We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
ClinicalTrials.gov Menu

Pharmacokinetics of Oseltamivir Carboxylate In Morbidly Obese Subjects

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01179919
Recruitment Status : Completed
First Posted : August 11, 2010
Results First Posted : December 6, 2016
Last Update Posted : February 9, 2017
Hoffmann-La Roche
Information provided by (Responsible Party):
Manjunath Prakash Pai, University of Michigan

Brief 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 non-obese volunteers.

Condition or disease Intervention/treatment Phase
Obesity Drug: Oseltamivir Phase 1 Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 21 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Official Title: Oseltamivir and Oseltamivir Carboxylate Pharmacokinetics in Obese Adults
Study Start Date : July 2010
Actual Primary Completion Date : September 2010
Actual Study Completion Date : December 2010

Resource links provided by the National Library of Medicine

Drug Information available for: Oseltamivir

Arm Intervention/treatment
Experimental: Oseltamivir Dosed Group
Oseltamivir 75 mg by mouth every 12 hours for 9 doses
Drug: Oseltamivir
Capsule, 75 mg by mouth for 9 doses
Other Name: Tamiflu

Primary Outcome Measures :
  1. 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)

Secondary Outcome Measures :
  1. Steady-State Cmax and Cmin of Oseltamivir Carboxylate [ Time Frame: 6 days ]
    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)

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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)
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01179919

Layout table for location information
United States, New Jersey
TKL Research
Paramaus, New Jersey, United States, 07652
Sponsors and Collaborators
Manjunath Prakash Pai
Hoffmann-La Roche
Layout table for investigator information
Principal Investigator: Manjunath Pai, PharmD ACPHS
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Manjunath Prakash Pai, Associate Professor, University of Michigan
ClinicalTrials.gov Identifier: NCT01179919    
Other Study ID Numbers: 10-002
First Posted: August 11, 2010    Key Record Dates
Results First Posted: December 6, 2016
Last Update Posted: February 9, 2017
Last Verified: December 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: The summative data have been published and are available as open-access to the public: doi10.1128/AAC.00422-11
Keywords provided by Manjunath Prakash Pai, University of Michigan:
Pharmacokinetics in Obesity
Additional relevant MeSH terms:
Layout table for MeSH terms
Nutrition Disorders
Body Weight
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action