An Open Label, Single Arm Study to Evaluate Single and Multiple Dose Pharmacokinetics, Safety and Tolerability, and to Explore Clinical Outcomes of Treatment With Intravenous (IV) Zanamivir in Neonates and Infants Under 6 Months of Age With Confirmed Complicated Influenza Infection
Overview
- Phase
- Phase 2
- Intervention
- Zanamivir
- Conditions
- Influenza, Human
- Sponsor
- GlaxoSmithKline
- Enrollment
- 12
- Locations
- 1
- Primary Endpoint
- Clearance (CL) in plasma following administration of zanamivir
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
Influenza infection is an important public health priority, with seasonal outbreaks and pandemics causing considerable global morbidity and mortality. The PK, pharmacodynamics (PD), safety and efficacy of IV zanamivir have been evaluated in adults, adolescents and infants more than or equal to (>=) 6 months of age with hospitalized influenza in the IV zanamivir global development program. However, antiviral treatment of neonates and infants under 6 months of age hospitalized with influenza infection remains a medical unmet need. Given the immaturity of the immune system at this age, there are no licensed influenza vaccines for children aged less than six months old. As a requirement of the Pediatric Investigation Plan European Union (EU), GlaxoSmithKline (GSK) will be conducting this open-label, multi-center, single arm, post-marketing authorization study to evaluate the PK and collect safety and tolerability information of IV zanamivir in hospitalized neonates and infants under 6 months of age with confirmed complicated influenza infection. The total duration of study participation for each participant will be up to 24 days with a study treatment period up to 10 days and 14 days of post-treatment follow up. However, for a given participant, the initial 5-day treatment course may be extended for up to 5 additional days if clinical symptoms, participant characteristics or virological tests as assessed by the investigator warrant further treatment. DECTOVA is a trademark of GlaxoSmithKline group of companies.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Neonates and infants who are aged less than 6 months (corrected age) at the time of the informed consent signed by legally acceptable representative (LAR) of minors. Preterm neonates and infants will be eligible for inclusion but must have reached PMA of at least 28 weeks.
- •Participants who are hospitalized with influenza infection, confirmed by a positive rapid molecular diagnostic test for influenza, or a local quantitative Reverse transcriptase-polymerase chain reaction (RT-PCR) test and who must have a potential for improvement Participants with negative rapid molecular test result suspected of having influenza can be enrolled following confirmatory testing by quantitative RT-PCR.
- •Participants with a high risk of altered oral drug absorption, represented by multi-organ dysfunction (dysfunction of at least 2 organs, as defined by the treating physician). (applicable only for Netherlands)
- •Body weight \>=1 kilograms (kg).
- •No gender restriction.
- •LAR of minors are willing and able to give written informed consent to participate in the study (or included as permitted by local regulatory authorities, Independent Ethics Committees \[IECs\] or local laws).
- •Exclusion criteria:
- •Participants who are known or suspected to be hypersensitive to any component of the study medication.
- •Participants with a disease process which is likely to be irreversible.
- •Liver function:
Exclusion Criteria
- Not provided
Arms & Interventions
Hospitalized neonates and infants with influenza infection
Preterm neonates and infants who have reached Post-Menstrual Age (PMA) of at least 28 weeks and have a confirmed complicated influenza infection will be included. Participants will receive daily IV infusion of zanamivir for up to 5 days. This initial 5-day treatment course may be extended for up to 5 additional days if clinical symptoms, participant characteristics or virological tests warrant further treatment. The initial dose of IV zanamivir will be determined by PMA/corrected age and body weight. The maintenance dose and interval between the initial dose and subsequent twice-daily maintenance dose will be further determined by Principal Investigator based on renal function.
Intervention: Zanamivir
Outcomes
Primary Outcomes
Clearance (CL) in plasma following administration of zanamivir
Time Frame: 30 minutes, 2 hours, 6 hours, 12 hours post dose on Day 1; predose on Days 3, 4 or 5
Blood samples will be collected at indicated time points for pharmacokinetic analysis of zanamivir.
Area under the serum concentration-time curve (AUC) of zanamivir
Time Frame: Up to 12 hours after end of infusion on Day 1
Blood samples will be collected at indicated time points for pharmacokinetic analysis of zanamivir.
Maximum observed serum concentration (Cmax) of zanamivir
Time Frame: Up to 12 hours after end of infusion on Day 1
Blood samples will be collected at indicated time points for pharmacokinetic analysis of zanamivir.
Terminal half-life (t1/2) of zanamivir
Time Frame: 30 minutes, 2 hours, 6 hours, 12 hours post dose on Day 1; predose on Days 3, 4 or 5
Blood samples will be collected at indicated time points for pharmacokinetic analysis of zanamivir.
Secondary Outcomes
- Number of participants with adverse event(s) (AE) and serious adverse event(s) (SAE)(From start of treatment (Day 1) up to Day 24)
- Number of participants with emergence of resistance to zanamivir(Up to Day 24)
- Number of participants with abnormal findings in body temperature(From start of treatment (Day 1) up to Day 24)
- Viral load over time after administration of zanamivir(Day 1 up to Maximum Day 24)
- Number of participants with phenotypic resistance(Up to Day 24)
- Number of participants with abnormal findings in Oxygen Saturation(From start of treatment (Day 1) up to Day 24)
- Change From Baseline in viral load after administration of zanamivir(Baseline (Day 1) and up to maximum Day 24)
- Number of participants with abnormal findings in heart rate(From start of treatment (Day 1) up to Day 24)
- Number of participants with abnormal findings in respiration rate(From start of treatment (Day 1) up to Day 24)
- Number of participants with genotypic resistance(Up to Day 24)