InfluenzaPhase 1NCT01053663

A Study of Intravenous Oseltamivir [Tamiflu] in Infants With Influenza

A Phase 1 study testing Tamiflu in people with Influenza, run by Hoffmann-La Roche at 39 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages Up to 365 days
Conditions the study is for: Influenza
What is being tested?: Tamiflu
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 9 participants
Where: 39 sitesin 2 countries
Study dates: Jan 2011to Jan 2013
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 Up to 365 days
All sexes
No healthy volunteers
Child

Who may be able to join

Infant patients
Date of birth to date of enrollment is <1 year
Diagnosis of influenza
Duration of influenza symptoms </=96 hours prior to first dose
- Parent/guardian willing to have patient receive intravenous therapy for 3 or 4 days (5 or 6 doses of study drug)

Who cannot join

Date of conception to date of birth + date of birth to enrollment is <36 weeks
Creatinine clearance <30 mL/min/1.73m2
Patients receiving any form of renal replacement therapy at baseline
Clinical evidence of severe hepatic decompensation at the time of enrollment
Patients taking probenecid medication within 1 week prior to study day 1 or during the study

Trial locations and contacts

39 sites in 2 countries.

Country

City, postcode or hospital

39 sites in 2 countries

United States38 sites

Study site
Akron, Ohio, 44308
Study site
Aurora, Colorado, 80045
Study site
Austin, Texas, 78723
Study site
Boston, Massachusetts, 02111
Study site
Boston, Massachusetts, 02115
Study site
Boston, Massachusetts, 02118
Study site
Brooklyn, New York, 11203
Study site
Chicago, Illinois, 60611
Study site
Cleveland, Ohio, 44106
Study site
Dallas, Texas, 75390-9063
Study site
Dayton, Ohio, 45404
Study site
Detroit, Michigan, 48201
Study site
Durham, North Carolina, 27705
Study site
Houston, Texas, 77030
Study site
Jacksonville, Florida, 32209
Study site
Little Rock, Arkansas, 45229-3039
Study site
Los Angeles, California, 90095
Study site
Louisville, Kentucky, 40202
Study site
Madison, Wisconsin, 53792
Study site
Morristown, New Jersey, 07960
Study site
New Brunswick, New Jersey, 08901
Study site
New York, New York, 10016
Study site
Oakland, California, 94609-1809
Study site
Omaha, Nebraska, 68131
Study site
Orange, California, 92868
Study site
Providence, Rhode Island, 02903
Study site
Raleigh, North Carolina, 27610
Study site
Richmond, Virginia, 23292
Study site
San Diego, California, 92123
Study site
South Bend, Indiana, 46601
Study site
Springfield, Massachusetts, 01199
Study site
Stony Brook, New York, 11794
Study site
Syracuse, New York, 13210
Study site
The Bronx, New York, 10461
Study site
Toledo, Ohio, 43606
Study site
Toledo, Ohio, 43608
Study site
Wichita, Kansas, 67214
Study site
Wilmington, Delaware, 19803

Other trials in United States

Israel1 site

Study site
Petah Tikva, 49100

Other trials in Israel

About this study

Official title: An Open-label, Prospective, Pharmacokinetic/Pharmacodynamic and Safety Evaluation of Intravenous Oseltamivir in the Treatment of Infants Less Than One Year of Age With Influenza Infection

This open-label study will assess the pharmacokinetics and safety of oseltamivir [Tamiflu] in 3 cohorts of infants, aged 0-30 days, 31-90 days and 91-<365 days with influenza infection. Patients will receive 10 doses of intravenous oseltamivir [Tamiflu] therapy over 5 or 6 days. Optional oral therapy with oseltamivir [Tamiflu] may be considered following the intravenous dose associated with pharmacokinetic blood sampling. Evidence of continued virus shedding at day 6 can allow for up to 5 additional days (10 doses) of oral or intravenous administration. Anticipated time on study drug is 5-11 days. Target sample size is <50 patients.

Conditions: Influenza
Being tested: Tamiflu
Medical subject headings: Influenza, Human

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

TamifluDrug
10 doses over 5 or 6 days of which the first 5 or 6 doses must be intravenous, up to 5 days (10 doses) of additional intravenously or oral treatment if virus shedding continues at day 6

Study groups in NCT01053663
Study group	Role	What they receive
1	Experimental	Not described Receives: Drug: Tamiflu

What is being measured

The primary outcome is the main question the study is designed to answer.

Area Under the Concentration Versus Time Curve From Time Zero to Last Measurable Plasma Concentration (AUClast) of Oseltamivir and Oseltamivir Carboxylate on Day 1
Measured: Pre-dose (Hour 0), 2, 3-4, 5-7, and 10-12 hours post-dose on Day 1
AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 2
Measured: Pre-dose (Hour 0), 2, 3-4, 5-7, and 10-12 hours post-dose on Day 2
AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 4
Measured: Pre-dose (Hour 0), 2 and 4 hours post-dose on Day 4
Maximum Observed Plasma Concentration (Cmax) of Oseltamivir and Oseltamivir Carboxylate on Day 1
Measured: Pre-dose (Hour 0), 2, 3-4, 5-7, and 10-12 hours post-dose on Day 1
Cmax of Oseltamivir and Oseltamivir Carboxylate on Day 2
Measured: Pre-dose (Hour 0), 2, 3-4, 5-7, and 10-12 hours post-dose on Day 2
Cmax of Oseltamivir and Oseltamivir Carboxylate on Day 4
Measured: Pre-dose (Hour 0), 2 and 4 hours post-dose on Day 4

Secondary outcomes (5)

Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate
Measured: Pre-dose (Hour 0), 2, 3-4, 5-7, and 10-12 hours post-dose on Day 1 and Day 2, pre-dose (Hour 0), 2 and 4 hours post-dose on Day 4
Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate
Measured: Pre-dose (Hour 0), 2, 3-4, 5-7, and 10-12 hours post-dose on Day 1 and Day 2, pre-dose (Hour 0), 2 and 4 hours post-dose on Day 4
Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate
Measured: Pre-dose (Hour 0), 2, 3-4, 5-7, and 10-12 hours post-dose on Day 1 and Day 2, pre-dose (Hour 0), 2 and 4 hours post-dose on Day 4
Number of Participants With Greater Than or Equal to (≥) 5-Fold Change in Neuraminidase Inhibition (NAI) Assay 50 Percent (%) Inhibitory Concentration (IC50) Values
IC50 was defined as the concentration that causes 50% inhibition of viral activity. IC50 values were calculated using NAI assay. The 5-fold change was calculated as either ≥5 times change in the NAI IC50 visit value from the Reference value at a visit or ≥5 times change in the NAI IC50 Visit value from the Baseline value.
Measured: Baseline, Days 1, 3, 4, 6, 15
Number of Participants With Oseltamivir Resistance Mutation
Resistance was assessed by neuraminidase (NA) and hemagglutinin (HA) genes sequencing analysis, using Reverse Transcription Polymerase Chain Reaction (RT-PCR).
Measured: Up to Day 30

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 2011Jan 2013

First posted21 Jan 2010 (estimated)
Study startJan 2011
Primary completionJan 2013
Study completionJan 2013

Why it stopped: The study was terminated prematurely after three influenza seasons.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for InfluenzaStudies of the same condition, open and under way.
More trials run by Hoffmann-La RocheThe 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: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 9 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01053663
Sponsor's protocol ID: NP25138
Status last verified: Jun 2016
First submitted: 20 Jan 2010
Last updated: 27 Jul 2016
Results posted: Yes, on ClinicalTrials.gov

Publications

Munoz FM, Anderson EJ, Deville JG, Clinch B, Kamal MA. Pharmacokinetics and safety of intravenous oseltamivir in infants and children in open-label studies. Int J Clin Pharmacol Ther. 2015 Jul;53(7):531-40. doi: 10.5414/CP202307.
PubMed 26042486

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 27 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open-label, Prospective, Pharmacokinetic/Pharmacodynamic and Safety Evaluation of Intravenous Oseltamivir in the Treatment of Infants Less Than One Year of Age With Influenza Infection
ClinicalTrials.gov ID: NCT01053663
Acronym / sponsor ID: NP25138
Conditions: Influenza
Phase: Phase 1
Study type: Interventional
Recruitment status: TerminatedReason stopped: The study was terminated prematurely after three influenza seasons.
Enrolment: 9 participants (actual)
Lead sponsor: Hoffmann-La RocheIndustry (pharma, biotech, devices)
Study start: Jan 2011
Primary completion: Jan 2013 (actual)
Study completion: Jan 2013 (actual)
First posted: 21 Jan 2010 (estimated)
Results: Posted 27 Jul 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
1	Experimental	Drug: Tamiflu

Who may qualify

Ages: Up to 365 days
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (5 listed)

Infant patients
Date of birth to date of enrollment is <1 year
Diagnosis of influenza
Duration of influenza symptoms </=96 hours prior to first dose
- Parent/guardian willing to have patient receive intravenous therapy for 3 or 4 days (5 or 6 doses of study drug)

Key exclusion criteria (5 listed)

Date of conception to date of birth + date of birth to enrollment is <36 weeks
Creatinine clearance <30 mL/min/1.73m2
Patients receiving any form of renal replacement therapy at baseline
Clinical evidence of severe hepatic decompensation at the time of enrollment
Patients taking probenecid medication within 1 week prior to study day 1 or during the study

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
Tamiflu10 doses over 5 or 6 days of which the first 5 or 6 doses must be intravenous, up to 5 days (10 doses) of additional intravenously or oral treatment if virus shedding continues at day 6	Drug	1

Primary outcome

Area Under the Concentration Versus Time Curve From Time Zero to Last Measurable Plasma Concentration (AUClast) of Oseltamivir and Oseltamivir Carboxylate on Day 1
Time frame: Pre-dose (Hour 0), 2, 3-4, 5-7, and 10-12 hours post-dose on Day 1
AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 2
Time frame: Pre-dose (Hour 0), 2, 3-4, 5-7, and 10-12 hours post-dose on Day 2
AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 4
Time frame: Pre-dose (Hour 0), 2 and 4 hours post-dose on Day 4
Maximum Observed Plasma Concentration (Cmax) of Oseltamivir and Oseltamivir Carboxylate on Day 1
Time frame: Pre-dose (Hour 0), 2, 3-4, 5-7, and 10-12 hours post-dose on Day 1
Cmax of Oseltamivir and Oseltamivir Carboxylate on Day 2
Time frame: Pre-dose (Hour 0), 2, 3-4, 5-7, and 10-12 hours post-dose on Day 2
Cmax of Oseltamivir and Oseltamivir Carboxylate on Day 4
Time frame: Pre-dose (Hour 0), 2 and 4 hours post-dose on Day 4

5 secondary outcomes

Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate
Time frame: Pre-dose (Hour 0), 2, 3-4, 5-7, and 10-12 hours post-dose on Day 1 and Day 2, pre-dose (Hour 0), 2 and 4 hours post-dose on Day 4
Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate
Time frame: Pre-dose (Hour 0), 2, 3-4, 5-7, and 10-12 hours post-dose on Day 1 and Day 2, pre-dose (Hour 0), 2 and 4 hours post-dose on Day 4
Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate
Time frame: Pre-dose (Hour 0), 2, 3-4, 5-7, and 10-12 hours post-dose on Day 1 and Day 2, pre-dose (Hour 0), 2 and 4 hours post-dose on Day 4
Number of Participants With Greater Than or Equal to (≥) 5-Fold Change in Neuraminidase Inhibition (NAI) Assay 50 Percent (%) Inhibitory Concentration (IC50) Values
Time frame: Baseline, Days 1, 3, 4, 6, 15
Number of Participants With Oseltamivir Resistance Mutation
Time frame: Up to Day 30

Results and safety

Results posted to the registry on 27 Jul 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Oseltamivir - All Participants	9	3

Primary outcome: Area Under the Concentration Versus Time Curve From Time Zero to Last Measurable Plasma Concentration (AUClast) of Oseltamivir and Oseltamivir Carboxylate on Day 1

Time frame: Pre-dose (Hour 0), 2, 3-4, 5-7, and 10-12 hours post-dose on Day 1. Geometric mean (Geometric Coefficient of Variation). Unit: hour*nanogram/milliliter (h*ng/mL)

Measure	Oseltamivir: Age 91 to < 365 Days n = 3	Oseltamivir: Age 31 to 90 Days n = 0	Oseltamivir: Age 0 to 30 Days n = 1
Oseltamivir	777 (162.8)	–	494
Oseltamivir Carboxylate	5200 (87.8)	–	7510

Population analysed: Pharmacokinetic (PK) population included all treated participants who had at least one blood sample evaluable for drug concentration level. Number of participants analyzed = participants who were evaluable for this outcome.

Primary outcome: AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 2

Time frame: Pre-dose (Hour 0), 2, 3-4, 5-7, and 10-12 hours post-dose on Day 2. Geometric mean (Geometric Coefficient of Variation). Unit: h*ng/mL

Measure	Oseltamivir: Age 91 to < 365 Days n = 3	Oseltamivir: Age 31 to 90 Days n = 1	Oseltamivir: Age 0 to 30 Days n = 0
Oseltamivir	988 (57.8)	481	–
Oseltamivir Carboxylate	7270 (42.2)	5330	–

Population analysed: PK population. Number of participants analyzed = participants who were evaluable for this outcome.

Primary outcome: AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 4

Time frame: Pre-dose (Hour 0), 2 and 4 hours post-dose on Day 4. Geometric mean (Geometric Coefficient of Variation). Unit: h*ng/mL

Measure	Oseltamivir: Age 91 to < 365 Days n = 2	Oseltamivir: Age 31 to 90 Days n = 0	Oseltamivir: Age 0 to 30 Days n = 1
Oseltamivir	1520 (33.9)	–	389
Oseltamivir Carboxylate	3880 (98.0)	–	2070

Population analysed: PK population. Number of participants analyzed = participants who were evaluable for this outcome.

Primary outcome: Maximum Observed Plasma Concentration (Cmax) of Oseltamivir and Oseltamivir Carboxylate on Day 1

Time frame: Pre-dose (Hour 0), 2, 3-4, 5-7, and 10-12 hours post-dose on Day 1. Geometric mean (Geometric Coefficient of Variation). Unit: nanogram/milliliter (ng/mL)

Measure	Oseltamivir: Age 91 to < 365 Days n = 3	Oseltamivir: Age 31 to 90 Days n = 0	Oseltamivir: Age 0 to 30 Days n = 1
Oseltamivir	307 (315.7)	–	203
Oseltamivir Carboxylate	736 (55.5)	–	871

Population analysed: PK population. Number of participants analyzed = participants who were evaluable for this outcome.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to Day 30. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Oseltamivir: Age 91 to < 365 Days	5 of 7 (71.4%)	4 of 7 (57.1%)	Not reported
Oseltamivir: Age 31 to 90 Days	0 of 1 (0%)	0 of 1 (0%)	Not reported
Oseltamivir: Age 0 to 30 Days	0 of 1 (0%)	1 of 1 (100%)	Not reported
Oseltamivir: All Participants	5 of 9 (55.6%)	5 of 9 (55.6%)	Not reported

Limitations and caveats (from the sponsor): Low number of participants enrolled in the study at the time that the study was terminated limits conclusions that can be derived from the study data.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 26042486Munoz FM, Anderson EJ, Deville JG, Clinch B, Kamal MA. Pharmacokinetics and safety of intravenous oseltamivir in infants and children in open-label studies. Int J Clin Pharmacol Ther. 2015 Jul;53(7):531-40. doi: 10.5414/CP202307.

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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.

Clinical Trials study director

Hoffmann-La Roche

39 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Tamiflu in people with Influenza, run by Hoffmann-La Roche at 39 sites in 2 countries.

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 5 inclusion and 5 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: stopped early, as of the sponsor's last update on 27 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 39 sites in United States, Israel. 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?

Yes. Results are posted in the registry (first posted 27 Jul 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Area Under the Concentration Versus Time Curve From Time Zero to Last Measurable Plasma Concentration (AUClast) of Oseltamivir and Oseltamivir Carboxylate on Day 1 (time frame: Pre-dose (Hour 0), 2, 3-4, 5-7, and 10-12 hours post-dose on Day 1). The study lists 6 primary outcomes in all. 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 NCT01053663, which also lists 1 linked publication.

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 27 Jul 2016.