Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
GSK2140944 · 7 trials · 3 indications
Pre-treatment urogenital, pharyngeal, and rectal swab specimens were obtained for bacteriological culture for neisseria (N.) gonorrhoeae at the Baseline visit. Test- of-Cure was defined by infection site (that is urogenital and, as appropriate, rectal and/or pharyngeal) as culture confirmed bacterial eradication of N. gonorrhoeae observed 3 to 7 days post-treatment. Pre-treatment urogenital specimens were obtained for nucleic acid amplification test (NAAT) assay to detect the presence of N. gonorrhoeae and chlamydia trachomatis at the Baseline visit. Only participants who had a pre-therapy N. gonorrhoeae isolate recovered from their urogenital specimen were evaluated. Microbiologically evaluable (ME) Population comprised of all randomized participants who had N. gonorrhoeae isolated from Baseline cultures of urogenital swab specimens, received any dose of gepotidacin, and returned for their TOC visit.
ECGs will be measured using a 24-hour continuous 12-lead Holter monitor. ECGs will be extracted up to 10 replicates at the following time points: at 3 time points pre-dose (45, 30, and 15 minutes prior to starting the infusion) and 0.25, 0.5, 1.0, 1.5, 2.0 (end of infusion), 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 24 and 48 hours after dosing, for a total of 16 time points per treatment period
PK parameters will include area under the concentration-time curve (AUC) from time zero (pre-dose) extrapolated to infinite time AUC(0-infinity), AUC from time zero to last quantifiable concentration AUC(0-t), relative bioavailability of drug (Frel), maximum observed concentration (Cmax), time of occurrence of Cmax (tmax), lag time before observation of drug concentration (tlag) and terminal phase half-life (t1/2) in the fasted state; AUC(0-infinity), AUC(0-t), tmax, tlag and Cmax after moderate fat meal.
PK parameters will include AUC(0-infinity), AUC(0-t), tmax, tlag and Cmax of GSK2140944.
Laboratory assessments will include hematology, clinical chemistry, urinalysis parameters
All 12-lead ECGs will be obtained after the subject has rested in a supine position for at least 10 minutes
Vital signs will be measured for subjects in supine position and will include systolic and diastolic blood pressure, pulse rate and temperature
From the plasma concentration-time and blood/plasma radioactivity concentration-time data, the following pharmacokinetic parameters will be determined, as data permit: maximum observed plasma concentration (Cmax), time to Cmax (tmax), area under the plasma concentration-time curve \[AUC(0-t) and AUC(0-∞)\], and apparent terminal phase half-life (t1/2). Systemic clearance (CL) and volume of distribution (Vdss) of GSK2140944 may be calculated for IV regimen only.
Total recovery of radioactivity in urine and feces is defined as a percentage of total radioactive dose in each interval and cumulatively.
Blood samples will be collected assessment of PK parameters including Epithelial Lining Fluid (ELF) and Alveolar Macrophages (AM) (AUC\[0- τ\]), Area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration within a participant across all treatments (AUC\[0-t\]), Maximum observed concentration (Cmax), Time of occurrence of Cmax (tmax), ELF and AM/plasma ratios for GSK2140944 at the early, mid and late dosing interval timepoints, and AUCELF/AUC plasma and AUCAM/AUC plasma ratios, as data permit.
Blood sample will be collected for estimation of relative bioavailability and assessment of PK parameters including maximum observed concentration; Cmax, area under the concentration-time curve from time 0 to time t; AUC (0-t) and area under the concentration-time curve from time 0 to infinity; AUC(0-infinity), Systemic clearance of parent drug (CL), Volume of distribution at steady state of parent drug after intravascular (e.g., IV) administration (Vdss) and Terminal phase half-life (t½).
Blood samples will be collected assessment of PK parameters including ELF and AM AUC(0- τ)), AUC(0-t), Cmax, tmax, ELF and AM/plasma ratios for GSK2140944 at the early, mid and late dosing interval timepoints, and AUCELF/AUC plasma and AUCAM/AUC plasma ratios, as data permit.
Blood sample will be collected for estimation of relative bioavailability and assessment of PK parameters including maximum observed concentration; Cmax, area under the concentration-time curve from time 0 to time t; AUC (0-t) and area under the concentration-time curve from time 0 to infinity; AUC(0-infinity), Systemic clearance of parent drug (CL), Volume of distribution at steady state of parent drug after intravascular (e.g., IV) administration (Vdss) and Terminal phase half-life (t½).
12-lead ECGs will be obtained at each timepoint using an ECG machine, after the subject has rested in a semi-supine position for at least 10 minutes
Continuous dual-lead cardiac monitoring will be obtained at each timepoints using an ECG machine
Clinical laboratory assessments will include hematology, clinical chemistry, routine urinalysis and additional parameters
Safety and tolerability parameters will include recording of AEs, throughout the study
Vital sign measurements will be done in semi-supine position and will include systolic and diastolic blood pressure
Vital sign measurements will be done in semi-supine position and will include pulse rate
Pharmacokinetic data will include area under the curve from time zero (pre-dose) to 12 hour post-dose (AUC(0-12)) following single dose of GSK2140944
Pharmacokinetic data will include area under the curve from time zero (pre-dose) to 24 hour post-dose (AUC(0-24)) following single dose of GSK2140944
Pharmacokinetic data will include area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration (AUC(0-t)) following single dose of GSK2140944
Pharmacokinetic data will include area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC(0-infinity)) following single dose of GSK2140944
Pharmacokinetic data will include maximum observed concentration (Cmax) following single dose of GSK2140944
Pharmacokinetic data will include time of occurrence of Cmax (tmax) following single dose of GSK2140944
Pharmacokinetic data will include terminal phase half-life (t1/2) following single dose of GSK2140944
Pharmacokinetic data will include area under the concentration-time curve over the dosing interval (AUC(0-tau)) following repeat dose of GSK2140944
Pharmacokinetic data will include Cmax following repeat dose of GSK2140944
Pharmacokinetic data will include tmax following repeat dose of GSK2140944
Pharmacokinetic data will include pre-dose (trough) concentration at the end of the dosing interval (Ctau) following repeat dose of GSK2140944
Pharmacokinetic data will include accumulation ratio (Ro) following repeat dose of GSK2140944
Pharmacokinetic data will include area under the curve from time zero (pre-dose) to 8 hour post-dose (AUC\[0-8\]) following single dose of GSK2140944
| Arm | Type | Description |
|---|---|---|
| GSK2140944 1500 mg | EXPERIMENTAL | Subjects will receive single oral dose of GSK2140944 1500 mg. |
| GSK2140944 3000 mg | EXPERIMENTAL | Subjects will receive single oral dose of GSK2140944 3000 mg. |
| Sequence ABDC | EXPERIMENTAL | Subjects will be administered treatments in Sequence ABDC where, A= GSK2140944 1000 mg IV infusion over 120 minutes and single dose of moxifloxacin placebo administered orally in morning; B= GSK2140944 1800 mg IV infusion over 120 minutes and single dose of moxifloxacin placebo administered orally in morning; C= GSK2140944 placebo IV infusion over 120 minutes and single dose of moxifloxacin placebo administered orally in morning and D= Moxifloxacin 400 mg administered orally in morning and GSK2140944 placebo administered as IV infusion over 120 minutes |
| Sequence BCAD | EXPERIMENTAL | Subjects will be administered treatments in Sequence BCAD where, A= GSK2140944 1000 mg IV infusion over 120 minutes and single dose of moxifloxacin placebo administered orally in morning; B= GSK2140944 1800 mg IV infusion over 120 minutes and single dose of moxifloxacin placebo administered orally in morning; C= GSK2140944 placebo IV infusion over 120 minutes and single dose of moxifloxacin placebo administered orally in morning and D= Moxifloxacin 400 mg administered orally in morning and GSK2140944 placebo administered as IV infusion over 120 minutes |
| Sequence CDBA | EXPERIMENTAL | Subjects will be administered treatments in Sequence CDBA where, A= GSK2140944 1000 mg IV infusion over 120 minutes and single dose of moxifloxacin placebo administered orally in morning; B= GSK2140944 1800 mg IV infusion over 120 minutes and single dose of moxifloxacin placebo administered orally in morning; C= GSK2140944 placebo IV infusion over 120 minutes and single dose of moxifloxacin placebo administered orally in morning and D= Moxifloxacin 400 mg administered orally in morning and GSK2140944 placebo administered as IV infusion over 120 minutes |
| Sequence DACB | EXPERIMENTAL | Subjects will be administered treatments in Sequence DACB where, A= GSK2140944 1000 mg IV infusion over 120 minutes and single dose of moxifloxacin placebo administered orally in morning; B= GSK2140944 1800 mg IV infusion over 120 minutes and single dose of moxifloxacin placebo administered orally in morning; C= GSK2140944 placebo IV infusion over 120 minutes and single dose of moxifloxacin placebo administered orally in morning and D= Moxifloxacin 400 mg administered orally in morning and GSK2140944 placebo administered as IV infusion over 120 minutes |
| Part 1 | EXPERIMENTAL | Subjects will receive either GSK2140944 1500 mg (500 mg x 3) capsules under fasted conditions or GSK2140944 1500 mg (750 mg x 2) tablets under fasted conditions or GSK2140944 1500 mg (750 mg x 2) tablets under fed conditions as per the randomization schedule in each of the three periods with a washout period of at least 3 days between the doses. There will also be a follow-up visit within 5-7 days after the last dose of study drug. |
| Part 2 | EXPERIMENTAL | Subjects will receive a single dose of GSK2140944 1500 mg (tablet or capsule) on Day 1 followed by a repeat dose of Itraconazole 200 mg once daily for 6 days from Day 4 to Day 9. On Day 7, subjects will receive a single dose of GSK2140944 1500 mg (tablet or capsule) one hour after the dose of Itraconazole. There will also be a follow-up visit within 5-7 days after the last dose of study drug. |
| Part 3 | EXPERIMENTAL | Subjects in Group 1 will receive GSK2140944 1500 mg (750 mg x 2) tablets twice daily from Day 1 to Day 5 under fasting and fed conditions in Period I and Period II, respectively. Subjects in Group 2 will receive GSK2140944 1500 mg (750 mg x 2) tablets twice daily from Day 1 to Day 5 under fed and fasting conditions in Period I and Period II, respectively. There will be a washout of at least 7 days between the periods. Subjects will have a follow up visit 5-7 days after the last dose of study drug in both the groups. |
| GSK2140944 for Injection and Capsule | EXPERIMENTAL | Each subject will receive a single 1000 milligram (mg) IV dose of GSK2140944 containing \[14C\]-GSK2140944 of approximately 22.5 microcurie \[μCi\] (approximately 0.8 megabecquerel \[MBq\]) of radioactivity given as a 2 hour infusion on Day 1 of treatment period 1 and 2000 mg oral dose of GSK2140944 containing \[14C\]-GSK2140944 of approximately 45 μCi (approximately 1.7 MBq) of radioactivity on Day 1 of treatment period 2. Each treatment period will be followed with washout of atleast 8 Days. |
| Part A(Cohort1) | EXPERIMENTAL | Study BTZ116666 has two parts. Each part will consist of a maximum of 6 cohorts. Part A will be initiated with 4 initial cohorts/timepoints in order to minimize the number of healthy volunteers that undergo bronchoscopy in this study. After review of data from Cohorts 1 through 4 of Part A, the study team will determine if additional cohorts are needed to be studied in Part A and/ or if Part B is needed. If the study team determines that additional cohorts are needed, then only the necessary cohorts in Parts A and/or B will be executed. In Part A, participants will receive GSK2140944 1000 mg intravenous (IV) infusion over 2 hours x 1 dose |
| Part A (Cohort2) | EXPERIMENTAL | In Part A, participants will receive GSK2140944 1000 mg intravenous (IV) infusion over 4 hours x 1 dose |
| Part A (Cohort3) | EXPERIMENTAL | In Part A, participants will receive GSK2140944 1000 mg intravenous (IV) infusion over 8 hours x 1 dose |
| Part A (Cohort4) | EXPERIMENTAL | In Part A, participants will receive GSK2140944 1000 mg intravenous (IV) infusion over 12 hours x 1 dose |
| Part A (Cohort5) | EXPERIMENTAL | In Part A, participants will receive GSK2140944 1000 mg intravenous (IV) infusion. Optional Cohort or Part and will only be used if necessary. Sampling times are to be determined based on the review of preliminary PK results from prior study parts and/or cohorts. |
| Part A (Cohort6) | EXPERIMENTAL | In Part A, participants will receive GSK2140944 1000 mg intravenous (IV) infusion. Optional Cohort or Part and will only be used if necessary. Sampling times are to be determined based on the review of preliminary PK results from prior study parts and/or cohorts. |
| Part B (Cohort1) | EXPERIMENTAL | In Part B, participants will receive GSK2140944 1000 mg IV infusion, q12h x 5 doses. Optional Cohort or Part and will only be used if necessary. Sampling times are to be determined based on the review of preliminary PK results from prior study parts and/or cohorts. |
| Part B (Cohort2) | EXPERIMENTAL | In Part B, participants will receive GSK2140944 1000 mg IV infusion over, q12h x 5 doses. Optional Cohort or Part and will only be used if necessary. Sampling times are to be determined based on the review of preliminary PK results from prior study parts and/or cohorts. |
| Part B (Cohort3) | EXPERIMENTAL | In Part B, participants will receive GSK2140944 1000 mg IV infusion over, q12h x 5 doses. Optional Cohort or Part and will only be used if necessary. Sampling times are to be determined based on the review of preliminary PK results from prior study parts and/or cohorts. |
| Part B (Cohort4) | EXPERIMENTAL | In Part B, participants will receive GSK2140944 1000 mg IV infusion over q12h x 5 doses. Optional Cohort or Part and will only be used if necessary. Sampling times are to be determined based on the review of preliminary PK results from prior study parts and/or cohorts. |
| Part B (Cohort5) | EXPERIMENTAL | In Part B, participants will receive GSK2140944 1000 mg IV infusion over, q12h x 5 doses. Optional Cohort or Part and will only be used if necessary. Sampling times are to be determined based on the review of preliminary PK results from prior study parts and/or cohorts. |
| Part B (Cohort6) | EXPERIMENTAL | In Part B, participants will receive GSK2140944 1000 mg IV infusion over, q12h x 5 doses. Optional Cohort or Part and will only be used if necessary. Sampling times are to be determined based on the review of preliminary PK results from prior study parts and/or cohorts. |
| Cohort 1 - GSK2140944 400 mg | EXPERIMENTAL | Subjects will be randomized in 6:2 ratio to receive either GSK2140944 (Day 1: Single oral dose Days 3 to 16: (14 Days) BID oral doses) or placebo for approximately 15 days |
| Cohort 1 - Placebo | PLACEBO_COMPARATOR | Subjects will be randomized in 6:2 ratio to receive either GSK2140944 BID or matching placebo for approximately 15 days |
| Cohort 2 - GSK2140944 800 mg | EXPERIMENTAL | Subjects will be randomized in 12:4 ratio to receive either GSK2140944 (Day 1: Single oral dose Days 3 to 16: (14 Days) BID oral doses) or placebo for approximately 15 days. GSK2140944 dose in Cohort 2 will be decided based on the safety and PK data from six subjects in Cohort 1 |
| Cohort 2 - Placebo | PLACEBO_COMPARATOR | Subjects will be randomized in 12:4 ratio to receive either GSK2140944 BID or matching placebo for approximately 15 days |
| Cohort 3 - GSK2140944 1500 mg | EXPERIMENTAL | Subjects will be randomized in 12:4 ratio to receive either GSK2140944 (Day 1: Single oral dose Days 3 to 16: (14 Days) BID oral doses) or placebo for approximately 15 days. GSK2140944 dose in Cohort 3 will be decided on the safety data and available PK data from at least 12 subjects dosed at the Cohort 2 |
| Cohort 3 - Placebo | PLACEBO_COMPARATOR | Subjects will be randomized in 12:4 ratio to receive either GSK2140944 bid or matching placebo for approximately 15 days |
| Cohort 4 - GSK2140944 2500 mg | EXPERIMENTAL | Subjects will be randomized in 12:4 ratio to receive either GSK2140944 (Day 1: Single oral dose Days 3 to 16: (14 Days) BID oral doses) or placebo for approximately 15 days. GSK2140944 dose in Cohort 4 will be decided on the safety data and available PK data from at least 12 subjects dosed at the Cohort 3 |
| Cohort 4 - Placebo | PLACEBO_COMPARATOR | Subjects will be randomized in 12:4 ratio to receive either GSK2140944 bid or matching placebo for approximately 15 days |
| Cohort 5 - GSK2140944 TBD | EXPERIMENTAL | Subjects will be randomized in 6:2 ratio to receive either GSK2140944 (Day 1: Single oral dose Days 3 to 16: (14 Days) TID oral doses) or placebo for approximately 15 days. GSK2140944 dose in Cohort 5 will be decided on the safety data and available PK data from at least 12 subjects dosed at the Cohort 4 |
| Cohort 5 - Placebo | PLACEBO_COMPARATOR | Subjects will be randomized in 6:2 ratio to receive either GSK2140944 TID or matching placebo for approximately 15 days |
| Cohort 6 - GSK2140944 TBD | EXPERIMENTAL | Subjects will be randomized in 6:2 ratio to receive either GSK2140944 (Day 1: Single oral dose Days 3 to 16: (14 Days) TID oral doses) or placebo for approximately 15 days. GSK2140944 dose in Cohort 5 will be decided on the safety data and available PK data from at least 6 subjects dosed at the Cohort 5 |
| Cohort 6 - Placebo | PLACEBO_COMPARATOR | Subjects will be randomized in 6:2 ratio to receive either GSK2140944 TID or matching placebo for approximately 15 days |
| GSK2140944 | EXPERIMENTAL | Dose range 100mg to 3000mg single dose |
| Matching Placebo | PLACEBO_COMPARATOR | Placebo |
| Name | Type | Description |
|---|---|---|
| GSK2140944 | DRUG | Immediate release capsules (pink hard gelatin size 00 capsule, with no external marking, filled with slightly agglomerated pale yellowish to grayish yellow powder) containing GSK2140944 500 mg and inactive formulation excipients. GSK2140944 will be administered orally once 1500 mg (3 capsules) or 3000 mg (6 capsules). |
| GSK2140944 placebo | DRUG | GSK2140944 placebo is 0.9% sodium chloride available for single IV dose over 2 hours administration. |
| Moxifloxacin | DRUG | Moxifloxacin is available as pinkish red tablet with dose strength 400 mg for single oral dose to be administered in the morning in the fasted state with approximately 240 mL of water. |
| Moxifloxacin placebo | DRUG | Moxifloxacin placebo is available as white, film-coated tablet. containing nonactive material for single oral dose to be administered in the morning in the fasted state with approximately 240 mL of water. |
| GSK2140944 capsule | DRUG | Immediate release capsule containing GSK2140944 and inactive formulation excipients with a unit dose strength of 500 mg |
| GSK2140944 tablet | DRUG | Immediate release tablet containing GSK2140944 and inactive formulation excipients with a unit dose strength of 750 mg |
| Itraconazole capsule | DRUG | Capsule containing Itraconazole with a unit dose strength of 100 mg |
| GSK2140944 for Injection | DRUG | GSK2140944 (1 gram) for Injection will be supplied as powder for injection containing \[14C\] GSK2140944. Non sterile powder is to be dissolved aseptically in sterile water for injection to a concentration of 4 mg/mL free base equivalent. IV solution is prepared by sterile filtration. 250 mL of IV solution, equivalent to 1000 mg GSK2140944, is then administered intravenously. |
| GSK2140944 (Single dose) | DRUG | A lyophilized formulation, pale yellow to grayish yellow cake containing 750 mg of GSK2140944 (as free base) per vial, Administered intravenously as a single dose. |
| GSK2140944 (Multiple dose) | DRUG | A lyophilized formulation, pale yellow to grayish yellow cake containing 750 mg of GSK2140944 (as free base) per vial, Administered intravenously every 12 hours for 5 doses (3 days). |
| Placebo | DRUG | Matching placebo will be available |
Inclusion Criteria: * The subject is an adult male or female at least 18 years of age at the time of signing informed consent who meets one of the following criteria: 1. A non-pregnant, non-lactating female of childbearing potential who 1) is sexually inactive by abstinence, 2) has a sole male p...
GSK2140944 is an investigational small molecule being developed for infectious disease indications, including bacterial infections, respiratory tract infections, and gonorrhea. It is currently in Phase 2 clinical development. The drug has been studied in healthy volunteers for pharmacokinetics, safety, and tolerability, but is not yet approved for any use.
GSK2140944 is being developed by GSK plc, a global pharmaceutical company traded on the New York Stock Exchange under the ticker GSK. The company has sponsored all four clinical trials of the drug, which are now completed.
GSK2140944 is in Phase 2 clinical development. All four completed trials were Phase 1 studies, which evaluated the drug's pharmacokinetics, safety, tolerability, and food effects in healthy volunteers. The drug is investigational and has not received FDA approval.
GSK2140944 has been studied in four completed Phase 1 trials: NCT01934205 (plasma and pulmonary pharmacokinetics), NCT02045849 (relative bioavailability and food effect), NCT02202187 (single oral escalating dose), and NCT02257398 (cardiac conduction study). All trials enrolled healthy volunteers in the United States.
GSK2140944 is the only name provided for this drug in the available data. No alternative names, such as a brand name or other code, have been disclosed. The drug is consistently referred to as GSK2140944 across all clinical trial records.