Clinical Trial Result Information

Protocol number
NV20236

Title of Study
An open-label, multi-center trial of oseltamivir for the seasonal prophylaxis of influenza in children.

Sponsor
Hoffmann-La Roche

Company division
Pharmaceutical

Product name
Tamiflu

Generic name
oseltamivir

Therapeutic area
Influenza

Clinical study summary
This was an open-label study to collect safety data on the use of Tamiflu for 6 weeks for the prevention of influenza in children during the influenza season.

Study center(s)
4 centers in Canada and USA.

Phase of development
IV

Objectives
The primary objective of this study was to evaluate the safety of 6 weeks of seasonal prophylaxis of influenza with Tamiflu (oseltamivir) in children.
Additionally the effect of Tamiflu in preventing laboratory confirmed clinical influenza in children was evaluated.

Methodology
Fifty-two children aged between 1 and 12 years were enrolled into this study if, in the opinion of the investigator, they were at risk for morbidity or mortality from influenza and could therefore benefit from seasonal prophylaxis. Subjects received one daily dose of Tamiflu (dependent on weight) during a period of 6 weeks. Daily diary cards were supplied to the parents/guardians of the subjects to collect data on influenza symptoms, temperature and dosing times. The baseline assessment included a rapid diagnostic test for influenza virus shedding, nasal and throat swabs for viral shedding, safety laboratory assessments, serology, a physical examination (weight and height) and vital sign assessment. On Day 21, weight was assessed, vital signs were measured and the diary card was reviewed. Safety labs were only reassessed at this visit if baseline levels were abnormal. Safety labs, serology, weight and vital signs were assessed and the diary card was reviewed on Day 42 of treatment. At the follow-up visit on Day 72, serology, weight and vital signs were assessed and the diary card was reviewed. Safety labs were assessed if Day 42 levels were abnormal. Subjects were encouraged to make illness visits at any time during the study if they had influenza-like symptoms whereby nasal and throat swabs were taken, vital signs and safety labs were assessed if indicated and the diary card was reviewed. Adverse events, secondary illnesses and treatments were recorded throughout the study, from Day 1 until Day 70.

Number of patients (planned/analyzed)
52 subjects were enrolled

Diagnosis and main criteria for inclusion
Children, 1 to 12 years of age who, in the opinion of their primary care physician, could benefit from seasonal prophylaxis during times when local surveillance indicated that influenza was present in the community. Children were negative for an influenza rapid diagnostic test at baseline and had no symptom suggestive of an influenza-like illness.

Test product, dose and mode of administration or test procedure
Tamiflu (oseltamivir). Children 1-12 years:
≤15kg              30mg once daily (syrup)
>15-23kg          45mg once daily (syrup)
>23-40              60mg once daily (syrup)
>40kg                75mg once daily (syrup or capsules)
Dose adjustments were not permitted

Duration of treatment
6 weeks

Reference therapy, dose and mode of administration or reference procedure
N/A

Criteria for evaluation (efficacy, safety)
Efficacy: Proportion of subjects with laboratory confirmed clinical influenxa at any time post baseline up to and including the 70 day assessment.

Safety: Adverse events, physical examination, vital signs and clinical laboratory evaluations.

Statistical methods
This study was conducted primarily to evaluate safety and therefore no formal statistical analysis was performed.

Summary (efficacy, safety, other results)
Efficacy: No cases of laboratory confirmed clinical influenza were confirmed. Three subjects had laboratory influenza confirmed by a ≥ 4-fold increase in antibody titer at the end of treatment assessment. A further 3 subjects had laboratory influenza confirmed by a ≥ 4-fold increase in antibody titer at the follow-up visit. Of the 6 subjects with laboratory confirmed influenza, 4 were asymptomatic and 2 experienced limited influenza symptoms, not meeting the criteria for clinical influenza.

Safety: There were no unexpected safety concerns observed during the conduct of this study. There were no deaths or serious adverse events. Over the treatment period of 42 days, up to and including 2 days after last day of Tamiflu administration, 17/49 (35%) subjects reported 22 adverse events. The most common adverse events were gastrointestinal disorder (6 subjects), infection (6 subjects) and respiratory disorder (3 subjects). Twelve of the 22 adverse events were rated by the investigator as mild in intensity, 8 were rated as moderate and 2 events (toothache and otitis media) were rated as severe. The investigator considered 3 adverse events (1 moderate nausea, 1 mild nausea and 1 vomiting) probably related to treatment and 19 adverse events not related to treatment. Two subjects were withdrawn from the study due to adverse events. A 3-year-old male was withdrawn due to oral mucosal blistering, considered by the investigator as unrelated to treatment, and an 11-year-old female was withdrawn due to nausea which the investigator considered related to treatment.
Six subjects reported a further 6 adverse events (3 infections, including otitis media, tonsillitis and sinusitis, 1 joint injury, 1 headache and 1 wheezing) from the period >2 days after stopping treatment up until the Day 70 follow-up.

Conclusions
Once daily administration of Tamiflu (dose dependent on weight) to children aged between 1 and 12 years of age was well-tolerated in this study.

Date of report
5/1/2008

Click here for the protocol registry listing of this trial.