HealthyPhase 4NCT01030653
Pharmacokinetics of Voriconazole in Obese Subjects
A Phase 4 study testing Voriconazole low dose and Voriconazole high dose in people with Healthy, run by Manjunath Prakash Pai at 1 site in United States.
Trial summary
Obese subjects may require a higher fixed oral maintenance dosing regimen of voriconazole compared to normal weight subjects to achieve comparable plasma exposures. The current study is designed to address this issue. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Voriconazole low dose and Voriconazole high dose
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2009to May 2010
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- males and females, 18 to 50 years of age;
- non-smoking or light-smoking (≤5 cigarettes per day) volunteers;
- BMI ≥ 35 kg/m2;
- female subjects of childbearing potential either surgically sterilized, using an effective method of contraception (diaphragm, cervical cap, condom) or agree to abstain from sex from time of prestudy screening, during entire study period and 1 week following the study period.
Who cannot join
- History of significant hypersensitivity reaction or intolerance to voriconazole, fluconazole,itraconazole, posaconazole, or ketoconazole ;
- history of significant clinical illness requiring pharmacological management;
- abnormal serum electrolyte or complete blood count requiring further clinical work-up;
- transaminases (AST or ALT) >2.5 x upper limit of normal;
- estimated creatinine clearance <50 mL/min (Cockcroft-Gault equation);
- positive urine pregnancy test (if female);
Show all 9Show fewer
- abnormal electrocardiogram (ECG) as judged by study physician;
- unable to tolerate venipuncture and multiple blood draws;
- clinically significant abnormal physical examination defined as a physical finding requiring further clinical work-up.
Trial locations and contacts
1 site in 1 country.
About this study
Obese subjects may require a higher fixed oral maintenance dosing regimen of voriconazole compared to normal weight subjects to achieve comparable plasma exposures. The current study is designed to address this issue.
Read the detailed description
The prevalence of obesity has increased tremendously in the past two decades. An estimated 1 out of 5 persons in the United States are classified as obese. Under representation of obese patients in pharmacokinetic trials grossly limit generalizability of drug dosing recommendations in this emerging population. No published pharmacokinetic studies of voriconazole dosing in patients with obesity currently exist in the literature. Specifically,voriconazole pharmacokinetic data from subjects with a body mass index (BMI) ≥ 35 kg/m2(Class II and III obesity) are limited.
Voriconazole is available as both an intravenous and oral formulation. Anecdotal experience suggest that the use of oral voriconazole to be significantly more prevalent that that of intravenous therapy. The current oral recommended dosing regimen for voriconazole includes use of 200 mg every 12 hours for patients who are over 40 kg. The dosage can be increased to 300 mg by mouth every 12 hours in situations where a sufficient clinical response is not noted. A weight based dosing strategy is also utilized in patients with more serious infections (3-6 mg/kg IV Q 12 hours) such as invasive aspergillosis. Voriconazole demonstrates non-linear pharmacokinetics and so dosing based on total body weight may result in non-dose proportional exposure. For example, a 1.5 fold dose increment in voriconazole from 200 mg to 300 mg every 12 hours results in a 2.5 fold increase in exposure. The most appropriate body size descriptor is unknown (i.e. ideal body weight, fat free weight, lean body weight, etc.) for most antimicrobials, including voriconazole. As a consequence, the appropriateness of weight-based voriconazole dosage selection in obese patients is not known. Intuitively, weight based dosing (on total body weight) in this population could lead to higher than expected exposures (non-linear pharmacokinetics) and lead to potential adverse events. Therapeutic drug monitoring is increasingly advocated as a system to improve voriconazole dosing. However, an assay to measure voriconazole concentrations in the clinic is not routinely available. Hence, the current pilot study proposes to characterize the pharmacokinetic profile of voriconazole in obese subjects using two fixed dose regimens.
- Conditions
- Healthy
- Being tested
- Voriconazole low dose, Voriconazole high dose
- Keywords
- Voriconazole, Pharmacokinetics, Obese, Healthy Volunteer
- Medical subject headings
- Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Voriconazole low doseDrug
Also called Vfend
Voriconazole 400 mg po x 2 doses (loading dose)then 200 mg po twice daily x 7 doses
Voriconazole high doseDrug
Also called Vfend
Voriconazole 400 mg po x 2 doses (loading dose)then 300 mg po twice daily x 7 doses
| Study group | Role | What they receive |
|---|---|---|
| Voriconazole low dose first then high dose | Experimental | Voriconazole administered by Mouth as a Loading Dose (400 mg x 2 Doses, Day 1) and as Maintenance Doses (200 mg Every 12 Hours x 7 Doses) followed by 7 day washout followed by Loading Dose (400 mg x 2 Doses, Day 1) and a Maintenance Doses (300 mg Every 12 Hours x 7 Doses) Receives: Drug: Voriconazole low dose; Drug: Voriconazole high dose |
| Voriconazole high dose first then low dose | Experimental | Voriconazole administered by Mouth as a Loading Dose (400 mg x 2 Doses, Day 1) and as Maintenance Doses (300 mg Every 12 Hours x 7 Doses) followed by 7 day washout followed by Loading Dose (400 mg x 2 Doses, Day 1) and a Maintenance Doses (200 mg Every 12 Hours x 7 Doses) Receives: Drug: Voriconazole low dose; Drug: Voriconazole high dose |
What is being measured
The primary outcome is the main question the study is designed to answer.
Steady-State Cmax and Cmin of Two Voriconazole Dosing Regimens
Cmax is the maximum concentration, and Cmin is the minimum concentration. These measurements are based on analysis of plasma. The units shown are milligrams of voriconazole per liter of plasma. The two dosing regimens are:
- a loading dose (400 mg x 2 doses, day 1) and maintenance doses (200 mg every 12 hours x 7 doses) in obese subjects.
- a loading dose (400 mg x 2 doses, day 1) and maintenance doses (300 mg every 12 hours x 7 doses) in obese subjects.
Measured: Day 5
Geometric Mean Ratio of the AUC Between the High and Low Dose Voriconazole
AUC is the area under the concentration-time curve. The Geometric Mean Ratio and 90% confidence interval around this value permit an assessment of the bioequivalence of two dosing regimens in the same group. The geometric mean is computed based on the ratio of the AUC value from the high dose compared to the AUC value from the low dose for each individual. This ratio provides a more robust interpretation of the differences between the two dosing arms because each individual serves as their own control.
Measured: 14 days
Secondary outcomes (1)
The Area Under the Curve Over the Dosing Interval for All Participants While on the High Dose and Low Dose Interventions.
Measured: 12 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2009 (estimated)
- Study startNov 2009
- Primary completionApr 2010
- Study completionMay 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies 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
- Health services research
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Manjunath Prakash Pai
- Sponsor type
- University, hospital or other
- Collaborators
- TKL Research, Inc., Pfizer
- Responsible party
- Sponsor-investigator, Manjunath Prakash Pai, University of Michigan
- Investigators
- Manjunath P Pai, PharmD, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01030653
- Sponsor's protocol ID
- 09010
- Status last verified
- Dec 2016
- First submitted
- 10 Dec 2009
- Last updated
- 9 Feb 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Pai MP, Norenberg JP, Anderson T, Goade DW, Rodvold KA, Telepak RA, Mercier RC. Influence of morbid obesity on the single-dose pharmacokinetics of daptomycin. Antimicrob Agents Chemother. 2007 Aug;51(8):2741-7. doi: 10.1128/AAC.00059-07. Epub 2007 Jun 4.
PubMed 17548489
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetics of Voriconazole in Obese Subjects
- ClinicalTrials.gov ID
- NCT01030653
- Acronym / sponsor ID
- 09010
- Conditions
- Healthy
- Keywords
- Voriconazole, Pharmacokinetics, Obese, Healthy Volunteer
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Manjunath Prakash PaiUniversity, hospital or other
- Collaborators
- TKL Research, Inc., Pfizer
- Study start
- Nov 2009
- Primary completion
- Apr 2010 (actual)
- Study completion
- May 2010 (actual)
- First posted
- 11 Dec 2009 (estimated)
- Results
- Posted 9 Feb 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Obese subjects may require a higher fixed oral maintenance dosing regimen of voriconazole compared to normal weight subjects to achieve comparable plasma exposures. The current study is designed to address this issue.
Detailed description
The prevalence of obesity has increased tremendously in the past two decades. An estimated 1 out of 5 persons in the United States are classified as obese. Under representation of obese patients in pharmacokinetic trials grossly limit generalizability of drug dosing recommendations in this emerging population. No published pharmacokinetic studies of voriconazole dosing in patients with obesity currently exist in the literature. Specifically,voriconazole pharmacokinetic data from subjects with a body mass index (BMI) ≥ 35 kg/m2(Class II and III obesity) are limited.
Voriconazole is available as both an intravenous and oral formulation. Anecdotal experience suggest that the use of oral voriconazole to be significantly more prevalent that that of intravenous therapy. The current oral recommended dosing regimen for voriconazole includes use of 200 mg every 12 hours for patients who are over 40 kg. The dosage can be increased to 300 mg by mouth every 12 hours in situations where a sufficient clinical response is not noted. A weight based dosing strategy is also utilized in patients with more serious infections (3-6 mg/kg IV Q 12 hours) such as invasive aspergillosis. Voriconazole demonstrates non-linear pharmacokinetics and so dosing based on total body weight may result in non-dose proportional exposure. For example, a 1.5 fold dose increment in voriconazole from 200 mg to 300 mg every 12 hours results in a 2.5 fold increase in exposure. The most appropriate body size descriptor is unknown (i.e. ideal body weight, fat free weight, lean body weight, etc.) for most antimicrobials, including voriconazole. As a consequence, the appropriateness of weight-based voriconazole dosage selection in obese patients is not known. Intuitively, weight based dosing (on total body weight) in this population could lead to higher than expected exposures (non-linear pharmacokinetics) and lead to potential adverse events. Therapeutic drug monitoring is increasingly advocated as a system to improve voriconazole dosing. However, an assay to measure voriconazole concentrations in the clinic is not routinely available. Hence, the current pilot study proposes to characterize the pharmacokinetic profile of voriconazole in obese subjects using two fixed dose regimens.
Study design
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Voriconazole low dose first then high dose | Experimental | Drug: Voriconazole low dose, Drug: Voriconazole high doseVoriconazole administered by Mouth as a Loading Dose (400 mg x 2 Doses, Day 1) and as Maintenance Doses (200 mg Every 12 Hours x 7 Doses) followed by 7 day washout followed by Loading Dose (400 mg x 2 Doses, Day 1) and a Maintenance Doses (300 mg Every 12 Hours x 7 Doses) |
| Voriconazole high dose first then low dose | Experimental | Drug: Voriconazole low dose, Drug: Voriconazole high doseVoriconazole administered by Mouth as a Loading Dose (400 mg x 2 Doses, Day 1) and as Maintenance Doses (300 mg Every 12 Hours x 7 Doses) followed by 7 day washout followed by Loading Dose (400 mg x 2 Doses, Day 1) and a Maintenance Doses (200 mg Every 12 Hours x 7 Doses) |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- males and females, 18 to 50 years of age;
- non-smoking or light-smoking (≤5 cigarettes per day) volunteers;
- BMI ≥ 35 kg/m2;
- female subjects of childbearing potential either surgically sterilized, using an effective method of contraception (diaphragm, cervical cap, condom) or agree to abstain from sex from time of prestudy screening, during entire study period and 1 week following the study period.
Key exclusion criteria (9 listed)
- History of significant hypersensitivity reaction or intolerance to voriconazole, fluconazole,itraconazole, posaconazole, or ketoconazole ;
- history of significant clinical illness requiring pharmacological management;
- abnormal serum electrolyte or complete blood count requiring further clinical work-up;
- transaminases (AST or ALT) >2.5 x upper limit of normal;
- estimated creatinine clearance <50 mL/min (Cockcroft-Gault equation);
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 |
|---|---|---|
| Voriconazole low doseAlso: VfendVoriconazole 400 mg po x 2 doses (loading dose)then 200 mg po twice daily x 7 doses | Drug | Voriconazole high dose first then low dose, Voriconazole low dose first then high dose |
| Voriconazole high doseAlso: VfendVoriconazole 400 mg po x 2 doses (loading dose)then 300 mg po twice daily x 7 doses | Drug | Voriconazole high dose first then low dose, Voriconazole low dose first then high dose |
Primary outcome
Steady-State Cmax and Cmin of Two Voriconazole Dosing Regimens
Time frame: Day 5
Cmax is the maximum concentration, and Cmin is the minimum concentration. These measurements are based on analysis of plasma. The units shown are milligrams of voriconazole per liter of plasma. The two dosing regimens are: 1. a loading dose (400 mg x 2 doses, day 1) and maintenance doses (200 mg every 12 hours x 7 doses) in obese subjects. 2. a loading dose (400 mg x 2 doses, day 1) and maintenance doses (300 mg every 12 hours x 7 doses) in obese subjects.
Geometric Mean Ratio of the AUC Between the High and Low Dose Voriconazole
Time frame: 14 days
AUC is the area under the concentration-time curve. The Geometric Mean Ratio and 90% confidence interval around this value permit an assessment of the bioequivalence of two dosing regimens in the same group. The geometric mean is computed based on the ratio of the AUC value from the high dose compared to the AUC value from the low dose for each individual. This ratio provides a more robust interpretation of the differences between the two dosing arms because each individual serves as their own control.
1 secondary outcome
The Area Under the Curve Over the Dosing Interval for All Participants While on the High Dose and Low Dose Interventions.
Time frame: 12 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 17548489Pai MP, Norenberg JP, Anderson T, Goade DW, Rodvold KA, Telepak RA, Mercier RC. Influence of morbid obesity on the single-dose pharmacokinetics of daptomycin. Antimicrob Agents Chemother. 2007 Aug;51(8):2741-7. doi: 10.1128/AAC.00059-07. Epub 2007 Jun 4.
Related trials for Healthy
Recruiting
THE EFFECTS OF GAME-BASED EXERCISE PROGRAMS
Physical Activity, Body Image
Not yet recruitingPhase 1
A Phase I Study of GLR2053 Tablets in Chinese Healthy Adult Participants
Atopic Dermatitis
Recruiting
Colon-delivered Riboflavin and Gut Microbiota Composition
Microbiome Dysbiosis, Gut Health
Not yet recruiting
Neuroergonomic Analysis of a Brain-Computer Interface Device (BCI)
Healthy Volunteers - Male and Female
RecruitingPhase 1
First-in-Human Trial to Assess REGN20423 in Healthy Adult Participants and Adult Participants With Atopic Dermatitis
Healthy Volunteer, Atopic Dermatitis
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.
Manjunath P Pai, PharmD principal investigator
University of Michigan
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 Voriconazole low dose and Voriconazole high dose in people with Healthy, run by Manjunath Prakash Pai at 1 site in United States.
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 9 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 9 Feb 2017. 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 United States. 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?
Yes. Results are posted in the registry (first posted 9 Feb 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Steady-State Cmax and Cmin of Two Voriconazole Dosing Regimens (time frame: Day 5). The study lists 2 primary outcomes in all. 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 NCT01030653, 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 9 Feb 2017.