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Also known as GSK1322322 (mesylate salt) Powder for Injection, GSK1322322 (freebase) tablets FED, GSK1322322 FED
GSK1322322 · 5 trials · 2 indications
An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as 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, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition, associated with liver injury and impaired liver function defined as alanine aminotransferase (ALT) \>=3 x upper limit of normal (ULN), and total bilirubin \>=2 x ULN or international normalised ratio \>1.5.
Blood samples were obtained for analysis of albumin and total protein at Day 1, Day 4, Day 8, Day 11, 7 Day Follow-up and 28 Day Follow-up. Baseline value was defined as the assessment done on Day 1.
Blood samples were obtained for analysis of ALT, ALP, AST, FSH, GGT, LDH and creatine kinase at Day 1, Day 4, Day 8, Day 11, 7 Day Follow-up and 28 Day Follow-up. Baseline value was defined as the assessment done on Day 1.
Blood samples were obtained for analysis of creatinine, uric acid, direct bilirubin and total bilirubin at Day 1, Day 4, Day 8, Day 11, 7 Day Follow-up and 28 Day Follow-up. Baseline value was defined as the assessment done on Day 1.
Blood samples were obtained for analysis of glucose, sodium, calcium, potassium, chloride, CO2 content /bicarbonate and urea/BUN at Day 1, Day 4, Day 8, Day 11, 7 Day Follow-up and 28 Day Follow-up. Baseline value was defined as the assessment done on Day 1.
Blood samples were obtained for analysis of estradiol at Day 1.
Blood samples were obtained for analysis of high sensitivity C-Reactive protein at Day 1, Day 2, Day 3, Day 4, Day 8, Day 11 and 7 Day Follow-up. Baseline value was defined as the assessment done on Day 1.
Blood samples were obtained for analysis of basophils, eosinophils, lymphocytes, monocytes, total neutrophils, WBC and platelet count at Day 1, Day 4, Day 8, Day 11, 7 Day Follow-up and 28 Day Follow-up. Baseline value was defined as the assessment done on Day 1.
Blood samples were obtained for analysis of MCV at Day 1, Day 4, Day 8, Day 11, 7 Day Follow-up and 28 Day Follow-up. Baseline value was defined as the assessment done on Day 1.
Blood samples were obtained for analysis of MCHC at Day 1, Day 4, Day 8, Day 11, 7 Day Follow-up and 28 Day Follow-up. Baseline value was defined as the assessment done on Day 1.
Blood samples were obtained for analysis of MCH at Day 1, Day 4, Day 8, Day 11, 7 Day Follow-up and 28 Day Follow-up. Baseline value was defined as the assessment done on Day 1.
Blood samples were obtained for analysis of RBC count and reticulocyte at Day 1, Day 4, Day 8, Day 11, 7 Day Follow-up and 28 Day Follow-up. Baseline value was defined as the assessment done on Day 1.
Vital sign assessments were conducted at Day 1 (pre-dose), Day 2 (pre-dose), Day 3 (pre-dose), Day 4 (4-12 hours post-dose), Day 8 (pre-dose) and Day 11. The assessments were made with the participant in a semi-supine position, having rested in that position for at least 10 minutes beforehand. Three BP measurements were taken at pre-dose on Day 1. The mean value recorded at pre-dose was classified as Baseline. Single BP was obtained at all other time points during the study.
Vital sign assessments were conducted at Day 1 (pre-dose), Day 2 (pre-dose), Day 3 (pre-dose), Day 4 (4-12 hours post-dose), Day 8 (pre-dose) and Day 11. The assessments were made with the participant in a semi-supine position, having rested in that position for at least 10 minutes beforehand. Three HR measurements were taken at pre-dose on Day 1. The mean value recorded at pre-dose was classified as Baseline. Single HR was obtained at all other time points during the study.
Vital sign assessments were conducted at Day 1 (pre-dose), Day 2 (pre-dose), Day 3 (pre-dose), Day 4 (4-12 hours post-dose), Day 8 (pre-dose) and Day 11. The assessments were made with the participant in a semi-supine position, having rested in that position for at least 10 minutes beforehand. Three RR measurements were taken at pre-dose on Day 1. The mean value recorded at pre-dose was classified as Baseline. Single RR was obtained at all other time points during the study.
Vital sign assessments were conducted at Day 1 (pre-dose), Day 2 (pre-dose), Day 3 (pre-dose), Day 4 (4-12 hours post-dose), Day 8 (pre-dose) and Day 11. The assessments were made with the participant in a semi-supine position, having rested in that position for at least 10 minutes beforehand. Three BP measurements were taken at pre-dose on Day 1. The mean value recorded at pre-dose was classified as Baseline. Single BP was obtained at all other time points during the study. The change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 2, Day 3, Day 4, Day 8 and Day 11) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to missing as well.
Vital sign assessments were conducted at Day 1 (pre-dose), Day 2 (pre-dose), Day 3 (pre-dose), Day 4 (4-12 hours post-dose), Day 8 (pre-dose) and Day 11. The assessments were made with the participant in a semi-supine position, having rested in that position for at least 10 minutes beforehand. Three HR measurements were taken at pre-dose on Day 1. The mean value recorded at pre-dose was classified as Baseline. Single HR was obtained at all other time points during the study. The change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 2, Day 3, Day 4, Day 8 and Day 11) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to missing as well.
Vital sign assessments were conducted at Day 1 (pre-dose), Day 2 (pre-dose), Day 3 (pre-dose), Day 4 (4-12 hours post-dose), Day 8 (pre-dose) and Day 11. The assessments were made with the participant in a semi-supine position, having rested in that position for at least 10 minutes beforehand. Three RR measurements were taken at pre-dose on Day 1. The mean value recorded at pre-dose was classified as Baseline. Single RR was obtained at all other time points during the study. The change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 2, Day 3, Day 4, Day 8 and Day 11) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to missing as well.
12-lead ECGs were obtained during the study using an ECG machine that automatically calculated the heart rate and measured PR, QRS, RR, QT, and QTc intervals. It was performed with the participant in a semi-supine position having rested in that position for at least 10 minutes beforehand. Three measurements were taken at pre-dose on Day 1 at least 5 minutes apart. The mean PR interval, RR interval, QRS duration, uncorrected QT interval (UncQT) and QTcB (QT corrected by Bazett's formula) and QTcF (corrected by Friedericia's formula) was calculated from automated ECG readings. The assessments were done at Day 1 (pre-dose, 0.25-1.5 hours post-initial dose and 1.5-3 hours post-initial dose), Day 4 (4-12 hours post-morning dose), Day 8 (pre-morning dose) and Day 11 (0 hour). The mean value recorded pre-dose on Day 1 was classified as Baseline.
12-lead ECGs were obtained during the study using an ECG machine that automatically calculated the heart rate and measured PR, QRS, RR, QT, and QTc intervals. It was performed with the participant in a semi-supine position having rested in that position for at least 10 minutes beforehand. Three measurements were taken at pre-dose on Day 1 at least 5 minutes apart. The mean PR interval, RR interval, QRS duration, uncorrected QT interval (UncQT) and QTcB (QT corrected by Bazett's formula) and QTcF (corrected by Friedericia's formula) was calculated from automated ECG readings. The assessments were done at Day 1 (pre-dose, 0.25-1.5 hours post-initial dose and 1.5-3 hours post-initial dose), Day 4 (4-12 hours post-morning dose), Day 8 (pre-morning dose) and Day 11 (0 hour). Mean value recorded pre-dose on Day 1 was classified as Baseline. Change from Baseline was calculated by subtracting the Baseline value from individual post-Baseline (Day 1 post-dose, Day 4, Day 8 and Day 11) values.
12-lead ECGs were obtained during the study using an ECG machine that automatically calculated the heart rhythm and measured PR, QRS, RR, QT, and QTc intervals. It was performed with the participant in a semi-supine position having rested in that position for at least 10 minutes beforehand. Three measurements were taken at pre-dose on Day 1 at least 5 minutes apart and the mean of the three measurements was calculated. The assessments were done at Day 1 (pre-dose, 0.25-1.5 hours post-initial dose and 1.5-3 hours post-initial dose), Day 4 (4-12 hours post-morning dose), Day 8 (pre-morning dose) and Day 11 (0 hour).
12-lead ECGs were obtained during the study using an ECG machine that automatically calculated the heart rhythm and measured PR, QRS, RR, QT, and QTc intervals. It was performed with the participant in a semi-supine position having rested in that position for at least 10 minutes beforehand. Three measurements were taken at pre-dose on Day 1 at least 5 minutes apart and the mean of the three measurements was calculated. The assessments were done at Day 1 (pre-dose, 0.25-1.5 hours post-initial dose and 1.5-3 hours post-initial dose), Day 4 (4-12 hours post-morning dose), Day 8 (pre-morning dose) and Day 11 (0 hour). The value recorded pre-dose on Day 1 was the Baseline. The change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 1 post-dose, Day 4, Day 8 and Day 11) values.
The parameters of clinical chemistry included albumin, total protein, ALT, ALP, AST, GGT, LDH and creatine kinase, creatinine, uric acid, direct bilirubin, total bilirubin, glucose, sodium, calcium, potassium, chloride, CO2 content /bicarbonate and urea/BUN and high sensitivity C-Reactive protein. The assessments were done at Day 1, Day 4, Day 8, Day 11, 7 Day Follow-up and 28 Day Follow-up. Baseline was defined as the assessment done on Day 1 (pre-dose). Data is reported for number of participants with abnormal transition from Baseline 'to high' or 'to low' relative to normal range. Only those parameters for which at least one value of abnormal transition was reported are summarized.
The parameters of clinical chemistry included basophils, eosinophils, lymphocytes, monocytes, total neutrophils, WBC count, platelet count, MCV, hemoglobin, MCHC, MCH, RBC count and reticulocyte count. The assessments were done at Day 1, Day 4, Day 8, Day 11, 7 Day Follow-up and 28 Day Follow-up. Baseline was defined as the assessment done on Day 1 (pre-dose). Data is reported for number of participants with abnormal transition from Baseline 'to high' or 'to low' relative to normal range. Only those parameters for which at least one value of abnormal transition was reported are summarized.
GSK1322322 AUC(0-∞) and Cmax following wet milled tablet formulation administered with and without moderate fat/calorie meal. GSK1322322 AUC(0-∞) and Cmax following oral mesylate salt solution administration.
GSK1322322 AUC(0-∞) and Cmax in each body weight group following IV or oral formulation administration to assess effect of body weight.
| Arm | Type | Description |
|---|---|---|
| Regimen 1 | EXPERIMENTAL | GSK1322322 1500mg and Placebo Linezolid given twice a day (BID) for 10 days |
| Regimen 2 | ACTIVE_COMPARATOR | Linezolid 600mg and placebo GSK1322322 given BID for 10 days |
| GSK1322322 IV formulation | EXPERIMENTAL | Subjects will be randomized in a cross over fashion to receive the GSK1322322 administered via IV formulation |
| GSK1322322 Wet milled Tablet (Fasted) | EXPERIMENTAL | Subjects will be randomized in a cross over fashion to receive the GSK1322322 administered via Wet milled Tablet (Fasted) |
| GSK1322322 Oral mesylate salt solution | EXPERIMENTAL | Subjects will be randomized in a cross over fashion to receive the GSK1322322 administered via Oral mesylate salt solution |
| GSK1322322 Wet milled Tablet (Fed) | EXPERIMENTAL | Subjects will be randomized in a cross over fashion to receive the GSK1322322 administered via Wet milled Tablet (Fed) |
| Cohort A1 | EXPERIMENTAL | Single dose 60 minute infusion of 500mg IV GSK1322322/placebo followed by BID for 4 days |
| Cohort A2 | EXPERIMENTAL | Single dose 30 minute infusion of 500mg IV GSK1322322/placebo followed by BID for 4 days |
| Cohort B | EXPERIMENTAL | Initial single 1000mg oral GSK1322322/placebo dose, initial single dose 1000mg IV GSK1322322/placebo followed by BID for 4 days |
| Cohort C | EXPERIMENTAL | Initial single 1500mg oral GSK1322322/placebo dose, initial single dose 1500mg IV GSK1322322/placebo followed by BID for 4 days |
| Cohort D | EXPERIMENTAL | Single dose 2000mg IV GSK1322322J/placebo |
| Cohort E | EXPERIMENTAL | Single dose 3000mg IV GSK1322322J/placebo |
| Cohort F | EXPERIMENTAL | 1000mg IV GSK1322322J/placebo followed by BID for 4 days |
| Cohort A | EXPERIMENTAL | A single AM dose of GSK1322322/placebo on Day 1, no dosing on Day 2, and BID dosing on Days 3-12. |
| Part 1 | EXPERIMENTAL | A 4 way crossover of three GSK1322322 tablet formulations and GSK1322322 powder in bottle |
| Part 2 | EXPERIMENTAL | A 3 way crossover of a GSK1322322 tablet with a high fat meal, with Ranitidine, and with Ranitidine and Vitamin C. |
| Name | Type | Description |
|---|---|---|
| GSK1322322 | DRUG | GSK1322322 1500mg BID |
| Linezolid | DRUG | Linezolid 600mg |
| GSK1322322 placebo | DRUG | Placebo |
| Linezolid placebo | DRUG | placebo |
| GSK1322322 (mesylate salt) Powder for Injection | DRUG | 1500 mg (mesylate salt) as free base, dissolved in sterile water for injection to a concentration of 100 mg/mL free base equivalent and sterilized via filtration. 15 mL of solution, equivalent to 1500 mg GSK 1322322, is the diluted into 0.9% Sodium Chloride Injection prior to infusion |
| GSK1322322 (freebase) tablets | DRUG | 500 mg tablets for a 1500 mg total single dose (3 tablets). Taken with 240 mL of water |
| GSK1322322 (mesylate salt) Powder for Oral Solution | DRUG | 1500 mg as a free base, dissolved in purified water to a concentration of 100 mg/mL free base equivalent. 15 mL of solution, equivalent to1500 mg GSK1322322 is administered orally with 225 mL of water |
| GSK1322322 (freebase) tablets FED | DRUG | Drug 500 mg tablets for a 1500 mg total single dose (3 tablets) (FED moderate fat meal) Taken with 240 mL of water |
| 500mg IV GSK1322322/placebo | DRUG | 500mg IV |
| 1000mg oral GSK1322322/placebo | DRUG | 1000mg oral |
| 1000mg IV GSK1322322/placebo | DRUG | 1000mg IV |
| 1500mg oral GSK1322322/placebo dose | DRUG | 1500mg oral |
| 1500mg IV GSK1322322/placebo | DRUG | 1500mg IV |
| 2000mg IV GSK1322322J/placebo | DRUG | 2000mg IV |
| 3000mg IV GSK1322322J/placebo | DRUG | 3000mg IV |
| 1000mg IV GSK1322322J/placebo | DRUG | 1000mg IV |
| GSK1322322/placebo | DRUG | GSK1322322/placebo escalating doses from 500mg to 1500mg |
| GSK1322322/placebo and midazolam | DRUG | GSK1322322/placebo and 5mg midazolam |
Inclusion Criteria: * Male or female subject age 18 years or older at the time of signing the informed consent * Male subjects must agree to use one of the contraception methods listed * A female is eligible to enter and participate in this study if she is of non-childbearing potential * The subjec...
GSK1322322 is an investigational antibacterial small molecule being studied for bacterial infections, including acute bacterial skin and skin structure infections. It has been evaluated in clinical trials in patients with skin infections and in healthy volunteers. It is not approved for any indication and remains in clinical development.
GSK1322322 is developed by GSK plc, which trades under the ticker GSK. The company sponsored all four registered clinical trials of the compound, which were conducted in the United States. Development has focused on bacterial infections, including skin infections.
GSK1322322 is in Phase 1 development. Four trials have been completed, including three Phase 1 studies and one Phase 2 study, and no trials are currently active. The compound is investigational and has not been approved by the FDA for any indication.
GSK1322322 has completed four trials: NCT01648179, NCT01610388, NCT01209078, and NCT00924911. These include a Phase 2 study comparing GSK1322322 with linezolid in acute bacterial skin and skin structure infection, plus Phase 1 studies of bioavailability, food effect, safety, tolerability, and pharmacokinetics in healthy subjects.
Yes. GSK1322322 refers to the same investigational compound studied in different forms, including GSK1322322 mesylate powder for injection and GSK1322322 freebase tablets. Trials have evaluated oral and intravenous formulations, as well as food effects on the tablet form. All refer to the same GSK plc antibacterial program.
Across the four completed trials, 157 participants have been enrolled. Three Phase 1 studies in healthy volunteers enrolled 24, 61, and 20 subjects, while the Phase 2 study in acute bacterial skin and skin structure infection enrolled 84 patients. The trials were randomized, double blind, and controlled.