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Pharmacokinetics of Oseltamivir Carboxylate In Morbidly Obese Subjects

This study has been completed.
Sponsor:
Collaborator:
Hoffmann-La Roche
Information provided by (Responsible Party):
Manjunath Prakash Pai, University of Michigan
ClinicalTrials.gov Identifier:
NCT01179919
First received: August 10, 2010
Last updated: October 11, 2016
Last verified: October 2016
  Purpose
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 Intervention Phase
Obesity
Drug: Oseltamivir
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: Oseltamivir and Oseltamivir Carboxylate Pharmacokinetics in Obese Adults

Resource links provided by NLM:


Further study details as provided by University of Michigan:

Primary Outcome Measures:
  • Steady-State AUC of Oseltamivir Carboxylate [ Time Frame: 6 days ] [ Designated as safety issue: No ]
    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:
  • Steady-State Cmax and Cmin of Oseltamivir Carboxylate [ Time Frame: 6 days ] [ Designated as safety issue: No ]
    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)


Enrollment: 21
Study Start Date: July 2010
Study Completion Date: December 2010
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01179919

Locations
United States, New Jersey
TKL Research
Paramaus, New Jersey, United States, 07652
Sponsors and Collaborators
Manjunath Prakash Pai
Hoffmann-La Roche
Investigators
Principal Investigator: Manjunath Pai, PharmD ACPHS
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Manjunath Prakash Pai, Associate Professor, University of Michigan
ClinicalTrials.gov Identifier: NCT01179919     History of Changes
Other Study ID Numbers: 10-002 
Study First Received: August 10, 2010
Results First Received: October 11, 2016
Last Updated: October 11, 2016
Health Authority: United States: Food and Drug Administration
Individual Participant Data  
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 University of Michigan:
Oseltamivir
Obesity
Influenza
Pharmacokinetics in Obesity

Additional relevant MeSH terms:
Obesity
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Oseltamivir
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on December 08, 2016