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

NCT ID: NCT01353729

Last Updated: 2017-07-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-05-19
• Study Completion Date: 2011-08-02

Brief Summary

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.

Conditions

Influenza, Human

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: DOUBLE

Study Groups

Treatment A

Treatment A will include combination of zanamivir 600 mg IV plus placebo for moxifloxacin

Group Type: EXPERIMENTAL

600 mg zanamivir + moxifloxacin placebo

Intervention Type: DRUG

zanamivir 600 mg IV over 30 min x 1 dose + moxifloxacin placebo administered orally x 1 dose

Treatment B

Treatment A will include combination of zanamivir 1200 mg IV plus placebo for moxifloxacin

Group Type: EXPERIMENTAL

1200 mg zanamivir + moxifloxacin placebo

Intervention Type: DRUG

zanamivir 1200 mg IV over 30 min x 1 dose + moxifloxacin placebo administered orally x 1 dose

Treatment C

Treatment C will include zanamivir placebo plus placebo for moxifloxacin

Group Type: EXPERIMENTAL

zanamivir placebo + moxifloxacin placebo

Intervention Type: DRUG

zanamivir placebo IV over 30 min x 1 dose + moxifloxacin placebo administered orally x 1 dose

Treatment D

Treatment D will include moxifloxacin plus zanamivir placebo

Group Type: EXPERIMENTAL

zanamivir placebo + 400 mg moxifloxacin

Intervention Type: DRUG

moxifloxacin 400 mg administered orally x 1 dose + zanamivir placebo IV over 30 min x 1 dose

Interventions

600 mg zanamivir + moxifloxacin placebo

zanamivir 600 mg IV over 30 min x 1 dose + moxifloxacin placebo administered orally x 1 dose

Intervention Type: DRUG

1200 mg zanamivir + moxifloxacin placebo

zanamivir 1200 mg IV over 30 min x 1 dose + moxifloxacin placebo administered orally x 1 dose

Intervention Type: DRUG

zanamivir placebo + moxifloxacin placebo

zanamivir placebo IV over 30 min x 1 dose + moxifloxacin placebo administered orally x 1 dose

Intervention Type: DRUG

zanamivir placebo + 400 mg moxifloxacin

moxifloxacin 400 mg administered orally x 1 dose + zanamivir placebo IV over 30 min x 1 dose

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Austin, Texas, United States

Countries

United States

References

Lou Y, Gan J, Peppercorn A, Gould E, Weller S, Piscitelli SC, Patel P. Effect of intravenous zanamivir on cardiac repolarization. Pharmacotherapy. 2013 Jul;33(7):701-9. doi: 10.1002/phar.1261. Epub 2013 Apr 3.

Reference Type: BACKGROUND

PMID: 23553534 (View on PubMed)

Study Documents

Document Type: Annotated Case Report Form

For additional information about this study please refer to the GSK Clinical Study Register

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Document Type: Clinical Study Report

For additional information about this study please refer to the GSK Clinical Study Register

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Document Type: Statistical Analysis Plan

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Individual Participant Data Set

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Dataset Specification

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Study Protocol

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Informed Consent Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Related Links

https://www.clinicalstudydatarequest.com

Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Other Identifiers

114346

Identifier Type: -

Identifier Source: org_study_id