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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02469298




Registration number
NCT02469298
Ethics application status
Date submitted
23/04/2015
Date registered
11/06/2015
Date last updated
23/07/2019

Titles & IDs
Public title
Safety, Tolerability and Clinical Effect of Danirixin in Adults With Influenza
Scientific 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)
Secondary ID [1] 0 0
201682
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Virus Diseases 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - GSK1325756 (Danirixin)
Treatment: Drugs - Placebo To Match GSK1325756
Treatment: Drugs - Oseltamivir Phosphate
Treatment: Drugs - Placebo To Match Oseltamivir Phosphate

Experimental: Danirixin + Oseltamivir matching placebo - Subjects will receive 75 mg oral Danirixin twice daily with Oseltamivir matching placebo twice daily for a total of ten doses over five days

Placebo Comparator: Danirixin matching placebo + Oseltamivir matching placebo - Subjects will receive Danirixin matching placebo twice daily with Oseltamivir matching placebo twice daily for a total of ten doses over five days

Experimental: Danirixin + Oseltamivir - Subjects will receive 75 mg oral Danirixin twice daily with 75 mg Oseltamivir twice daily for a total of ten doses over five days

Active Comparator: Danirixin matching placebo + Oseltamivir - Subjects will receive Danirixin matching placebo twice daily with 75 mg Oseltamivir twice daily for a total of ten doses over five days


Treatment: Drugs: GSK1325756 (Danirixin)
It will be supplied as capsule shaped white film coated tablet containing 75 mg GSK1325756 for oral use

Treatment: Drugs: Placebo To Match GSK1325756
It will be supplied as capsule shaped white film coated placebo tablet for oral use

Treatment: Drugs: Oseltamivir Phosphate
It will be supplied as size 0 Swedish Orange capsule containing 75 mg Oseltamivir phosphate and overfill of pre-gelatinized starch for oral use

Treatment: Drugs: Placebo To Match Oseltamivir Phosphate
It will be supplied as size 0 Swedish Orange capsule containing pre-gelatinized starch and magnesium stearate for oral use

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) - AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse or misuse. SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant.
Timepoint [1] 0 0
Up to Day 28/withdrawal
Primary outcome [2] 0 0
Change From Baseline in Hematology Parameters-Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (Total Absolute Neutrophil Count [Total ANC]), Platelet Count and White Blood Cell (WBC) Count - Hematology parameters included Basophils, Eosinophils, Lymphocytes, Monocytes, Total neutrophils (Total ANC), Platelet count and WBC count. Blood samples were collected on Day 1, Day 3, Day 5 and Day28/withdrawal. Assessments recorded on Day 1 were considered as Baseline. Change from Baseline was equal to Post-Dose Visit Value minus Baseline.
Timepoint [2] 0 0
Baseline (Day 1) and up to Day 28/withdrawal
Primary outcome [3] 0 0
Change From Baseline in Hematology Parameters- Hemoglobin - Hematology parameters included Hemoglobin. Blood samples were collected on Day 1, Day 3, Day 5 and Day28/withdrawal. Assessments recorded on Day 1 were considered as Baseline. Change from Baseline was equal to Post-Dose Visit Value minus Baseline.
Timepoint [3] 0 0
Baseline (Day 1) and up to Day 28/withdrawal
Primary outcome [4] 0 0
Change From Baseline in Hematology Parameters- Hematocrit - Hematology parameters included Hematocrit. Blood samples were collected on Day 1, Day 3, Day 5 and Day28/withdrawal. Assessments recorded on Day 1 were considered as Baseline. Change from Baseline was equal to Post-Dose Visit Value minus Baseline.
Timepoint [4] 0 0
Baseline (Day 1) and up to Day 28/withdrawal
Primary outcome [5] 0 0
Change From Baseline in Hematology Parameters- Mean Corpuscle Hemoglobin (MCH) - Hematology parameters included Mean corpuscle hemoglobin (MCH). Blood samples were collected on Day 1, Day 3, Day 5 and Day28/withdrawal. Assessments recorded on Day 1 were considered as Baseline. Change from Baseline was equal to Post-Dose Visit Value minus Baseline.
Timepoint [5] 0 0
Baseline (Day 1) and up to Day 28/withdrawal
Primary outcome [6] 0 0
Change From Baseline in Hematology Parameters- Mean Corpuscle Volume (MCV) - Hematology parameters included Mean corpuscle volume (MCV). Blood samples were collected on Day 1, Day 3, Day 5 and Day28/withdrawal. Assessments recorded on Day 1 were considered as Baseline. Change from Baseline was equal to Post-Dose Visit Value minus Baseline.
Timepoint [6] 0 0
Baseline (Day 1) and up to Day 28/withdrawal
Primary outcome [7] 0 0
Change From Baseline in Hematology Parameters- Red Blood Cell (RBC) Count and Reticulocytes Count - Hematology parameters included RBC count and Reticulocytes count. Blood samples were collected on Day 1, Day 3, Day 5 and Day28/withdrawal. Assessments recorded on Day 1 were considered as Baseline. Change from Baseline was equal to Post-Dose Visit Value minus Baseline.
Timepoint [7] 0 0
Baseline (Day 1) and up to Day 28/withdrawal
Primary outcome [8] 0 0
Change From Baseline in Clinical Chemistry Parameters- Albumin and Total Protein - Clinical chemistry parameters included Albumin and Total protein. Blood samples were collected on Day 1, Day 3, Day 5 and Day28/withdrawal. Assessments recorded on Day 1 were considered as Baseline. Change from Baseline was equal to Post-Dose Visit Value minus Baseline.
Timepoint [8] 0 0
Baseline (Day 1) and up to Day 28/withdrawal
Primary outcome [9] 0 0
Change From Baseline in Clinical Chemistry- Alkaline Phosphatase (ALP), Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST) and Gamma Glutamyl Transferase (GGT) - Clinical chemistry parameters included Alkaline phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase and Gamma Glutamyl Transferase. Blood samples were collected on Day 1, Day 3, Day 5 and Day28/withdrawal. Assessments recorded on Day 1 were considered as Baseline. Change from Baseline was equal to Post-Dose Visit Value minus Baseline.
Timepoint [9] 0 0
Baseline (Day 1) and up to Day 28/withdrawal
Primary outcome [10] 0 0
Change From Baseline in Clinical Chemistry Parameters- Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid - Clinical chemistry parameters included Direct Bilirubin, Total Bilirubin, Creatinine and Uric acid. Blood samples were collected on Day 1, Day 3, Day 5 and Day28/withdrawal. Assessments recorded on Day 1 were considered as Baseline. Change from Baseline was equal to Post-Dose Visit Value minus Baseline.
Timepoint [10] 0 0
Baseline (Day 1) and up to Day 28/withdrawal
Primary outcome [11] 0 0
Change From Baseline in Clinical Chemistry Parameters- Calcium, Carbon Dioxide (CO2) Content/ Bicarbonate, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) - Clinical chemistry parameters included Calcium, CO2 content/ Bicarbonate, Glucose, Potassium, Sodium and Urea/(BUN). Blood samples were collected on Day 1, Day 3, Day 5 and Day 28/withdrawal. Assessments recorded on Day 1 were considered as Baseline. Change from Baseline was equal to Post-Dose Visit Value minus Baseline.
Timepoint [11] 0 0
Baseline (Day 1) and up to Day 28/withdrawal
Primary outcome [12] 0 0
Change From Baseline in Urinalysis Parameters- Urine pH - Urinalysis parameters included urine pH. pH is calculated on a scale of 0 to 14, such that, the lower the number, more acidic the urine and higher the number, more alkaline the urine with 7 being neutral. Urinalysis was done on Day 1, Day 5 and Day 28/withdrawal. Assessments recorded on Day 1 were considered as Baseline. Change from Baseline was equal to Post-Dose Visit Value minus Baseline.
Timepoint [12] 0 0
Baseline (Day 1), Day 5 and Day 28/withdrawal
Primary outcome [13] 0 0
Change From Baseline in Urinalysis Parameters- Urine Specific Gravity - Urinalysis parameter included Urine specific gravity and was measured on Day 1, Day 5 and Day 28. Urinary specific gravity is a measure of the concentration of solutes in the urine. It measures the ratio of urine density compared with water density and provides information on the kidney's ability to concentrate urine. Assessments recorded on Day 1 were considered as Baseline. Change from Baseline was equal to Post-Dose Visit Value minus Baseline.
Timepoint [13] 0 0
Baseline (Day 1), Day 5 and Day 28/withdrawal
Primary outcome [14] 0 0
Number of Participants With Maximum Post-baseline Urine Dipstick Abnormalities- Urine Occult Blood (Dipstick) - The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameter of urine occult blood can be read as negative, Trace, 1+, 2+, 3+ and 4+, indicating proportional concentrations in the urine sample. Assessments recorded on Day 1 were considered as Baseline.
Timepoint [14] 0 0
Up to Day 28/withdrawal
Primary outcome [15] 0 0
Number of Participants With Maximum Post-baseline Urine Dipstick Abnormalities- Urine Glucose (Dipstick) - The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameter of urine glucose can be read as negative, Trace, 1+ or 1/4 gram per deciliter (G/dL), 2+ OR 1/2 G/dL, 3+ or 1 G/dL and 4+ indicating proportional concentrations in the urine sample. Assessments recorded on Day 1 were considered as Baseline.
Timepoint [15] 0 0
Up to Day 28/withdrawal
Primary outcome [16] 0 0
Number of Participants With Maximum Post-baseline Urine Dipstick Abnormalities- Urine Protein (Dipstick) - The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameter of urine protein can be read as negative, Trace, 1+, 2+, 3+ and 4+, indicating proportional concentrations in the urine sample. Assessments recorded on Day 1 were considered as Baseline.
Timepoint [16] 0 0
Up to Day 28/withdrawal
Primary outcome [17] 0 0
Change From Baseline in Vital Signs- Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) - Vital signs were measured in semi-supine position after 5 minutes rest and included systolic and diastolic blood pressure. Three readings of blood pressure were taken; the first reading was rejected and the second and third readings were averaged to give the measurement to be recorded. Vital signs were obtained on Baseline (Day 1), Day 3, Day 5, Day 8, Day 14 and Day 28/withdrawal. Assessments recorded on Day 1 were considered as Baseline. Change from Baseline was equal to Post-Dose Visit Value minus Baseline.
Timepoint [17] 0 0
Baseline (Day 1) and up to Day 28/withdrawal
Primary outcome [18] 0 0
Change From Baseline in Vital Signs- Heart Rate (HR) - Vital signs were measured in semi-supine position after 5 minutes rest and included HR. Three readings of pulse rate were taken; the first reading was rejected and the second and third readings were averaged to give the measurement to be recorded. Vital signs were obtained on Day 1, Day 3, Day 5, Day 8, Day 14 and Day 28/withdrawal. Assessments recorded on Day 1 were considered as Baseline. Change from Baseline was equal to Post-Dose Visit Value minus Baseline.
Timepoint [18] 0 0
Baseline (Day 1) and up to Day 28/withdrawal
Primary outcome [19] 0 0
Change From Baseline in Vital Signs- Respiration Rate (RR) - Vital signs were measured in semi-supine position after 5 minutes rest and included RR. RR was obtained on Day 1, Day 3, Day 5, Day 8, Day 14 and Day 28/withdrawal. Assessments recorded on Day 1 were considered as Baseline. Change from Baseline was equal to Post-Dose Visit Value minus Baseline.
Timepoint [19] 0 0
Baseline (Day 1) and up to Day 28/withdrawal
Primary outcome [20] 0 0
Change From Baseline in Vital Signs- Temperature - Vital signs were measured in semi-supine position after 5 minutes rest and included temperature. Oral temperature was obtained on Day 1, Day 3, Day 5, Day 8, Day 14 and Day 28/withdrawal. Assessments recorded on Day 1 were considered as Baseline. Change from Baseline was equal to Post-Dose Visit Value minus Baseline.
Timepoint [20] 0 0
Baseline (Day 1) and up to Day 28/withdrawal
Primary outcome [21] 0 0
Change From Baseline in Vital Signs- Percent Oxygen in Blood (POB) - Vital signs were measured in semi-supine position after 5 minutes rest and included POB. POB was obtained on Baseline (Day 1), Day 3, Day 5, Day 8, Day 14 and Day 28/withdrawal. Assessments recorded on Day 1 were considered as Baseline. Change from Baseline was equal to Post-Dose Visit Value minus Baseline.
Timepoint [21] 0 0
Baseline (Day 1) and up to Day 28/withdrawal
Primary outcome [22] 0 0
Change From Baseline in Electrocardiogram (ECG) Parameters - 12-lead ECGs were obtained on Day 1, Day 3 and Day28/withdrawal using an ECG machine that automatically calculates and measures RR, PR, QRS, QT, and Corrected QT Interval using Bazette's formula (QTcB) and Corrected QT Interval using Fridericia forumula (QTcF) intervals. Assessments recorded on Day 1 were considered as Baseline. Change from Baseline was equal to Post-Dose Visit Value minus Baseline.
Timepoint [22] 0 0
Baseline (Day 1) and up to Day 28/withdrawal
Primary outcome [23] 0 0
Number of Participants With Disease Related Events (DREs) of Interest - Disease-related events of interest included Otitis media, Sinusitis, Bronchitis and Pneumonia and were captured separately from AEs and SAEs. DREs of interest were assessed and recorded by the site on all clinical visit days.
Timepoint [23] 0 0
Up to Day 28/withdrawal
Primary outcome [24] 0 0
Number of Participants With DRE of Interest-associated Antibiotic Use - Use of antibiotics for DREs of interest was monitored. Roxithromycin was used for DRE sinusitis by one participant.
Timepoint [24] 0 0
Up to Day 28/withdrawal
Secondary outcome [1] 0 0
Time to Resolution of Fever Over Time Post Initiation of Treatment - Time to resolution of fever was defined as the time when oral temperature was <= 37.2 degree Celsius (<=99.0 degree Fahrenheit) for at least 24 hours (with one hour window) without having taken any antipyretic medication for at least 4 hours. Temperature was taken orally and recorded in the eDiary, thrice daily from Day 1 to Day 5 (morning, noon, evening) and twice daily (morning, evening) from Day 6 to Day 14 by the participant using a digital thermometer provided by the study. For participants whose fever was not resolved by the Day 14 visit then after Day 14, participants continued to take oral temperature twice daily until temperature <=37.2 degree Celsius or <=99 degree Fahrenheit for 24 hours.
Timepoint [1] 0 0
Up to Day 28/withdrawal
Secondary outcome [2] 0 0
Number of Afebrile Participants Over Time Post Initiation of Treatment - Afebrile participants were defined as participants with oral temperature <=37.2 degree Celsius, <=99.0 degree Fahrenheit over time post initiation of treatment. Temperature was taken orally and recorded in the eDiary, thrice daily from Day 1 to Day 5 (morning, noon, evening) and twice daily (morning, evening) from Day 6 to Day 14 by the participant using a digital thermometer provided by the study. For participants whose fever was not resolved by the Day 14 visit then after Day 14, participants continued to take oral temperature twice daily until temperature <=37.2 degree Celsius or <=99 degree Fahrenheit for 24 hours.
Timepoint [2] 0 0
Up to Day 28/withdrawal
Secondary outcome [3] 0 0
Number of Participants Who Used Relief Medication - Use of study supplied relief medications (paracetamol and dextromethorphan for symptom relief were recorded in the eDiary and accordingly number of participants using these medications were recorded.
Timepoint [3] 0 0
Up to Day 28/withdrawal
Secondary outcome [4] 0 0
Number of Hospital Admissions Due to Influenza Infection - Number of participants admitted in hospital due to influenza infection was recorded.
Timepoint [4] 0 0
Up to Day 28/withdrawal
Secondary outcome [5] 0 0
Change From Baseline in Influenza Viral Load as Measured by Quantitative Reverse Transcription-polymerase Chain Reaction (qRT-PCR) From Nasopharyngeal Swabs on Day 3, Day 5, Day 8 and Day 14 - Influenza viral load as measured by quantitative reverse transcription - polymerase chain reaction (qRT-PCR) from nasopharyngeal swabs on Baseline (Day 1), Day 3, Day 5, Day 8 and Day 14 was recorded. Assessments recorded on Day 1 were considered as Baseline. Change from Baseline was equal to Post-Dose Visit Value minus Baseline.
Timepoint [5] 0 0
Baseline (Day 1) and Day 3, Day 5, Day 8 and Day 14
Secondary outcome [6] 0 0
Number of Participants With no Detectable Influenza Viral RNA by qRT-PCR From Nasopharyngeal Swabs on Baseline (Day 1), Day 3, Day 5, Day 8 and Day 14 - Number of participants with no detectable influenza viral ribonucleic acid (RNA) by qRT-PCR from nasopharyngeal swabs on Baseline (Day1), Day 3, Day 5, Day 8 and Day 14 were recorded. Assessments recorded on Day 1 were considered as Baseline.
Timepoint [6] 0 0
Up to Day 14
Secondary outcome [7] 0 0
Total Dose of Relief Medication - Use of study supplied relief medications (paracetamol and dextromethorphan for symptom relief were recorded in the eDiary and accordingly number of participants using these medications were recorded. The total dose of these relief medications used by these participants are presented.
Timepoint [7] 0 0
Up to Day 28/withdrawal
Secondary outcome [8] 0 0
Change From Baseline in Influenza Viral Load as Measured by Quantitative Virus Culture From Nasopharyngeal Swabs on Day 3, Day 5, Day 8 and Day 14 - Influenza viral load as measured by quantitative virus culture from nasopharyngeal swabs on Baseline (Day 1), Day 3, Day 5, Day 8 and Day 14 was recorded. Assessments recorded on Day 1 were considered as Baseline. Change from Baseline was equal to Post-Dose Visit Value minus Baseline.
Timepoint [8] 0 0
Baseline (Day 1) and Day 3, Day 5, Day 8 and Day 14
Secondary outcome [9] 0 0
Number of Participants With no Detectable Influenza Viral RNA by Quantitative Virus Culture From Nasopharyngeal Swabs on Baseline (Day 1), Day 3, Day 5, Day 8 and Day 14 - Number of participants with no detectable influenza viral RNA by quantitative virus culture from nasopharyngeal swabs on Baseline (Day1), Day 3, Day 5, Day 8 and Day 14 were recorded. Assessments recorded on Day 1 were considered as Baseline.
Timepoint [9] 0 0
Up to Day 14

Eligibility
Key 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) 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;

- Female subject: is eligible to participate if she is not pregnant (as confirmed by a
negative urine human chorionic gonadotrophin [hCG] test), not lactating, and at least
one of the following conditions applies

Non-reproductive potential defined as:

Pre-menopausal females with one of the following: documented Tubal ligation; Documented
Hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal
occlusion; Hysterectomy; Documented Bilateral oophorectomy; Postmenopausal defined as 12
months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous
follicle stimulating hormone [FSH] and estradiol levels consistent with menopause). Females
on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be
required to use one of the highly effective contraception methods if they wish to continue
their HRT during the study.

Reproductive potential agrees to follow one of the options listed below in the GSK Modified
List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive
Potential (FRP) requirements from the time of screening, during dosing, and until at least
36 hrs after the last dose of study medication and completion of the follow-up visit.

GSK List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive
Potential (FRP) meeting GSK criteria 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. This list does not apply to FRP with same sex partners, when this
is their preferred and usual lifestyle or for subjects who are and will continue to be
abstinent from penilevaginal intercourse on a long term and persistent basis.

Contraceptive subdermal implant; Intrauterine device or intrauterine system; Combined
estrogen and progestogen oral contraceptive; Injectable progestogen; Contraceptive vaginal
ring; Percutaneous contraceptive patches; Male partner sterilization with documentation of
azoospermia prior to the female subject's entry into the study, and this male is the sole
partner for that subject.

These allowed methods of contraception are only effective when used consistently, correctly
and in accordance with the product label. The investigator is responsible for ensuring that
subjects understand how to properly use these methods of contraception.

- Subjects willing and able to give written informed consent to participate in the study
and to adhere to the procedures stated in the protocol.
Minimum age
18 Years
Maximum age
64 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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. Mild persistent, Moderate or severe 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: oral or injectable Cytochrome P450 3A4
(CYP3A4) or Breast Cancer Resistance Protein (BCRP) substrates with a narrow
therapeutic index, 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; proton pump inhibitors and histamine
H2-receptor antagonists are prohibited from the screening visit until 12 hours after
completion of the final dose of study treatment.

- 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
GSK Investigational Site - Baulkham Hills
Recruitment hospital [2] 0 0
GSK Investigational Site - Brookvale
Recruitment hospital [3] 0 0
GSK Investigational Site - Hinchinbrook
Recruitment hospital [4] 0 0
GSK Investigational Site - Liverpool
Recruitment hospital [5] 0 0
GSK Investigational Site - Browns Plains
Recruitment hospital [6] 0 0
GSK Investigational Site - Everton Plaza
Recruitment hospital [7] 0 0
GSK Investigational Site - Kedron
Recruitment hospital [8] 0 0
GSK Investigational Site - Springfield
Recruitment hospital [9] 0 0
GSK Investigational Site - Glenelg East
Recruitment hospital [10] 0 0
GSK Investigational Site - Happy Valley
Recruitment hospital [11] 0 0
GSK Investigational Site - Berwick
Recruitment hospital [12] 0 0
GSK Investigational Site - Lynbrook
Recruitment hospital [13] 0 0
GSK Investigational Site - Noble Park
Recruitment hospital [14] 0 0
GSK Investigational Site - Pakenham
Recruitment hospital [15] 0 0
GSK Investigational Site - Tarneit
Recruitment hospital [16] 0 0
GSK Investigational Site - Applecross
Recruitment hospital [17] 0 0
GSK Investigational Site - Baldivis
Recruitment hospital [18] 0 0
GSK Investigational Site - Claremont
Recruitment hospital [19] 0 0
GSK Investigational Site - Morley
Recruitment hospital [20] 0 0
GSK Investigational Site - Yokine
Recruitment postcode(s) [1] 0 0
2153 - Baulkham Hills
Recruitment postcode(s) [2] 0 0
2100 - Brookvale
Recruitment postcode(s) [3] 0 0
2168 - Hinchinbrook
Recruitment postcode(s) [4] 0 0
2170 - Liverpool
Recruitment postcode(s) [5] 0 0
4118 - Browns Plains
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4053 - Everton Plaza
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4031 - Kedron
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5045 - Glenelg East
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5159 - Happy Valley
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3806 - Berwick
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3975 - Lynbrook
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3174 - Noble Park
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3180 - Pakenham
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3029 - Tarneit
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6153 - Applecross
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6171 - Baldivis
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6010 - Claremont
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6062 - Morley
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6060 - Yokine
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Florida
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Wisconsin
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Eastern Cape
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Gauteng
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Mpumalanga
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South Africa
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Reiger Park

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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 endpoints are
intended to test the hypothesis that inhibition of neutrophil activation by approximately
50-60% (as previously measured by cluster of differentiation [CD11b] expression in response
to chemokine [C-X-C motif] ligand 1 [CXCL1] stimulation ex vivo in human studies) 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 prior to future evaluation in hospitalized patients with complicated 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 and associated antibiotic use. The
Influenza Intensity and Impact Questionnaire (FluiiQâ„¢) will be used in the study to document
patient reported outcomes (PROs). The screening visit in Australia will be composed of a
pre-screen for influenza infection with an influenza rapid antigen test followed by a screen
for the remaining eligibility criteria for those subjects with a positive result on the
influenza rapid antigen test. FluiiQ is trademark owned by Measured Solutions for Health
Private Limited.
Trial website
https://clinicaltrials.gov/show/NCT02469298
Trial related presentations / publications
Roberts G, Chen S, Yates P, Madan A, Walker J, Washburn ML, Peat AJ, Soucie G, Kerwin E, Roy-Ghanta S. Randomized, Double-Blind, Placebo-Controlled Study of the Safety, Tolerability, and Clinical Effect of Danirixin in Adults With Acute, Uncomplicated Influenza. Open Forum Infect Dis. 2019 Apr 22;6(4):ofz072. doi: 10.1093/ofid/ofz072. eCollection 2019 Apr.
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
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GlaxoSmithKline
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Contact person for scientific queries

Summary results
Other publications