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Safety, Tolerability and Clinical Effect of Danirixin in Adults With Influenza

Information source: GlaxoSmithKline
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Virus Diseases

Intervention: GSK1325756 (Danirixin) (Drug); Placebo To Match GSK1325756 (Drug); Oseltamivir Phosphate (Drug); Placebo To Match Oseltamivir Phosphate (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: GlaxoSmithKline

Official(s) and/or principal investigator(s):
GSK Clinical Trials, Study Director, Affiliation: GlaxoSmithKline

Overall contact:
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com

Summary

Study 201682 is a Phase IIa, randomized, double blind, placebo-controlled four arm outpatient study evaluating the safety, tolerability and clinical effect of danirixin or danirixin + oseltamivir combination in comparison to placebo or oseltamivir twice daily for 5 days in otherwise healthy adults with laboratory confirmed influenza infection. Danirixin is a selective and reversible C-X-C Chemokine Receptor 2 (CXCR2) antagonist that inhibits neutrophil transmigration and activation to areas of inflammation. The study is intended to test the hypothesis that inhibition of neutrophil activation will not impact safety parameters or worsen clinical manifestations of disease, disease-related events of interest, or viral load, and may possibly improve these parameters when administered within 48 hours of symptom onset. The aim of this exploratory study is to obtain data on the safety, tolerability and clinical effect of GSK1325756 (danirixin [DNX]) alone or in combination with oseltamivir (OSV) in otherwise healthy adults with acute, uncomplicated influenza. The primary objective is to assess safety and tolerability of DNX with and without a neuraminidase inhibitor through the evaluation of AEs, SAEs, clinical laboratory tests, vital signs, and electrocardiogram (ECG) parameters. Safety assessments will also include an assessment of disease related events (DREs) of interest. The Influenza Intensity and Impact Questionnaire (FluiiQ™) will be used in the study to document patient reported outcomes (PROs). FluiiQ is trademark owned by Measured Solutions for Health Private Limited.

Clinical Details

Official title: A Randomized, Double-blind, Placebo Controlled Study to Evaluate the Safety, Tolerability and Clinical Effect of Oral Danirixin (GSK1325756) in the Treatment of Healthy Adults With Acute, Uncomplicated Influenza (201682)

Study design: Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Primary outcome:

Frequency of adverse events (AEs) and serious adverse events (SAEs)

Change from Baseline in hematology parameters

Change from Baseline in clinical chemistry parameters

Change from Baseline in urinalysis parameters

Change from Baseline in vital signs

Change from Baseline in electrocardiogram (ECG) parameters

Frequency of disease-related events of interest

Antibiotic use by participants for disease related events.

Secondary outcome:

Time to clinical resolution of illness

Severity of respiratory, systemic, and total influenza symptoms defined as the area under the curve (AUC) as measured by the FluiiQ questionnaire.

Time to clinical resolution of individual symptoms

Time to resolution of fever

Proportion of afebrile subjects

Total use of relief medications for symptom relief

Incidence of hospital admissions due to influenza infection

Change from Baseline in influenza viral load

Percentage of subjects with no detectable influenza viral Ribonucleic Acid (RNA)

Eligibility

Minimum age: 18 Years. Maximum age: 64 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Between 18 and 64 years of age inclusive, at the time of signing the informed

consent;

- Onset of influenza-like illness symptoms within 48 hours prior to study enrollment.

Onset of symptoms is defined as the time when the subject's temperature was measured as elevated (>=38. 0°C [>=100. 4°F]) OR the time when the subject first experienced at least one symptom (cough, sore throat, nasal congestion, headache, feeling feverish, body aches and pains, or fatigue);

- Subjects have an oral temperature >=38. 0°C (>=100. 4°F) at screening visit or history

of feeling feverish within the 24 hours prior to screening visit;

- At least one respiratory symptom (cough, sore throat, nasal congestion) and at least

one systemic symptom (headache, body aches and pain, fatigue) of at least moderate intensity due to influenza infection;

- A positive influenza rapid antigen test;

- Body weight >60 Kilogram (kg) for men and >45 kg for women; and Body Mass Index (BMI)

between 19 to 35 kilogram per meters squared (kg/m^2), inclusive;

- Male or Female subjects could be eligible if :

Male subjects with female partners of child-bearing potential must comply with the following contraception requirements from the time of first dose of study medication until at least 36 hours (five half-lives) of study medication after the last dose of study medication: Vasectomy with documentation of azoospermia; Male condom plus partner use of one of the following contraceptive options: Contraceptive subdermal implant; Intrauterine device or intrauterine system; Oral Contraceptive, either combined or progestogen alone; Injectable progestogen; Contraceptive vaginal ring ; Percutaneous contraceptive patches; This is an all-inclusive list of those methods that meet the following GlaxoSmithKline (GSK) definition of highly effective: having a failure rate of less than 1% per year when used consistently and correctly and, when applicable, in accordance with the product label. For non-product methods (e. g., male sterility), the investigator determines what is consistent and correct use. The GSK definition is based on the definition provided by the International Conference on Harmonisation (ICH). The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception; Females of reproductive potential with same sex partners, when this is their preferred lifestyle, who are not currently pregnant and don't intend to become pregnant during the study period, or for subjects who are and will continue to be abstinent from penile-vaginal intercourse on a long term and persistent basis; Females of non-reproductive potential defined as: Pre-menopausal females with one of the following documented either by verbal interview or medical record: Tubal ligation; Hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion; Hysterectomy; Bilateral oophorectomy; Postmenopausal females defined as 12 months of spontaneous amenorrhea. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt are not allowed to be enrolled in this study. In questionable cases the subject cannot be enrolled.

- Subjects willing and able to give written informed consent to participate in the

study and to adhere to the procedures stated in the protocol. Exclusion Criteria:

- Subject defined as being at high risk of complications from influenza infection

according to the World Health Organization (WHO) Guidelines for Pharmacological Management of Pandemic Influenza A (H1N1) and other Influenza Viruses: Pregnant women; Persons of any age with chronic pulmonary disease (e. g. adult asthma, Chronic Obstruction Pulmonary Disease [COPD], cystic fibrosis, bronchiectasis); Persons of any age with chronic cardiac disease (e. g. congestive cardiac failure); Persons with metabolic disorders (e. g. diabetes); Persons with chronic renal disease, chronic hepatic disease, certain neurological conditions (including neuromuscular, neurocognitive and seizure disorders, but not including autism spectrum disorders); Hemoglobinopathies, or immunosuppression, whether due to primary immunosuppressive conditions, such as Human Immunodeficiency Virus (HIV) infection, or secondary conditions, such as immunosuppressive medication or malignancy;

- Subjects in whom treatment with an influenza antiviral is considered essential;

- Severity of illness requiring or anticipated to require in-hospital care;

- Pulse Oximetry levels <92% (at rest on room air) at screening or requirement for

supplemental oxygen;

- Any complication of respiratory tract infection, signs of severe or progressive

disease, or worsening of any pre-existing medical condition at the time of enrollment, that, in the opinion of the investigator, would place the subject at an unreasonably increased risk of participation in this study;

- Suspicion or confirmation of bacterial infection (e. g. otitis media, sinusitis,

bronchitis, focal pneumonia) or who are requiring oral or systemic antibiotics within one week before enrollment;

- Women who are pregnant as determined by a positive urine human chorionic

gonadotrophin (hCG) test prior to dosing or women who are breastfeeding;

- Current or chronic documented history of liver disease (including Hepatitis A, B, or

C), or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones); In this case "documented" refers to the outcome of the investigator's/designee's review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject's medical records). In questionable cases the subject cannot be enrolled;

- Corrected QT interval (QTc) >450 millisecond (msec) or QTc >480 msec in subjects with

Bundle Branch Block.

- Subjects currently using or expected to use: proton pump inhibitors, histamine H2-

receptor antagonists, oral or injectable Cytochrome P450 3A4 (CYP3A4) or Breast Cancer Resistance Protein (BCRP) substrates with a narrow therapeutic index, non-steroidal anti-inflammatory drugs (NSAIDs) or oral or systemic glucocorticoids during the study period; Antacids can be used but should not be taken for at least 3 hours preceding and 2 hours after administration of study drug;

- Subjects who have taken an approved or investigational anti-influenza medication

(e. g., oseltamivir, zanamivir, peramivir, laninamivir, amantadine, rimantidine, ribavirin) within the past 4 weeks before enrollment;

- Subjects who received the live attenuated influenza virus vaccine within the past 21

days;

- Subjects treated with systemic steroids or immunosuppressants within 2 weeks of study

start.

- History of alcohol/drug abuse within 6 months of the study start;

- Consumption of >3 alcoholic units for males and females over the past 24 hours. One

unit is equivalent to 8 grams of alcohol: a half-pint (~240 milliliter [mL]) of beer; 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.

- 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 Medical Monitor, contraindicates their participation.

- Where participation in the study would result in donation of blood or blood products

in excess of 500 mL within a 56 day period;

- 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);

- Exposure to more than four investigational medicinal products within 12 months prior

to the first dosing day

Locations and Contacts

US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com

GSK Investigational Site, Reiger Park 1459, South Africa; Not yet recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com

GSK Investigational Site, Port Elizabeth, Eastern Cape 6001, South Africa; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com

GSK Investigational Site, Johannesburg, Gauteng 1818, South Africa; Not yet recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com

GSK Investigational Site, Johannesburg, Gauteng 2113, South Africa; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com

GSK Investigational Site, Moloto South, Gauteng 1022, South Africa; Not yet recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com

GSK Investigational Site, Pretoria, Gauteng 0183, South Africa; Not yet recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com

GSK Investigational Site, Pretoria, Gauteng 0152, South Africa; Not yet recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com

GSK Investigational Site, Middelburg, Mpumalanga 1055, South Africa; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com

GSK Investigational Site, Baulkham Hills, New South Wales 2153, Australia; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com

GSK Investigational Site, Brookvale, New South Wales 2100, Australia; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com

GSK Investigational Site, Hinchinbrook, New South Wales 2168, Australia; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com

GSK Investigational Site, Liverpool, New South Wales 2170, Australia; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com

GSK Investigational Site, Browns Plains, Queensland 4118, Australia; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com

GSK Investigational Site, Everton Plaza, Queensland 4053, Australia; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com

GSK Investigational Site, Kedron, Queensland 4031, Australia; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com

GSK Investigational Site, Springfield, Queensland 4300, Australia; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com

GSK Investigational Site, Glenelg East, South Australia 5045, Australia; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com

GSK Investigational Site, Happy Valley, South Australia 5159, Australia; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com

GSK Investigational Site, Berwick, Victoria 3806, Australia; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com

GSK Investigational Site, Lynbrook, Victoria 3975, Australia; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com

GSK Investigational Site, Noble Park, Victoria 3174, Australia; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com

GSK Investigational Site, Pakenham, Victoria 3180, Australia; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com

GSK Investigational Site, Tarneit, Victoria 3029, Australia; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com

GSK Investigational Site, Applecross, Western Australia 6153, Australia; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com

GSK Investigational Site, Baldivis, Western Australia 6171, Australia; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com

GSK Investigational Site, Claremont, Western Australia 6010, Australia; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com

GSK Investigational Site, Morley, Western Australia 6062, Australia; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com

GSK Investigational Site, Yokine, Western Australia 6060, Australia; Recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com

GSK Investigational Site, Western Cape, Western Province, South Africa; Not yet recruiting
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com

Additional Information

Starting date: June 2015
Last updated: August 20, 2015

Page last updated: August 23, 2015

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