Influenza, HumanPhase 1NCT02377401
Pharmacokinetics of Zanamivir After Single and Repeated Dose Infusion Administration in Healthy Chinese Adults
A Phase 1 study testing Zanamivir in people with Influenza, Human, run by GlaxoSmithKline at 1 site in China.
Trial summary
Zanamivir is a potent and highly selective inhibitor of the influenza virus neuraminidase. Intravenous (IV) zanamivir is being developed for treatment of hospitalized patients with influenza, especially for those patients who may be in greatest need of parenteral influenza antiviral agents. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Influenza, Human
- What is being tested?
- Zanamivir
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteChina
- Study dates
- 28 Apr 2015to 19 Jun 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Male or females aged between 18 and 65 years of age inclusive, at the time of signing the informed consent.
- Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination and laboratory tests.
- Body weight >=50 kilograms (kg) and body mass index (BMI) within the range 19-24 kilogram per meter square (kg/m^2) (inclusive). BMI = (weight in kg)/(height in meters) ^2.
- A female subject is eligible to participate if she is non-childbearing potential or child-bearing potential with negative pregnancy test as determined by urine human chorionic gonadotropin (hCG) test.
- Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods listed in protocol. This criterion must be followed from the time of the first dose of study medication until completion of the follow-up visit.
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
- Alanine amino transferase (ALT) and bilirubin <=1.5x upper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent).
- Based on single or averaged corrected QT (QTc) values of triplicate ECGs obtained over a brief recording period: QTc <450 milliseconds (msec).
Who cannot join
- Criteria Based Upon Medical Histories-
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- History of regular alcohol consumption within 6 months of the study defined as: An average weekly intake of >14 drinks for males or >7 drinks for females. One drink is equivalent to 12 grams (g) of alcohol: 12 ounces (360 milliliter [mL]) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.
- History of sensitivity to heparin or heparin-induced thrombocytopenia.
- History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK medical monitor, contraindicates their participation.
- Criteria Based Upon Diagnostic Assessments-
Show all 18Show fewer
- A positive pre-study hepatitis B surface antigen (HBsAg) or positive hepatitis C antibody result within 3 months of screening.
- A positive pre-study drug/alcohol screen.
- A positive test for human immunodeficiency virus (HIV) antibody.
- A positive test for syphilis.
- Pregnant females as determined by positive urine hCG test at screening or prior to dosing.
- Have a creatinine clearance <=80 milliliter per minute (mL/min) (Cockcroft-Gault).
- Estimated creatinine clearance rate (eCCr) = (140 - Age) x Mass (in Kg) x Constant/Serum Creatinine micromole per liter (μmol/L), where constant is 1.23 for men and 1.04 for women.
- Other Criteria-
- Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
- Lactating females.
- The subject has participated in a clinical trial and has received an investigational product within 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer) prior to the first dosing day in the current study.
- Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Double Blinded, Parallel Study to Evaluate the Pharmacokinetics of Zanamivir After Single and Repeated Dose (300 mg and 600 mg) Infusion Administration in Healthy Chinese Adults
Zanamivir is a potent and highly selective inhibitor of the influenza virus neuraminidase. Intravenous (IV) zanamivir is being developed for treatment of hospitalized patients with influenza, especially for those patients who may be in greatest need of parenteral influenza antiviral agents. This study is a pharmacokinetic (PK) study to evaluate the safety/tolerability and pharmacokinetic profiles of IV zanamivir 300 milligrams (mg) and 600 mg in Chinese healthy subjects. Subjects will be randomized to receive either 300 mg or 600 mg IV zanamivir as a single dose followed by repeated dose every 12 hours (h) for 5 days. Subjects will be contacted or will return to study center for a follow-up visit, 7 days after the last dose or withdrawal from the study. Total number of subjects planned for enrollment will be 24 such that approximately 10 subjects complete dosing and critical assessments in each dose cohort. The total duration of the study will be approximately 6 weeks from screening to follow-up.
- Conditions
- Influenza, Human
- Being tested
- Zanamivir
- Keywords
- healthy volunteer, Zanamivir, pharmacokinetics, intravenous
- Medical subject headings
- Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZanamivirDrug
Zanamivir will be supplied as 10 mg/mL sterile clear, colorless, aqueous solution in 20 mL clear glass vials, each containing 200 mg zanamivir. Intravenous solutions will be prepared with normal saline.
| Study group | Role | What they receive |
|---|---|---|
| Zanamivir 300 mg | Experimental | Subjects will receive a single dose of IV zanamivir 300 mg on Day 1 morning. The repeat dose session will begin on Day 3 evening. Subjects will receive IV zanamivir 300 mg every 12 hours for 5 days. Each dose will be administrated intravenously at a constant rate over 30 minutes (500 milliliter per hour [mL/hr]). Receives: Drug: Zanamivir |
| Zanamivir 600 mg | Experimental | Subjects will receive a single dose of IV zanamivir 600 mg on Day 1 morning. The repeat dose session will begin on Day 3 evening. Subjects will be receive IV zanamivir 600 mg every 12 hours for 5 days. Each dose will be administrated intravenously at a constant rate over 30 minutes (500 mL/hr). Receives: Drug: Zanamivir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite of PK parameters of zanamivir following single dose administration
PK parameter assessed following single dose administration include the observed maximum serum drug concentration (Cmax), time to reach Cmax (tmax), elimination half-time (t1/2), area under the concentration-time curve from administration extrapolated to the last time of quantifiable concentration (AUC [0-t]), area under the concentration-time curve from administration extrapolated to 12 hours of quantifiable concentration (AUC [0-12]), area under the concentration-time curve from time zero extrapolated to infinite time (AUC [0-infinity]), clearance (CL) and volume of distribution after intravenous administration (Vz).
Measured: Day 1: Pre-dose and 0.25 h, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h and 24 h post-dose
Composite of PK parameters of zanamivir following repeat dose administration
PK parameter assessed following repeat dose administration include Cmax, pre-dose trough concentration (Ctau), tmax, t1/2, AUC (0-t), area under the concentration-time curve during steady state (AUC [0-tau]), CL, Vz, volume of distribution after intravenous administration at steady state (Vss), observed accumulation ratios (Ro) and time invariance ratio (Rs).
Measured: Day 8: Pre-dose and 0.25 h, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h and 24 h post-dose
Secondary outcomes (7)
Safety as assessed by the number of subjects with adverse events (AEs)
AEs will be collected from the start of study treatment and until the follow-up contact.
Measured: Up to Day 15
Composite of clinical laboratory assessments as a measure of safety
Absolute values and change over time from pre-dose values of hematology and clinical chemistry parameters will be assessed
Measured: Up to Day 9
Absolute values and change over time from pre-dose values of blood pressure as a measure of safety
Measured: Up to Day 9
Absolute values and change over time from pre-dose values of pulse rate as a measure of safety
Measured: Up to Day 9
Absolute values and change over time from pre-dose values of respiratory rate as a measure of safety
Measured: Up to Day 9
Absolute values and change over time from pre-dose values of temperature as a safety measure
Measured: Up to Day 9
Absolute values and change over time from pre-dose values of electrocardiogram (ECG) parameters
A 12-lead ECG will be obtained at each time point during the study and will be evaluated for safety by a qualified physician.
Measured: Up to Day 9
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2015 (estimated)
- Study start28 Apr 2015
- Primary completion19 Jun 2015
- Study completion19 Jun 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Influenza, HumanStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02377401
- Sponsor's protocol ID
- 117104
- Status last verified
- May 2017
- First submitted
- 26 Feb 2015
- Last updated
- 9 May 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double Blinded, Parallel Study to Evaluate the Pharmacokinetics of Zanamivir After Single and Repeated Dose (300 mg and 600 mg) Infusion Administration in Healthy Chinese Adults
- ClinicalTrials.gov ID
- NCT02377401
- Acronym / sponsor ID
- 117104
- Conditions
- Influenza, Human
- Keywords
- healthy volunteer, Zanamivir, pharmacokinetics, intravenous
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 28 Apr 2015 (actual)
- Primary completion
- 19 Jun 2015 (actual)
- Study completion
- 19 Jun 2015 (actual)
- First posted
- 3 Mar 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Zanamivir is a potent and highly selective inhibitor of the influenza virus neuraminidase. Intravenous (IV) zanamivir is being developed for treatment of hospitalized patients with influenza, especially for those patients who may be in greatest need of parenteral influenza antiviral agents. This study is a pharmacokinetic (PK) study to evaluate the safety/tolerability and pharmacokinetic profiles of IV zanamivir 300 milligrams (mg) and 600 mg in Chinese healthy subjects. Subjects will be randomized to receive either 300 mg or 600 mg IV zanamivir as a single dose followed by repeated dose every 12 hours (h) for 5 days. Subjects will be contacted or will return to study center for a follow-up visit, 7 days after the last dose or withdrawal from the study. Total number of subjects planned for enrollment will be 24 such that approximately 10 subjects complete dosing and critical assessments in each dose cohort. The total duration of the study will be approximately 6 weeks from screening to follow-up.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Zanamivir 300 mg | Experimental | Drug: ZanamivirSubjects will receive a single dose of IV zanamivir 300 mg on Day 1 morning. The repeat dose session will begin on Day 3 evening. Subjects will receive IV zanamivir 300 mg every 12 hours for 5 days. Each dose will be administrated intravenously at a constant rate over 30 minutes (500 milliliter per hour [mL/hr]). |
| Zanamivir 600 mg | Experimental | Drug: ZanamivirSubjects will receive a single dose of IV zanamivir 600 mg on Day 1 morning. The repeat dose session will begin on Day 3 evening. Subjects will be receive IV zanamivir 600 mg every 12 hours for 5 days. Each dose will be administrated intravenously at a constant rate over 30 minutes (500 mL/hr). |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Male or females aged between 18 and 65 years of age inclusive, at the time of signing the informed consent.
- Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination and laboratory tests.
- Body weight >=50 kilograms (kg) and body mass index (BMI) within the range 19-24 kilogram per meter square (kg/m^2) (inclusive). BMI = (weight in kg)/(height in meters) ^2.
- A female subject is eligible to participate if she is non-childbearing potential or child-bearing potential with negative pregnancy test as determined by urine human chorionic gonadotropin (hCG) test.
- Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods listed in protocol. This criterion must be followed from the time of the first dose of study medication until completion of the follow-up visit.
Key exclusion criteria (18 listed)
- Criteria Based Upon Medical Histories-
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- History of regular alcohol consumption within 6 months of the study defined as: An average weekly intake of >14 drinks for males or >7 drinks for females. One drink is equivalent to 12 grams (g) of alcohol: 12 ounces (360 milliliter [mL]) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.
- History of sensitivity to heparin or heparin-induced thrombocytopenia.
- History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK medical monitor, contraindicates their participation.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ZanamivirZanamivir will be supplied as 10 mg/mL sterile clear, colorless, aqueous solution in 20 mL clear glass vials, each containing 200 mg zanamivir. Intravenous solutions will be prepared with normal saline. | Drug | Zanamivir 300 mg, Zanamivir 600 mg |
Primary outcome
Composite of PK parameters of zanamivir following single dose administration
Time frame: Day 1: Pre-dose and 0.25 h, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h and 24 h post-dose
PK parameter assessed following single dose administration include the observed maximum serum drug concentration (Cmax), time to reach Cmax (tmax), elimination half-time (t1/2), area under the concentration-time curve from administration extrapolated to the last time of quantifiable concentration (AUC [0-t]), area under the concentration-time curve from administration extrapolated to 12 hours of quantifiable concentration (AUC [0-12]), area under the concentration-time curve from time zero extrapolated to infinite time (AUC [0-infinity]), clearance (CL) and volume of distribution after intravenous administration (Vz).
Composite of PK parameters of zanamivir following repeat dose administration
Time frame: Day 8: Pre-dose and 0.25 h, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h and 24 h post-dose
PK parameter assessed following repeat dose administration include Cmax, pre-dose trough concentration (Ctau), tmax, t1/2, AUC (0-t), area under the concentration-time curve during steady state (AUC [0-tau]), CL, Vz, volume of distribution after intravenous administration at steady state (Vss), observed accumulation ratios (Ro) and time invariance ratio (Rs).
7 secondary outcomes
Safety as assessed by the number of subjects with adverse events (AEs)
Time frame: Up to Day 15
Composite of clinical laboratory assessments as a measure of safety
Time frame: Up to Day 9
Absolute values and change over time from pre-dose values of blood pressure as a measure of safety
Time frame: Up to Day 9
Absolute values and change over time from pre-dose values of pulse rate as a measure of safety
Time frame: Up to Day 9
Absolute values and change over time from pre-dose values of respiratory rate as a measure of safety
Time frame: Up to Day 9
Absolute values and change over time from pre-dose values of temperature as a safety measure
Time frame: Up to Day 9
Absolute values and change over time from pre-dose values of electrocardiogram (ECG) parameters
Time frame: Up to Day 9
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2017.
- Results for study 117104 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
Related trials for Influenza, Human
Enrolling by invitation
Personalized Ventilator Settings for Patients on ECMO
Acute Respiratory Distress Syndrome (ARDS), Extracorporeal Membrane Oxygenation
RecruitingPhase 2
BPL-1357 Against H1N1 Influenza Virus Challenge
Influenza, Human
Not yet recruitingPhase 1
Safety and Immunogenicity of Chimeric Hemagglutinin mRNA Vaccine Candidates
Influenza
RecruitingPhase 1
pH1N1 Blinded Challenge Study
Influenza
RecruitingPhase 3
A Study to Evaluate the Safety and Efficacy of MK-1406/CD388 for Prevention of Influenza (MK-1406-005/CD388.SQ.3.06)
Influenza
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Zanamivir in people with Influenza, Human, run by GlaxoSmithKline at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Composite of PK parameters of zanamivir following single dose administration (time frame: Day 1: Pre-dose and 0.25 h, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h and 24 h post-dose). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 May 2017.