Pharmacokinetics of Oseltamivir Carboxylate In Morbidly Obese Subjects

NCT ID: NCT01179919

Last Updated: 2017-02-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-07-31
• Study Completion Date: 2010-12-31

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.

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Blinding Strategy: NONE

Study Groups

Oseltamivir Dosed Group

Oseltamivir 75 mg by mouth every 12 hours for 9 doses

Group Type: EXPERIMENTAL

Oseltamivir

Intervention Type: DRUG

Capsule, 75 mg by mouth for 9 doses

Interventions

Oseltamivir

Capsule, 75 mg by mouth for 9 doses

Intervention Type: DRUG

Other Intervention Names

Tamiflu

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: collaborator

Manjunath Prakash Pai

OTHER

Sponsor Role: lead

Responsible Party

Manjunath Prakash Pai

Associate Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Manjunath Pai, PharmD

Role: PRINCIPAL_INVESTIGATOR

ACPHS

Locations

TKL Research

Paramaus, New Jersey, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 21930881 (View on PubMed)

Other Identifiers

10-002

Identifier Type: -

Identifier Source: org_study_id