Influenza
Conditions
Brief summary
This open-label randomized 2 arm study will determine the emergence of viral resistance in participants with seasonal influenza A infection treated with oseltamivir. Eligible participants less than or equal to (\</=) 5 years of age will be randomized to receive oseltamivir at either standard dose (30-75 milligrams \[mg\] orally twice daily \[bid\]) or double dose (60-150 mg orally bid) for 5 days. Target sample size is greater than (\>) 100.
Interventions
DRUGOseltamivir
Standard dose (30 - 75 mg orally bid) or double dose (60 - 150 mg orally bid); for 5 days
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* positive rapid antigen test for influenza A * onset of symptoms of influenza (fever, at least one respiratory symptom) \</=48 hours
Exclusion criteria
* clinical suspicion of infection with a respiratory virus other than influenza * suspicion of invasive bacterial infection * evidence of poorly controlled underlying disease * known immunosuppression * known allergy to Oseltamivir * women who are pregnant or planning to get pregnant during the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Excreting Resistant Virus | Day 5 | Resistant virus included new influenza A virus subtype hemagglutinin type 1 and neuraminidase type 1 (New AH1N1). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With A Reduction in Viral Load | Baseline, Day 5 | Viral load is defined as the amount of H1N1 virus in blood. As per investigator, a participant was considered as having viral load reduction at Day 5 if the Day 5 viral load was lower than the Baseline viral load. |
| Number of Participants With Various Clinical Signs and Symptoms | Day 5 | Number of participants with various clinical signs and symptoms, as per investigator's discretion, were reported. Same participants were reported in more than 1 category. Other in the category included abdominal pain, breathlessness, thoracic pain and tired. |
| Number of Participants With Various Clinical Signs and Symptoms in Whom Resistant Virus Were Detected | Day 5 | Number of participants with various clinical signs and symptoms, as per investigator's discretion, in whom new AH1N1 virus was detected, were reported. Same participants were reported in more than 1 category. |
Countries
Brazil
Participant flow
Pre-assignment details
Out of 199 participants, 162 were considered as screening failures, mainly due to the negative result detected by the quick test for Influenza A Antigen. Therefore, 37 participants included in the study.
Participants by arm
| Arm | Count |
|---|---|
| Standard Dose Oseltamivir capsule was administered orally at a dose of 75 mg BID in adult participants and children received oseltamivir powder for oral suspension dose (at 12 mg/mL) based on their body weight with a starting dose of 30 mg BID to a maximum dose of 75 mg BID; for 5 days. | 19 |
| Double Dose Oseltamivir capsule was administered orally at a dose of 150 mg BID in adult participants and children received oseltamivir powder for oral suspension dose (at 12 mg/mL) based on their body weight with a starting dose of 60 mg BID to a maximum dose of 150 mg BID; for 5 days. | 18 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
Baseline characteristics
| Characteristic | Standard Dose | Double Dose | Total |
|---|---|---|---|
| Age, Continuous | 21.6 years STANDARD_DEVIATION 11 | 22.0 years STANDARD_DEVIATION 12.7 | 21.8 years STANDARD_DEVIATION 11.7 |
| Sex: Female, Male Female | 11 Participants | 9 Participants | 20 Participants |
| Sex: Female, Male Male | 8 Participants | 9 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 8 / 19 | 7 / 18 |
| serious Total, serious adverse events | 0 / 19 | 0 / 18 |
Outcome results
Primary
Percentage of Participants Excreting Resistant Virus
Resistant virus included new influenza A virus subtype hemagglutinin type 1 and neuraminidase type 1 (New AH1N1).
Time frame: Day 5
Population: ITT population. Here number of participants analyzed included evaluable participants for the outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard Dose | Percentage of Participants Excreting Resistant Virus | 26.3 percentage of participants |
| Double Dose | Percentage of Participants Excreting Resistant Virus | 35.3 percentage of participants |
p-value: 0.825Pearson Chi-Square
Secondary
Number of Participants With Various Clinical Signs and Symptoms
Number of participants with various clinical signs and symptoms, as per investigator's discretion, were reported. Same participants were reported in more than 1 category. Other in the category included abdominal pain, breathlessness, thoracic pain and tired.
Time frame: Day 5
Population: ITT population. Here number of participants analyzed included evaluable participants for the outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Standard Dose | Number of Participants With Various Clinical Signs and Symptoms | Rhinorrhea | 10 participants |
| Standard Dose | Number of Participants With Various Clinical Signs and Symptoms | Headache | 1 participants |
| Standard Dose | Number of Participants With Various Clinical Signs and Symptoms | Shortness of breath | 2 participants |
| Standard Dose | Number of Participants With Various Clinical Signs and Symptoms | Conjunctivitis | 1 participants |
| Standard Dose | Number of Participants With Various Clinical Signs and Symptoms | Sore throat | 2 participants |
| Standard Dose | Number of Participants With Various Clinical Signs and Symptoms | Vomiting | 1 participants |
| Standard Dose | Number of Participants With Various Clinical Signs and Symptoms | Diarrhea | 2 participants |
| Standard Dose | Number of Participants With Various Clinical Signs and Symptoms | Other | 4 participants |
| Standard Dose | Number of Participants With Various Clinical Signs and Symptoms | Cough | 10 participants |
| Double Dose | Number of Participants With Various Clinical Signs and Symptoms | Other | 0 participants |
| Double Dose | Number of Participants With Various Clinical Signs and Symptoms | Cough | 9 participants |
| Double Dose | Number of Participants With Various Clinical Signs and Symptoms | Rhinorrhea | 5 participants |
| Double Dose | Number of Participants With Various Clinical Signs and Symptoms | Sore throat | 2 participants |
| Double Dose | Number of Participants With Various Clinical Signs and Symptoms | Shortness of breath | 1 participants |
| Double Dose | Number of Participants With Various Clinical Signs and Symptoms | Diarrhea | 0 participants |
| Double Dose | Number of Participants With Various Clinical Signs and Symptoms | Headache | 2 participants |
| Double Dose | Number of Participants With Various Clinical Signs and Symptoms | Conjunctivitis | 0 participants |
| Double Dose | Number of Participants With Various Clinical Signs and Symptoms | Vomiting | 0 participants |
Comparison: Cough: statistical difference between 2 groups was based on chi-squared test.p-value: 1Chi-squared
Comparison: Rhinorrhea: statistical difference between 2 groups was based on chi-squared test.p-value: 0.284Chi-squared
Comparison: Sore throat: statistical difference between 2 groups was based on fisher-exact test.p-value: 1Fisher Exact
Comparison: Shortness of breath: statistical difference between 2 groups was based on fisher-exact test.p-value: 1Fisher Exact
Comparison: Diarrhea: statistical difference between 2 groups was based on fisher-exact test.p-value: 0.487Fisher Exact
Comparison: Headache: statistical difference between 2 groups was based on fisher-exact test.p-value: 0.593Fisher Exact
Comparison: Conjunctivitis: statistical difference between 2 groups was based on fisher-exact test.p-value: 1Fisher Exact
Comparison: Vomiting: statistical difference between 2 groups was based on fisher-exact test.p-value: 1Fisher Exact
Comparison: Other: statistical difference between 2 groups was based on fisher-exact test.p-value: 0.106Fisher Exact
Secondary
Number of Participants With Various Clinical Signs and Symptoms in Whom Resistant Virus Were Detected
Number of participants with various clinical signs and symptoms, as per investigator's discretion, in whom new AH1N1 virus was detected, were reported. Same participants were reported in more than 1 category.
Time frame: Day 5
Population: ITT population. Here number of participants analyzed included evaluable participants for the outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Standard Dose | Number of Participants With Various Clinical Signs and Symptoms in Whom Resistant Virus Were Detected | Cough | 3 participants |
| Standard Dose | Number of Participants With Various Clinical Signs and Symptoms in Whom Resistant Virus Were Detected | Rhinorrhea | 3 participants |
| Standard Dose | Number of Participants With Various Clinical Signs and Symptoms in Whom Resistant Virus Were Detected | Shortness of breath | 0 participants |
| Double Dose | Number of Participants With Various Clinical Signs and Symptoms in Whom Resistant Virus Were Detected | Cough | 4 participants |
| Double Dose | Number of Participants With Various Clinical Signs and Symptoms in Whom Resistant Virus Were Detected | Rhinorrhea | 3 participants |
| Double Dose | Number of Participants With Various Clinical Signs and Symptoms in Whom Resistant Virus Were Detected | Shortness of breath | 1 participants |
Secondary
Percentage of Participants With A Reduction in Viral Load
Viral load is defined as the amount of H1N1 virus in blood. As per investigator, a participant was considered as having viral load reduction at Day 5 if the Day 5 viral load was lower than the Baseline viral load.
Time frame: Baseline, Day 5
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard Dose | Percentage of Participants With A Reduction in Viral Load | 100 percentage of participants |
| Double Dose | Percentage of Participants With A Reduction in Viral Load | 100 percentage of participants |
p-value: >0.05Chi-squared