ObesityPhase 1/2NCT01179919
Pharmacokinetics of Oseltamivir Carboxylate In Morbidly Obese Subjects
A Phase 1/2 study testing Oseltamivir in people with Obesity, run by Manjunath Prakash Pai at 1 site in United States.
Trial summary
One in three Americans are obese. Obese subjects may or may not need higher doses of the anti-flu drug known as Tamiflu (oseltamivir). The current study is being done to see if the FDA approved dose of oseltamivir will achieve similar concentrations in obese healthy volunteers compared to that previously shown in… Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Obesity
- What is being tested?
- Oseltamivir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2010to Dec 2010
- Phase
- Phase 1/2
- 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 ≥ 40 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 pre-study screening, during entire study period and 1 week following the study period.
Who cannot join
- history of significant hypersensitivity reaction to oseltamivir
- history of gastric bypass surgical procedure
- 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)
Show all 10Show fewer
- positive urine pregnancy test (if female)
- 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
Official title: Oseltamivir and Oseltamivir Carboxylate Pharmacokinetics in Obese Adults
One in three Americans are obese. Obese subjects may or may not need higher doses of the anti-flu drug known as Tamiflu (oseltamivir). The current study is being done to see if the FDA approved dose of oseltamivir will achieve similar concentrations in obese healthy volunteers compared to that previously shown in non-obese volunteers.
Read the detailed description
The incidence of obesity has increased dramatically over the past two decades in the United States (US). Twenty-five percent of adult Americans are now classified as obese. Obesity is associated with physiological alterations that can affect drug clearance and volume of distribution. Obese subjects are often excluded from phase 1 pharmacokinetic studies. As a result, drug dosing regimens developed for clinical use may not be appropriate for the obese population. Use of fixed dosing regimens may result in under dosing of obese patients. In contrast adjustment of drug dosing based on total body weight may lead to over dosing of obese patients. Oseltamivir phosphate (Tamiflu®) is an antiviral agent that is currently dosed as 75 mg once daily for chemoprophylaxis and twice daily for treatment of influenza in adults.
Oseltamivir is rapidly converted to its active metabolite, oseltamivir carboxylate by esterases. The clearance of oseltamivir carboxylate is dependent on tubular secretion and glomerular filtration. Given that these drug elimination pathways may be enhanced in obese individuals, oseltamivir carboxylate plasma exposures may be lower in obese subjects compared to normal weight subjects. Although a specific plasma exposure target for oseltamivir carboxylate has not been established, lower oseltamivir carboxylate exposures may predispose obese patients to treatment failure and increase the probability for emergence of oseltamivir-resistant influenza virus. The current study proposes to characterize the plasma oseltamivir carboxylate concentration-time profile after multiple doses of oral oseltamivir in a cohort of healthy morbidly obese subjects. The study will be performed using a phase 1, open-label,multiple dose, pharmacokinetic study design in twenty obese adult subjects. This pilot study will provide pharmacokinetic data that may be incorporated into existing oseltamivir carboxylate population pharmacokinetic models to define appropriate doses of oseltamivir in obese patients.
- Conditions
- Obesity
- Being tested
- Oseltamivir
- Keywords
- Oseltamivir, Obesity, Influenza, Pharmacokinetics in Obesity
- Medical subject headings
- Obesity, Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OseltamivirDrug
Also called Tamiflu
Capsule, 75 mg by mouth for 9 doses
| Study group | Role | What they receive |
|---|---|---|
| Oseltamivir Dosed Group | Experimental | Oseltamivir 75 mg by mouth every 12 hours for 9 doses Receives: Drug: Oseltamivir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Steady-State AUC of Oseltamivir Carboxylate
AUC is the area under the concentration-time curve. This is measured as concentration in nanograms of oseltamivir carboxylate per milliliter of plasma multiplied by time in hours (hour*ng/mL)
Measured: 6 days
Secondary outcomes (1)
Steady-State Cmax and Cmin of Oseltamivir Carboxylate
Cmax is the maximum concentration and Cmin in the minimum concentration of oseltamivir carboxylate measured in nanogram of oseltamivir carboxylate per milliliter of plasma (ng/mL)
Measured: 6 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Aug 2010 (estimated)
- Study startJul 2010
- Primary completionSep 2010
- Study completionDec 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 ObesityStudies 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 1/2
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Manjunath Prakash Pai
- Sponsor type
- University, hospital or other
- Collaborators
- Hoffmann-La Roche
- Responsible party
- Sponsor-investigator, Manjunath Prakash Pai, University of Michigan
- Investigators
- Manjunath Pai, PharmD, Principal investigator, ACPHS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01179919
- Sponsor's protocol ID
- 10-002
- Status last verified
- Dec 2016
- First submitted
- 10 Aug 2010
- Last updated
- 9 Feb 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No: The summative data have been published and are available as open-access to the public: doi10.1128/AAC.00422-11
Publications
Pai MP, Lodise TP Jr. Oseltamivir and oseltamivir carboxylate pharmacokinetics in obese adults: dose modification for weight is not necessary. Antimicrob Agents Chemother. 2011 Dec;55(12):5640-5. doi: 10.1128/AAC.00422-11. Epub 2011 Sep 19.
PubMed 21930881
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
- Oseltamivir and Oseltamivir Carboxylate Pharmacokinetics in Obese Adults
- ClinicalTrials.gov ID
- NCT01179919
- Acronym / sponsor ID
- 10-002
- Conditions
- Obesity
- Keywords
- Oseltamivir, Obesity, Influenza, Pharmacokinetics in Obesity
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Manjunath Prakash PaiUniversity, hospital or other
- Collaborators
- Hoffmann-La Roche
- Study start
- Jul 2010
- Primary completion
- Sep 2010 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 11 Aug 2010 (estimated)
- Results
- Posted 6 Dec 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
One in three Americans are obese. Obese subjects may or may not need higher doses of the anti-flu drug known as Tamiflu (oseltamivir). The current study is being done to see if the FDA approved dose of oseltamivir will achieve similar concentrations in obese healthy volunteers compared to that previously shown in non-obese volunteers.
Detailed description
The incidence of obesity has increased dramatically over the past two decades in the United States (US). Twenty-five percent of adult Americans are now classified as obese. Obesity is associated with physiological alterations that can affect drug clearance and volume of distribution. Obese subjects are often excluded from phase 1 pharmacokinetic studies. As a result, drug dosing regimens developed for clinical use may not be appropriate for the obese population. Use of fixed dosing regimens may result in under dosing of obese patients. In contrast adjustment of drug dosing based on total body weight may lead to over dosing of obese patients. Oseltamivir phosphate (Tamiflu®) is an antiviral agent that is currently dosed as 75 mg once daily for chemoprophylaxis and twice daily for treatment of influenza in adults.
Oseltamivir is rapidly converted to its active metabolite, oseltamivir carboxylate by esterases. The clearance of oseltamivir carboxylate is dependent on tubular secretion and glomerular filtration. Given that these drug elimination pathways may be enhanced in obese individuals, oseltamivir carboxylate plasma exposures may be lower in obese subjects compared to normal weight subjects. Although a specific plasma exposure target for oseltamivir carboxylate has not been established, lower oseltamivir carboxylate exposures may predispose obese patients to treatment failure and increase the probability for emergence of oseltamivir-resistant influenza virus. The current study proposes to characterize the plasma oseltamivir carboxylate concentration-time profile after multiple doses of oral oseltamivir in a cohort of healthy morbidly obese subjects. The study will be performed using a phase 1, open-label,multiple dose, pharmacokinetic study design in twenty obese adult subjects. This pilot study will provide pharmacokinetic data that may be incorporated into existing oseltamivir carboxylate population pharmacokinetic models to define appropriate doses of oseltamivir in obese patients.
Study design
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Oseltamivir Dosed Group | Experimental | Drug: OseltamivirOseltamivir 75 mg by mouth every 12 hours for 9 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 ≥ 40 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 pre-study screening, during entire study period and 1 week following the study period.
Key exclusion criteria (10 listed)
- history of significant hypersensitivity reaction to oseltamivir
- history of gastric bypass surgical procedure
- 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
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 |
|---|---|---|
| OseltamivirAlso: TamifluCapsule, 75 mg by mouth for 9 doses | Drug | Oseltamivir Dosed Group |
Primary outcome
Steady-State AUC of Oseltamivir Carboxylate
Time frame: 6 days
AUC is the area under the concentration-time curve. This is measured as concentration in nanograms of oseltamivir carboxylate per milliliter of plasma multiplied by time in hours (hour*ng/mL)
1 secondary outcome
Steady-State Cmax and Cmin of Oseltamivir Carboxylate
Time frame: 6 days
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.
- Derived from this study: PubMed 21930881Pai MP, Lodise TP Jr. Oseltamivir and oseltamivir carboxylate pharmacokinetics in obese adults: dose modification for weight is not necessary. Antimicrob Agents Chemother. 2011 Dec;55(12):5640-5. doi: 10.1128/AAC.00422-11. Epub 2011 Sep 19.
- Individual participant dataSharing planned: No. The summative data have been published and are available as open-access to the public: doi10.1128/AAC.00422-11
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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.
Manjunath Pai, PharmD principal investigator
ACPHS
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Oseltamivir in people with Obesity, 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 10 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 6 Dec 2016). 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 AUC of Oseltamivir Carboxylate (time frame: 6 days). 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 NCT01179919, 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.