Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
GSK1325756 · 6 trials · 4 indications
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Use of antibiotics for DREs of interest was monitored. Roxithromycin was used for DRE sinusitis by one participant.
An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product
Clinical laboratory assessments will include hematology, clinical chemistry, urinalysis parameters
Vital sign measurements will include systolic and diastolic blood pressure and pulse rate
12-lead ECGs will be obtained at each timepoint
PK parameters will include area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time \[AUC(0-infinity)\], area under the concentration-time curve from time zero (pre-dose) to time t \[AUC(0-t)\], area under the concentration-time curve from time zero (pre-dose) to 24 hours \[AUC(0-24)\], maximum observed concentration (Cmax), time to maximum observed concentration (tmax), observed concentration at 24 hours post-dose (C24), terminal half-life (t1/2), time of last measurable concentration (tlast), clearance (CL) and volume of distribution (Vz)
PK parameters will include area under the concentration-time curve from time zero (pre-dose) to the end of the dosing interval \[AUC(0-tau)\], concentration at the end of the dosing interval (Ctau), Cmax, tmax, t1/2, Volume of distribution at steady-state (Vdss), and oral clearance (CL/F)
For determination of Area Under the blood concentration time Curve (AUC) for GSK1325756
| Arm | Type | Description |
|---|---|---|
| Danirixin + Oseltamivir matching placebo | EXPERIMENTAL | Subjects will receive 75 mg oral Danirixin twice daily with Oseltamivir matching placebo twice daily for a total of ten doses over five days |
| Danirixin matching placebo + Oseltamivir matching placebo | PLACEBO_COMPARATOR | Subjects will receive Danirixin matching placebo twice daily with Oseltamivir matching placebo twice daily for a total of ten doses over five days |
| Danirixin + Oseltamivir | EXPERIMENTAL | Subjects will receive 75 mg oral Danirixin twice daily with 75 mg Oseltamivir twice daily for a total of ten doses over five days |
| Danirixin matching placebo + Oseltamivir | ACTIVE_COMPARATOR | Subjects will receive Danirixin matching placebo twice daily with 75 mg Oseltamivir twice daily for a total of ten doses over five days |
| Part A (Cohort 1) | EXPERIMENTAL | Approximately 8 subjects (6 Active, 2 Placebo) will be randomized to receive single escalating IV doses i.e.10 milligrams (mg), 25 mg and 100 mg, plus one oral 100 mg dose (on the last occasion) of GSK1325756 or matching placebo, with a 7-days washout between doses. Dose escalations will be based on review of PK and safety data from preceding dose level. The projected doses for each group are subject to modification based upon PK and safety data from preceding cohorts. Pharmacokinetic parameters will be reviewed from at least 4 active subjects from preceding dose before dose escalating to the next dose level. The maximum dose administered will be 100 mg. Additional subjects/Cohorts may be enrolled. |
| Part B (Cohorts 2 and 3) | EXPERIMENTAL | Approximately 8 subjects (6 Active, 2 Placebo) per cohort will be randomized to receive escalating repeated IV doses of GSK1325756 or matching placebo (Cohort 2: 25 mg, Cohort 3: 50 mg) for 5 days. Repeated (BID) doses of GSK1325756 will begin the morning of Day 1 and continue through the morning of Day 5 (9 total doses). Dose escalations will be based on review of PK and safety data from preceding dose level. The projected doses for each group are subject to modification based upon PK and safety data from preceding cohorts. Pharmacokinetic parameters will be reviewed from at least 4 active subjects from preceding dose before dose escalating to the next dose level. The maximum dose administered will be 50 mg BID. Additional subjects/Cohorts may be enrolled. |
| GSK1325756 Immediate Release 50 mg | EXPERIMENTAL | Administered to volunteers in the fasted and fed states |
| GSK1325756 Bioenhanced Formulation 1 50 mg | EXPERIMENTAL | Administered to volunteers in the fasted and/or fed states |
| GSK1325756 Bioenhanced Formulation 2 50 mg | EXPERIMENTAL | Administered to volunteers in the fasted and/or fed states |
| Placebo | PLACEBO_COMPARATOR | Part A - Cohort 1 subjects will be administered GSK1325756 matching placebo tablets twice daily following a light meal for one day in accordance with the randomization schedule. |
| GSK1325756 200 mg | EXPERIMENTAL | Part A - Cohort 1 subjects will be administered GSK1325756 200 mg immediate release tablets twice daily following a light meal for one day in accordance with the randomization schedule. |
| GSK1325756 50 mg | EXPERIMENTAL | Part A - Cohort 1 subjects will be administered GSK1325756 50 mg immediate release tablets twice daily following a light meal for one day in accordance with the randomization schedule. |
| GSK1325756 100 mg | EXPERIMENTAL | Part B - Cohort 2 subjects will be administered GSK1325756 100 mg following a light meal (Fed) or in the fasted state twice daily for one day in accordance with the randomization schedule. |
| Cohort 1-PK and and safety of GSK1325756 in subjects 40-64y | EXPERIMENTAL | This arm assesses the pharmacokinetics and safety of a single oral ose of 100mg of GSK1325756 administered to subjects in the age range 40y-64y when administered in the fasted state, in the presence of a high-fat meal and in the presence of a proton-pump inhibitor. |
| Cohort 2- PK and safety of GSK1325756 in subjects aged 65y-80y | EXPERIMENTAL | This arm assesses the pharmacokinetics and safety of a single dose of 100mg of GSK1325756 administered to a group of subjects in the 64y-80y age range in the fasted state |
| COHORT 1 | EXPERIMENTAL | Interlocking design with Cohort 2. Single dose; treatment period over 2 days such that two subjects will receive GSK1325756 and at least one subject will receive placebo on Day 1. The remaining subjects will be dosed on day 2 of each treatment period assuming adequate safety from Day 1. Placebo and an escalation of GSK1325756 from 10mg, to 50mg, and 200mg, will be administered over the 6 week long treatment period allowing adequate washout period between doses. |
| COHORT 2 | EXPERIMENTAL | Interlocking design with Cohort 1. Single dose; treatment period over 2 days such that two subjects will receive GSK1325756 and at least one subject will receive placebo on Day 1. The remaining subjects will be dosed on day 2 of each treatment period assuming adequate safety from Day 1. Placebo and an escalation of GSK1325756 from 25mg, to 100mg, and 400mg, will be administered over the 6 week long treatment period allowing adequate washout period between doses. |
| COHORT 3 | EXPERIMENTAL | Placebo controlled, 14-day, once daily, repeat-dose evaluation with one selected dose of GSK1325756 in 14 subjects. Dose selection based on review of safety and tolerability data from cohorts 1 and 2. |
| COHORT 4 | EXPERIMENTAL | Placebo controlled, 14-day, once daily, repeat-dose evaluation with a higher selected dose of GSK1325756 in 14 subjects. Dose selection based on review of safety and tolerability data from cohort 3. |
| Name | Type | Description |
|---|---|---|
| GSK1325756 (Danirixin) | DRUG | It will be supplied as capsule shaped white film coated tablet containing 75 mg GSK1325756 for oral use |
| Placebo To Match GSK1325756 | DRUG | It will be supplied as capsule shaped white film coated placebo tablet for oral use |
| Oseltamivir Phosphate | DRUG | It will be supplied as size 0 Swedish Orange capsule containing 75 mg Oseltamivir phosphate and overfill of pre-gelatinized starch for oral use |
| Placebo To Match Oseltamivir Phosphate | DRUG | It will be supplied as size 0 Swedish Orange capsule containing pre-gelatinized starch and magnesium stearate for oral use |
| GSK1325756 Solution | DRUG | Solution containing 2 mg/mL GSK1325756 in sterile water for injection, to be administered intravenously. |
| GSK1325756 Solution Matching Placebo | DRUG | Solution containing sterile water for injection matching GSK1325756 solution, to be administered intravenously. |
| GSK1325756 Tablet | DRUG | A white film coated tablet containing 50 mg GSK1325756 to be administered orally. |
| GSK1325756 Tablet Matching Placebo | DRUG | A white film coated tablet matching GSK1325756 tablet, to be administered orally. |
| GSK1325756 | DRUG | CXCR2 antagonist |
| Placebo tablet | DRUG | Placebo will be available as white film coated GSK1325756 matching tablet which will be administered twice daily by oral route with 240 milliliters of water. |
| Placebo | OTHER | Placebo will be orally administered to at least 4 subjects in each treatment period of each cohort. In each sequence in each cohort, all subjects will receive one dose of placebo. |
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....
GSK1325756 is an investigational small molecule being developed by GSK plc for infectious disease indications, including virus diseases, infections, respiratory tract conditions, and chronic obstructive pulmonary disease. It is currently in Phase 1 clinical development and has not been approved by regulatory authorities.
GSK1325756 is being developed by GSK plc, a global biopharma company listed on the London Stock Exchange under the ticker GSK. The drug is in Phase 1 clinical development for infectious disease indications.
GSK1325756 is in Phase 1 clinical development. It is an investigational drug and has not been approved by regulatory authorities. All three completed clinical trials for GSK1325756 were Phase 1 studies.
GSK1325756 has completed three Phase 1 clinical trials: NCT01209052, a first-time-in-human study in healthy male volunteers; NCT01209104, a pharmacokinetics and safety study in elderly and adult subjects; and NCT01267006, a blood levels and effects study in healthy adults aged 40 to 80 years.
No alternative names for GSK1325756 have been disclosed in the available clinical trial information. The drug is identified solely by its compound number GSK1325756 in all registered studies.