Influenza, HumanPhase 1NCT01353729
A Study to Evaluate the Effect of Intravenous Zanamivir on Cardiac Conduction in Healthy Volunteers
A Phase 1 study of Influenza, Human, run by GlaxoSmithKline at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Influenza, Human
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 19 May 2011to 2 Aug 2011
- 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 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 18Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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
- Being tested
- 600 mg zanamivir + moxifloxacin placebo, 1200 mg zanamivir + moxifloxacin placebo, zanamivir placebo + moxifloxacin placebo, zanamivir placebo + 400 mg moxifloxacin
- Keywords
- 12-lead ECG, cardiac repolarization, QTc, influenza, GR121167, zanamivir
- Medical subject headings
- Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
600 mg zanamivir + moxifloxacin placeboDrug
zanamivir 600 mg IV over 30 min x 1 dose + moxifloxacin placebo administered orally x 1 dose
1200 mg zanamivir + moxifloxacin placeboDrug
zanamivir 1200 mg IV over 30 min x 1 dose + moxifloxacin placebo administered orally x 1 dose
zanamivir placebo + moxifloxacin placeboDrug
zanamivir placebo IV over 30 min x 1 dose + moxifloxacin placebo administered orally x 1 dose
zanamivir placebo + 400 mg moxifloxacinDrug
moxifloxacin 400 mg administered orally x 1 dose + zanamivir placebo IV over 30 min x 1 dose
| Study group | Role | What they receive |
|---|---|---|
| Treatment A | Experimental | Treatment A will include combination of zanamivir 600 mg IV plus placebo for moxifloxacin Receives: Drug: 600 mg zanamivir + moxifloxacin placebo |
| Treatment B | Experimental | Treatment A will include combination of zanamivir 1200 mg IV plus placebo for moxifloxacin Receives: Drug: 1200 mg zanamivir + moxifloxacin placebo |
| Treatment C | Experimental | Treatment C will include zanamivir placebo plus placebo for moxifloxacin Receives: Drug: zanamivir placebo + moxifloxacin placebo |
| Treatment D | Experimental | Treatment D will include moxifloxacin plus zanamivir placebo Receives: Drug: zanamivir placebo + 400 mg moxifloxacin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in QTcF for zanamivir
Measured: 9 weeks
Secondary outcomes (22)
Change from baseline in QTcB
Measured: 9 weeks
Change from baseline in QTci
Measured: 9 weeks
Change from baseline in QT
Measured: 9 weeks
Change from baseline in Heart Rate
Measured: 9 weeks
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
Measured: 9 weeks
Pharmacokinetic parameters of Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time from serum zanamivir concentration-time data
Measured: 9 weeks
Pharmacokinetic parameters of maximum observed concentration from serum zanamivir concentration-time data
Measured: 9 weeks
Pharmacokinetic parameters of time of occurrence of cmax from serum zanamivir concentration-time data
Measured: 9 weeks
Pharmacokinetic parameters of systemic clearance of parent drug from serum zanamivir concentration-time data
Measured: 9 weeks
Pharmacokinetic parameters of volume of distribution in terminal phase from serum zanamivir concentration-time data
Measured: 9 weeks
Pharmacokinetic parameters of terminal phase half-life from serum zanamivir concentration-time data
Measured: 9 weeks
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
Measured: 9 weeks
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
Measured: 9 weeks
Pharmacokinetic parameters of maximum observed concentration (if needed) from plasma moxifloxacin concentration-time data
Measured: 9 weeks
Pharmacokinetic parameters of time of occurrence of cmax (if needed) from plasma moxifloxacin concentration-time data
Measured: 9 weeks
Pharmacokinetic parameters of systemic clearance of parent drug (if needed) from plasma moxifloxacin concentration-time data
Measured: 9 weeks
Pharmacokinetic parameters of volume of distribution in terminal phase (if needed) from plasma moxifloxacin concentration-time data
Measured: 9 weeks
Pharmacokinetic parameters of terminal phase half-life (if needed) from plasm moxifloxacin concentration-time data
Measured: 9 weeks
Safety and tolerability of zanamivir as assessed by change from baseline in 12-lead Electrocardiograms (ECG)
Measured: 9 weeks
Safety and tolerability of zanamivir as assessed by change from baseline in blood pressure and heart rate
Measured: 9 weeks
Safety and tolerability of zanamivir as assessed by change from baseline in the collection of adverse events
Measured: 9 weeks
Safety and tolerability of zanamivir as assessed by change from baseline in toxicity grading of clinical laboratory tests
Measured: 9 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2011 (estimated)
- Study start19 May 2011
- Primary completion2 Aug 2011
- Study completion2 Aug 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 40 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
- NCT01353729
- Sponsor's protocol ID
- 114346
- Status last verified
- Jul 2017
- First submitted
- 12 May 2011
- Last updated
- 21 Jul 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Publications
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.
PubMed 23553534
Study at a glance
From the registry record, last updated by the sponsor on 21 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01353729
- Acronym / sponsor ID
- 114346
- Conditions
- Influenza, Human
- Keywords
- 12-lead ECG, cardiac repolarization, QTc, influenza, GR121167, zanamivir
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 19 May 2011 (actual)
- Primary completion
- 2 Aug 2011 (actual)
- Study completion
- 2 Aug 2011 (actual)
- First posted
- 16 May 2011 (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.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Treatment A | Experimental | Drug: 600 mg zanamivir + moxifloxacin placeboTreatment A will include combination of zanamivir 600 mg IV plus placebo for moxifloxacin |
| Treatment B | Experimental | Drug: 1200 mg zanamivir + moxifloxacin placeboTreatment A will include combination of zanamivir 1200 mg IV plus placebo for moxifloxacin |
| Treatment C | Experimental | Drug: zanamivir placebo + moxifloxacin placeboTreatment C will include zanamivir placebo plus placebo for moxifloxacin |
| Treatment D | Experimental | Drug: zanamivir placebo + 400 mg moxifloxacinTreatment D will include moxifloxacin plus zanamivir placebo |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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%).
Key exclusion criteria (18 listed)
- 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.
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 |
|---|---|---|
| 600 mg zanamivir + moxifloxacin placebozanamivir 600 mg IV over 30 min x 1 dose + moxifloxacin placebo administered orally x 1 dose | Drug | Treatment A |
| 1200 mg zanamivir + moxifloxacin placebozanamivir 1200 mg IV over 30 min x 1 dose + moxifloxacin placebo administered orally x 1 dose | Drug | Treatment B |
| zanamivir placebo + moxifloxacin placebozanamivir placebo IV over 30 min x 1 dose + moxifloxacin placebo administered orally x 1 dose | Drug | Treatment C |
| zanamivir placebo + 400 mg moxifloxacinmoxifloxacin 400 mg administered orally x 1 dose + zanamivir placebo IV over 30 min x 1 dose | Drug | Treatment D |
Primary outcome
Change from baseline in QTcF for zanamivir
Time frame: 9 weeks
22 secondary outcomes
Change from baseline in QTcB
Time frame: 9 weeks
Change from baseline in QTci
Time frame: 9 weeks
Change from baseline in QT
Time frame: 9 weeks
Change from baseline in Heart Rate
Time frame: 9 weeks
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
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
Pharmacokinetic parameters of maximum observed concentration from serum zanamivir concentration-time data
Time frame: 9 weeks
Pharmacokinetic parameters of time of occurrence of cmax from serum zanamivir concentration-time data
Time frame: 9 weeks
Pharmacokinetic parameters of systemic clearance of parent drug from serum zanamivir concentration-time data
Time frame: 9 weeks
Pharmacokinetic parameters of volume of distribution in terminal phase from serum zanamivir concentration-time data
Time frame: 9 weeks
Pharmacokinetic parameters of terminal phase half-life from serum zanamivir concentration-time data
Time frame: 9 weeks
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
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
Pharmacokinetic parameters of maximum observed concentration (if needed) from plasma moxifloxacin concentration-time data
Time frame: 9 weeks
Pharmacokinetic parameters of time of occurrence of cmax (if needed) from plasma moxifloxacin concentration-time data
Time frame: 9 weeks
Pharmacokinetic parameters of systemic clearance of parent drug (if needed) from plasma moxifloxacin concentration-time data
Time frame: 9 weeks
Pharmacokinetic parameters of volume of distribution in terminal phase (if needed) from plasma moxifloxacin concentration-time data
Time frame: 9 weeks
Pharmacokinetic parameters of terminal phase half-life (if needed) from plasm moxifloxacin concentration-time data
Time frame: 9 weeks
Safety and tolerability of zanamivir as assessed by change from baseline in 12-lead Electrocardiograms (ECG)
Time frame: 9 weeks
Safety and tolerability of zanamivir as assessed by change from baseline in blood pressure and heart rate
Time frame: 9 weeks
Safety and tolerability of zanamivir as assessed by change from baseline in the collection of adverse events
Time frame: 9 weeks
Safety and tolerability of zanamivir as assessed by change from baseline in toxicity grading of clinical laboratory tests
Time frame: 9 weeks
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 21 Jul 2017.
- Background: PubMed 23553534Lou 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.
- Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.Link provided by the sponsor.
- Results for study 114346 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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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 of Influenza, Human, run by GlaxoSmithKline at 1 site in United States.
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 6 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 21 Jul 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 United States. 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?
Change from baseline in QTcF for zanamivir (time frame: 9 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01353729, which also lists 1 linked publication.
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 21 Jul 2017.