co., Ltd
- Study start
- May 2014
- Primary completion
- Jul 2014 (actual)
- Study completion
- Sep 2014 (actual)
- First posted
- 28 May 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The study design is a two-diet, two-period, two-sequence, randomized, open label and cross-over with 1-week diet-washout and 2-weeks drug-washout interval. The participants (n=16) are randomly assigned to either of 7 days of low sodium (50 mmol/day) or high sodium diet (300 mol) after hospitalization. After completion of 7-days of first period, all participants are discharge and recommended to eat usual diet. After 1-week of diet washout, all participants are hospitalized for second period. The compliance of diet is determined by measurement of 24-hour urine sodium excretion. The 24-hour urine sodium excretion should be < 100 mmol/24-hour in the low sodium diet period and > 200 mmol/24-hour in high sodium diet period.
On the morning of 7th day of each period (high sodium or low sodium diet period), all participants receive 60 mg of fimasartan in the fasting state. Blood samples for pharmacokinetic and pharmacodynamic study are drawn for 24-hour.
The detailed measures are as followings:
- High- and low-sodium intake
- One of high- or low sodium intake for 7 days during each period
- Low sodium intake : 50 mmol/day by diet
- High sodium intake: 50 mmol/day by diet + 250 mmol/day by salt tablets
- 24 hour excreted amount of sodium in urine to determine the compliance for the high- and low-sodium intake
- 24 hour excreted amount of sodium in urine for low sodium intake < 100 mmol
- 24 hour excreted amount of sodium in urine for high sodium intake > 200 mmol
- Vital signs
- Systolic and diastolic blood pressures and pulse rate in sitting position and body temperature
- Blood chemistry and complete blood count
- Measure at the morning of first day after overnight fasting
- white blood cell count, red blood count, hemoglobin, hematocrit, platelet, Calcium, sodium, potassium, glucose, blood urea nitrogen, creatinine, uric acid, cholesterol, albumin, total bilirubin, AST, ALT, blood urea nitrogen
- Urinalysis
- potential of hydrogen, protein, bilirubin, glucose, urobilinogen, ketone, nitrite, blood
- Pharmacokinetic blood sampling
- Plasma samples for fimasartan concentration
- Pharmacodynamic blood sampling
- Plasma samples for renin activity
- Serum samples for aldosterone concentration
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Goup I | Other | Dietary Supplement: High-sodium diet, Dietary Supplement: low-sodium dietGroup I: Fimasartan 60 mg in a low-sodium intake period --> Fimasartan 60 mg in a high-sodium intake period |
| Group II | Other | Dietary Supplement: High-sodium diet, Dietary Supplement: low-sodium dietGroup II: Fimasartan 60 mg in a high-sodium intake period --> Fimasartan 60 mg in a low-sodium intake period |
Who may qualify
- Ages
- 20 to 45 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (17 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| High-sodium diet1. 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 | Dietary supplement | Goup I, Group II |
| low-sodium diet1. One of high- or low sodium intake for 7 days during each period 2. Low sodium intake : 50 mmol/day by diet | Dietary supplement | Goup I, Group II |
Primary outcome
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
Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hr after dose
1 secondary outcome
Cmax of the study drug in each diet period
Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hr after dose
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Moo-Yong Rhee, MD, PhD principal investigator
Clinical Trial Center, Dongguk University Ilsan Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing High-sodium diet and low-sodium diet in people with Hypertension, run by DongGuk University at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hr after dose). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jul 2016.