LeishmaniasisPhase 1NCT03874234

Safety, Tolerability and Pharmacokinetics (PKs) Investigation of GSK3186899 in Healthy Subjects

A Phase 1 study testing GSK3186899 in people with Leishmaniasis, 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 55 yearsHealthy volunteers can take part
Conditions the study is for: Leishmaniasis
What is being tested?: GSK3186899
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 25 participants
Where: 1 siteUnited Kingdom
Study dates: 30 Apr 2019to 17 Oct 2019
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 55 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Subject must be 18 to 55 years of age inclusive, at the time of signing the informed consent.
Healthy as determined by the Investigator or medically qualified designee based on a 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 normal 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 >=50 kilogram (kg) and body mass index (BMI) within the range 18.5 to 28 kilogram per square meter (kg/m^2) (inclusive).
Male and/or female subjects: A male subject with a female partner of reproductive potential must agree to use contraception during the treatment period and for at least 90 days after the last dose of study treatment and refrain from donating sperm during this period. A female subject is eligible to participate if she is not a woman of childbearing potential (WONCBP).
Capable of giving signed informed consent.

Who cannot join

History or presence of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatment; or interfering with the interpretation of data.
Previous history of leishmaniasis.
ALT >1.5* upper limit of normal (ULN).
Bilirubin >1.5*ULN (isolated bilirubin >1.5*ULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent).
Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
Current or past history of clinically significant gastritis or gastroduodenal ulcers or regular use of non-steroidal anti-inflammatory drugs (NSAID).

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ECG QT interval corrected for heart rate (QTc) >450 milliseconds (msec).
Past or intended use of over-the-counter or prescription medication, including herbal medications, NSAIDs, proton-pump inhibitors (PPIs) or anti-H2 antagonists within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is the longest) prior to dosing. Other concomitant medication may be considered on a case by case basis by the Investigator in consultation with the medical monitor.
Participation in the study would result in loss of blood or blood products in excess of 500 milliliter (mL) within a 56-day period.
Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
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).
Sensitivity to any of the study treatments, or components thereof, or drug or other allergy that, in the opinion of the Investigator or GlaxoSmithKline (GSK) Medical Monitor, contraindicates participation in the study.
Regular use of known drugs of abuse.
Subjects with renal function defined as Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) with an age appropriate glomerular filtration rate (GFR) <=80 (mL/minute/1.73m^2).
Presence of Hepatitis B surface antigen (HBsAg) or Positive Hepatitis C antibody test result at screening.
Positive human immunodeficiency virus (HIV) antibody test.
Positive pre-study drug/alcohol screen.
Presence of clinically significant hematuria and/or proteinuria.
Carbon monoxide levels indicative of smoking or history or regular use of tobacco or nicotine-containing products within 3 months prior to screening.
Part A (Food effect) Cohort 3 only: Subject must have no dietary restrictions (example, lactose intolerance) or inability to eat an adapted standard meal (includes 35-40 percent fat content).
Part A (Food effect) Cohort 3 only: History of gall bladder surgery or gall bladder removal, or history of an acute disease state (example, cholelithiasis) within 14 days prior to receiving the study treatment.
Part B only: Early morning cortisol <420 nanomoles per liter (nmol/L) and inadequate response (rise of <250 millimoles per liter (mmol/L) from Baseline) to adrenocorticotropic hormone (ACTH) stimulation test at Day -1.

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

GSK Investigational Site
Cambridge, CB2 2GG

Other trials in United Kingdom

About this study

Official title: A Randomized, Double-blind (Sponsor Unblinded), Placebo-controlled, First Time in Human Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single (in Both Fed and Fasted States) and Repeat Doses of GSK3186899 in Healthy Participants

The purpose of this study is to evaluate the safety, tolerability and PK profile of single and repeat ascending doses of GSK3186899 in healthy subjects. This is a Phase 1 first time in human study, to investigate the effect of food on PK of GSK3186899. This study will consists of two parts. Part A (dose escalation phase) will be a single ascending, sequential cross-over design in cohorts 1, 2 and 3 of subjects. Cohort 1 and 2 will be 4-way cross-over which includes 4 dosing regimens of GSK3186899 and placebo (3:1 ratio) under fasted conditions. Cohort 3 will be 2-way cross-over which includes 2 treatment periods, 2 dosing regimens in fasted and fed conditions. In Part B (repeat dose escalation phase) subjects will be randomized to receive repeat doses of either GSK3186899 or placebo (3:1 ratio) in either fed or fasted conditions. Part B will be conducted based on the review of all safety, tolerability and PK data from Part A. The study duration includes screening, treatment periods and follow-up.

Conditions: Leishmaniasis
Being tested: GSK3186899, Placebo
Keywords: Dose escalation phase, First time in human, Single ascending dose, Multiple ascending dose, GSK3186899
Medical subject headings: Leishmaniasis

What participants receive

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

GSK3186899Drug
GSK3186899 will be available as white to slightly colored, spray dried powder in a bottle to be administered orally along with mixture of propylene glycol and water.
PlaceboDrug
Placebo will be available as white to slightly colored, blend powder in a bottle to be administered orally along with mixture of propylene glycol and water.

Study groups in NCT03874234
Study group	Role	What they receive
Part A: Subjects receiving GSK3186899 + placebo in Cohort 1	Experimental	Subjects will receive 3 single ascending oral doses (SAD) of GSK3186899 and 1 dose of placebo as spray dried powder, under fasted conditions on Day 1 of cohort 1 in each of the four treatment periods. In each treatment period GSK3186899 and placebo will be administered in a 3:1 ratio. A wash out period of at least 10 days will be maintained between each treatment period. Receives: Drug: GSK3186899; Drug: Placebo
Part A: Subjects receiving GSK3186899 + placebo in Cohort 2	Experimental	Subjects will receive 3 SAD of GSK3186899 and 1 dose of placebo as spray dried powder, under fasted conditions on Day 1 of cohort 2 in each of the four treatment periods. In each treatment period GSK3186899 and placebo will be administered in a 3:1 ratio. A wash out period of at least 10 days will be maintained between each treatment period. Receives: Drug: GSK3186899; Drug: Placebo
Part A: Subjects receiving GSK3186899 in Cohort 3	Experimental	Subjects will receive GSK3186899 orally, under fasted condition and fed conditions on Day 1 of cohort 3 in each of the two treatment periods. There will be a wash out period of at least 10 days between each treatment period. A dose level will be determined based on the effect of food on the safety, tolerability and PK of a single dose of GSK3186899, with dose level selected from Cohorts 1 and 2. Receives: Drug: GSK3186899
Part B: Subjects receiving GSK3186899	Experimental	Subjects will receive GSK3186899, orally, twice daily (BID) on Days 1 to 10. Subjects will receive each dose after either fed or fasted conditions. Part B will be initiated based on the review of all safety, tolerability and PK data from Part A. Receives: Drug: GSK3186899
Part B: Subjects receiving placebo	Placebo comparator	Subjects will receive placebo, orally, BID on Days 1 to 10. Subjects will receive each dose after either fed or fasted conditions. Part B will be initiated based on the review of all safety, tolerability and PK data from Part A. Receives: Drug: Placebo

What is being measured

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

Part A- Cohorts 1 and 2: Number of Participants With Non-serious Adverse Events (Non-SAEs) and SAEs
An adverse event (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. A 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, important medical events that may jeopardize the participant or require medical or surgical intervention to prevent one of the outcomes listed above. Safety Population consisted of all randomized participants who received at least one dose of study treatment.
Measured: Up to Week 12
Part A- Cohort 3: Number of Participants With Non-SAEs and SAEs
An adverse event (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. A 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, important medical events that may jeopardize the participant or require medical or surgical intervention to prevent one of the outcomes listed above.
Measured: Up to Week 9
Part B: Number of Participants With Non-SAEs and SAEs
An adverse event (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. A 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, important medical events that may jeopardize the participant or require medical or surgical intervention to prevent one of the outcomes listed above.
Measured: Up to Week 9
Part A- Cohorts 1 and 2: Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline
PCI ranges were <0.0 or >0.1*10^9 cells per(/)liter(L)(basophils), <37 or >50 proportion of red blood cells(RBC) in blood(hematocrit),<130 or >170 grams/L(hemoglobin[Hb]), <1.2 or >3.65*10^9cells(c)/L (lymphocytes),<0.2 or >1*10^9c/L(monocytes), <2 or >7.5*10^9c/L(neutrophils), <150 or >400*10^9 c/L(platelets), <3.0 or >10*10^9c/L(white blood cell[WBC]count), <4.4 or >5.8*10^12 c/L(RBC count), <80 or >99 femtoliter(mean corpuscular[MC] volume), <26.0 or >33.5 picogram(MC Hb), <0.0 or >0.4*10^9 c/L(eosinophils). Participants were counted in worst case category that their value changes to (low, within range or no change or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High) or whose value became within range, were recorded in To within Range or No Change category.Participants were counted twice if participant had values that changed To Low and To High, so the percentages may not add to 100 percentage(%).
Measured: Up to Week 12
Part A- Cohort 3: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline
Blood samples were planned to be collected to analyze hematology parameters.
Measured: Up to Week 9
Part B: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline
Blood samples were planned to be collected to analyze hematology parameters.
Measured: Up to Week 9
Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline
PCI ranges were <34 or >50 grams/L(albumin),<40 or >129 international units/L[IU/L](alkaline phosphatase),<10 or >50 IU/L(alanine aminotransferase),<0 or >37(aspartate aminotransferase), <0 or >20 micromoles(mcmol)/L (direct bilirubin),<0 or >20 mcmol/L(bilirubin), <2.2 or >2.6 millimoles/L(mmol/L)(calcium),<66 or >112 upper limit of normal mmol/L(creatinine), <3.5 or >5.1 mmol/L (potassium),<0.6 or >1 mmol/L (magnesium),<0.87 or >1.45mmol/L (phosphate),<63 or >83 g/L (protein),<135 or >145 mmol/L (sodium), <0.0 or >5.0 mg/L (C-reactive protein). Participants were counted in worst case category that their value changes to(low, within range [WR] or no change[NC] or high), unless there is NC in their category. Participants whose laboratory value category was unchanged (e.g. High to High) or whose value became WR, were recorded in To WR or NC category. Participants were counted twice if participant had values that changed To Low and To High, so percentages may not add to 100%.
Measured: Up to Week 12
Part A- Cohort 3: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline
Blood samples were planned to be collected to analyze chemistry parameters.
Measured: Up to Week 9
Part B: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline
Blood samples were planned to be collected to analyze chemistry parameters.
Measured: Up to Week 9
Part A- Cohorts 1 and 2: Number of Participants With Worst-Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method
Urine samples were collected for analysis of occult blood, ketones and protein by a dipstick method. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters of urine occult blood and protein can be read as negative, trace, 1+, 2+, 3+ indicating proportional concentrations in the urine sample. Any increase means any increase to trace, 1+, 2+ or 3+ post-Baseline relative to Baseline. Number of participants with worst case any increase in urinalysis results post-Baseline relative to Baseline has been presented.
Measured: Up to Week 12
Part A- Cohort 3: Number of Participants With Worst-Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method
Urine samples were planned to be collected to analyze urine parameters.
Measured: Up to Week 9
Part B: Number of Participants With Worst-Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method
Urine samples were planned to be collected to analyze urine parameters.
Measured: Up to Week 9
Part A- Cohorts 1 and 2: Number of Participants With Worst Case Post-Baseline Abnormal Electrocardiogram (ECG) Findings
Twelve lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and corrected QT intervals. Abnormal findings were categorized as clinically significant (CS) and not clinically significant (NCS). Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for number of participants with worst case post-Baseline abnormal ECG findings have been presented.
Measured: Up to Week 12
Part A- Cohort 3: Number of Participants With Worst Case Post-Baseline Abnormal ECG Findings
Twelve lead ECGs were planned to be performed to measure PR interval, QRS duration, QT interval and corrected QT intervals.
Measured: Up to Week 9
Part B: Number of Participants With Worst Case Post-Baseline Abnormal ECG Findings
Twelve lead ECGs were planned to be performed to measure PR interval, QRS duration, QT interval and corrected QT intervals.
Measured: Up to Week 9
Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline
Vital signs included systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse rate, respiratory rate and body temperature and were measured in a semi-supine position after 5 minutes rest. PCI ranges were, SBP (millimeters of mercury [mmHg]): <85 (low) or >160 (high), DBP (mmHg): <45 (low) or >100 (high), pulse rate (beats per minute): <40 (low) or >110 (high), respiration rate (breaths per minute): <10(low) or >25(high) and body temperature (degrees Celsius) <35 (low) or >38 (high). Participants were counted in the worst case category that their value changes to (low, within range or no change, or high), unless there is no change in their category. Participants whose vital signs value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the "To within Range or No Change" category. Participants were counted twice if the participant had values that changed "To Low" and "To High", so the percentages may not add to 100%.
Measured: Up to Week 12
Part A- Cohort 3: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline
Vital signs were planned to be measured in a semi-supine position after 5 minutes of rest.
Measured: Up to Week 9
Part B: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline
Vital signs were planned to be measured in a semi-supine position after 5 minutes of rest.
Measured: Up to Week 9
Part A- Cohorts 1 and 2: Number of Participants With Abnormal Cardiac Telemetry Findings
Continuous cardiac telemetry was performed in a supine position after at least 5 minutes of rest. Abnormal findings were categorized as CS and not NCS. Clinically significant abnormal findings were those which were not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.
Measured: Up to 24 hours post-dose
Part A- Cohort 3: Number of Participants Abnormal Cardiac Telemetry Findings
Continuous cardiac telemetry was planned to be performed in a supine position after at least 5 minutes of rest.
Measured: Up to 24 hours post-dose
Part B: Number of Participants Abnormal Cardiac Telemetry Findings
Continuous cardiac telemetry was planned to be performed in a supine position after at least 5 minutes of rest.
Measured: Up to 24 hours post-dose

Secondary outcomes (34)

Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of GSK3186899. PK Population consisted of all participants in the Safety Population who received at least 1 non-missing PK assessment.
Measured: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part A- Cohort 3: Plasma Concentration After Single Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
Measured: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part A- Cohorts 1 and 2: Area Under the Plasma Concentration-time Curve From Time 0 to Last Time of Quantifiable Concentration (AUC[0-t]) After Single Dose Administration of GSK3186899
Blood samples were collected at indicated time points for PK analysis of GSK3186899.
Measured: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part A- Cohort 3: AUC(0-t) After Single Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
Measured: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part A- Cohorts 1 and 2: Area Under the Plasma Concentration-time Curve From Time 0 to Extrapolated to Infinity (AUC[0-infinity]) After Single Dose Administration of GSK3186899
Blood samples were collected at indicated time points for PK analysis of GSK3186899.
Measured: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part A- Cohort 3: AUC(0-infinity) After Single Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
Measured: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part A- Cohorts 1 and 2: Maximum Observed Plasma Drug Concentration (Cmax) After Single Dose Administration of GSK3186899
Blood samples were collected at indicated time points for PK analysis of GSK3186899.
Measured: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part A- Cohort 3: Cmax After Single Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
Measured: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part A- Cohorts 1 and 2: Time to Maximum Observed Plasma Drug Concentration (Tmax) After Single Dose Administration of GSK3186899
Blood samples were collected at indicated time points for PK analysis of GSK3186899.
Measured: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part A- Cohort 3: Tmax After Single Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
Measured: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part A- Cohorts 1 and 2: Trough Plasma Concentration (Ctau) After Single Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
Measured: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part A- Cohort 3: Ctau After Single Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
Measured: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part A- Cohorts 1 and 2: Apparent Terminal Half-life (T1/2) After Single Dose Administration of GSK3186899
Blood samples were collected at indicated time points for PK analysis of GSK3186899.
Measured: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part A- Cohort 3: T1/2 After Single Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
Measured: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part A- Cohorts 1 and 2: Predicted Accumulation Ratio After Single Dose Administration of GSK3186899
Blood samples were collected at indicated time points for PK analysis of GSK3186899. Predicted accumulation ratio is calculated as 1/(1-e^[k*tau]) where k is elimination rate constant following the single dose and tau is the dosing interval for the intended repeat dosing.
Measured: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part A- Cohort 3: Predicted Accumulation Ratio After Single Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
Measured: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part B: Plasma Concentration After Repeat Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
Measured: Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose
Part B: AUC(0-t) After Repeat Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
Measured: Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose
Part B: AUC(0-infinity) After Repeat Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
Measured: Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose
Part B: Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval (AUC[0-tau]) After Repeat Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
Measured: Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose
Part B: Cmax After Repeat Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
Measured: Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose
Part B: Tmax After Repeat Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
Measured: Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose
Part B: T1/2 After Repeat Dose Administration of GSK3186899
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3186899.
Measured: Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose
Part A- Cohorts 1 and 2: Dose-proportionality of GSK3186899 Administered as Single Dose Based on AUC(0-infinity)
Blood samples were collected at indicated time points for PK analysis. Dose proportionality was assessed using Power model with fixed effects of logarithm of treatment and participant as random effect. Slope and 90% confidence interval for the slope are presented.
Measured: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part A- Cohort 3: Dose-proportionality of GSK3186899 Administered as Single Dose Based on AUC(0-infinity)
Blood samples were planned to be collected at indicated time points for PK analysis.
Measured: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part A- Cohorts 1 and 2: Dose-proportionality of GSK3186899 Administered as Single Dose Based on Cmax
Blood samples were collected at indicated time points for PK analysis. Dose proportionality was assessed using Power model with fixed effects of logarithm of treatment and participant as random effect. Slope and 90% confidence interval for the slope are presented.
Measured: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part A- Cohort 3: Dose-proportionality of GSK3186899 Administered as Single Dose Based on Cmax
Blood samples were planned to be collected at indicated time points for PK analysis.
Measured: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part B: Dose-proportionality of GSK3186899 Administered as Repeat Dose Based on AUC(0-tau)
Blood samples were planned to be collected at indicated time points for PK analysis.
Measured: Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose
Part B: Dose-proportionality of GSK3186899 Administered as Repeat Dose Based on Cmax
Blood samples were planned to be collected at indicated time points for PK analysis.
Measured: Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose
Part B: Dose-proportionality of GSK3186899 Administered as Repeat Dose Based on Ctau
Blood samples were planned to be collected at indicated time points for PK analysis.
Measured: Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose
Part B: Relative Accumulation Ratio of GSK3186899 After Repeat Dose Administration by AUC(0-tau)
Blood samples were planned to be collected at indicated time points for PK analysis. Accumulation ratio was planned to be calculated as ratio of AUC(0-tau) at Day 10 to AUC(0-tau) at Day 1.
Measured: Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose
Part B: Relative Accumulation Ratio of GSK3186899 After Repeat Dose Administration by Cmax
Blood samples were planned to be collected at indicated time points for PK analysis. Accumulation ratio was planned to be calculated as ratio of Cmax at Day 10 to Cmax at Day 1.
Measured: Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose
Part B: Relative Accumulation Ratio of GSK3186899 After Repeat Dose Administration by Ctau
Blood samples were planned to be collected at indicated time points for PK analysis. Accumulation ratio was planned to be calculated as ratio of Ctau at Day 10 to Ctau at Day 1.
Measured: Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose
Part B: Time Invariance Ratio of GSK3186899 After Repeat Dose Administration Using AUC
Blood samples were planned to be collected at indicated time points for PK analysis. Time-invariance ratio was planned to be calculated as AUC(0-12) on Day 10 to AUC(0-infinity) on Day 1.
Measured: Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose

Timeline

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

30 Apr 201917 Oct 2019

First posted14 Mar 2019
Study start30 Apr 2019
Primary completion17 Oct 2019
Study completion17 Oct 2019

Why it stopped: The trial was terminated early following strategic review after emergence of nonclinical data with a non-GlaxoSmithKline asset.

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 LeishmaniasisStudies 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
Model description: Subjects will receive escalating doses of GSK3186899 and placebo in Part A of the study. Subjects will receive repeat doses either of GSK3186899 or placebo in Part B of the study.
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 25 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03874234
Sponsor's protocol ID: 208436
Status last verified: May 2022
First submitted: 12 Mar 2019
Last updated: 27 Feb 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: IPD for this study will be made available via the Clinical Study Data Request site.

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?

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Study at a glance

From the registry record, last updated by the sponsor on 27 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Double-blind (Sponsor Unblinded), Placebo-controlled, First Time in Human Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single (in Both Fed and Fasted States) and Repeat Doses of GSK3186899 in Healthy Participants
ClinicalTrials.gov ID: NCT03874234
Acronym / sponsor ID: 208436
Conditions: Leishmaniasis
Keywords: Dose escalation phase, First time in human, Single ascending dose, Multiple ascending dose, GSK3186899
Phase: Phase 1
Study type: Interventional
Recruitment status: TerminatedReason stopped: The trial was terminated early following strategic review after emergence of nonclinical data with a non-GlaxoSmithKline asset.
Enrolment: 25 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Study start: 30 Apr 2019 (actual)
Primary completion: 17 Oct 2019 (actual)
Study completion: 17 Oct 2019 (actual)
First posted: 14 Mar 2019 (actual)
Results: Posted 27 Feb 2023

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: 5
Model description: Subjects will receive escalating doses of GSK3186899 and placebo in Part A of the study. Subjects will receive repeat doses either of GSK3186899 or placebo in Part B of the study.

Arm	Type	Receives
Part A: Subjects receiving GSK3186899 + placebo in Cohort 1	Experimental	Drug: GSK3186899, Drug: PlaceboSubjects will receive 3 single ascending oral doses (SAD) of GSK3186899 and 1 dose of placebo as spray dried powder, under fasted conditions on Day 1 of cohort 1 in each of the four treatment periods. In each treatment period GSK3186899 and placebo will be administered in a 3:1 ratio. A wash out period of at least 10 days will be maintained between each treatment period.
Part A: Subjects receiving GSK3186899 + placebo in Cohort 2	Experimental	Drug: GSK3186899, Drug: PlaceboSubjects will receive 3 SAD of GSK3186899 and 1 dose of placebo as spray dried powder, under fasted conditions on Day 1 of cohort 2 in each of the four treatment periods. In each treatment period GSK3186899 and placebo will be administered in a 3:1 ratio. A wash out period of at least 10 days will be maintained between each treatment period.
Part A: Subjects receiving GSK3186899 in Cohort 3	Experimental	Drug: GSK3186899Subjects will receive GSK3186899 orally, under fasted condition and fed conditions on Day 1 of cohort 3 in each of the two treatment periods. There will be a wash out period of at least 10 days between each treatment period. A dose level will be determined based on the effect of food on the safety, tolerability and PK of a single dose of GSK3186899, with dose level selected from Cohorts 1 and 2.
Part B: Subjects receiving GSK3186899	Experimental	Drug: GSK3186899Subjects will receive GSK3186899, orally, twice daily (BID) on Days 1 to 10. Subjects will receive each dose after either fed or fasted conditions. Part B will be initiated based on the review of all safety, tolerability and PK data from Part A.
Part B: Subjects receiving placebo	Placebo comparator	Drug: PlaceboSubjects will receive placebo, orally, BID on Days 1 to 10. Subjects will receive each dose after either fed or fasted conditions. Part B will be initiated based on the review of all safety, tolerability and PK data from Part A.

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (5 listed)

Subject must be 18 to 55 years of age inclusive, at the time of signing the informed consent.
Healthy as determined by the Investigator or medically qualified designee based on a 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 normal 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 >=50 kilogram (kg) and body mass index (BMI) within the range 18.5 to 28 kilogram per square meter (kg/m^2) (inclusive).
Male and/or female subjects: A male subject with a female partner of reproductive potential must agree to use contraception during the treatment period and for at least 90 days after the last dose of study treatment and refrain from donating sperm during this period. A female subject is eligible to participate if she is not a woman of childbearing potential (WONCBP).
Capable of giving signed informed consent.

Key exclusion criteria (22 listed)

History or presence of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatment; or interfering with the interpretation of data.
Previous history of leishmaniasis.
ALT >1.5* upper limit of normal (ULN).
Bilirubin >1.5*ULN (isolated bilirubin >1.5*ULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent).
Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).

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
GSK3186899GSK3186899 will be available as white to slightly colored, spray dried powder in a bottle to be administered orally along with mixture of propylene glycol and water.	Drug	Part A: Subjects receiving GSK3186899 + placebo in Cohort 1, Part A: Subjects receiving GSK3186899 + placebo in Cohort 2, Part A: Subjects receiving GSK3186899 in Cohort 3, Part B: Subjects receiving GSK3186899
PlaceboPlacebo will be available as white to slightly colored, blend powder in a bottle to be administered orally along with mixture of propylene glycol and water.	Drug	Part A: Subjects receiving GSK3186899 + placebo in Cohort 1, Part A: Subjects receiving GSK3186899 + placebo in Cohort 2, Part B: Subjects receiving placebo

Primary outcome

Part A- Cohorts 1 and 2: Number of Participants With Non-serious Adverse Events (Non-SAEs) and SAEs
Time frame: Up to Week 12
An adverse event (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. A 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, important medical events that may jeopardize the participant or require medical or surgical intervention to prevent one of the outcomes listed above. Safety Population consisted of all randomized participants who received at least one dose of study treatment.
Part A- Cohort 3: Number of Participants With Non-SAEs and SAEs
Time frame: Up to Week 9
An adverse event (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. A 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, important medical events that may jeopardize the participant or require medical or surgical intervention to prevent one of the outcomes listed above.
Part B: Number of Participants With Non-SAEs and SAEs
Time frame: Up to Week 9
An adverse event (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. A 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, important medical events that may jeopardize the participant or require medical or surgical intervention to prevent one of the outcomes listed above.
Part A- Cohorts 1 and 2: Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline
Time frame: Up to Week 12
PCI ranges were <0.0 or >0.1*10^9 cells per(/)liter(L)(basophils), <37 or >50 proportion of red blood cells(RBC) in blood(hematocrit),<130 or >170 grams/L(hemoglobin[Hb]), <1.2 or >3.65*10^9cells(c)/L (lymphocytes),<0.2 or >1*10^9c/L(monocytes), <2 or >7.5*10^9c/L(neutrophils), <150 or >400*10^9 c/L(platelets), <3.0 or >10*10^9c/L(white blood cell[WBC]count), <4.4 or >5.8*10^12 c/L(RBC count), <80 or >99 femtoliter(mean corpuscular[MC] volume), <26.0 or >33.5 picogram(MC Hb), <0.0 or >0.4*10^9 c/L(eosinophils). Participants were counted in worst case category that their value changes to (low, within range or no change or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High) or whose value became within range, were recorded in To within Range or No Change category.Participants were counted twice if participant had values that changed To Low and To High, so the percentages may not add to 100 percentage(%).
Part A- Cohort 3: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline
Time frame: Up to Week 9
Blood samples were planned to be collected to analyze hematology parameters.
Part B: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline
Time frame: Up to Week 9
Blood samples were planned to be collected to analyze hematology parameters.
Part A- Cohorts 1 and 2: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline
Time frame: Up to Week 12
PCI ranges were <34 or >50 grams/L(albumin),<40 or >129 international units/L[IU/L](alkaline phosphatase),<10 or >50 IU/L(alanine aminotransferase),<0 or >37(aspartate aminotransferase), <0 or >20 micromoles(mcmol)/L (direct bilirubin),<0 or >20 mcmol/L(bilirubin), <2.2 or >2.6 millimoles/L(mmol/L)(calcium),<66 or >112 upper limit of normal mmol/L(creatinine), <3.5 or >5.1 mmol/L (potassium),<0.6 or >1 mmol/L (magnesium),<0.87 or >1.45mmol/L (phosphate),<63 or >83 g/L (protein),<135 or >145 mmol/L (sodium), <0.0 or >5.0 mg/L (C-reactive protein). Participants were counted in worst case category that their value changes to(low, within range [WR] or no change[NC] or high), unless there is NC in their category. Participants whose laboratory value category was unchanged (e.g. High to High) or whose value became WR, were recorded in To WR or NC category. Participants were counted twice if participant had values that changed To Low and To High, so percentages may not add to 100%.
Part A- Cohort 3: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline
Time frame: Up to Week 9
Blood samples were planned to be collected to analyze chemistry parameters.
Part B: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline
Time frame: Up to Week 9
Blood samples were planned to be collected to analyze chemistry parameters.
Part A- Cohorts 1 and 2: Number of Participants With Worst-Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method
Time frame: Up to Week 12
Urine samples were collected for analysis of occult blood, ketones and protein by a dipstick method. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters of urine occult blood and protein can be read as negative, trace, 1+, 2+, 3+ indicating proportional concentrations in the urine sample. Any increase means any increase to trace, 1+, 2+ or 3+ post-Baseline relative to Baseline. Number of participants with worst case any increase in urinalysis results post-Baseline relative to Baseline has been presented.
Part A- Cohort 3: Number of Participants With Worst-Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method
Time frame: Up to Week 9
Urine samples were planned to be collected to analyze urine parameters.
Part B: Number of Participants With Worst-Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method
Time frame: Up to Week 9
Urine samples were planned to be collected to analyze urine parameters.
Part A- Cohorts 1 and 2: Number of Participants With Worst Case Post-Baseline Abnormal Electrocardiogram (ECG) Findings
Time frame: Up to Week 12
Twelve lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and corrected QT intervals. Abnormal findings were categorized as clinically significant (CS) and not clinically significant (NCS). Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for number of participants with worst case post-Baseline abnormal ECG findings have been presented.
Part A- Cohort 3: Number of Participants With Worst Case Post-Baseline Abnormal ECG Findings
Time frame: Up to Week 9
Twelve lead ECGs were planned to be performed to measure PR interval, QRS duration, QT interval and corrected QT intervals.
Part B: Number of Participants With Worst Case Post-Baseline Abnormal ECG Findings
Time frame: Up to Week 9
Twelve lead ECGs were planned to be performed to measure PR interval, QRS duration, QT interval and corrected QT intervals.
Part A- Cohorts 1 and 2: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline
Time frame: Up to Week 12
Vital signs included systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse rate, respiratory rate and body temperature and were measured in a semi-supine position after 5 minutes rest. PCI ranges were, SBP (millimeters of mercury [mmHg]): <85 (low) or >160 (high), DBP (mmHg): <45 (low) or >100 (high), pulse rate (beats per minute): <40 (low) or >110 (high), respiration rate (breaths per minute): <10(low) or >25(high) and body temperature (degrees Celsius) <35 (low) or >38 (high). Participants were counted in the worst case category that their value changes to (low, within range or no change, or high), unless there is no change in their category. Participants whose vital signs value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the "To within Range or No Change" category. Participants were counted twice if the participant had values that changed "To Low" and "To High", so the percentages may not add to 100%.
Part A- Cohort 3: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline
Time frame: Up to Week 9
Vital signs were planned to be measured in a semi-supine position after 5 minutes of rest.
Part B: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline
Time frame: Up to Week 9
Vital signs were planned to be measured in a semi-supine position after 5 minutes of rest.
Part A- Cohorts 1 and 2: Number of Participants With Abnormal Cardiac Telemetry Findings
Time frame: Up to 24 hours post-dose
Continuous cardiac telemetry was performed in a supine position after at least 5 minutes of rest. Abnormal findings were categorized as CS and not NCS. Clinically significant abnormal findings were those which were not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.
Part A- Cohort 3: Number of Participants Abnormal Cardiac Telemetry Findings
Time frame: Up to 24 hours post-dose
Continuous cardiac telemetry was planned to be performed in a supine position after at least 5 minutes of rest.
Part B: Number of Participants Abnormal Cardiac Telemetry Findings
Time frame: Up to 24 hours post-dose
Continuous cardiac telemetry was planned to be performed in a supine position after at least 5 minutes of rest.

34 secondary outcomes

Part A- Cohorts 1 and 2: Plasma Concentration After Single Dose Administration of GSK3186899
Time frame: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part A- Cohort 3: Plasma Concentration After Single Dose Administration of GSK3186899
Time frame: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part A- Cohorts 1 and 2: Area Under the Plasma Concentration-time Curve From Time 0 to Last Time of Quantifiable Concentration (AUC[0-t]) After Single Dose Administration of GSK3186899
Time frame: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part A- Cohort 3: AUC(0-t) After Single Dose Administration of GSK3186899
Time frame: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part A- Cohorts 1 and 2: Area Under the Plasma Concentration-time Curve From Time 0 to Extrapolated to Infinity (AUC[0-infinity]) After Single Dose Administration of GSK3186899
Time frame: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part A- Cohort 3: AUC(0-infinity) After Single Dose Administration of GSK3186899
Time frame: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part A- Cohorts 1 and 2: Maximum Observed Plasma Drug Concentration (Cmax) After Single Dose Administration of GSK3186899
Time frame: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part A- Cohort 3: Cmax After Single Dose Administration of GSK3186899
Time frame: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part A- Cohorts 1 and 2: Time to Maximum Observed Plasma Drug Concentration (Tmax) After Single Dose Administration of GSK3186899
Time frame: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part A- Cohort 3: Tmax After Single Dose Administration of GSK3186899
Time frame: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part A- Cohorts 1 and 2: Trough Plasma Concentration (Ctau) After Single Dose Administration of GSK3186899
Time frame: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part A- Cohort 3: Ctau After Single Dose Administration of GSK3186899
Time frame: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part A- Cohorts 1 and 2: Apparent Terminal Half-life (T1/2) After Single Dose Administration of GSK3186899
Time frame: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part A- Cohort 3: T1/2 After Single Dose Administration of GSK3186899
Time frame: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part A- Cohorts 1 and 2: Predicted Accumulation Ratio After Single Dose Administration of GSK3186899
Time frame: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part A- Cohort 3: Predicted Accumulation Ratio After Single Dose Administration of GSK3186899
Time frame: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part B: Plasma Concentration After Repeat Dose Administration of GSK3186899
Time frame: Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose
Part B: AUC(0-t) After Repeat Dose Administration of GSK3186899
Time frame: Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose
Part B: AUC(0-infinity) After Repeat Dose Administration of GSK3186899
Time frame: Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose
Part B: Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval (AUC[0-tau]) After Repeat Dose Administration of GSK3186899
Time frame: Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose
Part B: Cmax After Repeat Dose Administration of GSK3186899
Time frame: Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose
Part B: Tmax After Repeat Dose Administration of GSK3186899
Time frame: Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose
Part B: T1/2 After Repeat Dose Administration of GSK3186899
Time frame: Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose
Part A- Cohorts 1 and 2: Dose-proportionality of GSK3186899 Administered as Single Dose Based on AUC(0-infinity)
Time frame: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part A- Cohort 3: Dose-proportionality of GSK3186899 Administered as Single Dose Based on AUC(0-infinity)
Time frame: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part A- Cohorts 1 and 2: Dose-proportionality of GSK3186899 Administered as Single Dose Based on Cmax
Time frame: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part A- Cohort 3: Dose-proportionality of GSK3186899 Administered as Single Dose Based on Cmax
Time frame: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose in each treatment period
Part B: Dose-proportionality of GSK3186899 Administered as Repeat Dose Based on AUC(0-tau)
Time frame: Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose
Part B: Dose-proportionality of GSK3186899 Administered as Repeat Dose Based on Cmax
Time frame: Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose
Part B: Dose-proportionality of GSK3186899 Administered as Repeat Dose Based on Ctau
Time frame: Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose; Days 2 to 9: Pre-dose
Part B: Relative Accumulation Ratio of GSK3186899 After Repeat Dose Administration by AUC(0-tau)
Time frame: Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose
Part B: Relative Accumulation Ratio of GSK3186899 After Repeat Dose Administration by Cmax
Time frame: Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose
Part B: Relative Accumulation Ratio of GSK3186899 After Repeat Dose Administration by Ctau
Time frame: Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose
Part B: Time Invariance Ratio of GSK3186899 After Repeat Dose Administration Using AUC
Time frame: Days 1 and 10: Pre-dose, 10, 30 minutes, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 hours post-dose

Results and safety

Results posted to the registry on 27 Feb 2023, 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: Cohort 1-GSK3186899 30 mg/60 mg/120 mg/Placebo	2	2
Part A:Cohort 1-GSK3186899 30 mg/60 mg/Placebo/300 mg	2	2
Part A:Cohort 1-GSK3186899 30 mg/Placebo/120 mg/300 mg	2	2
Part A:Cohort 1-Placebo/GSK3186899 60 mg/120 mg/300 mg	2	1
Part A:Cohort 2-GSK3186899 300 mg/600 mg/800 mg/Placebo	0	0
Part A:Cohort 2-GSK3186899 300 mg/600 mg/Placebo/Dose Level 7	0	0
Part A:Cohort 2-GSK3186899 300 mg/Placebo/800 mg/Dose Level 7	0	0
Part A:Cohort 2-Placebo/GSK3186899 600 mg/800 mg/Dose Level 7	0	0
Part A: Cohort 3- GSK3186899 (Fasted) + GSK3186899 (Fed)	0	0
Part A: Cohort 3- GSK3186899 (Fed) + GSK3186899 (Fasted)	0	0
Part B: Cohort 4- GSK3186899 or Placebo	0	0
Part B: Cohort 5- GSK3186899 or Placebo	0	0
Part B: Cohort 6- GSK3186899 or Placebo	0	0

Primary outcome: Part A- Cohorts 1 and 2: Number of Participants With Non-serious Adverse Events (Non-SAEs) and SAEs

Time frame: Up to Week 12. Count of participants. Unit: Participants

Measure	Part A: Cohorts 1 and 2- Placebo n = 14	Part A: Cohort 1- GSK3186899 30 mg n = 6	Part A: Cohort 1- GSK3186899 60 mg n = 6	Part A: Cohort 1- GSK3186899 120 mg n = 6	Part A: Cohorts 1 and 2- GSK3186899 300 mg n = 12	Part A: Cohort 2- GSK3186899 600 mg n = 6	Part A: Cohort 2- GSK3186899 800 mg n = 6	Part A: Cohort 2- GSK3186899 Dose Level 7 n = 0
Non-SAEs	5	1	2	3	5	2	3	–
SAEs	0	0	0	0	0	0	0	–

Population analysed: Safety Population. Data for Part A: Cohorts 1 and 2- Placebo and Part A: Cohorts 1 and 2- GSK3186899 300 mg arms were presented in a single arm because of similar dosing strategies as pre-defined in the protocol. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as the stopping criteria was reached with the 800mg dose and no further dose escalation was recommended.

Primary outcome: Part A- Cohort 3: Number of Participants With Non-SAEs and SAEs

Time frame: Up to Week 9

Population analysed: Safety Population. Data was not collected as no participants were enrolled in Part A Cohort 3.

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

Time frame: Up to Week 9

Population analysed: Safety Population. Data was not collected as no participants were enrolled in Part B.

Primary outcome: Part A- Cohorts 1 and 2: Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline

Time frame: Up to Week 12. Count of participants. Unit: Participants

Measure	Part A: Cohorts 1 and 2- Placebo n = 14	Part A: Cohort 1- GSK3186899 30 mg n = 6	Part A: Cohort 1- GSK3186899 60 mg n = 6	Part A: Cohort 1- GSK3186899 120 mg n = 6	Part A: Cohorts 1 and 2- GSK3186899 300 mg n = 12	Part A: Cohort 2- GSK3186899 600 mg n = 6	Part A: Cohort 2- GSK3186899 800 mg n = 6	Part A: Cohort 2- GSK3186899 Dose Level 7 n = 0
Basophils: To low	0	0	0	0	0	0	0	–
Basophils: To within range or no change	14	6	6	6	12	5	6	–
Basophils: To high	0	0	0	0	0	1	0	–
Hematocrit: To low	0	0	0	0	0	0	0	–
Hematocrit: To within range or no change	14	6	6	6	12	6	6	–
Hematocrit: To high	0	0	0	0	0	0	0	–
Hemoglobin: To low	0	0	0	0	0	0	0	–
Hemoglobin: To within range or no change	13	6	6	6	12	6	6	–

34 secondary outcomes are reported in the full results.

Adverse events

Time frame: All-cause mortality, non-SAE and SAE were collected up to Week 12 in Part A. Data for Part A: Cohorts 1 and 2- Placebo and Part A: Cohorts 1 and 2- GSK3186899 300 mg arms were presented in a single arm because of similar dosing strategies as pre-defined in the protocol. Dose level 7 was not conducted as dose escalation was stopped at dose level 6 (800 mg), as stopping criteria was reached with 800 mg dose and no further dose escalation was recommended.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part A: Cohorts 1 and 2- Placebo	0 of 14 (0%)	5 of 14 (35.7%)	0 of 14
Part A: Cohort 1- GSK3186899 30 mg	0 of 6 (0%)	1 of 6 (16.7%)	0 of 6
Part A: Cohort 1- GSK3186899 60 mg	0 of 6 (0%)	2 of 6 (33.3%)	0 of 6
Part A: Cohort 1- GSK3186899 120 mg	0 of 6 (0%)	3 of 6 (50%)	0 of 6
Part A: Cohorts 1 and 2- GSK3186899 300 mg	0 of 12 (0%)	5 of 12 (41.7%)	0 of 12
Part A: Cohort 2- GSK3186899 600 mg	0 of 6 (0%)	2 of 6 (33.3%)	0 of 6
Part A: Cohort 2- GSK3186899 800 mg	0 of 6 (0%)	3 of 6 (50%)	0 of 6
Part A: Cohort 2- GSK3186899 Dose Level 7	0 of 0	0 of 0	0
Part A: Cohort 3- GSK3186899 (Fasted) + GSK3186899 (Fed)	0 of 0	0 of 0	0
Part A: Cohort 3- GSK3186899 (Fed) + GSK3186899 (Fasted)	0 of 0	0 of 0	0
Part B: Cohort 4- GSK3186899 or Placebo	0 of 0	0 of 0	0
Part B: Cohort 5- GSK3186899 or Placebo	0 of 0	0 of 0	0
Part B: Cohort 6- GSK3186899 or Placebo	0 of 0	0 of 0	0

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: Yes. IPD for this study will be made available via the Clinical Study Data Request site.

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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 GSK3186899 in people with Leishmaniasis, 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 5 inclusion and 22 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 27 Feb 2023. 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. Some participants in this study may receive a placebo. 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 27 Feb 2023). 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?

Part A- Cohorts 1 and 2: Number of Participants With Non-serious Adverse Events (Non-SAEs) and SAEs (time frame: Up to Week 12). The study lists 21 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 NCT03874234.

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 27 Feb 2023.