InfluenzaPhase 1NCT00921726
Pharmacokinetic Study of Oseltamivir and Intravenous Zanamivir in Healthy Adults
A Phase 1 study testing Zanamivir and Oseltamivir in people with Influenza and Virus Diseases, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in Thailand.
Trial summary
Due in part to widespread availability of oseltamivir and clinical experience using oseltamivir to treat H5N1 influenza virus infections, many strains of influenza have become resistant to it. Other reliable methods of treating H5N1 must be identified in case of a pandemic. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Influenza, Virus Diseases
- What is being tested?
- Zanamivir and Oseltamivir
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteThailand
- Study dates
- Jul 2009to Oct 2009
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Good general health
- Body mass index between 17 - 32 kg/m^2
- Body weight of at least 37 kg
- Able to read, comprehend, and write at a sufficient level to complete study-related materials
- Normal ECG with QTC less than 450 msec as judged by cardiologist
- Willing and ability to comply with the study protocol for the duration of the trial
Who cannot join
- History of cardiac disease or abnormality. More information on this criterion can be found in the protocol.
- Family history of sudden cardiac death
- HIV-infected
- Hepatitis C virus infected
- Positive for hepatitis B surface antigen (HBsAg)
- History of renal disease, hepatic disease, and/or cholecystectomy
Show all 20Show fewer
- Evidence of active substance abuse
- History of alcohol or substance abuse or dependence within 6 months prior to study entry. More information on this criterion can be found in the protocol.
- Use of prescription or non-prescription drugs, except paracetamol, at doses of up to 2 g/day. More information on this criterion can be found in the protocol.
- Use of FluMist, inactivated influenza vaccine, or any other anti-influenza antiviral medications within 14 days prior to study entry
- Participated in a clinical trial and received a drug or new chemical entity within 30 days or five half-lives prior to study entry.
- Unwilling to abstain from ingesting alcohol within 48 hours prior to study entry until collection of the final pharmacokinetic sample during each period
- Donated blood to the extent that participation in this study would result in excess of 300 mL donated within a 30 day period
- History of allergy to the study drug or drugs of this class. More information on this criterion can be found in the protocol.
- Unstable medical condition that, in the opinion of the investigator, would interfere with the study
- Anyone that, in the opinion of the investigator, has a risk of non-compliance with study procedures
- AST or ALN of at least 1.5 ULN
- Certain abnormal laboratory values
- Agree to use effective methods of birth control. More information on this criterion can be found in the protocol.
- Pregnant or breastfeeding
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase 1, Open-Label Study to Evaluate Potential Pharmacokinetic Interactions Between Orally-Administered Oseltamivir and Intravenous Zanamivir in Healthy Thai Adult Subjects
Due in part to widespread availability of oseltamivir and clinical experience using oseltamivir to treat H5N1 influenza virus infections, many strains of influenza have become resistant to it. Other reliable methods of treating H5N1 must be identified in case of a pandemic. One such option is intravenous zanamivir used in combination with oseltamivir. The primary purpose of this study is to evaluate the interaction between oral oseltamivir and intravenous zanamivir administered as either a continuous or intermittent infusion in healthy adults.
Read the detailed description
It is very likely that during an influenza pandemic, intravenous zanamivir will be used in combination with oseltamivir. Although the potential for a drug interaction between the two drugs is very low, the likelihood of coadministration combined with the common route of renal clearance of both drugs and the current lack of information on the organic anion transporter polypeptides (OATP) inhibition potential of zanamivir in vivo warrants verification of a lack of an interaction. This study will provide clinical guidance for the use of intravenous zanamivir in settings where oral oseltamivir is commonly used, such as areas in which human cases of H5N1 have been reported.
The total duration of study participation is approximately 13 weeks. Each participant will have a screening visit, four treatment steps, and a follow-up visit. The screening visit to determine enrollment eligibility will be conducted within 45 days prior to receiving the first dose. Participants will be randomized to receive either Regimen A or B for Step 1. Participants who received Regimen A will receive Regimen B in Step 2 and vice versa. After completing Step 2, all participants will continue with Regimens C and D, consecutively, in Steps 3 and 4, with at least 3 days between each step. A follow-up visit will occur 7-10 days after completing the last treatment assessments or withdrawing from the study.
Regimen A consists of continuous intravenous zanamivir infusion (800 mg) for 16 hours. Regimen B consists of 150 mg oral oseltamivir tablets taken five times over 3 days. Regimen C consists of 150 mg oral oseltamivir tablets taken five times over 3 days plus continuous intravenous zanamivir infusion (3600 mg) for 36 hours. Regimen D consists of 150 mg oral oseltamivir tablets taken five times over 3 days plus intermittent intravenous zanamivir infusion received in five 30 minute intervals (3000 mg total).
Blood and urine collection, vital signs, pharmacokinetic sampling, adverse event assessment, and pregnancy test for females will occur at each step in the study. The follow-up visit will involve blood and urine collection, vital signs, adverse event assessment, and pregnancy test for females.
- Conditions
- Influenza, Virus Diseases
- Being tested
- Zanamivir, Oseltamivir
- Keywords
- Drug Interaction
- Medical subject headings
- Influenza, Human, Virus Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZanamivirDrug
Also called Relenza
Continuous (800 mg in Regimen A, 3600 mg in Regimen C) and intermittent (3600 mg in Regimen D) infusion
OseltamivirDrug
Also called Tamiflu
150 mg oral tablets taken five times over 3 days in Regimens A, B, C, and D
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Participants will receive treatment in the following order: Study Regimens A, B, C, D Receives: Drug: Zanamivir; Drug: Oseltamivir |
| 2 | Experimental | Participants will receive treatment in the following order: Study Regimens B, A, C, D Receives: Drug: Zanamivir; Drug: Oseltamivir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Oseltamivir carboxylate Cmax and AUC (0-12)
Measured: Throughout study
Secondary outcomes (3)
Zanamivir Cmax and AUC (0-12) for continuous infusion and Zanamivir Cmax, AUC (-12), and C12 for intermittent infusions
Measured: Throughout study
Oseltamivir Cmax, AUC (0-12), and C12
Measured: Throughout study
Oseltamivir carboxylate AUC (0-24), C12, delta-z, and t(1/2)
Measured: Throughout study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2009 (estimated)
- Study startJul 2009
- Primary completionOct 2009
- Study completionOct 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for InfluenzaStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Johns Hopkins Bloomberg School of Public Health
- Investigators
- Sasithon Pukrittayakamee, MD, Principal investigator, Mathidol University, Thailand
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00921726
- Sponsor's protocol ID
- SEA 003
- Status last verified
- May 2009
- First submitted
- 12 Jun 2009
- Last updated
- 19 Mar 2010
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Beigel J, Bray M. Current and future antiviral therapy of severe seasonal and avian influenza. Antiviral Res. 2008 Apr;78(1):91-102. doi: 10.1016/j.antiviral.2008.01.003. Epub 2008 Feb 4.
PubMed 18328578Hata K, Koseki K, Yamaguchi K, Moriya S, Suzuki Y, Yingsakmongkon S, Hirai G, Sodeoka M, von Itzstein M, Miyagi T. Limited inhibitory effects of oseltamivir and zanamivir on human sialidases. Antimicrob Agents Chemother. 2008 Oct;52(10):3484-91. doi: 10.1128/AAC.00344-08. Epub 2008 Aug 11.
PubMed 18694948Tappenden P, Jackson R, Cooper K, Rees A, Simpson E, Read R, Nicholson K. Amantadine, oseltamivir and zanamivir for the prophylaxis of influenza (including a review of existing guidance no. 67): a systematic review and economic evaluation. Health Technol Assess. 2009 Feb;13(11):iii, ix-xii, 1-246. doi: 10.3310/hta13110.
PubMed 19215705
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1, Open-Label Study to Evaluate Potential Pharmacokinetic Interactions Between Orally-Administered Oseltamivir and Intravenous Zanamivir in Healthy Thai Adult Subjects
- ClinicalTrials.gov ID
- NCT00921726
- Acronym / sponsor ID
- SEA 003
- Conditions
- Influenza, Virus Diseases
- Keywords
- Drug Interaction
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- Johns Hopkins Bloomberg School of Public Health
- Study start
- Jul 2009
- Primary completion
- Oct 2009 (actual)
- Study completion
- Oct 2009 (actual)
- First posted
- 16 Jun 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Due in part to widespread availability of oseltamivir and clinical experience using oseltamivir to treat H5N1 influenza virus infections, many strains of influenza have become resistant to it. Other reliable methods of treating H5N1 must be identified in case of a pandemic. One such option is intravenous zanamivir used in combination with oseltamivir. The primary purpose of this study is to evaluate the interaction between oral oseltamivir and intravenous zanamivir administered as either a continuous or intermittent infusion in healthy adults.
Detailed description
It is very likely that during an influenza pandemic, intravenous zanamivir will be used in combination with oseltamivir. Although the potential for a drug interaction between the two drugs is very low, the likelihood of coadministration combined with the common route of renal clearance of both drugs and the current lack of information on the organic anion transporter polypeptides (OATP) inhibition potential of zanamivir in vivo warrants verification of a lack of an interaction. This study will provide clinical guidance for the use of intravenous zanamivir in settings where oral oseltamivir is commonly used, such as areas in which human cases of H5N1 have been reported.
The total duration of study participation is approximately 13 weeks. Each participant will have a screening visit, four treatment steps, and a follow-up visit. The screening visit to determine enrollment eligibility will be conducted within 45 days prior to receiving the first dose. Participants will be randomized to receive either Regimen A or B for Step 1. Participants who received Regimen A will receive Regimen B in Step 2 and vice versa. After completing Step 2, all participants will continue with Regimens C and D, consecutively, in Steps 3 and 4, with at least 3 days between each step. A follow-up visit will occur 7-10 days after completing the last treatment assessments or withdrawing from the study.
Regimen A consists of continuous intravenous zanamivir infusion (800 mg) for 16 hours. Regimen B consists of 150 mg oral oseltamivir tablets taken five times over 3 days. Regimen C consists of 150 mg oral oseltamivir tablets taken five times over 3 days plus continuous intravenous zanamivir infusion (3600 mg) for 36 hours. Regimen D consists of 150 mg oral oseltamivir tablets taken five times over 3 days plus intermittent intravenous zanamivir infusion received in five 30 minute intervals (3000 mg total).
Blood and urine collection, vital signs, pharmacokinetic sampling, adverse event assessment, and pregnancy test for females will occur at each step in the study. The follow-up visit will involve blood and urine collection, vital signs, adverse event assessment, and pregnancy test for females.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Zanamivir, Drug: OseltamivirParticipants will receive treatment in the following order: Study Regimens A, B, C, D |
| 2 | Experimental | Drug: Zanamivir, Drug: OseltamivirParticipants will receive treatment in the following order: Study Regimens B, A, C, D |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Good general health
- Body mass index between 17 - 32 kg/m^2
- Body weight of at least 37 kg
- Able to read, comprehend, and write at a sufficient level to complete study-related materials
- Normal ECG with QTC less than 450 msec as judged by cardiologist
Key exclusion criteria (20 listed)
- History of cardiac disease or abnormality. More information on this criterion can be found in the protocol.
- Family history of sudden cardiac death
- HIV-infected
- Hepatitis C virus infected
- Positive for hepatitis B surface antigen (HBsAg)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ZanamivirAlso: RelenzaContinuous (800 mg in Regimen A, 3600 mg in Regimen C) and intermittent (3600 mg in Regimen D) infusion | Drug | 1, 2 |
| OseltamivirAlso: Tamiflu150 mg oral tablets taken five times over 3 days in Regimens A, B, C, and D | Drug | 1, 2 |
Primary outcome
Oseltamivir carboxylate Cmax and AUC (0-12)
Time frame: Throughout study
3 secondary outcomes
Zanamivir Cmax and AUC (0-12) for continuous infusion and Zanamivir Cmax, AUC (-12), and C12 for intermittent infusions
Time frame: Throughout study
Oseltamivir Cmax, AUC (0-12), and C12
Time frame: Throughout study
Oseltamivir carboxylate AUC (0-24), C12, delta-z, and t(1/2)
Time frame: Throughout study
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Mar 2010.
- Background: PubMed 18328578Beigel J, Bray M. Current and future antiviral therapy of severe seasonal and avian influenza. Antiviral Res. 2008 Apr;78(1):91-102. doi: 10.1016/j.antiviral.2008.01.003. Epub 2008 Feb 4.
- Background: PubMed 18694948Hata K, Koseki K, Yamaguchi K, Moriya S, Suzuki Y, Yingsakmongkon S, Hirai G, Sodeoka M, von Itzstein M, Miyagi T. Limited inhibitory effects of oseltamivir and zanamivir on human sialidases. Antimicrob Agents Chemother. 2008 Oct;52(10):3484-91. doi: 10.1128/AAC.00344-08. Epub 2008 Aug 11.
- Background: PubMed 19215705Tappenden P, Jackson R, Cooper K, Rees A, Simpson E, Read R, Nicholson K. Amantadine, oseltamivir and zanamivir for the prophylaxis of influenza (including a review of existing guidance no. 67): a systematic review and economic evaluation. Health Technol Assess. 2009 Feb;13(11):iii, ix-xii, 1-246. doi: 10.3310/hta13110.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sasithon Pukrittayakamee, MD principal investigator
Mathidol University, Thailand
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Zanamivir and Oseltamivir in people with Influenza and Virus Diseases, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in Thailand.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Mar 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Thailand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Oseltamivir carboxylate Cmax and AUC (0-12) (time frame: Throughout study). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00921726, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Mar 2010.