Evaluation of Alternative Oseltamivir (Tamiflu) Dosing Strategies.

NCT00304434 | Completed Phase 4

• 1 other identifier: INDA-014-05F
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

Objective 1: Determine the safety and toxicity profile of Tamiflu administered in combination with probenecid in healthy adults.Objective 2: Determine the pharmacokinetic profile of Tamiflu and probenecid in healthy adults.

Conditions

Influenza

Keywords

Adverse effects; Antiviral; Clinical trial; Oseltamivir; Pharmacokinetics; Probenecid

Outcome Measures

Primary Outcomes (1)

• To determine whether the combination of oseltamivir and probenecid result in equivalent blood plasma concentrations compared to oseltamivir given alone

  15 days

Secondary Outcomes (1)

• The safety of combining oseltamivir and probenecid

Study Arms (1)

1

OTHER

Drug: Oseltamivir; Drug: Probenecid

Interventions

Oseltamivir DRUG

1

Probenecid DRUG

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects will include males and non-pregnant females 18 years or older Subjects who can understand the study and potential safety concerns and can sign the informed consent form prior to admission to this study Subjects that are willing to complete all the required assessments, tests and evaluations and able to make all study visits Hemoglobin \> 10.0 g/dL for males and \> 9.0 g/dL for females; b) Platelet count of \> 75,000 / L; c) Absolute neutrophil count \> 1000 / L; SGOT and SGPT \< than 2.5 times normal upper limit (UL); Serum uric acid WNL; Creatinine \< 1.5 times normal upper limit (normal UL 1.5 mg/dL) for the \< 65 years of age group and MUST be WNL for the \> 65 years of age group; creatinine clearance \> 50 mL/min

You may not qualify if:

• Subjects with a creatinine clearance of \< 50 mL/min Subjects who are pregnant or breast feeding females Subjects who are not employing adequate contraception Subjects who are drug or alcohol abusers and in the opinion of the investigator would interfere with subject compliance and safety Subjects who are currently participating in any other clinical research study Any acute serious infection requiring prescription therapy within 14 days prior to Day 1 of the study Subjects who may have or recently been exposed to influenza Subjects with gout, blood dyscrasias, or history of hypersensitivity to sulfonamide drugs Subjects with contraindications to the study medications History of allergic reaction to probenecid Have kidney disease, kidney stones, or poorly functioning kidneys Have active peptic ulcer disease On high dose aspirin or salicylate therapy
• Receiving any of the following medications (relative contraindication for probenecid):
• Acyclovir, allopurinol, penicillamine, clofibrate, rifampin, methotrexate, zidovudine, theophylline, dapsone, penicillins or cephalosporins, nonsteroidal anti-inflammatory drugs (NSAIDS) such as ibuprofen (Motrin, Advil, Nuprin, others), ketoprofen (Orudis, Oruvail, Orudis KT), diclofenac (Cataflam, Voltaren), etodolac (Lodine), fenoprofen (Nalfon), flurbiprofen (Ansaid), indomethacin (Indocin), ketorolac (Toradol), nabumetone (Relafen), oxaprozin (Daypro), piroxicam (Feldene), sulindac (Clinoril), tolmetin (Tolectin), and naproxen (Aleve, Anaprox, Naprosyn); a sulfa-based medication such as sulfamethoxazole (Bactrim, Septra, Gantanol), sulfasalazine (Azulfidine), sulfinpyrazone (Anturane), sulfisoxazole (Gantrisin), and others; an oral diabetes medicine such as glipizide (Glucotrol), glyburide (Micronase, Diabeta, Glynase), tolbutamide (Orinase), or tolazamide (Tolinase); a barbiturate such as phenobarbital (Luminal, Solfoton), amobarbital (Amytal), secobarbital (Seconal), and others; or a benzodiazepine (used to treat anxiety and panic disorders and to induce sleep) such as alprazolam (Xanax), diazepam (Valium), lorazepam (Ativan), temazepam (Restoril), chlordiazepoxide (Librium), clonazepam (Klonopin), clorazepate (Tranxene), oxazepam (Serax), estazolam (ProSom), flurazepam (Dalmane), quazepam (Doral), or triazolam (Halcion).

Sponsors & Collaborators

• US Department of Veterans Affairs: lead
• Brooke Army Medical Center: collaborator
• National Institutes of Health (NIH): collaborator

Study Sites (1)

VA Palo Alto Health Care System

Palo Alto, California, 94304-1207, United States

Location

Related Publications (5)

• He G, Massarella J, Ward P. Clinical pharmacokinetics of the prodrug oseltamivir and its active metabolite Ro 64-0802. Clin Pharmacokinet. 1999 Dec;37(6):471-84. doi: 10.2165/00003088-199937060-00003.

  PMID: 10628898 RESULT

• Massarella JW, He GZ, Dorr A, Nieforth K, Ward P, Brown A. The pharmacokinetics and tolerability of the oral neuraminidase inhibitor oseltamivir (Ro 64-0796/GS4104) in healthy adult and elderly volunteers. J Clin Pharmacol. 2000 Aug;40(8):836-43. doi: 10.1177/00912700022009567.

  PMID: 10934667 RESULT

• Hill G, Cihlar T, Oo C, Ho ES, Prior K, Wiltshire H, Barrett J, Liu B, Ward P. The anti-influenza drug oseltamivir exhibits low potential to induce pharmacokinetic drug interactions via renal secretion-correlation of in vivo and in vitro studies. Drug Metab Dispos. 2002 Jan;30(1):13-9. doi: 10.1124/dmd.30.1.13.

  PMID: 11744606 RESULT

• Holodniy M, Penzak SR, Straight TM, Davey RT, Lee KK, Goetz MB, Raisch DW, Cunningham F, Lin ET, Olivo N, Deyton LR. Pharmacokinetics and tolerability of oseltamivir combined with probenecid. Antimicrob Agents Chemother. 2008 Sep;52(9):3013-21. doi: 10.1128/AAC.00047-08. Epub 2008 Jun 16.

  PMID: 18559644 RESULT

• Raisch DW, Straight TM, Holodniy M. Thrombocytopenia from combination treatment with oseltamivir and probenecid: case report, MedWatch data summary, and review of the literature. Pharmacotherapy. 2009 Aug;29(8):988-92. doi: 10.1592/phco.29.8.988.

  PMID: 19637952 RESULT

MeSH Terms

Conditions

Influenza, Human

Interventions

Oseltamivir; Probenecid

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfonamides; Sulfones; Sulfur Compounds

Study Officials

• Mark Holodniy, MD

  VA Palo Alto Health Care System

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Intervention Model: PARALLEL
• Sponsor Type: FED

Study Record Dates

• First Submitted: March 16, 2006
• First Posted: March 17, 2006
• Study Start: February 1, 2005
• Primary Completion: February 1, 2007
• Study Completion: February 1, 2007
• Last Updated: September 23, 2009

Record last verified: 2009-09

Locations

US (1)