Drug Interaction of Olmesartan in Healthy Chinese VolunteersPhase 4NCT01907373
Drug Interaction Study of Olmesartan in Healthy Chinese Volunteers
A Phase 4 study testing olmesartan medoxomil and olmesartan medoxomil+probenecid in people with Drug Interaction of Olmesartan in Healthy Chinese Volunteers, run by Central South University at 1 site in China.
Trial summary
Hypertension and hyperuricaemia are widespread conditions. There is significant overlap between the two conditions. Serum uric acid (SUA) is currently recognized as a risk factor for cardiovascular disease. Read more about this study
- Who is it for?
- Ages 18 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Drug Interaction of Olmesartan in Healthy Chinese Volunteers
- What is being tested?
- olmesartan medoxomil and olmesartan medoxomil+probenecid
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteChina
- Study dates
- Aug 2009to Oct 2009
- 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 18 to 40 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- written informed consent obtained,
- age 18 to 40 years and a body mass index between 19 and 25 kg/m2;
- negative test results for HIV and hepatitis В and C non-smoking status and
- an unremarkable clinical history
Who cannot join
- has history or evidence of a renal, gastrointestinal, hepatic, or hematologic abnormality or
- any acute or chronic disease, or
- an allergy to any drugs
Trial locations and contacts
1 site in 1 country.
China1 site
Center of New Drug Clinical Trial, Hunan Provincial Tumor Hospital (The Affiliated Tumor Hospital of Xiangya Medical School of Central South University)
Changsha, Hunan, 410006
About this study
Official title: Effect of Probenecid on Pharmacokinetics, and Tolerability of Olmesartan in Healthy Chinese Volunteers
Hypertension and hyperuricaemia are widespread conditions. There is significant overlap between the two conditions. Serum uric acid (SUA) is currently recognized as a risk factor for cardiovascular disease. Thus, at some point in their therapy, hypertensive patients with hyperuricaemia are likely to require concurrent treatment with anti-hypertensive and hypouricaemic agents. For this reason, it is important to determine whether there are any pharmacokinetic interactions resulting from the concomitant administration of such agents.Olmesartan is an angiotensin II receptor antagonist and effective and well tolerated in the treatment of arterial hypertension. Probenecid is a well-established hypouricaemic agent for the treatment of hyperuricaemia and gout.The goal of this study was to examine the impact of coadministration of probenecid on the pharmacokinetic parameters and tolerability of olmesartan in healthy volunteers.
Read the detailed description
Probenecid is a well-established hypouricaemic agent for the treatment of hyperuricaemia and gout and is thought to act on urate transporter 1 (URAT1), a novel member of the organic anion transporter (OAT) family, thereby increasing uric acid excretion in the kidney by blocking urate reuptake, and then, resulting in a decrease of SUA.
Olmesartan is an angiotensin II receptor antagonist and effective and well tolerated in the treatment of arterial hypertension. Olmesartan is orally administered in the prodrug form, olmesartan medoxomil, which is converted to the pharmacologically-active compound olmesartan upon de-esterification by the enzyme arylesterase in the intestinal wall, portal blood, and liver. Olmesartan is excreted by hepatobiliary and renal systems without further metabolism, and its pharmacokinetic profile is not affected by age or gender. In addition, the pharmacokinetic and pharmacodynamic profile of olmesartan is favorable, both in terms of providing effective 24-hour blood pressure (BP) control with once-daily dosing, and in restricting the likelihood of pharmacokinetic interactions with other drugs. Studies in vitro show organic anion transporting polypeptide 1B1 (OATP1B1), OATP1B3, multidrug resistance-associated protein 2 (MRP 2), and breast cancer resistance protein (BCRP) are involved in hepatobiliary and renal transport of olmesartan. We know probenecid interferes with the kidneys' organic anion transporter (OAT). Will probenecid have effects on the pharmacokinetics of olmesartan thereby result in changes of antihypertensive effect and side effects of olmesartan? Until now, many clinical studies have shown olmesartan has no pharmacokinetic interactions with other drugs; moreover, there is no research about the interactions between olmesartan and probenecid. In this study, we assess the involvement of probenecid in the pharmacokinetics and tolerability of olmesartan.
- Being tested
- olmesartan medoxomil, olmesartan medoxomil+probenecid
- Keywords
- olmesartan, probenecid, pharmacokinetics, tolerability
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
olmesartan medoxomilDrug
Also called BENICAR, CS-866
olmesartan medoxomil+probenecidDrug
| Study group | Role | What they receive |
|---|---|---|
| olmesartan medoxomil, PK of olmesartan | Active comparator | drug: olmesartan medoxomil; dosage form: oral tablet; dosage: 20mg/time; frequency: once a day; duration: 4 days Receives: Drug: olmesartan medoxomil |
| olmesartan medoxomil+probenecid, PK of olmesartan | Experimental | drug1: olmesartan medoxomil; dosage form: oral tablet; dosage: 20mg/time; frequency: once a day; duration: 4 days; drug2: probenecid; dosage form: oral tablet; dosage: 500mg/time; frequency: 2 times/day; duration: 1 day Receives: Drug: olmesartan medoxomil+probenecid |
What is being measured
The primary outcome is the main question the study is designed to answer.
pharmacokinetic parameters
pharmacokinetic parameters:AUC0-48, AUC0→∞ and Css-av , tmax, t1/2, Css-max, and Css-min
Measured: 48 hours after last administration of olmesartan medoxomil
Secondary outcomes (1)
vital signs
vital signs: blood pressure, heart rate, and respiratory rate
Measured: at baseline (0) and at 1, 2, 3, 6, 12, 36, and 48 hours after last dosage of olmesartan medoxomil administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jul 2013 (estimated)
- Study startAug 2009
- Primary completionSep 2009
- Study completionOct 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Drug Interaction of Olmesartan in Healthy Chinese VolunteersStudies 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
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Central South University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kunyan Li, Central South University
- Investigators
- Kunyan Li, phD, Principal investigator, Center of New Drug Clinical Trial, Hunan Provincial Tumor Hospital (The Affiliated Tumor Hospital of Xiangya Medical School of Central South University)Nong Yang, MS, Study director, Center of New Drug Clinical Trial, Hunan Provincial Tumor Hospital (The Affiliated Tumor Hospital of Xiangya Medical School of Central South University)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01907373
- Sponsor's protocol ID
- 200704
- Status last verified
- Jul 2013
- First submitted
- 22 Jul 2013
- Last updated
- 25 Jul 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Li KY, Qiu Y, Jiang Y, Luo CH, Lin XP, Wang J, Yang N. Effect of probenecid on pharmacokinetics and tolerability of olmesartan in healthy chinese volunteers. Curr Ther Res Clin Exp. 2014 Jan 9;76:7-10. doi: 10.1016/j.curtheres.2013.11.004. eCollection 2014 Dec.
PubMed 25067982
Study at a glance
From the registry record, last updated by the sponsor on 25 Jul 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Probenecid on Pharmacokinetics, and Tolerability of Olmesartan in Healthy Chinese Volunteers
- ClinicalTrials.gov ID
- NCT01907373
- Acronym / sponsor ID
- 200704
- Keywords
- olmesartan, probenecid, pharmacokinetics, tolerability
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Central South UniversityUniversity, hospital or other
- Study start
- Aug 2009
- Primary completion
- Sep 2009 (actual)
- Study completion
- Oct 2009 (actual)
- First posted
- 25 Jul 2013 (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.
Hypertension and hyperuricaemia are widespread conditions. There is significant overlap between the two conditions. Serum uric acid (SUA) is currently recognized as a risk factor for cardiovascular disease. Thus, at some point in their therapy, hypertensive patients with hyperuricaemia are likely to require concurrent treatment with anti-hypertensive and hypouricaemic agents. For this reason, it is important to determine whether there are any pharmacokinetic interactions resulting from the concomitant administration of such agents.Olmesartan is an angiotensin II receptor antagonist and effective and well tolerated in the treatment of arterial hypertension. Probenecid is a well-established hypouricaemic agent for the treatment of hyperuricaemia and gout.The goal of this study was to examine the impact of coadministration of probenecid on the pharmacokinetic parameters and tolerability of olmesartan in healthy volunteers.
Detailed description
Probenecid is a well-established hypouricaemic agent for the treatment of hyperuricaemia and gout and is thought to act on urate transporter 1 (URAT1), a novel member of the organic anion transporter (OAT) family, thereby increasing uric acid excretion in the kidney by blocking urate reuptake, and then, resulting in a decrease of SUA.
Olmesartan is an angiotensin II receptor antagonist and effective and well tolerated in the treatment of arterial hypertension. Olmesartan is orally administered in the prodrug form, olmesartan medoxomil, which is converted to the pharmacologically-active compound olmesartan upon de-esterification by the enzyme arylesterase in the intestinal wall, portal blood, and liver. Olmesartan is excreted by hepatobiliary and renal systems without further metabolism, and its pharmacokinetic profile is not affected by age or gender. In addition, the pharmacokinetic and pharmacodynamic profile of olmesartan is favorable, both in terms of providing effective 24-hour blood pressure (BP) control with once-daily dosing, and in restricting the likelihood of pharmacokinetic interactions with other drugs. Studies in vitro show organic anion transporting polypeptide 1B1 (OATP1B1), OATP1B3, multidrug resistance-associated protein 2 (MRP 2), and breast cancer resistance protein (BCRP) are involved in hepatobiliary and renal transport of olmesartan. We know probenecid interferes with the kidneys' organic anion transporter (OAT). Will probenecid have effects on the pharmacokinetics of olmesartan thereby result in changes of antihypertensive effect and side effects of olmesartan? Until now, many clinical studies have shown olmesartan has no pharmacokinetic interactions with other drugs; moreover, there is no research about the interactions between olmesartan and probenecid. In this study, we assess the involvement of probenecid in the pharmacokinetics and tolerability of olmesartan.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| olmesartan medoxomil, PK of olmesartan | Active comparator | Drug: olmesartan medoxomildrug: olmesartan medoxomil; dosage form: oral tablet; dosage: 20mg/time; frequency: once a day; duration: 4 days |
| olmesartan medoxomil+probenecid, PK of olmesartan | Experimental | Drug: olmesartan medoxomil+probeneciddrug1: olmesartan medoxomil; dosage form: oral tablet; dosage: 20mg/time; frequency: once a day; duration: 4 days; drug2: probenecid; dosage form: oral tablet; dosage: 500mg/time; frequency: 2 times/day; duration: 1 day |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- written informed consent obtained,
- age 18 to 40 years and a body mass index between 19 and 25 kg/m2;
- negative test results for HIV and hepatitis В and C non-smoking status and
- an unremarkable clinical history
Key exclusion criteria (3 listed)
- has history or evidence of a renal, gastrointestinal, hepatic, or hematologic abnormality or
- any acute or chronic disease, or
- an allergy to any drugs
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 |
|---|---|---|
| olmesartan medoxomilAlso: BENICAR, CS-866 | Drug | olmesartan medoxomil, PK of olmesartan |
| olmesartan medoxomil+probenecid | Drug | olmesartan medoxomil+probenecid, PK of olmesartan |
Primary outcome
pharmacokinetic parameters
Time frame: 48 hours after last administration of olmesartan medoxomil
pharmacokinetic parameters:AUC0-48, AUC0→∞ and Css-av , tmax, t1/2, Css-max, and Css-min
1 secondary outcome
vital signs
Time frame: at baseline (0) and at 1, 2, 3, 6, 12, 36, and 48 hours after last dosage of olmesartan medoxomil administration
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 25 Jul 2013.
- Derived from this study: PubMed 25067982Li KY, Qiu Y, Jiang Y, Luo CH, Lin XP, Wang J, Yang N. Effect of probenecid on pharmacokinetics and tolerability of olmesartan in healthy chinese volunteers. Curr Ther Res Clin Exp. 2014 Jan 9;76:7-10. doi: 10.1016/j.curtheres.2013.11.004. eCollection 2014 Dec.
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.
Kunyan Li, phD principal investigator
Center of New Drug Clinical Trial, Hunan Provincial Tumor Hospital (The Affiliated Tumor Hospital of Xiangya Medical School of Central South University)
Nong Yang, MS study director
Center of New Drug Clinical Trial, Hunan Provincial Tumor Hospital (The Affiliated Tumor Hospital of Xiangya Medical School of Central South University)
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 olmesartan medoxomil and olmesartan medoxomil+probenecid in people with Drug Interaction of Olmesartan in Healthy Chinese Volunteers, run by Central South University at 1 site in China.
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 4 inclusion and 3 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 25 Jul 2013. 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 China. 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?
pharmacokinetic parameters (time frame: 48 hours after last administration of olmesartan medoxomil). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01907373, which also lists 1 linked publication.
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 25 Jul 2013.