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NCT03245619

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Investigation of GSK3335065 Intravenous (IV) Infusion in Healthy Adults

Terminated Phase 1 Results posted Last updated 16 June 2020
What this trial tests

Phase 1 trial testing GSK3335065 in Pancreatitis, Acute Necrotizing in 18 participants. Terminated before completion.

Timeline
22 August 2017
Primary endpoint
19 May 2018
19 May 2018

Quick facts

Lead sponsorGlaxoSmithKline
PhasePhase 1
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designsequential
Maskingdouble
Primary purposetreatment
Enrollment18
Start date22 August 2017
Primary completion19 May 2018
Estimated completion19 May 2018
Sites1 location across United Kingdom

Drugs / interventions tested

Conditions studied

Sponsor

GlaxoSmithKline — full company profile →

Who can join

Adults 18 to 60, any sex, with Pancreatitis, Acute Necrotizing. 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.

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)-Part A Primary · Up to Day 22

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; other important medical events that may jeopardize the participant or may require medical or surgical intervention to prevent one of the

Any AE
GroupValue95% CI
Part A: Placebo3
Part A-Cohort 1: GSK3335065 0.1 mg4
Part A-Cohort 2: GSK3335065 0.25 mg3
Part A-Cohort 3: GSK3335065 1.3 mg1
Any SAE
GroupValue95% CI
Part A: Placebo0
Part A-Cohort 1: GSK3335065 0.1 mg0
Part A-Cohort 2: GSK3335065 0.25 mg0
Part A-Cohort 3: GSK3335065 1.3 mg1
Number of Participants With Hematological Parameters of Potential Clinical Importance-Part A Primary · Up to Day 22

Blood samples were collected for the assessment of hematology parameters. The clinical concern range for the parameters were: hematocrit (high: \>0.54 proportion of red blood cells in blood); hemoglobin (high: \>180 grams per liter \[g/L\]), lymphocytes (low: \<0.8x10\^9 cells per liter \[cells/L\]); neutrophil count (low: \<1.5x10\^9 cells/L); platelet count (low: \<100x10\^9 cells/L and high: \>550x10\^9 cells/L); white blood cells count (low: \<3x10\^9 cells/L and high: \>20x10\^9 cells/L). Data for worst-case post-Baseline is presented. Baseline was defined as the latest pre-dose assessmen

Hemoglobin; Normal
GroupValue95% CI
Part A: Placebo5
Part A-Cohort 1: GSK3335065 0.1 mg6
Part A-Cohort 2: GSK3335065 0.25 mg6
Part A-Cohort 3: GSK3335065 1.3 mg1
Hemoglobin; High
GroupValue95% CI
Part A: Placebo0
Part A-Cohort 1: GSK3335065 0.1 mg0
Part A-Cohort 2: GSK3335065 0.25 mg0
Part A-Cohort 3: GSK3335065 1.3 mg0
Hematocrit; Normal
GroupValue95% CI
Part A: Placebo5
Part A-Cohort 1: GSK3335065 0.1 mg6
Part A-Cohort 2: GSK3335065 0.25 mg6
Part A-Cohort 3: GSK3335065 1.3 mg1
Hematocrit; High
GroupValue95% CI
Part A: Placebo0
Part A-Cohort 1: GSK3335065 0.1 mg0
Part A-Cohort 2: GSK3335065 0.25 mg0
Part A-Cohort 3: GSK3335065 1.3 mg0
Lymphocytes; Low
GroupValue95% CI
Part A: Placebo0
Part A-Cohort 1: GSK3335065 0.1 mg0
Part A-Cohort 2: GSK3335065 0.25 mg0
Part A-Cohort 3: GSK3335065 1.3 mg0
Lymphocytes; Normal
GroupValue95% CI
Part A: Placebo5
Part A-Cohort 1: GSK3335065 0.1 mg6
Part A-Cohort 2: GSK3335065 0.25 mg6
Part A-Cohort 3: GSK3335065 1.3 mg1
Neutrophils; Low
GroupValue95% CI
Part A: Placebo0
Part A-Cohort 1: GSK3335065 0.1 mg0
Part A-Cohort 2: GSK3335065 0.25 mg0
Part A-Cohort 3: GSK3335065 1.3 mg0
Neutrophils; Normal
GroupValue95% CI
Part A: Placebo5
Part A-Cohort 1: GSK3335065 0.1 mg6
Part A-Cohort 2: GSK3335065 0.25 mg6
Part A-Cohort 3: GSK3335065 1.3 mg1
Number of Participants With Clinical Chemistry Parameters of Potential Clinical Importance-Part A Primary · Up to Day 22

Blood samples were collected for the assessment of clinical chemistry parameters. The clinical concern range for the parameters were: albumin (low: \<30 millimoles per liter \[mmol/L\]); alanine aminotransferase (ALT) (high: \>=2xupper limit of normal \[ULN\]); aspartate aminotransferase (AST) (high: \>=2xULN); alkaline phosphatase (ALP) (high: \>=2xULN); total bilirubin (high: \>=1.5xULN); calcium (low: \<2 mmol/L and high: \>2.75 mmol/L); glucose (low: \<3 mmol/L and high: \>9 mmol/L); potassium (low: \<3 mmol/L and high: \>5.5 mmol/L) and sodium (low: \<130 mmol/L and high: \>150 mmol/L). D

Albumin; Low
GroupValue95% CI
Part A: Placebo0
Part A-Cohort 1: GSK3335065 0.1 mg0
Part A-Cohort 2: GSK3335065 0.25 mg0
Part A-Cohort 3: GSK3335065 1.3 mg0
Albumin; Normal
GroupValue95% CI
Part A: Placebo5
Part A-Cohort 1: GSK3335065 0.1 mg6
Part A-Cohort 2: GSK3335065 0.25 mg6
Part A-Cohort 3: GSK3335065 1.3 mg1
ALP; Normal
GroupValue95% CI
Part A: Placebo5
Part A-Cohort 1: GSK3335065 0.1 mg6
Part A-Cohort 2: GSK3335065 0.25 mg6
Part A-Cohort 3: GSK3335065 1.3 mg1
ALP; High
GroupValue95% CI
Part A: Placebo0
Part A-Cohort 1: GSK3335065 0.1 mg0
Part A-Cohort 2: GSK3335065 0.25 mg0
Part A-Cohort 3: GSK3335065 1.3 mg0
ALT; Normal
GroupValue95% CI
Part A: Placebo5
Part A-Cohort 1: GSK3335065 0.1 mg6
Part A-Cohort 2: GSK3335065 0.25 mg6
Part A-Cohort 3: GSK3335065 1.3 mg1
ALT; High
GroupValue95% CI
Part A: Placebo0
Part A-Cohort 1: GSK3335065 0.1 mg0
Part A-Cohort 2: GSK3335065 0.25 mg0
Part A-Cohort 3: GSK3335065 1.3 mg0
AST; Normal
GroupValue95% CI
Part A: Placebo5
Part A-Cohort 1: GSK3335065 0.1 mg6
Part A-Cohort 2: GSK3335065 0.25 mg6
Part A-Cohort 3: GSK3335065 1.3 mg1
AST; High
GroupValue95% CI
Part A: Placebo0
Part A-Cohort 1: GSK3335065 0.1 mg0
Part A-Cohort 2: GSK3335065 0.25 mg0
Part A-Cohort 3: GSK3335065 1.3 mg0
Number of Participants With Abnormal Urine Parameters-Part A Primary · Up to Day 22

Urine samples were taken for the assessment of following urine parameters: specific gravity, potential of hydrogen (pH), glucose, protein, blood and ketones by dipstick method. Microscopic examination was performed and collected for any abnormal dipstick results. Number of participants with abnormal urine parameters any time post-Baseline is presented. Baseline was defined as the latest pre-dose assessment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.

GroupValue95% CI
Part A: Placebo0
Part A-Cohort 1: GSK3335065 0.1 mg0
Part A-Cohort 2: GSK3335065 0.25 mg1
Part A-Cohort 3: GSK3335065 1.3 mg1
Number of Participants With Abnormal Electrocardiogram (ECG) Findings-Part A Primary · Up to Day 22

Triplicate 12-lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, QT interval corrected using Fridericia's formula (QTcF) and Bazett's QT interval corrected for heart rate (QTcB). ECG measurements were preceded by at least 5 minutes rest for the participant in a semi-recumbent position. Number of participants with abnormal-clinically significant and abnormal-not clinically significant ECG findings at worst case post-Baseline is presented. Baseline was defined as the latest pre-dose assessment. Placebo arms across similar dosing st

Abnormal-clinically significant
GroupValue95% CI
Part A: Placebo0
Part A-Cohort 1: GSK3335065 0.1 mg0
Part A-Cohort 2: GSK3335065 0.25 mg0
Part A-Cohort 3: GSK3335065 1.3 mg0
Abnormal-not clinically significant
GroupValue95% CI
Part A: Placebo0
Part A-Cohort 1: GSK3335065 0.1 mg0
Part A-Cohort 2: GSK3335065 0.25 mg3
Part A-Cohort 3: GSK3335065 1.3 mg0
Number of Participants With Abnormal Vital Signs-Part A Primary · Up to Day 22

Vital signs including systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate, respiration rate and temperature were measured in a semi-recumbent position with a completely automated device preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Participants are counted in the worst case category that their value changes to (low, normal or high), unless there is no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the "To Normal or No Change"

DBP; To Low
GroupValue95% CI
Part A: Placebo0
Part A-Cohort 1: GSK3335065 0.1 mg0
Part A-Cohort 2: GSK3335065 0.25 mg0
Part A-Cohort 3: GSK3335065 1.3 mg0
DBP; To Normal or no change
GroupValue95% CI
Part A: Placebo5
Part A-Cohort 1: GSK3335065 0.1 mg6
Part A-Cohort 2: GSK3335065 0.25 mg6
Part A-Cohort 3: GSK3335065 1.3 mg1
DBP; To High
GroupValue95% CI
Part A: Placebo0
Part A-Cohort 1: GSK3335065 0.1 mg0
Part A-Cohort 2: GSK3335065 0.25 mg0
Part A-Cohort 3: GSK3335065 1.3 mg0
SBP; To Low
GroupValue95% CI
Part A: Placebo1
Part A-Cohort 1: GSK3335065 0.1 mg0
Part A-Cohort 2: GSK3335065 0.25 mg0
Part A-Cohort 3: GSK3335065 1.3 mg0
SBP; To Normal or no change
GroupValue95% CI
Part A: Placebo4
Part A-Cohort 1: GSK3335065 0.1 mg6
Part A-Cohort 2: GSK3335065 0.25 mg6
Part A-Cohort 3: GSK3335065 1.3 mg1
SBP; To High
GroupValue95% CI
Part A: Placebo0
Part A-Cohort 1: GSK3335065 0.1 mg0
Part A-Cohort 2: GSK3335065 0.25 mg0
Part A-Cohort 3: GSK3335065 1.3 mg0
Heart rate; To Low
GroupValue95% CI
Part A: Placebo0
Part A-Cohort 1: GSK3335065 0.1 mg0
Part A-Cohort 2: GSK3335065 0.25 mg0
Part A-Cohort 3: GSK3335065 1.3 mg0
Heart rate; To Normal or no change
GroupValue95% CI
Part A: Placebo5
Part A-Cohort 1: GSK3335065 0.1 mg6
Part A-Cohort 2: GSK3335065 0.25 mg6
Part A-Cohort 3: GSK3335065 1.3 mg1
Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration (AUC[0-t]) for GSK3335065-Part A (Cohorts 1 and 2) Secondary · 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60 and 72 hours post-dose

Blood samples for pharmacokinetic (PK) analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis. PK Parameter Population comprised of all active participants whose PK sample was obtained and analyzed and who provided PK parameters.

GroupValue95% CI
Part A-Cohort 1: GSK3335065 0.1 mg14.1222± 576.3
Part A-Cohort 2: GSK3335065 0.25 mg201.1366± 30.9
AUC(0-t) for GSK3335065-Part A (Cohorts 3 to 8) Secondary · 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-dose

Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.

GroupValue95% CI
Part A-Cohort 3: GSK3335065 1.3 mg2701.9080± NA
Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC[0-Inf]) for GSK3335065-Part A (Cohorts 1 and 2) Secondary · 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60 and 72 hours post-dose

Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis. Data for Cohort 1 is derived only from time points up to 3 hours as later data in this participant was below limit of quantification.

GroupValue95% CI
Part A-Cohort 1: GSK3335065 0.1 mg51.68± NA
Part A-Cohort 2: GSK3335065 0.25 mg310.46± 26.2
AUC(0-Inf) for GSK3335065-Part A (Cohorts 3 to 8) Secondary · 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-dose

Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.

GroupValue95% CI
Part A-Cohort 3: GSK3335065 1.3 mg2811.51± NA
Time of the Last Measurable Concentration (Tlast) of GSK3335065-Part A (Cohorts 1 and 2) Secondary · 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60 and 72 hours post-dose

Blood samples for pharmacokinetic PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.

GroupValue95% CI
Part A-Cohort 1: GSK3335065 0.1 mg9.00060.333 – 71.700
Part A-Cohort 2: GSK3335065 0.25 mg72.025072.000 – 72.100
Tlast of GSK3335065-Part A (Cohorts 3 to 8) Secondary · 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-dose

Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.

GroupValue95% CI
Part A-Cohort 3: GSK3335065 1.3 mg168.0000168.000 – 168.000

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3).. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Part A: Placebo
Serious: 0/5 (0%)
Deaths: 0/5
Part A-Cohort 1: GSK3335065 0.1 mg
Serious: 0/6 (0%)
Deaths: 0/6
Part A-Cohort 2: GSK3335065 0.25 mg
Serious: 0/6 (0%)
Deaths: 0/6
Part A-Cohort 3: GSK3335065 1.3 mg
Serious: 1/1 (100%)
Deaths: 0/1
Part A-Cohort 4: GSK335065 2.6 mg
Serious: 0
Deaths: 0
Part A-Cohort 5: GSK335065 5.5 mg
Serious: 0
Deaths: 0
Part A-Cohort 6: GSK335065 12 mg
Serious: 0
Deaths: 0
Part A-Cohort 7: GSK335065 35 mg
Serious: 0
Deaths: 0
Part A-Cohort 8: GSK335065 54 mg
Serious: 0
Deaths: 0
Part B: Placebo
Serious: 0
Deaths: 0
Part B-Cohort 9: 0.14mg IV Bolus+0.012 mg/Hour IV Infusion
Serious: 0
Deaths: 0
Part B-Cohort 10: 7.5 mg IV Bolus+0.63 mg/Hour IV Infusion
Serious: 0
Deaths: 0
Part B-Cohort 11: 12 mg IV Bolus+1.1 mg/Hour IV Infusion
Serious: 0
Deaths: 0
Part B-Cohort 12: 23 mg IV Bolus Dose+2.1 mg/Hour IV Infusion
Serious: 0
Deaths: 0
Part C: Placebo
Serious: 0
Deaths: 0
Part C-Cohort 13: GSK3335065
Serious: 0
Deaths: 0
Part C-Cohort 14: GSK3335065
Serious: 0
Deaths: 0

Serious adverse events (1 terms)

ReactionSystemPart A: PlaceboPart A-Cohort 1: GSK333506…Part A-Cohort 2: GSK333506…Part A-Cohort 3: GSK333506…Part A-Cohort 4: GSK335065…Part A-Cohort 5: GSK335065…Part A-Cohort 6: GSK335065…Part A-Cohort 7: GSK335065…Part A-Cohort 8: GSK335065…Part B: PlaceboPart B-Cohort 9: 0.14mg IV…Part B-Cohort 10: 7.5 mg I…Part B-Cohort 11: 12 mg IV…Part B-Cohort 12: 23 mg IV…Part C: PlaceboPart C-Cohort 13: GSK3335065Part C-Cohort 14: GSK3335065
TachycardiaCardiac disorders
Other adverse events (14 terms — click to expand)

ReactionSystemPart A: PlaceboPart A-Cohort 1: GSK333506…Part A-Cohort 2: GSK333506…Part A-Cohort 3: GSK333506…Part A-Cohort 4: GSK335065…Part A-Cohort 5: GSK335065…Part A-Cohort 6: GSK335065…Part A-Cohort 7: GSK335065…Part A-Cohort 8: GSK335065…Part B: PlaceboPart B-Cohort 9: 0.14mg IV…Part B-Cohort 10: 7.5 mg I…Part B-Cohort 11: 12 mg IV…Part B-Cohort 12: 23 mg IV…Part C: PlaceboPart C-Cohort 13: GSK3335065Part C-Cohort 14: GSK3335065
HeadacheNervous system disorders
DizzinessNervous system disorders
NasopharyngitisInfections and infestations
TachycardiaCardiac disorders
Infusion site erythemaGeneral disorders
ContusionInjury, poisoning and procedural complications
Back painMusculoskeletal and connective tissue disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
Vessel puncture site bruiseGeneral disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
Dermatitis contactSkin and subcutaneous tissue disorders
Abscess oralInfections and infestations
Gingival abscessInfections and infestations
LethargyNervous system disorders

Most-reported serious reactions: Tachycardia.

Data from ClinicalTrials.gov NCT03245619 adverse events section.

Sponsor's own description

GSK3335065 is being developed as a treatment for acute pancreatitis with the intent of reducing 3-hydroxykynurenine (3HK) levels to the normal range (or lower) and maintaining them at this level throughout the treatment period. This study will utilize an adaptive design and is divided into 3 parts. Part A will consist of 8 cohorts (1-8) and is Single Ascending Dose (SAD) of GSK3335065 by IV bolus in males. Part B will be initiated after completion of dosing in Part A. It will involve ascending IV bolus doses of GSK3335065 followed by IV constant infusion for 7 days in males and will consist of four cohorts (9-12). Part C consists of a single dose of GSK3335065 by IV bolus (cohort 13), and a single dose followed by continuous infusion over 7 days (cohort 14) in females of non-child bearing potential (WONCBP). Total 64 subjects will be evaluated in the study of which Part A will include 16 healthy male subjects, Part B will include 32 healthy male subjects and Part C will include 16 WONCBP. In Part A, cohorts 1 and 2 will last up to 19 weeks and cohorts 3 to 8 will last up to 7 weeks and Part B will last up to 13 weeks. In Part C cohort 7 will last up to 7 weeks and cohort 8 will last for 13 weeks.

Publications & conference data

No peer-reviewed publications indexed yet for this trial.

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