Phase 2
N=201
Safety Study to Assess IV Zanamivir for Treatment of Influenza Infection in Patients Who Are in Hospital
Influenza, Human
Bottom Line
View on ClinicalTrials.gov: NCT01014988 ↗Enrolled (actual)
201
Serious AEs
29.3%
Results posted
Mar 2017
Primary outcome: Primary: Number of Participants With Any Adverse Event (AE) Considered to be Related to Study Treatment — 28; 5 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- zanamivir aqueous solution (Drug)
- Age
- Pediatric, Adult, Older Adult · 0+ yrs
- Sex
- All
- Sponsor
- GlaxoSmithKline
- Primary completion
- Feb 2015
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Any Adverse Event (AE) Considered to be Related to Study Treatment |
28; 5 | — |
| PRIMARY Number of Participants With Any Severe or Grade 3/4 AEs |
57; 23 | — |
| PRIMARY Number of Participants With Any Severe or Grade 3/4 Treatment-related AE |
16; 2 | — |
| PRIMARY Number of Participants Who Permanently Discontinued the Study Treatment Due to an AE |
17; 2 | — |
| PRIMARY Number of Participants Who Were Permanently Discontinued From the Study Due to an AE |
20; 5 | — |
| PRIMARY Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5 |
48; 21; 79; 49; 1; 1 | — |
| PRIMARY Number of Participants With the Indicated Hematology Values Relative to the Normal Range at Baseline (Day 1) and Day 5 |
0; 1; 48; 30; 82; 40 | — |
| PRIMARY Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Clinical Chemistry Toxicities |
10; 1; 5; 0; 3; 1 | — |
| PRIMARY Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities |
40; 12; 9; 2; 0; 3 | — |
| PRIMARY Median Heart Rate at Baseline (Day 1) and Day 5 |
93.00; 95.00; 119.0; 144.0; 115.5; 112.0 | — |
| PRIMARY Median Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline (Day 1) and Day 5 |
126.00; 118.00; 102.0; 100.0; 105.5; 108.0 | — |
| PRIMARY Median Oxygen Saturation Measured Via Transcutaneous Oximetry (TCPO2) at Baseline (Day 1) and Day 5 |
97.00; 96.00; 98.0; 100.0; 98.0; 98.0 | — |
| PRIMARY Median Respiration Rate at Baseline (Day 1) and Day 5 |
23.00; 22.00; 32.0; 34.0; 29.5; 20.0 | — |
| PRIMARY Median Body Temperature at Baseline (Day 1) and Day 5 |
37.30; 37.30; 36.8; 37.3; 37.5; 37.3 | — |
| PRIMARY Number of Participants Assessed as Normal/Abnormal (Clinically Significant [CS] and Not Clinically Significant [NCS]) for 12-lead Electrocardiogram (ECG) at Baseline (Day 1) |
68; 5; 7; 8; 20; 8 | — |
| PRIMARY Median Corrected QT Interval (QTc) for Heart Rate by Fridericia's Formula (QTcF) and Bazett's Formula (QTcB) at Baseline (Day 1) and Day 5 |
400.6; 413.5; 356.00; 362.00; 365.00; 387.50 | — |
| SECONDARY Median Time to Virologic Improvement |
3.0; 4.0; 4.0; 3.0; 5.0; 4.0 | — |
| SECONDARY Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points |
-0.92; NA; NA; -3.750; -1.160; -2.280 | — |
| SECONDARY Mean Viral Susceptibility to Zanamivir at Baseline (Day 1) and All Post-Baseline Visits Collectively |
0.2091; 0.1800; 0.2660; 0.2300; 1.6100; NA | — |
| SECONDARY Number of Participants With Treatment-emergent (TE) Mutations |
0; 5; 2; 4 | — |
| SECONDARY Median Time to Resolution of Individual Vital Signs |
3.0; 4.0; 2.0; 25.0; 3.0; 3.0 | — |
| SECONDARY Number of Participants With the Indicated Ventilation Status: Modality of Supplemental Oxygen Delivery and Mechanical Ventilation |
4; 0; 1; 0; 2; 1 | — |
| SECONDARY Duration of Mechanical Ventilation and Supplemental Oxygen Use |
— | — |
| SECONDARY Median Time to Return to Pre-morbid Functional Status |
10.0; 8.0; 3.0; 5.0; 5.5; 4.0 | — |
| SECONDARY Number of Participants With the Indicated Mortality Status at Day 14 and Day 28 |
113; 7; 11; 12; 26; 12 | — |
| SECONDARY Median Time to Clinical Response (Sustained Resolution) of All Vital Signs (Composite) |
9.0; 7.0; 3.5; 6.5; 4.0; 5.0 | — |
| SECONDARY Number of Participants With Any AE Categorized as an Influenza Complication |
45; 4; 4; 3; 8; 3 | — |
| SECONDARY Number of Participants Who Used Any Concomitant Antibiotic Medications for Complications of Influenza |
63; 5; 7; 7; 12; 6 | — |
| SECONDARY Median Duration of Hospitalization and Intensive Care Unit (ICU) Stays |
15.0; 7.0; 4.0; 6.5; 6.0; 6.5 | — |
| SECONDARY Geometric Mean Maximum Serum Concentration (Cmax) of Zanamivir at the End of Infusion |
32.77; NA; NA; NA; NA; 34.47 | — |
| SECONDARY Geometric Mean Area Under the Serum Drug Concentration-time Curve (AUC) Over a 12-hour Dosing Interval (AUC[0-tau]) and AUC Extrapolated to Infinity (AUC[0-inf]) of Zanamivir |
82.86; NA; NA; NA; NA; 91.07 | — |
| SECONDARY Geometric Mean Terminal Half Life (t1/2) of Zanamivir |
2.39; NA; NA; NA; NA; 2.06 | — |
| SECONDARY Geometric Mean Serum Clearance of Zanamivir |
120.68; NA; NA; NA; NA; 109.83 | — |
| SECONDARY Geometric Mean Volume of Distribution (Vd) of Zanamivir |
24.89; NA; NA; NA; NA; 18.57 | — |
Summary
The purpose of this study is to determine whether zanamivir aqueous solution given by intravenous injection is safe in treating hospitalized patients with confirmed influenza infection. A single arm open-label design has been selected to achieve the primary objective of providing regulatory authorities with safety data on IV zanamivir.
Eligibility Criteria
Inclusion Criteria
- Male or female aged greater than or equal to 6 months of age; a female is eligible to enter and participate in the study if she is:
- of non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post-menopausal); or,
- of child-bearing potential, has a negative pregnancy test at Baseline, and agrees to one of the following methods for avoidance of pregnancy during the study and until the Post-Treatment +23 Days Follow-up Assessment:
- Abstinence; or,
- Oral contraceptive, either combined or progestogen alone; or,
- Injectable progestogen; or,
- Implants of levonorgestrel; or,
- Estrogenic vaginal ring; or,
- Percutaneous contraceptive patches; or
- Intrauterine device (IUD) or intrauterine system (IUS) showing that the expected failure rate is less than 1% per year as stated in the IUD or IUS Product Label; or,
- Has a male partner who is sterilized; or,
- Double barrier method: condom and an occlusive cap (diaphragm or cervical/vault caps) with a vaginal spermicidal agent (foam/gel/film/cream/suppository).
- Subjects who have confirmed influenza as determined by a positive result in a rapid test for influenza A or influenza B, or a laboratory test for influenza including influenza virus antigen test, virus culture or RT-PCR test. Subjects with negative rapid test result suspected of having influenza can be enrolled following confirmatory testing by RT-PCR, antigen test or culture.
- Hospitalized subjects with symptomatic influenza
- Subjects who are able to receive their first dose of study medication within seven days of experiencing influenza-like symptoms.
- Subjects willing and able to adhere to the procedures stated in the protocol.
- Subjects/legally acceptable representative (LAR) of minors and unconscious adults willing and able to give written informed consent to participate in the study (or included as permitted by local regulatory authorities, IRBs/IECs or local laws).
- French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.
- UK subjects and subjects in Spain: Subjects should be in a high dependency or intensive care setting at the time of enrollment and either have severe and progressive illness on approved influenza antivirals, or are considered unsuitable for treatment with approved influenza antivirals.
- Subjects who have severe or progressive influenza illness on approved (fully licensed) influenza antivirals, or who are considered unsuitable or inappropriate for treatment with approved influenza antivirals, or who in the opinion of the investigator may benefit from IV zanamivir therapy.
Exclusion Criteria
- Subjects who, in the opinion of the investigator, are not likely to survive the next 48 hours beyond Baseline.
- Subjects who require concurrent therapy with another influenza antiviral drug.
- Subjects who have participated in a study using an investigational influenza antiviral drug within 30 days prior to Baseline.
- Subjects who are known or suspected to be hypersensitive to any component of the study medication.
- Subjects who meet the following criteria at Baseline:
- ALT greater than or equal to 3xULN and bilirubin greater than or equal to 2xULN or ALT greater than or equal to 5xULN
- History of cardiac disease or clinically significant arrhythmia (either on ECG or by history) which, in the opinion of the Investigator, will interfere with the safety of the individual subject.
- Child in care (CiC) as defined below:
A child who has been placed under the control or protection of an agency, organization, institution or entity by the courts, the government or a government body, acting in accordance with powers conferred on them by law or regulation.
The definition of a CiC can include a child cared for by foster parents or living in a care home or institution, provided that the arrangement falls within the definition
Data sourced from ClinicalTrials.gov (NCT01014988). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.