Open-Label Pharmacokinetic of Oseltamivir in Healthy Obese Thai Adult Subjects

October 7, 2010 updated by: South East Asia Infectious Disease Clinical Research Network

Phase I, Open-Label Study to Evaluate Potential Pharmacokinetic of Orally Administered Oseltamivir in Healthy Obese Thai Adult Subjects

This study is planned to characterize the pharmacokinetic properties of oseltamivir and the active product--oseltamivir carboxylate--in obesity in order to provide clinical guidance for the optimum oseltamivir treatment regimens for severe influenza. It is also a prompt response to a new era influenza plan along with recognition of growing numbers of obese persons.

The study findings will be available for a future management plan in dealing with this virus that is transmitted easily from person to person and has shown substantial antigenic changes over time.

The primary focus of statistical analysis is to verify the effect of obesity on oseltamivir/oseltamivir carboxylate pharmacokinetics as measured by oseltamivir carboxylate Cmax, AUC (0-12), AUC (0-24), C12, λz, and t1/2 and oseltamivir Cmax, AUC (0-12), and C12.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is an open-label, cross-over, randomized pharmacokinetic study conducted in approximately 12 obese and 12 non obese adult subjects at one study center in Thailand.

Subjects will receive 2 regimens in a random sequence for 2 visits.

  1. Regimen A; 75 mg single dose.
  2. Regimen B; 150 mg single dose. All dosing will be supervised and documented. Subjects will have 2 hospitalizations to complete visit 2 and visit 3 in their assigned sequence within each. Each visit will require hospitalization for about 40 hours (2 nights and 2 days). The subject will be randomized to receive either regimen A or B on first admission (visit 2). Treatment allocation will be performed using computer-generated list of random permutations of AB sequence.

Subjects who received regimen A will receive regimen B on second admission and vice versa, with more than 3 days wash out period in between. Subjects will return to the study centre for a follow-up visit 7-10 days after completing the last dosing assessments or withdrawing from the study. The total duration of study participation will be approximately 4 weeks from screening through follow-up.

Assessment of the safety profile will be done after each admission by the investigating team before proceeding to the other regimen.

Study Type

Interventional

Enrollment (Actual)

24

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Thailand
      • Bangkok,, Thailand
        • Mahidol-Oxford Tropical Medicine Research Unit Faculty of Tropical Medicine, Mahidol University Bangkok

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Healthy as judged by a responsible physician with no abnormality identified on a medical evaluation including medical history and physical examination.
  • Males and Females aged between 18 years to 60 years.
  • BMI >30 kg/ m2 (BMI = body weight [BW] (kg)/height (m2)) for obese group, BMI 18-24.9 kg/ m2 (BMI = BW (kg)/height (m2)) for control group.

  • A female is eligible to enter and participate in this study if she is:

    • of non-childbearing potential including pre-menopausal females with documented (medical report verification) hysterectomy or double oophorectomy
    • or postmenopausal defined as 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum follicle stimulating hormone levels >40 mIU/mL or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy
    • or of childbearing potential, has a negative serum pregnancy test at screening and prior to start the study drug in each period, and abstain from sexual intercourse or agrees to using effective contraceptive methods during the study until completion of the follow-up procedures
  • A male is eligible to enter and participate in this study if he: agrees to abstain from (or use a condom during) sexual intercourse with females of childbearing potential or lactating females; or is willing to use a condom/spermicide, during the study until completion of the follow-up procedures.
  • Read, comprehend, and write at a sufficient level to complete study-related materials.
  • Provide a signed and dated written informed consent prior to study participation.
  • Normal electrocardiogram (ECG) with QTc <450 msec.
  • Willingness and ability to comply with the study protocol for the duration of the trial.

Exclusion Criteria:

  • Females who are pregnant, trying to get pregnant, or are lactating.
  • The subject has evidence of active substance abuse that may compromise safety, pharmacokinetics, or ability to adhere with protocol instructions.
  • A positive pre-study hepatitis B surface antigen, positive hepatitis C antibody, or positive human immunodeficiency virus-1 (HIV-1) antibody result at screening.
  • Subjects with a personal history of cardiac disease, symptomatic or asymptomatic arrhythmias, syncopal episodes, or additional risk factors for torsades de points (heart failure, hypokalemia).
  • Subjects with a family history of sudden cardiac death.
  • A creatinine clearance <70 mL/min as determined by Cockcroft-Gault equation:

CLcr (mL/min) = (140 - age) * Wt / (72 * Scr) (multiply answer by 0.85 for females). Where age is in years, weight (wt) is in kg, and serum creatinine (Scr) is in units of mg/dL [Cockcroft, 1976].

  • History of alcohol or substance abuse or dependence within 6 months of the study: History of regular alcohol consumption averaging >7 drinks/wk for women or >14 drinks/wk for men. One drink is equivalent to 12 g alcohol = 5 oz (150 mL) of wine or 12 oz (360 mL) of beer or 1.5 oz (45 mL) of 80 proof distilled spirits within 6 months of screening.
  • Use of prescription or non-prescription drugs except paracetamol at doses of up to 2 grams/day, including vitamins, herbal and dietary supplements within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication until the completion of the follow-up procedure.
  • Use of live attenuated influenza vaccine, inactivated influenza vaccine, or any other antiinfluenza antiviral medications within 14 days prior to the first dose of investigational product.
  • The subject has participated in a clinical trial and has received a drug or a new chemical entity within 30 days or 5 half lives, or twice the duration of the biological effect of any drug (whichever is longer) prior to the first dose of study medication.
  • The subject is unwilling to abstain from ingesting alcohol within 48 hours prior to the first dose of study medication until collection of the final pharmacokinetic sample during each regimen.
  • Subjects who have donated blood to the extent that participation in the study would result in more than 300 mL blood donated within a 30-day period.
  • Subjects who have a history of allergy to the study drug or drugs of this class, or a history of drug or other allergy that, in the opinion of the investigator, contraindicates participation in the trial. In addition, if heparin is used during pharmacokinetic sampling, subjects with a history of sensitivity to heparin or heparin-induced thrombocytopenia should not be enrolled.
  • Subjects with unstable medical conditions that, in the opinion of the investigator would compromise their participation in the trial
  • Those who, in the opinion of the investigator, have a risk of non-compliance with study procedures.
  • Lack of suitability for participation in this study, for any reason, in the opinion of the investigator.
  • AST or ALT >1.5 upper limit of normal (ULN)
  • Subjects with history of renal disease, hepatic disease, and/or cholecystectomy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Regimen A
oseltamivir 75 mg single dose
Drug: oseltamivir
oseltamivir 150 mg single oral dose oseltamivir 75 mg single oral dose
Active Comparator: Regimen B
oseltamivir 150 mg single dose
Drug: oseltamivir
oseltamivir 150 mg single oral dose oseltamivir 75 mg single oral dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Oseltamivir carboxylate maximum concentration (OC Cmax) and area under the concentration curve 0-12h (OC AUC(0-12))
Time Frame: 12 hours
12 hours

Secondary Outcome Measures

Outcome Measure
Time Frame
Oseltamivir maximum concentration at 12 hours (OS C12) Oseltamivir carboxylate area under the concentration curve 0-24 hours AUC(0-24)), concentration at 24 hours (C24), elimination rate constant (OC-λz), and elimination half life (t1/2)
Time Frame: 1 weeks
1 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

South East Asia Infectious Disease Clinical Research Network

Collaborators

University of Oxford

Investigators

  • Principal Investigator: Podjanee Jittmala, MD, Mahidol-Oxford Tropical Medicine Research Unit Faculty of Tropical Medicine, Mahidol University
  • Study Chair: Sasithon Pukrittayakamee, Professor, Faculty of Tropical Medicine, Mahidol University Bangkok, Thailand
  • Study Chair: Pratap Singhasivanon, A/Professor, Faculty of Tropical Medicine, Mahidol University Bangkok, Thailand
  • Study Chair: Nick White, Professor, Mahidol-Oxford Tropical Medicine Research Unit Faculty of Tropical Medicine, Mahidol University Bangkok, Thailand
  • Study Chair: Nick Day, Professor, Mahidol-Oxford Tropical Medicine Research Unit Faculty of Tropical Medicine, Mahidol University Bangkok, Thailand
  • Study Chair: Niklas Lindegardh, A/Professor, Clinical Pharmacology Laboratory Faculty of Tropical Medicine, Mahidol University Bangkok, Thailand
  • Study Chair: Bob Taylor, MD, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University Bangkok, Thailand

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2010

Primary Completion (Actual)

September 1, 2010

Study Completion (Actual)

October 1, 2010

Study Registration Dates

First Submitted

January 13, 2010

First Submitted That Met QC Criteria

January 13, 2010

First Posted (Estimate)

January 14, 2010

Study Record Updates

Last Update Posted (Estimate)

October 8, 2010

Last Update Submitted That Met QC Criteria

October 7, 2010

Last Verified

October 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SEA 131

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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