Pancreatitis, Acute NecrotizingPhase 1NCT03245619

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

A Phase 1 study testing GSK3335065 in people with Pancreatitis, Acute Necrotizing, run by GlaxoSmithKline at 1 site in United Kingdom.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages 18 to 60 yearsHealthy volunteers can take part
Conditions the study is for: Pancreatitis, Acute Necrotizing
What is being tested?: GSK3335065
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 18 participants
Where: 1 siteUnited Kingdom
Study dates: 22 Aug 2017to 19 May 2018
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 60 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Subjects must be 18 to 50 years of age inclusive, at the time of signing the informed consent. In Part C (WONCBP) subjects must be between 18 and 60 years of age.
Subjects who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the investigator in consultation with the Medical Monitor if required agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
Body weight greater than 50 kilogram (kg) and body mass index (BMI) within the range 18.5 - 32 kilogram per meter square (kg/m^2).
Length of time required for abstinence or use of contraceptives should take into account the reproductive toxicity profile including genotoxicity and teratogenicity, the size of the molecule, and the number of doses. Male subjects must agree to use contraception during the treatment period and for at least 2 days after the last dose of study treatment and refrain from donating sperm during this period. Only female subjects of WONCBP are eligible to participate.
Capable of giving signed informed consent.

Who cannot join

ALT and bilirubin greater than 1.5 times upper limit of normal (ULN) (isolated bilirubin greater than 1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin less than 35%).
Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
QTc corrected by Fridericia's formula(QTcF) greater than 450 millisecond (msec) from a mean of triplicate readings taken 5 mins apart
Clinically significant abnormal echocardiogram
The subject has a history or current evidence of depression, bipolar disorder, suicidal ideation and behavior, or a lifetime history of suicide attempt
Cardiac troponin (cTn) or Brain natriuretic peptide (BNP) greater than ULN

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Use of prohibited medication
The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current 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 four new chemical entities within 12 months prior to the first dosing day
Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment. For potent immunosuppressive agents, subjects with presence of hepatitis B core antibody (HBcAb) should also be excluded.
A positive pre-study drug/alcohol screen
A positive test for human immunodeficiency virus (HIV) antibody
Where participation in the study would result in donation of blood or blood products in excess of 500 milliliter (mL) within 84 days.
Poor or unsuitable venous access
History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of >14 units. One unit is equivalent to 8 gram of alcohol: a half-pint (~240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.
History of smoking within 6 months of the study.

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

GSK Investigational Site
Cambridge, CB2 0GG

Other trials in United Kingdom

About this study

Official title: Randomized, Double-blind, Placebo Controlled Dose Escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Doses (Intravenous Bolus) and Constant Intravenous Infusion Over 7 Days of GSK3335065 in Healthy Adult Subjects

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.

Conditions: Pancreatitis, Acute Necrotizing
Being tested: GSK3335065, Placebo
Keywords: 3-hydroxykynurenine, Acute pancreatitis, Dose-escalation, Healthy subjects, GSK3335065
Medical subject headings: Pancreatitis, Acute Necrotizing, Pancreatitis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

GSK3335065Drug
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. GSK3335065 is a solution and will be administered as intravenous injection and infusion with dose strength of 5 milligram (mg)/mL that may be diluted in 0.9% weight by volume (w/v) sodium chloride.
PlaceboDrug
Placebo solution to match GSK3335065 will be given as intravenous injection and infusion.

Study groups in NCT03245619
Study group	Role	What they receive
Subjects receiving GSK3335065 (Cohorts 1 to 8) in Part A	Experimental	Male subjects will be assigned to Cohorts 1 to 8. In each cohort, six subjects will be randomized to receive alternating and escalated doses of GSK3335065. Receives: Drug: GSK3335065
Subjects receiving Placebo (Cohorts 1 to 8) in Part A	Experimental	Male subjects will be assigned to Cohort 1 and 2. In each cohort, two subjects will be randomized to receive placebo. Receives: Drug: Placebo
Subjects receiving GSK3335065 (Cohort 9 to 12) in Part B	Experimental	Male subjects will be assigned to one of four cohorts (9, 10, 11 or 12). In each cohort, six subjects will be randomized to receive GSK3335065. In all cohorts each dose level will consist of an IV bolus on Day 1 subsequently followed by a continuous IV infusion for seven days. Receives: Drug: GSK3335065
Subjects receiving Placebo (Cohort 9 to 12) in Part B	Experimental	Male subjects will be assigned to one of four cohorts (9, 10, 11 or 12). In each cohort, two subjects will be randomized to receive placebo. Receives: Drug: Placebo
Subjects receiving GSK3335065 (Cohort 13) in Part C	Experimental	WONCBP will be assigned to cohort 13. Six subjects will be randomized to receive a single IV dose of GSK3335065. Receives: Drug: GSK3335065
Subjects receiving Placebo (Cohort 13) in Part C	Experimental	WONCBP will be assigned to cohort 13. Two subjects will be randomized to receive placebo. Receives: Drug: Placebo
Subjects receiving GSK3335065 (Cohort 14) in Part C	Experimental	WONCBP will be assigned to cohort 14. Six subjects will be randomized to receive a continuous IV infusion over 7 days of GSK3335065. Receives: Drug: GSK3335065
Subjects receiving Placebo (Cohort 14) in Part C	Experimental	WONCBP will be assigned to cohort 14. Two subjects will be randomized to receive placebo. Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)-Part A
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 other outcomes listed before. All Subject Population comprised of all participants randomized to treatment who received at least one dose of study treatment. AEs and SAEs were collected from admission until follow-up. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
Measured: Up to Day 22
Number of Participants With AEs and SAEs-Part B
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 other outcomes listed before. AEs and SAEs were planned to be collected from admission until follow-up.
Measured: Up to Day 34
Number of Participants With AEs and SAEs-Part C
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 other outcomes listed before. AEs and SAEs were planned to be collected from admission until follow-up.
Measured: Up to Day 34
Number of Participants With Hematological Parameters of Potential Clinical Importance-Part A
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 assessment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
Measured: Up to Day 22
Number of Participants With Hematological Parameters of Potential Clinical Importance-Part B
Blood samples were planned to be collected for the assessment of hematology parameters.
Measured: Up to Day 34
Number of Participants With Hematological Parameters of Potential Clinical Importance-Part C
Blood samples were planned to be collected for the assessment of hematology parameters.
Measured: Up to Day 34
Number of Participants With Clinical Chemistry Parameters of Potential Clinical Importance-Part A
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). Data for worst-case 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.
Measured: Up to Day 22
Number of Participants With Clinical Chemistry Parameters of Potential Clinical Importance-Part B
Blood samples were planned to be collected for the assessment of clinical chemistry parameters.
Measured: Up to Day 34
Number of Participants With Clinical Chemistry Parameters of Potential Clinical Importance-Part C
Blood samples were planned to be collected for the assessment of clinical chemistry parameters.
Measured: Up to Day 34
Number of Participants With Abnormal Urine Parameters-Part A
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.
Measured: Up to Day 22
Number of Participants With Abnormal Urine Parameters-Part B
Urine samples were planned to be collected for the assessment of urine parameters.
Measured: Up to Day 34
Number of Participants With Abnormal Urine Parameters-Part C
Urine samples were planned to be collected for the assessment of urine parameters.
Measured: Up to Day 34
Number of Participants With Abnormal Electrocardiogram (ECG) Findings-Part A
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 strategies were combined as pre-specified in reporting and analysis plan.
Measured: Up to Day 22
Number of Participants With Abnormal ECG Findings-Part B
Triplicate 12-lead ECGs were planned to be obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, QTcF and QTcB intervals.
Measured: Up to Day 34
Number of Participants With Abnormal ECG Findings-Part C
Triplicate 12-lead ECGs were planned to be obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, QTcF and QTcB intervals.
Measured: Up to Day 34
Number of Participants With Abnormal Vital Signs-Part A
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" category. Data for worst case post-Baseline relative to 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.
Measured: Up to Day 22
Number of Participants With Abnormal Vital Signs-Part B
Vital signs including SBP, DBP, heart rate, respiration rate and temperature were planned to be 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.
Measured: Up to Day 34
Number of Participants With Abnormal Vital Signs-Part C
Vital signs including SBP, DBP, heart rate, respiration rate and temperature were planned to be 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.
Measured: Up to Day 34

Secondary outcomes (44)

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)
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.
Measured: 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
AUC(0-t) for GSK3335065-Part A (Cohorts 3 to 8)
Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.
Measured: 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
AUC(0-t) for GSK3335065-Part B
Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
Measured: Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion)
AUC(0-t) for GSK3335065-Part C (Cohort 13)
Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
Measured: 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
AUC(0-t) for GSK3335065-Part C (Cohort 14)
Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
Measured: Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion)
Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC[0-Inf]) for GSK3335065-Part A (Cohorts 1 and 2)
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.
Measured: 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
AUC(0-Inf) for GSK3335065-Part A (Cohorts 3 to 8)
Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.
Measured: 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
AUC(0-Inf) for GSK3335065-Part B
Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
Measured: Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion)
AUC(0-Inf) for GSK3335065-Part C (Cohort 13)
Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
Measured: 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
AUC(0-Inf) for GSK3335065-Part C (Cohort 14)
Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
Measured: Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion)
Time of the Last Measurable Concentration (Tlast) of GSK3335065-Part A (Cohorts 1 and 2)
Blood samples for pharmacokinetic PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.
Measured: 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
Tlast of GSK3335065-Part A (Cohorts 3 to 8)
Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.
Measured: 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
Tlast of GSK3335065-Part B
Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
Measured: Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion)
Tlast of GSK3335065-Part C (Cohort 13)
Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
Measured: 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
Tlast of GSK3335065-Part C (Cohort 14)
Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
Measured: Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion)
Maximum Observed Concentration (Cmax) of GSK3335065-Part A (Cohorts 1 and 2)
Blood samples for pharmacokinetic PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.
Measured: 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
Cmax of GSK3335065-Part A (Cohorts 3 to 8)
Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.
Measured: 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
Cmax of GSK3335065-Part B
Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
Measured: Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion)
Cmax of GSK3335065-Part C (Cohort 13)
Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
Measured: 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
Cmax of GSK3335065-Part C (Cohort 14)
Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
Measured: Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion)
Time to Reach Maximum Concentration (Tmax) for GSK3335065-Part A (Cohorts 1 and 2)
Blood samples for pharmacokinetic PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.
Measured: 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
Tmax of GSK3335065-Part A (Cohorts 3 to 8)
Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.
Measured: 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
Tmax of GSK3335065-Part B
Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
Measured: Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion)
Tmax of GSK3335065-Part C (Cohort 13)
Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
Measured: 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
Tmax of GSK3335065-Part C (Cohort 14)
Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
Measured: Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion)
Clearance for GSK3335065-Part A (Cohorts 1 and 2)
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.
Measured: 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
Clearance for GSK3335065-Part A (Cohorts 3 to 8)
Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.
Measured: 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
Clearance for GSK3335065-Part B
Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
Measured: Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion)
Clearance for GSK3335065-Part C (Cohort 13)
Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
Measured: 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
Clearance for GSK3335065-Part C (Cohort 14)
Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
Measured: Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion)
Volume of Distribution for GSK3335065-Part A (Cohorts 1 and 2)
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.
Measured: 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
Volume of Distribution for GSK3335065-Part A (Cohorts 3 to 8)
Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.
Measured: 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
Volume of Distribution for GSK3335065-Part B
Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
Measured: Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion)
Volume of Distribution for GSK3335065-Part C (Cohort 13)
Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
Measured: 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
Volume of Distribution for GSK3335065-Part C (Cohort 14)
Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
Measured: Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion)
Apparent Terminal Half Life (T1/2) for GSK3335065-Part A (Cohorts 1 and 2)
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.
Measured: 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
T1/2 for GSK3335065-Part A (Cohorts 3 to 8)
Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.
Measured: 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
T1/2 for GSK3335065-Part B
Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
Measured: Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion)
T1/2 for GSK3335065-Part C (Cohort 13)
Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
Measured: 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
T1/2 for GSK3335065-Part C (Cohort 14)
Blood samples for PK analysis of GSK3335065 were planned to be collected at the indicated time points.
Measured: Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion)
Change From Baseline in Levels of Tryptophan Metabolites-Part A (Cohort 1 and 2)
Blood samples were collected to measure the kynurenine-3-monooxygenase (KMO) enzyme inhibition by determining the levels of the biomarkers Kynurenine (Kyn) and 3-hydroxykynurenine (3-HK). Baseline was the average of all pre-dose measurements (Day 1 [pre-dose at 1 hour and 30 minutes]). Change from Baseline was calculated as value at the specified time point minus the Baseline value.
Measured: Baseline, 6, 15 and 30 minutes, 1, 1.5, 2, 3, 4.5, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60 and 72 hours post-dose
Change From Baseline in Levels of Tryptophan Metabolites-Part A (Cohorts 3 to 8)
Blood samples were collected to measure the KMO enzyme inhibition by determining the levels of the biomarkers Kyn and 3-HK. Baseline was the average of all pre-dose measurements (Day -1 [pre-dose at 16 hours, 14 hours, 12 hours and 10 hours] and Day 1 [pre-dose at 30 minutes and 2 hours]). Change from Baseline was calculated as value at the specified time point minus the Baseline value.
Measured: Baseline, 6, 15 and 30 minutes, 1, 1.5, 2, 3, 4.5, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-dose
Change From Baseline in Levels of Tryptophan Metabolites-Part B
Blood samples were planned to be collected to measure the KMO enzyme inhibition by determining the levels of the biomarkers Kyn and 3-HK.
Measured: Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18 hours post-infusion), Days2 to 7 (pre-dose), Day8 (6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168 and 180 hours post-infusion)
Change From Baseline in Levels of Tryptophan Metabolites-Part C
Blood samples were planned to be collected to measure the KMO enzyme inhibition by determining the levels of the biomarkers Kyn and 3-HK.
Measured: Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18 hours post-infusion), Days2 to 7 (pre-dose), Day8 (6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168 and 180 hours post-infusion)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

22 Aug 201719 May 2018

First posted10 Aug 2017
Study start22 Aug 2017
Primary completion19 May 2018
Study completion19 May 2018

Why it stopped: The study was terminated as relationship between GSK3335065 and ventricular tachycardia could not be excluded.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Pancreatitis, Acute NecrotizingStudies of the same condition, open and under way.
More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Sequential
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 18 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03245619
Sponsor's protocol ID: 201570
Other IDs: 2016-001303-22, 2016
Status last verified: Jun 2020
First submitted: 7 Aug 2017
Last updated: 16 Jun 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Pancreatitis, Acute Necrotizing trials

Study at a glance

From the registry record, last updated by the sponsor on 16 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Randomized, Double-blind, Placebo Controlled Dose Escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Doses (Intravenous Bolus) and Constant Intravenous Infusion Over 7 Days of GSK3335065 in Healthy Adult Subjects
ClinicalTrials.gov ID: NCT03245619
Acronym / sponsor ID: 201570
Conditions: Pancreatitis, Acute Necrotizing
Keywords: 3-hydroxykynurenine, Acute pancreatitis, Dose-escalation, Healthy subjects, GSK3335065
Phase: Phase 1
Study type: Interventional
Recruitment status: TerminatedReason stopped: The study was terminated as relationship between GSK3335065 and ventricular tachycardia could not be excluded.
Enrolment: 18 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Study start: 22 Aug 2017 (actual)
Primary completion: 19 May 2018 (actual)
Study completion: 19 May 2018 (actual)
First posted: 10 Aug 2017 (actual)
Results: Posted 20 Sep 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Sequential
Masking: Double blind (participant, investigator)
Number of arms: 8

Arm	Type	Receives
Subjects receiving GSK3335065 (Cohorts 1 to 8) in Part A	Experimental	Drug: GSK3335065Male subjects will be assigned to Cohorts 1 to 8. In each cohort, six subjects will be randomized to receive alternating and escalated doses of GSK3335065.
Subjects receiving Placebo (Cohorts 1 to 8) in Part A	Experimental	Drug: PlaceboMale subjects will be assigned to Cohort 1 and 2. In each cohort, two subjects will be randomized to receive placebo.
Subjects receiving GSK3335065 (Cohort 9 to 12) in Part B	Experimental	Drug: GSK3335065Male subjects will be assigned to one of four cohorts (9, 10, 11 or 12). In each cohort, six subjects will be randomized to receive GSK3335065. In all cohorts each dose level will consist of an IV bolus on Day 1 subsequently followed by a continuous IV infusion for seven days.
Subjects receiving Placebo (Cohort 9 to 12) in Part B	Experimental	Drug: PlaceboMale subjects will be assigned to one of four cohorts (9, 10, 11 or 12). In each cohort, two subjects will be randomized to receive placebo.
Subjects receiving GSK3335065 (Cohort 13) in Part C	Experimental	Drug: GSK3335065WONCBP will be assigned to cohort 13. Six subjects will be randomized to receive a single IV dose of GSK3335065.
Subjects receiving Placebo (Cohort 13) in Part C	Experimental	Drug: PlaceboWONCBP will be assigned to cohort 13. Two subjects will be randomized to receive placebo.
Subjects receiving GSK3335065 (Cohort 14) in Part C	Experimental	Drug: GSK3335065WONCBP will be assigned to cohort 14. Six subjects will be randomized to receive a continuous IV infusion over 7 days of GSK3335065.
Subjects receiving Placebo (Cohort 14) in Part C	Experimental	Drug: PlaceboWONCBP will be assigned to cohort 14. Two subjects will be randomized to receive placebo.

Who may qualify

Ages: 18 to 60 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (6 listed)

Subjects must be 18 to 50 years of age inclusive, at the time of signing the informed consent. In Part C (WONCBP) subjects must be between 18 and 60 years of age.
Subjects who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the investigator in consultation with the Medical Monitor if required agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
Body weight greater than 50 kilogram (kg) and body mass index (BMI) within the range 18.5 - 32 kilogram per meter square (kg/m^2).
Length of time required for abstinence or use of contraceptives should take into account the reproductive toxicity profile including genotoxicity and teratogenicity, the size of the molecule, and the number of doses. Male subjects must agree to use contraception during the treatment period and for at least 2 days after the last dose of study treatment and refrain from donating sperm during this period. Only female subjects of WONCBP are eligible to participate.

Key exclusion criteria (17 listed)

ALT and bilirubin greater than 1.5 times upper limit of normal (ULN) (isolated bilirubin greater than 1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin less than 35%).
Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
QTc corrected by Fridericia's formula(QTcF) greater than 450 millisecond (msec) from a mean of triplicate readings taken 5 mins apart
Clinically significant abnormal echocardiogram
The subject has a history or current evidence of depression, bipolar disorder, suicidal ideation and behavior, or a lifetime history of suicide attempt

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
GSK3335065GSK3335065 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. GSK3335065 is a solution and will be administered as intravenous injection and infusion with dose strength of 5 milligram (mg)/mL that may be diluted in 0.9% weight by volume (w/v) sodium chloride.	Drug	Subjects receiving GSK3335065 (Cohort 13) in Part C, Subjects receiving GSK3335065 (Cohort 14) in Part C, Subjects receiving GSK3335065 (Cohort 9 to 12) in Part B, Subjects receiving GSK3335065 (Cohorts 1 to 8) in Part A
PlaceboPlacebo solution to match GSK3335065 will be given as intravenous injection and infusion.	Drug	Subjects receiving Placebo (Cohort 13) in Part C, Subjects receiving Placebo (Cohort 14) in Part C, Subjects receiving Placebo (Cohort 9 to 12) in Part B, Subjects receiving Placebo (Cohorts 1 to 8) in Part A

Primary outcome

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)-Part A
Time frame: 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 other outcomes listed before. All Subject Population comprised of all participants randomized to treatment who received at least one dose of study treatment. AEs and SAEs were collected from admission until follow-up. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
Number of Participants With AEs and SAEs-Part B
Time frame: Up to Day 34
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 other outcomes listed before. AEs and SAEs were planned to be collected from admission until follow-up.
Number of Participants With AEs and SAEs-Part C
Time frame: Up to Day 34
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 other outcomes listed before. AEs and SAEs were planned to be collected from admission until follow-up.
Number of Participants With Hematological Parameters of Potential Clinical Importance-Part A
Time frame: 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 assessment. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
Number of Participants With Hematological Parameters of Potential Clinical Importance-Part B
Time frame: Up to Day 34
Blood samples were planned to be collected for the assessment of hematology parameters.
Number of Participants With Hematological Parameters of Potential Clinical Importance-Part C
Time frame: Up to Day 34
Blood samples were planned to be collected for the assessment of hematology parameters.
Number of Participants With Clinical Chemistry Parameters of Potential Clinical Importance-Part A
Time frame: 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). Data for worst-case 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.
Number of Participants With Clinical Chemistry Parameters of Potential Clinical Importance-Part B
Time frame: Up to Day 34
Blood samples were planned to be collected for the assessment of clinical chemistry parameters.
Number of Participants With Clinical Chemistry Parameters of Potential Clinical Importance-Part C
Time frame: Up to Day 34
Blood samples were planned to be collected for the assessment of clinical chemistry parameters.
Number of Participants With Abnormal Urine Parameters-Part A
Time frame: 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.
Number of Participants With Abnormal Urine Parameters-Part B
Time frame: Up to Day 34
Urine samples were planned to be collected for the assessment of urine parameters.
Number of Participants With Abnormal Urine Parameters-Part C
Time frame: Up to Day 34
Urine samples were planned to be collected for the assessment of urine parameters.
Number of Participants With Abnormal Electrocardiogram (ECG) Findings-Part A
Time frame: 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 strategies were combined as pre-specified in reporting and analysis plan.
Number of Participants With Abnormal ECG Findings-Part B
Time frame: Up to Day 34
Triplicate 12-lead ECGs were planned to be obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, QTcF and QTcB intervals.
Number of Participants With Abnormal ECG Findings-Part C
Time frame: Up to Day 34
Triplicate 12-lead ECGs were planned to be obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, QTcF and QTcB intervals.
Number of Participants With Abnormal Vital Signs-Part A
Time frame: 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" category. Data for worst case post-Baseline relative to 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.
Number of Participants With Abnormal Vital Signs-Part B
Time frame: Up to Day 34
Vital signs including SBP, DBP, heart rate, respiration rate and temperature were planned to be 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.
Number of Participants With Abnormal Vital Signs-Part C
Time frame: Up to Day 34
Vital signs including SBP, DBP, heart rate, respiration rate and temperature were planned to be 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.

44 secondary outcomes

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)
Time frame: 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
AUC(0-t) for GSK3335065-Part A (Cohorts 3 to 8)
Time frame: 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
AUC(0-t) for GSK3335065-Part B
Time frame: Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion)
AUC(0-t) for GSK3335065-Part C (Cohort 13)
Time frame: 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
AUC(0-t) for GSK3335065-Part C (Cohort 14)
Time frame: Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion)
Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC[0-Inf]) for GSK3335065-Part A (Cohorts 1 and 2)
Time frame: 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
AUC(0-Inf) for GSK3335065-Part A (Cohorts 3 to 8)
Time frame: 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
AUC(0-Inf) for GSK3335065-Part B
Time frame: Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion)
AUC(0-Inf) for GSK3335065-Part C (Cohort 13)
Time frame: 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
AUC(0-Inf) for GSK3335065-Part C (Cohort 14)
Time frame: Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion)
Time of the Last Measurable Concentration (Tlast) of GSK3335065-Part A (Cohorts 1 and 2)
Time frame: 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
Tlast of GSK3335065-Part A (Cohorts 3 to 8)
Time frame: 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
Tlast of GSK3335065-Part B
Time frame: Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion)
Tlast of GSK3335065-Part C (Cohort 13)
Time frame: 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
Tlast of GSK3335065-Part C (Cohort 14)
Time frame: Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion)
Maximum Observed Concentration (Cmax) of GSK3335065-Part A (Cohorts 1 and 2)
Time frame: 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
Cmax of GSK3335065-Part A (Cohorts 3 to 8)
Time frame: 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
Cmax of GSK3335065-Part B
Time frame: Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion)
Cmax of GSK3335065-Part C (Cohort 13)
Time frame: 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
Cmax of GSK3335065-Part C (Cohort 14)
Time frame: Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion)
Time to Reach Maximum Concentration (Tmax) for GSK3335065-Part A (Cohorts 1 and 2)
Time frame: 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
Tmax of GSK3335065-Part A (Cohorts 3 to 8)
Time frame: 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
Tmax of GSK3335065-Part B
Time frame: Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion)
Tmax of GSK3335065-Part C (Cohort 13)
Time frame: 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
Tmax of GSK3335065-Part C (Cohort 14)
Time frame: Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion)
Clearance for GSK3335065-Part A (Cohorts 1 and 2)
Time frame: 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
Clearance for GSK3335065-Part A (Cohorts 3 to 8)
Time frame: 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
Clearance for GSK3335065-Part B
Time frame: Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion)
Clearance for GSK3335065-Part C (Cohort 13)
Time frame: 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
Clearance for GSK3335065-Part C (Cohort 14)
Time frame: Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion)
Volume of Distribution for GSK3335065-Part A (Cohorts 1 and 2)
Time frame: 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
Volume of Distribution for GSK3335065-Part A (Cohorts 3 to 8)
Time frame: 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
Volume of Distribution for GSK3335065-Part B
Time frame: Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion)
Volume of Distribution for GSK3335065-Part C (Cohort 13)
Time frame: 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
Volume of Distribution for GSK3335065-Part C (Cohort 14)
Time frame: Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion)
Apparent Terminal Half Life (T1/2) for GSK3335065-Part A (Cohorts 1 and 2)
Time frame: 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
T1/2 for GSK3335065-Part A (Cohorts 3 to 8)
Time frame: 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
T1/2 for GSK3335065-Part B
Time frame: Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion)
T1/2 for GSK3335065-Part C (Cohort 13)
Time frame: 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
T1/2 for GSK3335065-Part C (Cohort 14)
Time frame: Day1 (Pre-dose, 6, 15, 30 minutes, 1, 2, 3, 4.5, 6, 9, 12, 18hours post-infusion), Days2 to 7 (pre-dose), Day8 (end of infusion, 6 and 12 hours post-infusion), Day9 (18, 24, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-infusion)

Results and safety

Results posted to the registry on 20 Sep 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

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

Primary outcome: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)-Part A

Time frame: Up to Day 22. Count of participants. Unit: Participants

Measure	Part A: Placebo n = 5	Part A-Cohort 1: GSK3335065 0.1 mg n = 6	Part A-Cohort 2: GSK3335065 0.25 mg n = 6	Part A-Cohort 3: GSK3335065 1.3 mg n = 1	Part A-Cohort 4: GSK335065 2.6 mg n = 0	Part A-Cohort 5: GSK335065 5.5 mg n = 0	Part A-Cohort 6: GSK335065 12 mg n = 0	Part A-Cohort 7: GSK335065 35 mg n = 0	Part A-Cohort 8: GSK335065 54 mg n = 0
Any AE	3	4	3	1	–	–	–	–	–
Any SAE	0	0	0	1	–	–	–	–	–

Population analysed: All Subject Population. Data was not collected for Cohorts 4 to 8 as no participants were enrolled.

Primary outcome: Number of Participants With AEs and SAEs-Part B

Time frame: Up to Day 34

Population analysed: All Subjects Population. Data was not collected as no participants were enrolled in Part B of the study.

Primary outcome: Number of Participants With AEs and SAEs-Part C

Time frame: Up to Day 34

Population analysed: All Subjects Population. Data was not collected as no participants were enrolled in Part C of the study.

Primary outcome: Number of Participants With Hematological Parameters of Potential Clinical Importance-Part A

Time frame: Up to Day 22. Count of participants. Unit: Participants

Measure	Part A: Placebo n = 5	Part A-Cohort 1: GSK3335065 0.1 mg n = 6	Part A-Cohort 2: GSK3335065 0.25 mg n = 6	Part A-Cohort 3: GSK3335065 1.3 mg n = 1	Part A-Cohort 4: GSK335065 2.6 mg n = 0	Part A-Cohort 5: GSK335065 5.5 mg n = 0	Part A-Cohort 6: GSK335065 12 mg n = 0	Part A-Cohort 7: GSK335065 35 mg n = 0	Part A-Cohort 8: GSK335065 54 mg n = 0
Hemoglobin; Normal	5	6	6	1	–	–	–	–	–
Hemoglobin; High	0	0	0	0	–	–	–	–	–
Hematocrit; Normal	5	6	6	1	–	–	–	–	–
Hematocrit; High	0	0	0	0	–	–	–	–	–
Lymphocytes; Low	0	0	0	0	–	–	–	–	–
Lymphocytes; Normal	5	6	6	1	–	–	–	–	–
Neutrophils; Low	0	0	0	0	–	–	–	–	–
Neutrophils; Normal	5	6	6	1	–	–	–	–	–

Population analysed: All Subject Population. Data was not collected for Cohorts 4 to 8 as no participants were enrolled.

44 secondary outcomes are reported in the full results.

Adverse events

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).. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part A: Placebo	0 of 5 (0%)	3 of 5 (60%)	0 of 5
Part A-Cohort 1: GSK3335065 0.1 mg	0 of 6 (0%)	4 of 6 (66.7%)	0 of 6
Part A-Cohort 2: GSK3335065 0.25 mg	0 of 6 (0%)	3 of 6 (50%)	0 of 6
Part A-Cohort 3: GSK3335065 1.3 mg	1 of 1 (100%)	1 of 1 (100%)	0 of 1
Part A-Cohort 4: GSK335065 2.6 mg	0 of 0	0 of 0	0
Part A-Cohort 5: GSK335065 5.5 mg	0 of 0	0 of 0	0
Part A-Cohort 6: GSK335065 12 mg	0 of 0	0 of 0	0
Part A-Cohort 7: GSK335065 35 mg	0 of 0	0 of 0	0
Part A-Cohort 8: GSK335065 54 mg	0 of 0	0 of 0	0
Part B: Placebo	0 of 0	0 of 0	0
Part B-Cohort 9: 0.14mg IV Bolus+0.012 mg/Hour IV Infusion	0 of 0	0 of 0	0
Part B-Cohort 10: 7.5 mg IV Bolus+0.63 mg/Hour IV Infusion	0 of 0	0 of 0	0
Part B-Cohort 11: 12 mg IV Bolus+1.1 mg/Hour IV Infusion	0 of 0	0 of 0	0
Part B-Cohort 12: 23 mg IV Bolus Dose+2.1 mg/Hour IV Infusion	0 of 0	0 of 0	0
Part C: Placebo	0 of 0	0 of 0	0
Part C-Cohort 13: GSK3335065	0 of 0	0 of 0	0
Part C-Cohort 14: GSK3335065	0 of 0	0 of 0	0

Limitations and caveats (from the sponsor): Due to sample handling errors at clinical site, reported results (3HK/Kyn) in Cohort 3 are characterized by a consistent negative bias; therefore must not be compared with concentration data from Cohort 1 or 2.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 16 Jun 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

GSK Clinical Trials study director

GlaxoSmithKline

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing GSK3335065 in people with Pancreatitis, Acute Necrotizing, run by GlaxoSmithKline at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 16 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)-Part A (time frame: Up to Day 22). The study lists 18 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03245619.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jun 2020.