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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT02469298
Ethics application status
Date submitted
23/04/2015
Date registered
11/06/2015

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)
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
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
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
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)
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)
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
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
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)
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
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)
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
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
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)
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)
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)
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)
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)
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)
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
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)
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
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
Timepoint [23] 0 0
Up to Day 28/withdrawal
Primary outcome [24] 0 0
Number of Participants With DRE of Interest-associated Antibiotic Use
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
Timepoint [1] 0 0
Up to Day 28/withdrawal
Secondary outcome [2] 0 0
Number of Afebrile Participants Over Time Post Initiation of Treatment
Timepoint [2] 0 0
Up to Day 28/withdrawal
Secondary outcome [3] 0 0
Number of Participants Who Used Relief Medication
Timepoint [3] 0 0
Up to Day 28/withdrawal
Secondary outcome [4] 0 0
Number of Hospital Admissions Due to Influenza Infection
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
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
Timepoint [6] 0 0
Up to Day 14
Secondary outcome [7] 0 0
Total Dose of Relief Medication
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
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
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
Sex
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
1/06/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
25/04/2016
Sample size
Target
Accrual to date
Final
45
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
Recruitment postcode(s) [6] 0 0
4053 - Everton Plaza
Recruitment postcode(s) [7] 0 0
4031 - Kedron
Recruitment postcode(s) [8] 0 0
4300 - Springfield
Recruitment postcode(s) [9] 0 0
5045 - Glenelg East
Recruitment postcode(s) [10] 0 0
5159 - Happy Valley
Recruitment postcode(s) [11] 0 0
3806 - Berwick
Recruitment postcode(s) [12] 0 0
3975 - Lynbrook
Recruitment postcode(s) [13] 0 0
3174 - Noble Park
Recruitment postcode(s) [14] 0 0
3180 - Pakenham
Recruitment postcode(s) [15] 0 0
3029 - Tarneit
Recruitment postcode(s) [16] 0 0
6153 - Applecross
Recruitment postcode(s) [17] 0 0
6171 - Baldivis
Recruitment postcode(s) [18] 0 0
6010 - Claremont
Recruitment postcode(s) [19] 0 0
6062 - Morley
Recruitment postcode(s) [20] 0 0
6060 - Yokine
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
Idaho
Country [3] 0 0
United States of America
State/province [3] 0 0
Oklahoma
Country [4] 0 0
United States of America
State/province [4] 0 0
Oregon
Country [5] 0 0
United States of America
State/province [5] 0 0
Wisconsin
Country [6] 0 0
South Africa
State/province [6] 0 0
Eastern Cape
Country [7] 0 0
South Africa
State/province [7] 0 0
Gauteng
Country [8] 0 0
South Africa
State/province [8] 0 0
Mpumalanga
Country [9] 0 0
South Africa
State/province [9] 0 0
Western Province
Country [10] 0 0
South Africa
State/province [10] 0 0
Reiger Park

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
IPD for this study will be made available via the Clinical Study Data Request site.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
IPD is available via the Clinical Study Data Request site (click on the link provided below)
Available to whom?
Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.clinicalstudydatarequest.com/SearchAllPostings.aspx?searchparam=201682


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT02469298