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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02751424




Registration number
NCT02751424
Ethics application status
Date submitted
21/04/2016
Date registered
26/04/2016
Date last updated
12/09/2018

Titles & IDs
Public title
A Study to Evaluate Safety, Tolerability and Pharmacokinetics of Ascending Intravenous Single Dose and Repeat Dose of GSK3342830
Scientific title
A Phase I, Randomized, Double-Blind (Sponsor Unblinded), Single-Center, Placebo-Controlled, Two-Part Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Ascending Single and Repeat Intravenous Doses of GSK3342830 in Healthy Adult Subjects
Secondary ID [1] 0 0
204847
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Infections, Bacterial 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - GSK3342830
Treatment: Drugs - Placebo

Experimental: GSK3342830 single dose in Part 1 - Enrolled subject will receive single escalation dose of GSK3342830. The escalating doses will be evaluated in six cohorts as A- 250 mg, B-500 mg, C-1000 mg, D-2000 mg, E-4000 mg, and F-=<6000 mg. In each cohort 6 subjects will receive GSK3342830 in form of infusion for 1 h, therefore approximately 36 subjects will receive GSK3342830. Dose escalation will be based on evaluation of the preceding dose levels in the study.

Placebo Comparator: Placebo single dose in Part 1 - Enrolled subject will receive single escalation dose of placebo. In each cohort, 2 subjects will receive placebo in form of infusion for 1 h, therefore approximately 12 subjects will receive placebo.

Experimental: GSK3342830 repeat Dose in Part 2 - Enrolled subject will receive repeat escalating dose of GSK3342830. GSK3342830 as a single IV infusion will be administered on Day 1, TID (8 hours apart) IV infusions on Days 2 through 14, and a single IV infusion on Day 15. The escalating doses will be evaluated in three cohorts as G-1000 mg, H-2000 and I-4000 mg. In each cohort 8 subjects will receive GSK3342830 in form of infusion for 1 h, therefore approximately 24 subjects will receive GSK3342830. The starting dose and maximum dose may change based on clinical safety and PK findings in Part 1 or earlier doses in Part 2 respectively.

Placebo Comparator: Placebo repeat Dose in Part 2 - Enrolled subject will receive repeat escalation dose of placebo. Placebo as a single IV infusion will be administered on Day 1, TID (8 hours apart) IV infusions on Days 2 through 14, and a single IV infusion on Day 15. In each cohort, 2 subjects will receive placebo in form of infusion for 1 h, therefore approximately 6 subjects will receive placebo.


Treatment: Drugs: GSK3342830
A pyrogen free lyophilized formulation, white to yellowish brown powder containing 1000 mg of GSK3342830A (as free base) per vial. The reconstituted solution looks like a clear, colorless to yellow or brownish yellow liquid, free from visible particulate matter will be administered as IV infusion over 1 hour.

Treatment: Drugs: Placebo
A clear and colorless solution containing 0.9% sodium chloride. It will administered as IV infusion over 1 hour.

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

Outcomes
Primary outcome [1] 0 0
Part 1: Number of Participants With Adverse Event (AE) and Serious Adverse Event (SAE) - An 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. 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, Is a congenital anomaly/birth defect, medical judgement and is associated with liver injury or liver impartment. The number of participants with AEs and SAEs assessed in Part 1 (Single dose) of the study were reported.
Timepoint [1] 0 0
Up to Day 43
Primary outcome [2] 0 0
Part 2: Number of Participants With AE and SAE - An 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. 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, Is a congenital anomaly/birth defect, medical judgement and is associated with liver injury or liver impartment. The number of participants with AEs and SAEs assessed in Part 2 (Repeat dose) of the study were reported.
Timepoint [2] 0 0
Up to Day 56
Primary outcome [3] 0 0
Part 1: Number of Participants With Abnormal Hematology Parameters as a Measure of Safety-Grade 3 or Higher - Blood samples were collected and processed to measure the number of participants with abnormal platelet counts, red blood cells (RBC) count, white blood cells (WBC) count (absolute), hemoglobin, hematocrit, reticulocytes, total iron, total iron binding capacity (TIBC), ferritin, RBC indices (mean corpuscle volume [MCV], mean corpuscle hemoglobin [MCH] and mean corpuscle hemoglobin concentration [MCHC]) and differential WBC count (neutrophils, lymphocytes, monocytes, eosinophil's, and basophils). Participants with abnormalities of Grade 3 or higher have been reported.
Timepoint [3] 0 0
Up to Day 2
Primary outcome [4] 0 0
Part 2: Number of Participants With Abnormal Hematology Parameters as a Measure of Safety-Grade 3 or Higher - Blood samples were collected and processed to measure the number of participants with abnormal platelet counts, RBC count, WBC count (absolute), hemoglobin, hematocrit, reticulocytes, total iron, TIBC, ferritin, RBC indices MCV, MCH and MCHC and differential WBC count (neutrophils, lymphocytes, monocytes, eosinophils, and basophils). These were collected on Day 2, 5, 10 and Day 15, during Part 2 of the study. Part 2 is repeat dose escalation. Participants with abnormalities of Grade 3 or higher have been reported.
Timepoint [4] 0 0
Up to Day 15
Primary outcome [5] 0 0
Part 1: Number of Participants With Abnormal Clinical Chemistry Parameters as a Measure of Safety-Grade 3 or Higher - Blood samples were collected and processed to measure the number of participants with abnormal blood urea nitrogen (BUN), creatinine, glucose, bicarbonate, sodium, potassium, chloride, calcium, aspartate aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT), alkaline phosphatase (ALP) levels, uric acid, total and direct bilirubin, total protein and albumin. These were collected on Day 1, during Part 1(single dose escalation) of the study. Participants with abnormalities Grade 3 or higher were reported.
Timepoint [5] 0 0
Day 2
Primary outcome [6] 0 0
Part 2: Number of Participants With Abnormal Clinical Chemistry Parameters as a Measure of Safety-Grade 3 or Higher - Blood samples were collected and processed to measure the number of participants with abnormal BUN, creat, glucose, bicarbonate, sodium, potassium, chloride, calcium, AST/SGOT, ALT/SGPT, ALP levels, uric acid, total and direct bilirubin, total protein and albumin. These were collected on Day 2, 5, 10 and Day 15 during Part 2 (repeat dose escalation), of the study. Participants with abnormalities Grade 3 or higher were reported.
Timepoint [6] 0 0
Up to Day 15
Primary outcome [7] 0 0
Part 1: Number of Participants Having Abnormal Urine Parameters (Using Dipstick Test) as a Measure of Safety - An aliquot of the urine samples from first morning void urine samples was collected to analyze specific gravity, pH, glucose, protein, blood and ketone bodies by dipstick method, microscopic examination (if blood or protein is abnormal), albumin to creatinine ration (ACR), neutrophil gelatinase associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1). Urine samples were analyzed after the end of the study to verify if a clinical signal is detected. Urine samples were collected on Day 1 of Part 1 (Single-dose escalation) of the study.
Timepoint [7] 0 0
Up to Day 2
Primary outcome [8] 0 0
Part 2: Number of Participants Having Abnormal Urine Parameters (Using Dipstick Test) as a Measure of Safety - An aliquot of the urine samples from first morning void urine samples was collected to analyze specific gravity, pH, glucose, protein, blood and ketone bodies by dipstick method, microscopic examination (if blood or protein is abnormal), ACR, NGAL and KIM-1. These urine samples were analyzed after the end of the study to verify if a clinical signal is detected. The samples were collected on Day 2, 5, 10, and Day 15 of Part 2 (Repeat dose escalation) of the study.
Timepoint [8] 0 0
Day 2, 5, 10 and Day 15
Primary outcome [9] 0 0
Part 1: Number of Participants With Electrocardiogram (ECG) Parameters of Potential Clinical Importance (PCI) - Triplicate 12-lead ECGs were obtained at least 5 minutes apart within 1 hr before dosing. Single ECGs were obtained at all other time points on Day 1 at 0.5 hr, 1 hr, 1.5 hr, 2, 3, 4, 6, 12 and 24 hr, Day 2 (36 hr) and Day 3 (48 hr) during Part 1 (single dose escalation phase) of the study. All the 12-lead ECGs were measured using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals.
Timepoint [9] 0 0
Up to Day 3
Primary outcome [10] 0 0
Part 2: Number of Participants With ECG Parameters of PCI - Triplicate 12-lead ECGs were obtained at least 5 minutes apart within 1 hr before the start of infusion (pre-dose) on Day 1. Single ECGs were obtained at 0.5, 1, 1.5, 2, 3, 4, 6, and 12 hrs after the start of infusion on Day 1 and Day 15, within 1 hr before the start of the morning infusion on Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, and 14, and in the morning on Day 16. All the 12-lead ECGs were measured using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals.
Timepoint [10] 0 0
Up to Day 16
Primary outcome [11] 0 0
Part 1: Number of Participants With Vital Signs of Potential Clinical Importance (PCI) - The vital sign includes systolic blood pressure, diastolic blood pressure, heart rate, respiratory rate and temperature which were measured in a semi-supine position, where the participant had rested in the same position for at least 5 minutes. The number of participants with vital values, of PCI were reported. These were collected on Day 1 at pre-dose, 0.5 hr, 1 hr, 1.5 hr, 2, 3, 4, 6, 12 and 24 hr, Day 2 (36 hr) and Day 3 (48 hr) during Part 1 (single dose escalation phase) of the study.
Timepoint [11] 0 0
Up to Day 3
Primary outcome [12] 0 0
Part 2: Number of Participants With Vital Signs of PCI - The vitals for systolic, diastolic blood pressure, heart rate, respiratory rate and temperature were taken in a semi-supine position, where the participant had rested in the same position for atleast 5 minutes. The number of participants with vital values, of PCI were reported. These were collected from Day 1 to Day 16. Assessments were done within 1 hr before the start of infusion (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, and 12 hrs after the start of infusion on Days 1 and 15, within 1 hr before the start of the morning infusion and on Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, and 14, and in the morning on Day 16.
Timepoint [12] 0 0
Up to Day 16
Secondary outcome [1] 0 0
Part 1-Area Under the Plasma Concentration (AUC) From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration Across All Treatments AUC(0-t) for GSK3342830 - AUC (0-t) is defined as AUC from time zero to the last quantifiable concentration after dosing. Blood samples were collected on Day 1 at indicated timepoints (pre-dose, 0.5 hr, 1hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr,3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr 24 hr, 36 hr and 48 hr post-dose. The Part 1 phase of the study comprised of single dosing of participants. Log untransformed values for AUC (0-t) have been presented.
Timepoint [1] 0 0
Day 1 (pre-dose, 0.5 hr, 1 hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr, 3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr, 48 hr post-dose
Secondary outcome [2] 0 0
Part 1-AUC Pre Dose to Infinite (Inf) Time (AUC [0-inf]) of GSK3342830 - AUC (0-inf) is defined as AUC extrapolated from time zero to infinity. Blood samples were collected on Day 1 at indicated timepoints pre-dose, 0.5 hr, 1hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr,3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr 24 hr, 36 hr and 48 hr post-dose. This part 1 phase of the study comprised of single dosing of the participants. Log untransformed values for AUC (0-inf) have been presented.
Timepoint [2] 0 0
Day 1 (pre-dose, 0.5 hr, 1 hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr, 3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr, 48hr post-dose
Secondary outcome [3] 0 0
Part 1-Maximum Plasma Concentration (Cmax) of GSK3342830 - Cmax was defined as the maximum concentration of drug GSK3342830, in plasma. Blood samples were collected on Day 1 at indicated timepoints pre-dose, 0.5 hr, 1hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr,3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr 24 hr, 36 hr and 48 hr post-dose. This part 1 phase of the study comprised of single dosing of the participants. Log untransformed values for Cmax have been presented.
Timepoint [3] 0 0
Day 1 (pre-dose, 0.5 hr, 1 hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr, 3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr, 48 hr post-dose
Secondary outcome [4] 0 0
Part 1-Time to Maximum Plasma Concentration (Tmax) of GSK3342830 - Tmax was defined as time required to achieve Cmax for drug GSK3342830, in plasma. Blood samples were collected on Day 1 at indicated timepoints pre-dose, 0.5 hr, 1hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr,3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr 24 hr, 36 hr and 48 hr post-dose. This part 1 phase of the study comprised of single dosing of the participants. Log untransformed values for tmax have been presented.
Timepoint [4] 0 0
Day 1 (pre-dose, 0.5 hr, 1 hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr, 3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr, 48hr post-dose
Secondary outcome [5] 0 0
Part 1-Terminal Elimination Half-life (t1/2) of GSK3342830 in Plasma - t ½ is defined as the time required by the drug to reduce to half its quantity. Blood samples were collected on Day 1 at indicated timepoints pre-dose, 0.5 hr, 1hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr,3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr 24 hr, 36 hr and 48 hr post-dose. This part 1 phase of the study comprised of single dosing of the participants. Log untransformed values for t1/2 have been presented.
Timepoint [5] 0 0
Day 1 (pre-dose, 0.5 hr, 1 hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr, 3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr, 48 hr post-dose
Secondary outcome [6] 0 0
Part 1-Total Systemic Clearance (CL) of GSK3342830 in Plasma - The systemic CL is a PK measure of volume of plasma from which the drug is removed per unit time. Blood samples were collected on Day 1 at indicated timepoints pre-dose, 0.5 hr, 1hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr,3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr 24 hr, 36 hr and 48 hr post-dose. This part 1 phase of the study comprised of single dosing of the participants. Log untransformed values for CL have been presented.
Timepoint [6] 0 0
Day 1 (pre-dose, 0.5 hr, 1 hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr, 3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr, 48 hr post-dose
Secondary outcome [7] 0 0
Part 1-Steady-state Volume (Vss) of Distribution of GSK3342830 in Plasma - Vss reflects the actual blood and tissue volume into which a drug is distributed and the relative binding of drug to protein in these spaces. Blood samples were collected on Day 1 at indicated timepoints pre-dose, 0.5 hr, 1hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr,3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr 24 hr, 36 hr and 48 hr post-dose. This part 1 phase of the study comprised of single dosing of the participants. Log untransformed values for Vss have been presented.
Timepoint [7] 0 0
Day 1 (pre-dose, 0.5 hr, 1 hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr, 3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr, 48 hr post-dose
Secondary outcome [8] 0 0
Part 1-Urinary Excretion Ratio Relative to Dose (Feu [t1-t2]) of GSK3342830 - Urine samples were collected at indicated timepoints pre-dose and post dose. The Feu has been reported from 0 to 4, 4 to 8, 8 to 12, 12 to 24 and 24 to 48 hrs. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates that data is not available. The standard deviation could not be calculated as only single participant was present. Log untransformed values for Feu (t1-t2) have been presented.
Timepoint [8] 0 0
Day 1 (pre-dose, 0.5 hr, 1 hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr, 3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr, 48 hr post-dose
Secondary outcome [9] 0 0
Part 1-Renal Clearance (CLr) of GSK3342830 in Urine - The renal clearance (CLr) is a PK measure of volume of drug is removed per unit time. Urine samples were collected at indicated timepoints pre-dose and post dose. This part 1 phase of the study comprised of single dosing of the participants. Log untransformed values for CLr have been presented.
Timepoint [9] 0 0
Day 1 (pre-dose, 0.5 hr, 1 hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr, 3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr, 48hr post-dose
Secondary outcome [10] 0 0
Part 1-Amount Excreted in Urine (Ae) of GSK3342830 in Urine - Ae is defined as amount of drug GSK3342830, excreted in urine. Urine samples were collected pre-dose (within a 24-hr period before dosing, may begin on Day -1) and 0 to 4, 4 to 8, 8 to 12, 12 to 24, and 24 to 48 hrs post-dose. Log untransformed values for Ae have been presented.
Timepoint [10] 0 0
Day 1 (pre-dose, 0.5 hr, 1 hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr, 3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr, 48hr post-dose
Secondary outcome [11] 0 0
Part 1:Dose Proportionality: AUC (0-t) - Blood samples were collected at Day 1 (pre-dose, 0.5 hr, 1 hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr, 3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr, 48hr post-dose. Dose proportionality was assessed for AUC(0-inf) and Cmax after single dose administration. AUC(0-inf) was selected as the AUC exposure measure as it is the default AUC parameter for single dose administration and the observed data permitted its calculation.
Timepoint [11] 0 0
Day 1 (pre-dose, 0.5 hr, 1 hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr, 3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr, 48hr post-dose
Secondary outcome [12] 0 0
Part 1:Dose Proportionality: AUC (0-inf) - Blood samples were collected at Day 1 (pre-dose, 0.5 hr, 1 hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr, 3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr, 48 hr post-dose. The data for estimate slope for log dose, has been reported.
Timepoint [12] 0 0
Day 1 (pre-dose, 0.5 hr, 1 hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr, 3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr, 48hr post-dose
Secondary outcome [13] 0 0
Part 1:Dose Proportionality: Cmax - Blood samples were collected at Day 1 (pre-dose, 0.5 hr, 1 hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr, 3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr, 48hr post-dose. The data for estimate slope for log dose, has been reported.
Timepoint [13] 0 0
Day 1 (pre-dose, 0.5 hr, 1 hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr, 3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr, 48hr post-dose
Secondary outcome [14] 0 0
Part 2-AUC (0-inf) of GSK3342830 - AUC (0-inf), was defined as AUC extrapolated from time zero to infinity Day 1 at pre-dose (15 minutes) and 0.5 hr, 1 hr (end of infusion), 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 hrs after start of infusion. Single pre-dose samples on mornings of Days 3, 6, 9, 12, and 13. Serial samples (Day 15) time points: pre-dose (15 minutes) and 0.5 hr, 1 (end of infusion), 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 hrs after start of infusion. The untransformed values for AUC(0-inf) have been presented.
Timepoint [14] 0 0
Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 hr post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 hr post-dose at Day 15
Secondary outcome [15] 0 0
Part 2-Cmax of GSK3342830 - Cmax was defined as the maximum concentration of drug GSK3342830, in plasma. It was collected at Day 1 at pre-dose (15 minutes) and 0.5 hr, 1 hr (end of infusion), 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 hrs after start of infusion. Single pre-dose samples on mornings of Days 3, 6, 9, 12, and 13. Serial samples (Day 15) time points: pre-dose (15 minutes) and 0.5 hr, 1 (end of infusion), 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 hrs after start of infusion.
Timepoint [15] 0 0
Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 hr, post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 hr post-dose at Day 15
Secondary outcome [16] 0 0
Part 2-Tmax of GSK3342830 - Tmax was defined as time required to achieve Cmax for drug GSK3342830, in plasma. It was collected at Day 1 at pre-dose (15 minutes) and 0.5 hr, 1 hr (end of infusion), 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 hrs after start of infusion. Single pre-dose samples on mornings of Days 3, 6, 9, 12, and 13. Serial samples (Day 15) time points: pre-dose (15 minutes) and 0.5 hr, 1 (end of infusion), 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 hrs after start of infusion.
Timepoint [16] 0 0
Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 h post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 h post-dose at Day 15
Secondary outcome [17] 0 0
Part 2-Terminal t1/2 of GSK3342830 in Plasma - t ½ is defined as the time required by the drug to reduce to half its quantity. Blood samples were collected at Day 1 at pre-dose (15 minutes) and 0.5 hr, 1 hr (end of infusion), 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 hrs after start of infusion. Single pre-dose samples on mornings of Days 3, 6, 9, 12, and 13. Serial samples (Day 15) time points: pre-dose (15 minutes) and 0.5 hr, 1 (end of infusion), 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 hrs after start of infusion.
Timepoint [17] 0 0
Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 h post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 h post-dose at Day 15
Secondary outcome [18] 0 0
Part 2-Total CL of GSK3342830 in Plasma - The systemic CL is a PK measure of volume of plasma from which the drug is removed per unit time. The blood samples of 3 mL were collected at Day 1 at pre-dose (15 minutes) and 0.5 hr, 1 hr (end of infusion), 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 hrs after start of infusion. Single pre-dose samples on mornings of Days 3, 6, 9, 12, and 13. Serial samples (Day 15) time points: pre-dose (15 minutes) and 0.5 hr, 1 (end of infusion), 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 hrs after start of infusion.
Timepoint [18] 0 0
Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 hr post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 hr post-dose at Day 15
Secondary outcome [19] 0 0
Part 2- Vss of Distribution of GSK3342830 in Plasma - Vss reflects the actual blood and tissue volume into which a drug is distributed and the relative binding of drug to protein in these spaces. The blood samples of 3 mL were collected at Day 1 at pre-dose (15 minutes) and 0.5 hr, 1 hr (end of infusion), 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 hrs after start of infusion. Single pre-dose samples on mornings of Days 3, 6, 9, 12, and 13. Serial samples (Day 15) time points: pre-dose (15 minutes) and 0.5 hr, 1 (end of infusion), 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 hrs after start of infusion.
Timepoint [19] 0 0
Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 h post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 h post-dose at Day 15
Secondary outcome [20] 0 0
Part 2-Urinary Excretion Ratio Relative to Dose Feu (t1-t2) of GSK3342830 - The Feu has been reported from 0 to 4, 4 to 8, 8 to 12, 12 to 24 and 24 to 48 hrs. These were collected in opaque bottles at pre-dose (within a 24-hr period before dosing, may begin on Day -1) and 0 to 4, 4 to 8, 8 to 12, 12 to 24, and 24 to 48 hrs post-dose.
Timepoint [20] 0 0
Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 hr post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 hr post-dose at Day 15
Secondary outcome [21] 0 0
Part 2- Trough Concentration (Ctau) - Blood samples were collected on Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 h post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 h post-dose at Day 15. The untransformed values for Ctau have been presented.
Timepoint [21] 0 0
Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 h post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 h post-dose at Day 15
Secondary outcome [22] 0 0
Part 2-CLr of GSK3342830 in Urine - The renal CLr is a PK measure of volume of plasma from which the drug is removed per unit time.These were collected in opaque bottles on Day 1 and Day 15 at (Pre-dose, 0 to 8 and 8 to 24 hrs post-dose). The untransformed values for CLr have been presented.
Timepoint [22] 0 0
Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 h post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 h post-dose at Day 15
Secondary outcome [23] 0 0
Part 2- Ae of GSK3342830 in Urine - Ae defines as the amount of drug GSK3342830, excreted in urine. These were collected in opaque bottles on Day 1 and Day 15 at (Pre-dose, 0 to 8 and 8 to 24 hrs post-dose). The untransformed values for Ae have been presented.
Timepoint [23] 0 0
Day 1 and Day 15 at (Pre-dose, 0 to 8 and 8 to 24 hrs post-dose)
Secondary outcome [24] 0 0
Part 2: AUC From Time Zero to Last Measurable Concentration AUC (0- Tau) - It was defined as Area Under the Concentration-time Curve From Time Zero (Pre-dose) to the time of the last measureable concentration. Blood samples were collected on Day 1 at indicated timepoints pre-dose, 0.5 hr, 1hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr,3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr 24 hr, 36 hr and 48 hr post-dose. Log untransformed values for AUC (0 to tau) have been presented.
Timepoint [24] 0 0
Day 1 (pre-dose, 0.5 hr, 1 hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr, 3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr, 48hr post-dose
Secondary outcome [25] 0 0
Part 2: Dose Proportionality: AUC (0-tau) - Blood samples were collected at Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 hr post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 hr post-dose at Day 15. Data cannot be summarized because only 1 dose level studied so dose proportionality analysis cannot be performed as no comparison can be conducted.
Timepoint [25] 0 0
Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 hr, post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 hr post-dose at Day 15
Secondary outcome [26] 0 0
Part 2: Observed Accumulation Ratio (Ro) Based on AUC and Cmax of GSK3342830 After Administration of Repeat IV Doses, as Data Permit - The accumulation ratio has been reported. Sampling was done at Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 h post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 h post-dose at Day 15. Data cannot be summarized because only 1 dose level studied so dose proportionality analysis cannot be performed as no comparison can be conducted.
Timepoint [26] 0 0
Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 h post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 h post-dose at Day 15
Secondary outcome [27] 0 0
Part 2: Steady-state Ratio (Rss) of GSK3342830 to Assess Time Invariance, as Data Permit - Sampling was done at Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 h post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 h post-dose at Day 15. Since the study was terminated early, data is only available for one dose level for Part 2. Some subjects have only partial data and were not dosed on Day 15.
Timepoint [27] 0 0
Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 h post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 h post-dose at Day 15
Secondary outcome [28] 0 0
Part 2: Trough Plasma Concentrations at the End of the Dosing Interval (Ctau) to Assess the Achievement of Steady-state of GSK3342830 After Administration of Repeat IV Doses, as Data Permit - Sampling was done at Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 h post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 h post-dose at Day 15. The untransformed values for Ctau have been presented.
Timepoint [28] 0 0
Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 h post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 h post-dose at Day 15

Eligibility
Key inclusion criteria
- Between 18 and 55 years of age, inclusive, at the time of signing the informed
consent.

- Healthy as determined by a responsible and experienced physician, based on a medical
evaluation including medical history, physical examination, laboratory tests and
cardiac monitoring. A subject with a clinical abnormality or laboratory parameter
outside the reference range for the population being studied may be included only if
the investigator feels and documents that the finding is unlikely to introduce
additional risk factors and will not interfere with the study procedures.

- Body weight >50 kilogram (kg) (110 pounds [lb]) for men and >40 kg (99 lb) for women
and body mass index within the range of 18.5 to 30 kg per square meter (m^2),
inclusive.

- Male or Female subjects. Males: Male subjects with female partners of child-bearing
potential must agree to use one of the highly effective contraception from the time of
first dose of study drug until completion of the Follow-up visit, and Females: A
female subject is eligible to participate if she is not pregnant (as confirmed by a
negative serum human chorionic gonadotropin [hCG] test), not lactating, and considered
to be of non-reproductive potential (non-reproductive potential is defined as:
Pre-menopausal females with one of the following: Documented tubal ligation or
Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of
bilateral tubal occlusion or Hysterectomy or Documented bilateral oophorectomy).

- Postmenopausal defined as 12 months of spontaneous amenorrhea and in questionable
cases a blood sample with simultaneous follicle-stimulating hormone (FSH) and
estradiol levels consistent with menopause (refer to laboratory reference ranges for
confirmatory levels)

- 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. Otherwise, they must discontinue HRT to
allow confirmation of post menopausal status before study enrolment.

- Capable of giving signed informed consent, which includes compliance with the
requirements and restrictions.
Minimum age
18 Years
Maximum age
55 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- Alanine aminotransferase (ALT) not within normal limits; bilirubin >1.5× upper limit
of normal (ULN; isolated bilirubin >1.5× ULN is acceptable if bilirubin is
fractionated and direct bilirubin is <35%).

- Current or chronic history of liver disease, or known hepatic or biliary abnormalities
(with the exception of Gilbert's syndrome or asymptomatic gallstones).

- Corrected QT (QTc) >450 milliseconds (msec).

- Any clinically significant central nervous system (e.g., seizures), cardiac,
pulmonary, metabolic, renal, hepatic, or gastrointestinal condition or history of such
a condition that, in the opinion of the investigator, may place the subject at an
unacceptable risk as a participant in this trial or may interfere with the absorption,
distribution, metabolism, or excretion of drugs.

- Use of a systemic antibiotic within 30 days of screening.

- Ongoing febrile illness.

- Confirmed history of Clostridium difficile diarrhea

- Unable to refrain from the use of prescription or non-prescription drugs, including
vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or
14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is
longer) before the first dose of study treatment, unless in the opinion of the
Investigator, the medication will not interfere with the study procedures or
compromise subject safety.

- History of regular alcohol consumption within 6 months of screening defined as an
average weekly intake of >21 units (or an average daily intake of >3 units) for males
or an average weekly intake of >14 units (or an average daily intake >2 units) for
females. One unit is equivalent to 270 milliliter (mL) of full strength beer, 470 mL
of light beer, 30 mL of spirits, or 100 mL of wine.

- Urinary cotinine level indicative of smoking or history or regular use of tobacco- or
nicotine containing products within 3 months before screening.

- History of hypersensitivity attributed to beta-lactam antibiotics (including
cephalosporin, carbapenem, or penicillin antibiotics) or other drugs, a history of
multiple antibiotic intolerances, or a history of serious adverse drug reactions.

- Sensitivity to poison ivy or other catechol-related hypersensitivity (e.g., mango
allergy).

- History of sensitivity to heparin or heparin-induced thrombocytopenia.

- History of latex allergy.

- History of sensitivity to any of the study treatments or components thereof, or a
history of drug or other allergy that, in the opinion of the investigator,
contraindicates participation in the study.

- Presence of hepatitis B surface antigen or positive hepatitis C antibody test result
at screening or within 3 months before the first dosing day in this study.

- Serum creatinine >ULN.

- Glomerular filtration rate <90 millilter per minute per 1.73 square meter
(mL/min/1.73m^2) as calculated by the Chronic Kidney Disease Epidemiology
Collaboration formula

- Albumin to creatinine ratio (ACR) >0.03 mg/mg. In the event of an ACR above this
threshold, eligibility may be confirmed by a second measurement.

- Urinalysis positive for blood without other cause identified.

- A positive pre-study drug or alcohol screen.

- A positive test for human immunodeficiency virus antibody at or before screening.

- 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 before the first dosing day in this 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 4 new chemical entities within 12 months before the first dosing
day in this study.

- Exclusion criteria for screening and baseline 12-lead ECG: Heart rate <40 and >100
beats per minute for males and <50 and >100 beats per minute (for females), pulse rate
is <120 and >220 msec, QRS is <70 and >120 msec, and corrected QT interval using
Bazett's formula (QTcB ) and corrected QT interval using Fridericia's formula (QTcF )
>450 msec.. Also apart from this, subject having evidence of previous myocardial
infarction, bundle branch block and Any conduction abnormality (including but not
specific to left or right complete bundle branch block, AV block [2nd degree or
higher], Wolf-Parkinson-White syndrome), sinus pauses more than 3 seconds,
non-sustained or sustained ventricular tachycardia (>=3 consecutive ventricular
ectopic beats), or any significant arrhythmia that, in the opinion of the investigator
will interfere with the safety of the individual subject.

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 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
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)
SA
Recruitment hospital [1] 0 0
GSK Investigational Site - Adelaide
Recruitment postcode(s) [1] 0 0
5000 - Adelaide

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

Ethics approval
Ethics application status

Summary
Brief summary
A phase I, first-time-in-human (FTIH), randomized, double-blind, placebo controlled,
dose-escalation study is conducted to determine the safety, tolerability, and pharmacokinetic
(PK) profile of GSK3342830 after administration of single intravenous (IV) infusion in Part 1
and repeat IV infusion in Part 2 in healthy subjects. Part 1 will investigate escalating
single IV doses of GSK3342830. Part 2, will investigate escalating repeat IV doses of
GSK3342830 with repeat dosing for 15 days as follows: a single IV infusion on Day 1, TID
(three times a day) IV infusions on Days 2 through 14 (approximately every 8 hours), and a
single IV infusion on Day 15. The planned starting GSK3342830 dose in Part 1 is 250 milligram
(mg) administered as a single IV infusion. The dose is planned to increase in subsequent
cohorts to 500, 1000, 2000, 4000, and less than or equal to (=) 6000 mg. Part 1 will be
divided into 6 cohorts (A-F) and each cohort will enroll 10 subjects (6 in active and 2 in
placebo). Dose escalation will be conducted only if it is supported by the preliminary
safety, tolerability, and PK results from the preceding dose levels in the study. The repeat
dose escalation component (Part 2) of this study will be planned to be initiated after
completion and evaluation of the all single dose cohorts up to and including 4000 mg.
Trial website
https://clinicaltrials.gov/show/NCT02751424
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

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02751424