A Study to Evaluate the Effect of Intravenous Zanamivir on Cardiac Conduction in Healthy Volunteers

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01353729
First received: May 12, 2011
Last updated: August 4, 2011
Last verified: August 2011
  Purpose

Approximately 40 healthy subjects will be enrolled. Each subject will participate in the study for approximately 9 weeks. There will be four treatment sequences with a 5-7 day washout between treatments. Subjects will be admitted to the clinical unit on Day-1 of each dosing period and will remain in the unit until Day 2. Each subject will receive a single dose of each of the four treatments on Day 1 of each treatment period in a randomized fashion. Subjects will be discharged from the clinical research unit after the completion of all assessments on Day 2 of each period and return approximately 5-7 days later for the next dose period. Serial pharmacokinetic samples will be collected for up to 24 hours following each treatment.


Condition Intervention Phase
Influenza, Human
Drug: 600 mg zanamivir + moxifoxacin placebo
Drug: 1200 mg zanamivir + moxacin placebo
Drug: zanamivir placebo + moxifloxacin placebo
Drug: zanamivir placebo + 400 mg moxifloxacin
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Official Title: A Phase I, Randomized, Placebo-Controlled, Four-Way Crossover Study to Evaluate the Effect of Intravenous (IV) Zanamivir on Cardiac Conduction as Assessed by 12-lead Electrocardiogram (ECG) With Moxifloxacin as a Positive Control in Healthy Volunteers

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Change from baseline in QTcF for zanamivir [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from baseline in QTcB [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in QTci [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in QT [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in Heart Rate [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  • Pharmacokinetic parameters of Area under the concentration-time curve from time zero (pre-dose) to time of last quantifiable concentration from serum zanamivir concentration-time data [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  • Pharmacokinetic parameters of Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time from serum zanamivir concentration-time data [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  • Pharmacokinetic parameters of maximum observed concentration from serum zanamivir concentration-time data [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  • Pharmacokinetic parameters of time of occurrence of cmax from serum zanamivir concentration-time data [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  • Pharmacokinetic parameters of systemic clearance of parent drug from serum zanamivir concentration-time data [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  • Pharmacokinetic parameters of volume of distribution in terminal phase from serum zanamivir concentration-time data [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  • Pharmacokinetic parameters of terminal phase half-life from serum zanamivir concentration-time data [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  • Pharmacokinetic parameters of Area under the concentration-time curve from time zero (pre-dose) to time of last quantifiable concentration (if needed) from plasma moxifloxacin concentration-time data [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  • Pharmacokinetic parameters of area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (if needed) from plasma moxifloxacin concentration-time data [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  • Pharmacokinetic parameters of maximum observed concentration (if needed) from plasma moxifloxacin concentration-time data [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  • Pharmacokinetic parameters of time of occurrence of cmax (if needed) from plasma moxifloxacin concentration-time data [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  • Pharmacokinetic parameters of systemic clearance of parent drug (if needed) from plasma moxifloxacin concentration-time data [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  • Pharmacokinetic parameters of volume of distribution in terminal phase (if needed) from plasma moxifloxacin concentration-time data [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  • Pharmacokinetic parameters of terminal phase half-life (if needed) from plasm moxifloxacin concentration-time data [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  • Safety and tolerability of zanamivir as assessed by change from baseline in 12-lead Electrocardiograms (ECG) [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  • Safety and tolerability of zanamivir as assessed by change from baseline in blood pressure and heart rate [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  • Safety and tolerability of zanamivir as assessed by change from baseline in the collection of adverse events [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  • Safety and tolerability of zanamivir as assessed by change from baseline in toxicity grading of clinical laboratory tests [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]

Enrollment: 40
Study Start Date: May 2011
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment A Drug: 600 mg zanamivir + moxifoxacin placebo
600 mg IV over 30 min x 1 dose + moxifloxacin placebo administered orally x 1 dose
Experimental: Treatment B Drug: 1200 mg zanamivir + moxacin placebo
1200 mg IV over 30 min x 1 dose + moxifloxacin placebo administered orally x 1 dose
Experimental: Treatment C Drug: zanamivir placebo + moxifloxacin placebo
zanamivir Placebo IV over 30 min x 1 dose + moxifloxacin placebo administered orally x 1 dose
Experimental: Treatment D Drug: zanamivir placebo + 400 mg moxifloxacin
moxifloxacin 400 mg administered orally x 1 dose + zanamivir placebo IV over 30 min x 1 dose

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.
  • Male or female between 18 and 55 years of age inclusive, at the time of signing the informed consent.
  • A female subject is eligible to participate if she is of non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea or of child-bearing potential and agrees to use one of the contraception methods listed in the protocol.
  • Body weight greater than or equal to 50 kg for men and greater than or equal to 45 kg for women and BMI within the range 18.5-31.0 kg/m2 (inclusive).
  • AST, ALT, alkaline phosphatase and bilirubin less than or equal to 1.5xULN (isolated bilirubin >1.5x upper limit of normal (ULN) is acceptable if bilirubin is fractionated and direct bilirubin <35%).
  • Capable of giving written informed consent, which includes agreement to comply with the requirements and restrictions listed in the consent form

Exclusion Criteria:

  • The subject has a positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines.
  • The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
  • 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.
  • Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
  • A history of sensitivity to heparin or heparin-induced thrombocytopenia should not be enrolled.
  • History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of >14 drinks/week for men or >7 drinks/week for women.
  • Has a history or regular use of tobacco- or nicotine-containing products within 3 months prior to screening.
  • Pregnant females as determined by positive serum or urine human chorionic gonadotrophin (hCG) test at screening or prior to dosing.
  • Lactating females.
  • Unwillingness or inability to follow the procedures outlined in the protocol.
  • Subjects with a pre-existing condition interfering with normal gastrointestinal anatomy or motility, hepatic and/or renal function, that could interfere with the absorption, metabolism, and/or excretion of the study drugs. Subjects with a history of cholecystectomy, inflammatory bowel disease or pancreatitis should be excluded. Subjects with active peptic ulcer disease or a history of upper gastrointestinal bleeding
  • A creatinine clearance less than 80mL/min as determined by Cockcroft-Gault equation.
  • History/evidence of clinically significant pulmonary disease, renal or hepatobiliary diseases. Subjects with a history of nephrolithiasis will be excluded.
  • A positive pre-study Human immunodeficiency virus (HIV) antibody test, a positive Hepatitis B surface antigen or Hepatitis C antibody result within 3 months of screening.
  • Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
  • Subjects with a hemoglobin <11 g/dL. A single repeat is allowed for eligibility determination.
  • The subject's systolic blood pressure is outside the range of 90-140mmHg, or diastolic blood pressure is outside the range of 45-90mmHg or heart rate is outside the range of 45-100bpm for female subjects or 45-100 bpm for male subjects.
  • Exclusion criteria for screening ECG (a single repeat is allowed for eligibility determination) per protocol.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01353729

Locations
United States, Texas
GSK Investigational Site
Austin, Texas, United States, 78744
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Cheri Hudson; Clinical Disclosure Advisor, GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01353729     History of Changes
Other Study ID Numbers: 114346
Study First Received: May 12, 2011
Last Updated: August 4, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
12-lead ECG
cardiac repolarization
QTc
influenza
GR121167
zanamivir

Additional relevant MeSH terms:
Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Zanamivir
Moxifloxacin
Norgestimate, ethinyl estradiol drug combination
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Contraceptives, Oral, Combined
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 23, 2014