Primary: To assess the efficacy of treatment with 300 mg or 600 mg of intravenous (IV) zanamivir twice daily compared to 75 mg of oral oseltamivir twice daily on time to clinical response. Secondary: reduction in viral load from nasopharyngeal swabs…
ID
Source
Brief title
Condition
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Time to clinical response in subjects with confirmed influenza.
Secondary outcome
Include a series of clinical efficacy, virologic, PK and safety endpoints.
Background summary
Neuraminidase inhibitors have been shown to be effective and well tolerated in
the treatment and prophylaxis of acute uncomplicated seasonal influenza and are
available as inhaled zanamivir and oral oseltamivir. An unmet medical need
exists for a parenteral formulation.
Emergence of virus isolates resistant to influenza antiviral agents continues
to be a potential issue. As of September 2010, 304 cases of
oseltamivir-resistant isolates of the pandemic H1N1 2009 virus have been
reported. All but one of these isolates have been identified to carry the H275Y
mutation and thus remain sensitive to zanamivir. Virtually 100% of seasonal
influenza A (H1N1) isolates tested during the 2008-2009 influenza season were
resistant to oseltamivir. In addition, sporadic cases of resistance to
oseltamivir have also been reported in H5N1 infection. Thus far, these isolates
have been reported to remain susceptible to zanamivir.
The purpose of this Phase III study is to obtain comprehensive data on the
clinical efficacy, antiviral activity, and safety of 2 dosages of IV zanamivir
relative to oral oseltamivir in adults and adolescents hospitalized with
influenza infection.
In the Netherlands no minors will be included.
Study objective
Primary: To assess the efficacy of treatment with 300 mg or 600 mg of
intravenous (IV) zanamivir twice daily compared to 75 mg of oral oseltamivir
twice daily on time to clinical response. Secondary: reduction in viral load
from nasopharyngeal swabs, clinical improvement, safety and tolerability,
development of resistance, PK.
Study design
Multicenter randomized double blind double dummy phase III parallel group study.
Randomization (1:1:1) to treatment with:
• Zanamivir 300 mg i.v. infusion (30 minutes) twice daily.
• Zanamivir 600 mg i.v. infusion (30 minutes) twice daily.
• Oseltamivir 75 mg orally twice daily.
Treatment duration 5-10 days.
In case of insufficient clinical response, patients may be switched to 600 mg
IV zanamivir twice daily, leading to a maximum treatment duration of 14 days.
Follow-up until 4 weeks post-treatment.
Interim-analysis after 150 patients have completed the study.
IDMC.
Approx 460 patients.
In the Netherlands no minors will be included.
Intervention
Treatment with zanamivir or oseltamivir.
Study burden and risks
Risk: Adverse effects of study medication.
Burden: At study start all patients are hospitalized for medical reasons.
Depending on the moment of discharge, there are max. 3 visits to the outpatient
clinic and 7 phone contacts.
Tests/procedures: blood tests (2-20 ml/occasion) daily during study treatment
and max. 4x thereafter. Pregnancy test (if indicated) 2x, nose swab during
study treatment: 1st 5 days: daily, thereafter every 2nd day. ECG 4x.
Huis ter Heideweg 62
3705 LZ Zeist
NL
Huis ter Heideweg 62
3705 LZ Zeist
NL
Listed location countries
Age
Inclusion criteria
• Male or female aged >=16 years (in the Netherlands: 18 years and above).
• 3 or more of the following criteria at Baseline:
o Temperature >= 38,5oC rectal (alternative methods: see protocol) with 2 exceptions (see protocol for details).
o Arterial oxygen saturation <95%.
o Respiration rate >24 breaths per minute.
o HR >100 bpm.
o SBP <90 mmHg.
• Onset of influenza symptoms within 6 days prior to study enrolment.
• Confirmed influenza as determined by a positive RAT for influenza A or B, or a laboratory test for influenza. Subjects with a negative RAT or other test may be enrolled based on strong clinical suspicion of influenza.
• Safe contraception for women of childbearing potential.
Exclusion criteria
• Breastfeeding, pregnancy.
• Subjects who have taken more than a total of 6 doses of approved anti-influenza therapy.
• Life expectancy less than 48 hours.
• Treatment with investigational parenteral anti-influenza drugs in the 4 weeks prior to Baseline.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | clinicaltrials.gov, registratienummer n.n.b. |
| EudraCT | EUCTR2010-021621-12-NL |
| CCMO | NL34832.091.10 |