Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Pharmacokinetics of Zanamivir After Single and Repeated Dose Infusion Administration in Healthy Chinese Adults

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02377401
Recruitment Status : Completed
First Posted : March 3, 2015
Last Update Posted : May 9, 2017
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Brief 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. 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.

Condition or disease Intervention/treatment Phase
Influenza, Human Drug: Zanamivir Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : April 28, 2015
Actual Primary Completion Date : June 19, 2015
Actual Study Completion Date : June 19, 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Flu
Drug Information available for: Zanamivir

Arm Intervention/treatment
Experimental: Zanamivir 300 mg
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]).
Drug: Zanamivir
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.

Experimental: Zanamivir 600 mg
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).
Drug: Zanamivir
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.




Primary Outcome Measures :
  1. 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).

  2. 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).


Secondary Outcome Measures :
  1. Safety as assessed by the number of subjects with adverse events (AEs) [ Time Frame: Up to Day 15 ]
    AEs will be collected from the start of study treatment and until the follow-up contact.

  2. 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 hematology and clinical chemistry parameters will be assessed

  3. Absolute values and change over time from pre-dose values of blood pressure as a measure of safety [ Time Frame: Up to Day 9 ]
  4. Absolute values and change over time from pre-dose values of pulse rate as a measure of safety [ Time Frame: Up to Day 9 ]
  5. Absolute values and change over time from pre-dose values of respiratory rate as a measure of safety [ Time Frame: Up to Day 9 ]
  6. Absolute values and change over time from pre-dose values of temperature as a safety measure [ Time Frame: Up to Day 9 ]
  7. Absolute values and change over time from pre-dose values of electrocardiogram (ECG) parameters [ Time Frame: Up to Day 9 ]
    A 12-lead ECG will be obtained at each time point during the study and will be evaluated for safety by a qualified physician.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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).

Exclusion Criteria:

  • 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-

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02377401


Locations
Layout table for location information
China
GSK Investigational Site
Shanghai, China, 200030
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Layout table for investigator information
Study Director: GSK Clinical Trials GlaxoSmithKline
Layout table for additonal information
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT02377401    
Other Study ID Numbers: 117104
First Posted: March 3, 2015    Key Record Dates
Last Update Posted: May 9, 2017
Last Verified: May 2017
Keywords provided by GlaxoSmithKline:
healthy volunteer
Zanamivir
pharmacokinetics
intravenous
Additional relevant MeSH terms:
Layout table for MeSH terms
Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Zanamivir
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action