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NCT02751424

A Study to Evaluate Safety, Tolerability and Pharmacokinetics of Ascending Intravenous Single Dose and Repeat Dose of GSK3342830

Terminated Phase 1 Results posted Last updated 12 September 2018
What this trial tests

Phase 1 trial testing GSK3342830 in Infections, Bacterial in 62 participants. Terminated before completion.

Timeline
13 June 2016
Primary endpoint
2 February 2017
2 February 2017

Quick facts

Lead sponsorGlaxoSmithKline
PhasePhase 1
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment62
Start date13 June 2016
Primary completion2 February 2017
Estimated completion2 February 2017
Sites1 location across Australia

Drugs / interventions tested

Conditions studied

Sponsor

GlaxoSmithKline — full company profile →

Who can join

Adults 18 to 55, any sex, with Infections, Bacterial. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Part 1: Number of Participants With Adverse Event (AE) and Serious Adverse Event (SAE) Primary · Up to Day 43

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 Par

Any AE
GroupValue95% CI
GSK3342830 250 mg5
GSK3342830 500 mg4
GSK3342830 1000 mg6
GSK3342830 2000 mg5
GSK3342830 4000 mg5
GSK3342830 6000 mg4
Placebo, Part 111
Any SAE
GroupValue95% CI
GSK3342830 250 mg0
GSK3342830 500 mg0
GSK3342830 1000 mg0
GSK3342830 2000 mg0
GSK3342830 4000 mg0
GSK3342830 6000 mg0
Placebo, Part 10
Part 2: Number of Participants With AE and SAE Primary · Up to Day 56

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 Par

Any AE
GroupValue95% CI
GSK3342830 1000 mg TID11
Placebo, Part 23
Any SAE
GroupValue95% CI
GSK3342830 1000 mg TID0
Placebo, Part 20
Part 1: Number of Participants With Abnormal Hematology Parameters as a Measure of Safety-Grade 3 or Higher Primary · Up to Day 2

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.

GroupValue95% CI
GSK3342830 250 mg0
GSK3342830 500 mg0
GSK3342830 1000 mg0
GSK3342830 2000 mg0
GSK3342830 4000 mg0
GSK3342830 6000 mg0
Placebo, Part 10
Part 2: Number of Participants With Abnormal Hematology Parameters as a Measure of Safety-Grade 3 or Higher Primary · Up to Day 15

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.

GroupValue95% CI
GSK3342830 1000 mg TID0
Placebo, Part 20
Part 1: Number of Participants With Abnormal Clinical Chemistry Parameters as a Measure of Safety-Grade 3 or Higher Primary · Day 2

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.

GroupValue95% CI
GSK3342830 250 mg0
GSK3342830 500 mg0
GSK3342830 1000 mg0
GSK3342830 2000 mg0
GSK3342830 4000 mg0
GSK3342830 6000 mg0
Placebo, Part 10
Part 2: Number of Participants With Abnormal Clinical Chemistry Parameters as a Measure of Safety-Grade 3 or Higher Primary · Up to Day 15

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.

Serum Glucose
GroupValue95% CI
GSK3342830 1000 mg TID1
Placebo, Part 20
Serum or Plasma ALT
GroupValue95% CI
GSK3342830 1000 mg TID1
Placebo, Part 20
Serum or Plasma albumin
GroupValue95% CI
GSK3342830 1000 mg TID1
Placebo, Part 20
Serum or Plasma ALP
GroupValue95% CI
GSK3342830 1000 mg TID0
Placebo, Part 20
Serum or Plasma AST
GroupValue95% CI
GSK3342830 1000 mg TID2
Placebo, Part 20
Serum or Plasma Calcium
GroupValue95% CI
GSK3342830 1000 mg TID0
Placebo, Part 20
Serum or Plasma Chloride
GroupValue95% CI
GSK3342830 1000 mg TID0
Placebo, Part 20
Serum or Plasma Creat
GroupValue95% CI
GSK3342830 1000 mg TID0
Placebo, Part 20
Part 1: Number of Participants Having Abnormal Urine Parameters (Using Dipstick Test) as a Measure of Safety Primary · Up to Day 2

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.

GroupValue95% CI
GSK3342830 250 mg0
GSK3342830 500 mg0
GSK3342830 1000 mg0
GSK3342830 2000 mg0
GSK3342830 4000 mg0
GSK3342830 6000 mg0
Placebo, Part 10
Part 2: Number of Participants Having Abnormal Urine Parameters (Using Dipstick Test) as a Measure of Safety Primary · Day 2, 5, 10 and Day 15

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.

GroupValue95% CI
GSK3342830 1000 mg TID0
Placebo, Part 20
Part 1: Number of Participants With Electrocardiogram (ECG) Parameters of Potential Clinical Importance (PCI) Primary · Up to Day 3

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.

Heart Rate
GroupValue95% CI
GSK3342830 250 mg0
GSK3342830 500 mg0
GSK3342830 1000 mg0
GSK3342830 2000 mg0
GSK3342830 4000 mg0
GSK3342830 6000 mg0
Placebo, Part 10
PR Interval
GroupValue95% CI
GSK3342830 250 mg0
GSK3342830 500 mg1
GSK3342830 1000 mg0
GSK3342830 2000 mg0
GSK3342830 4000 mg0
GSK3342830 6000 mg0
Placebo, Part 10
QRS Duration
GroupValue95% CI
GSK3342830 250 mg0
GSK3342830 500 mg0
GSK3342830 1000 mg1
GSK3342830 2000 mg3
GSK3342830 4000 mg1
GSK3342830 6000 mg1
Placebo, Part 12
QT Interval
GroupValue95% CI
GSK3342830 250 mg1
GSK3342830 500 mg2
GSK3342830 1000 mg1
GSK3342830 2000 mg0
GSK3342830 4000 mg0
GSK3342830 6000 mg1
Placebo, Part 12
QTc (Bazett)
GroupValue95% CI
GSK3342830 250 mg1
GSK3342830 500 mg1
GSK3342830 1000 mg1
GSK3342830 2000 mg1
GSK3342830 4000 mg2
GSK3342830 6000 mg2
Placebo, Part 13
QTc (Fridericia)
GroupValue95% CI
GSK3342830 250 mg1
GSK3342830 500 mg0
GSK3342830 1000 mg1
GSK3342830 2000 mg0
GSK3342830 4000 mg1
GSK3342830 6000 mg0
Placebo, Part 11
RR Interval
GroupValue95% CI
GSK3342830 250 mg0
GSK3342830 500 mg0
GSK3342830 1000 mg0
GSK3342830 2000 mg0
GSK3342830 4000 mg0
GSK3342830 6000 mg0
Placebo, Part 10
Part 2: Number of Participants With ECG Parameters of PCI Primary · Up to Day 16

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.

Heart Rate
GroupValue95% CI
GSK3342830 1000 mg TID0
Placebo, Part 20
PR Interval
GroupValue95% CI
GSK3342830 1000 mg TID1
Placebo, Part 20
QRS Duration
GroupValue95% CI
GSK3342830 1000 mg TID0
Placebo, Part 20
QT Interval
GroupValue95% CI
GSK3342830 1000 mg TID1
Placebo, Part 22
QTc (Bazett)
GroupValue95% CI
GSK3342830 1000 mg TID2
Placebo, Part 21
QTc (Fridericia)
GroupValue95% CI
GSK3342830 1000 mg TID1
Placebo, Part 21
RR Interval
GroupValue95% CI
GSK3342830 1000 mg TID0
Placebo, Part 20
Part 1: Number of Participants With Vital Signs of Potential Clinical Importance (PCI) Primary · Up to Day 3

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.

Systolic Blood Pressure
GroupValue95% CI
GSK3342830 250 mg1
GSK3342830 500 mg0
GSK3342830 1000 mg0
GSK3342830 2000 mg1
GSK3342830 4000 mg0
GSK3342830 6000 mg0
Placebo, Part 11
Diastolic Blood Pressue
GroupValue95% CI
GSK3342830 250 mg0
GSK3342830 500 mg0
GSK3342830 1000 mg0
GSK3342830 2000 mg1
GSK3342830 4000 mg0
GSK3342830 6000 mg0
Placebo, Part 11
Pulse rate
GroupValue95% CI
GSK3342830 250 mg0
GSK3342830 500 mg1
GSK3342830 1000 mg0
GSK3342830 2000 mg0
GSK3342830 4000 mg0
GSK3342830 6000 mg0
Placebo, Part 10
Temperature
GroupValue95% CI
GSK3342830 250 mg0
GSK3342830 500 mg0
GSK3342830 1000 mg0
GSK3342830 2000 mg0
GSK3342830 4000 mg0
GSK3342830 6000 mg0
Placebo, Part 10
Respiratory rate
GroupValue95% CI
GSK3342830 250 mg0
GSK3342830 500 mg0
GSK3342830 1000 mg0
GSK3342830 2000 mg0
GSK3342830 4000 mg0
GSK3342830 6000 mg0
Placebo, Part 10
Part 2: Number of Participants With Vital Signs of PCI Primary · Up to Day 16

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, an

SBP
GroupValue95% CI
GSK3342830 1000 mg TID0
Placebo, Part 20
DBP
GroupValue95% CI
GSK3342830 1000 mg TID0
Placebo, Part 21
Pulse rate
GroupValue95% CI
GSK3342830 1000 mg TID1
Placebo, Part 20
Temperature
GroupValue95% CI
GSK3342830 1000 mg TID0
Placebo, Part 20
Respiratory rate
GroupValue95% CI
GSK3342830 1000 mg TID0
Placebo, Part 20

Adverse events — posted to ClinicalTrials.gov

Time frame: SAEs and AEs were collected from start of study treatment (Day 1) up to Day 56. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

GSK3342830 250 mg
Serious: 0/6 (0%)
Deaths: 0/6
GSK3342830 500 mg
Serious: 0/6 (0%)
Deaths: 0/6
GSK3342830 1000 mg
Serious: 0/6 (0%)
Deaths: 0/6
GSK3342830 2000 mg
Serious: 0/6 (0%)
Deaths: 0/6
GSK3342830 4000 mg
Serious: 0/6 (0%)
Deaths: 0/6
GSK3342830 6000 mg
Serious: 0/6 (0%)
Deaths: 0/6
Placebo, Part 1
Serious: 0/12 (0%)
Deaths: 0/12
GSK3342830 1000 mg TID
Serious: 0/11 (0%)
Deaths: 0/11
Placebo, Part 2
Serious: 0/3 (0%)
Deaths: 0/3
Other adverse events (52 terms — click to expand)

ReactionSystemGSK3342830 250 mgGSK3342830 500 mgGSK3342830 1000 mgGSK3342830 2000 mgGSK3342830 4000 mgGSK3342830 6000 mgPlacebo, Part 1GSK3342830 1000 mg TIDPlacebo, Part 2
Catheter site painGeneral disorders
HeadacheNervous system disorders
Application site dermatitisGeneral disorders
Urine odour abnormalRenal and urinary disorders
MyalgiaMusculoskeletal and connective tissue disorders
Catheter site erythemaGeneral disorders
FatigueGeneral disorders
PyrexiaGeneral disorders
Neck painMusculoskeletal and connective tissue disorders
Application site reactionGeneral disorders
DiarrhoeaGastrointestinal disorders
CoughRespiratory, thoracic and mediastinal disorders
Catheter site bruiseGeneral disorders
Throat irritationRespiratory, thoracic and mediastinal disorders
BlisterSkin and subcutaneous tissue disorders
Dermatitis contactSkin and subcutaneous tissue disorders
Rash macularSkin and subcutaneous tissue disorders
Dyshidrotic eczemaSkin and subcutaneous tissue disorders
PharyngitisInfections and infestations
Upper respiratory tract infectionInfections and infestations
Pain in extremityMusculoskeletal and connective tissue disorders
Back painMusculoskeletal and connective tissue disorders
Musculoskeletal painMusculoskeletal and connective tissue disorders
Catheter site related reactionGeneral disorders
Catheter site inflammationGeneral disorders
ChillsGeneral disorders
ExtravasationGeneral disorders
Feeling hotGeneral disorders
Infusion site extravasationGeneral disorders
Peripheral swellingGeneral disorders
DizzinessNervous system disorders
NauseaGastrointestinal disorders
Abdominal discomfortGastrointestinal disorders
Abdominal painGastrointestinal disorders
Aphthous ulcerGastrointestinal disorders
FlatulenceGastrointestinal disorders
Musculoskeletal chest painMusculoskeletal and connective tissue disorders
Nasal congestionRespiratory, thoracic and mediastinal disorders
Nasal obstructionRespiratory, thoracic and mediastinal disorders
ScratchInjury, poisoning and procedural complications

Data from ClinicalTrials.gov NCT02751424 adverse events section.

Sponsor's own description

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.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Antibiotics in the clinical pipeline in October 2019.
    Butler MS, Paterson DL. · · 2020 · cited 174× · PMID 32152527 · DOI 10.1038/s41429-020-0291-8
  2. The Role of Iron and Siderophores in Infection, and the Development of Siderophore Antibiotics.
    Page MGP. · · 2019 · cited 157× · PMID 31724044 · DOI 10.1093/cid/ciz825

Verify or expand the search:

Other recruiting trials for Infections, Bacterial

Currently open trials in the same condition.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02751424.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing