Infections, Bacterial
Conditions
Keywords
Multidrug-resistant, Gram negative bacterial infection, Safety, Pharmacokinetic
Brief summary
A phase I, first-time-in-human (FTIH), randomized, double-blind, placebo controlled, dose-escalation study is conducted to determine the safety, tolerability, and pharmacokinetic (PK) profile of GSK3342830 after administration of single intravenous (IV) infusion in Part 1 and repeat IV infusion in Part 2 in healthy subjects. Part 1 will investigate escalating single IV doses of GSK3342830. Part 2, will investigate escalating repeat IV doses of GSK3342830 with repeat dosing for 15 days as follows: a single IV infusion on Day 1, TID (three times a day) IV infusions on Days 2 through 14 (approximately every 8 hours), and a single IV infusion on Day 15. The planned starting GSK3342830 dose in Part 1 is 250 milligram (mg) administered as a single IV infusion. The dose is planned to increase in subsequent cohorts to 500, 1000, 2000, 4000, and less than or equal to (≤) 6000 mg. Part 1 will be divided into 6 cohorts (A-F) and each cohort will enroll 10 subjects (6 in active and 2 in placebo). Dose escalation will be conducted only if it is supported by the preliminary safety, tolerability, and PK results from the preceding dose levels in the study. The repeat dose escalation component (Part 2) of this study will be planned to be initiated after completion and evaluation of the all single dose cohorts up to and including 4000 mg.
Interventions
DRUGGSK3342830
A pyrogen free lyophilized formulation, white to yellowish brown powder containing 1000 mg of GSK3342830A (as free base) per vial. The reconstituted solution looks like a clear, colorless to yellow or brownish yellow liquid, free from visible particulate matter will be administered as IV infusion over 1 hour.
DRUGPlacebo
A clear and colorless solution containing 0.9% sodium chloride. It will administered as IV infusion over 1 hour.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Between 18 and 55 years of age, inclusive, at the time of signing the informed consent. * Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameter outside the reference range for the population being studied may be included only if the investigator feels and documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. * Body weight \>50 kilogram (kg) (110 pounds \[lb\]) for men and \>40 kg (99 lb) for women and body mass index within the range of 18.5 to 30 kg per square meter (m\^2), inclusive. * Male or Female subjects. Males: Male subjects with female partners of child-bearing potential must agree to use one of the highly effective contraception from the time of first dose of study drug until completion of the Follow-up visit, and Females: A female subject is eligible to participate if she is not pregnant (as confirmed by a negative serum human chorionic gonadotropin \[hCG\] test), not lactating, and considered to be of non-reproductive potential (non-reproductive potential is defined as: Pre-menopausal females with one of the following: Documented tubal ligation or Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion or Hysterectomy or Documented bilateral oophorectomy). * Postmenopausal defined as 12 months of spontaneous amenorrhea and in questionable cases a blood sample with simultaneous follicle-stimulating hormone (FSH) and estradiol levels consistent with menopause (refer to laboratory reference ranges for confirmatory levels) * Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods, if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post menopausal status before study enrolment. * Capable of giving signed informed consent, which includes compliance with the requirements and restrictions.
Exclusion criteria
* Alanine aminotransferase (ALT) not within normal limits; bilirubin \>1.5× upper limit of normal (ULN; isolated bilirubin \>1.5× ULN is acceptable if bilirubin is fractionated and direct bilirubin is \<35%). * Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). * Corrected QT (QTc) \>450 milliseconds (msec). * Any clinically significant central nervous system (e.g., seizures), cardiac, pulmonary, metabolic, renal, hepatic, or gastrointestinal condition or history of such a condition that, in the opinion of the investigator, may place the subject at an unacceptable risk as a participant in this trial or may interfere with the absorption, distribution, metabolism, or excretion of drugs. * Use of a systemic antibiotic within 30 days of screening. * Ongoing febrile illness. * Confirmed history of Clostridium difficile diarrhea * Unable to refrain from the use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) before the first dose of study treatment, unless in the opinion of the Investigator, the medication will not interfere with the study procedures or compromise subject safety. * History of regular alcohol consumption within 6 months of screening defined as an average weekly intake of \>21 units (or an average daily intake of \>3 units) for males or an average weekly intake of \>14 units (or an average daily intake \>2 units) for females. One unit is equivalent to 270 milliliter (mL) of full strength beer, 470 mL of light beer, 30 mL of spirits, or 100 mL of wine. * Urinary cotinine level indicative of smoking or history or regular use of tobacco- or nicotine containing products within 3 months before screening. * History of hypersensitivity attributed to beta-lactam antibiotics (including cephalosporin, carbapenem, or penicillin antibiotics) or other drugs, a history of multiple antibiotic intolerances, or a history of serious adverse drug reactions. * Sensitivity to poison ivy or other catechol-related hypersensitivity (e.g., mango allergy). * History of sensitivity to heparin or heparin-induced thrombocytopenia. * History of latex allergy. * History of sensitivity to any of the study treatments or components thereof, or a history of drug or other allergy that, in the opinion of the investigator, contraindicates participation in the study. * Presence of hepatitis B surface antigen or positive hepatitis C antibody test result at screening or within 3 months before the first dosing day in this study. * Serum creatinine \>ULN. * Glomerular filtration rate \<90 millilter per minute per 1.73 square meter (mL/min/1.73m\^2) as calculated by the Chronic Kidney Disease Epidemiology Collaboration formula * Albumin to creatinine ratio (ACR) \>0.03 mg/mg. In the event of an ACR above this threshold, eligibility may be confirmed by a second measurement. * Urinalysis positive for blood without other cause identified. * A positive pre-study drug or alcohol screen. * A positive test for human immunodeficiency virus antibody at or before screening. * Participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56-day period. * The subject has participated in a clinical trial and has received an investigational product within the following time period before the first dosing day in this study: 30 days, 5 half lives or twice the duration of the biological effect of the investigational product (whichever is longer). * Exposure to more than 4 new chemical entities within 12 months before the first dosing day in this study. *
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Number of Participants With Adverse Event (AE) and Serious Adverse Event (SAE) | Up to Day 43 | An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, Requires hospitalization or prolongation of existing hospitalization, Results in disability/incapacity, Is a congenital anomaly/birth defect, medical judgement and is associated with liver injury or liver impartment. The number of participants with AEs and SAEs assessed in Part 1 (Single dose) of the study were reported. |
| Part 2: Number of Participants With AE and SAE | Up to Day 56 | An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, Requires hospitalization or prolongation of existing hospitalization, Results in disability/incapacity, Is a congenital anomaly/birth defect, medical judgement and is associated with liver injury or liver impartment. The number of participants with AEs and SAEs assessed in Part 2 (Repeat dose) of the study were reported. |
| Part 1: Number of Participants With Abnormal Hematology Parameters as a Measure of Safety-Grade 3 or Higher | Up to Day 2 | Blood samples were collected and processed to measure the number of participants with abnormal platelet counts, red blood cells (RBC) count, white blood cells (WBC) count (absolute), hemoglobin, hematocrit, reticulocytes, total iron, total iron binding capacity (TIBC), ferritin, RBC indices (mean corpuscle volume \[MCV\], mean corpuscle hemoglobin \[MCH\] and mean corpuscle hemoglobin concentration \[MCHC\]) and differential WBC count (neutrophils, lymphocytes, monocytes, eosinophil's, and basophils). Participants with abnormalities of Grade 3 or higher have been reported. |
| Part 2: Number of Participants With Abnormal Hematology Parameters as a Measure of Safety-Grade 3 or Higher | Up to Day 15 | Blood samples were collected and processed to measure the number of participants with abnormal platelet counts, RBC count, WBC count (absolute), hemoglobin, hematocrit, reticulocytes, total iron, TIBC, ferritin, RBC indices MCV, MCH and MCHC and differential WBC count (neutrophils, lymphocytes, monocytes, eosinophils, and basophils). These were collected on Day 2, 5, 10 and Day 15, during Part 2 of the study. Part 2 is repeat dose escalation. Participants with abnormalities of Grade 3 or higher have been reported. |
| Part 1: Number of Participants With Abnormal Clinical Chemistry Parameters as a Measure of Safety-Grade 3 or Higher | Day 2 | Blood samples were collected and processed to measure the number of participants with abnormal blood urea nitrogen (BUN), creatinine, glucose, bicarbonate, sodium, potassium, chloride, calcium, aspartate aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT), alkaline phosphatase (ALP) levels, uric acid, total and direct bilirubin, total protein and albumin. These were collected on Day 1, during Part 1(single dose escalation) of the study. Participants with abnormalities Grade 3 or higher were reported. |
| Part 2: Number of Participants With Abnormal Clinical Chemistry Parameters as a Measure of Safety-Grade 3 or Higher | Up to Day 15 | Blood samples were collected and processed to measure the number of participants with abnormal BUN, creat, glucose, bicarbonate, sodium, potassium, chloride, calcium, AST/SGOT, ALT/SGPT, ALP levels, uric acid, total and direct bilirubin, total protein and albumin. These were collected on Day 2, 5, 10 and Day 15 during Part 2 (repeat dose escalation), of the study. Participants with abnormalities Grade 3 or higher were reported. |
| Part 1: Number of Participants Having Abnormal Urine Parameters (Using Dipstick Test) as a Measure of Safety | Up to Day 2 | An aliquot of the urine samples from first morning void urine samples was collected to analyze specific gravity, pH, glucose, protein, blood and ketone bodies by dipstick method, microscopic examination (if blood or protein is abnormal), albumin to creatinine ration (ACR), neutrophil gelatinase associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1). Urine samples were analyzed after the end of the study to verify if a clinical signal is detected. Urine samples were collected on Day 1 of Part 1 (Single-dose escalation) of the study. |
| Part 2: Number of Participants Having Abnormal Urine Parameters (Using Dipstick Test) as a Measure of Safety | Day 2, 5, 10 and Day 15 | An aliquot of the urine samples from first morning void urine samples was collected to analyze specific gravity, pH, glucose, protein, blood and ketone bodies by dipstick method, microscopic examination (if blood or protein is abnormal), ACR, NGAL and KIM-1. These urine samples were analyzed after the end of the study to verify if a clinical signal is detected. The samples were collected on Day 2, 5, 10, and Day 15 of Part 2 (Repeat dose escalation) of the study. |
| Part 1: Number of Participants With Electrocardiogram (ECG) Parameters of Potential Clinical Importance (PCI) | Up to Day 3 | Triplicate 12-lead ECGs were obtained at least 5 minutes apart within 1 hr before dosing. Single ECGs were obtained at all other time points on Day 1 at 0.5 hr, 1 hr, 1.5 hr, 2, 3, 4, 6, 12 and 24 hr, Day 2 (36 hr) and Day 3 (48 hr) during Part 1 (single dose escalation phase) of the study. All the 12-lead ECGs were measured using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. |
| Part 2: Number of Participants With ECG Parameters of PCI | Up to Day 16 | Triplicate 12-lead ECGs were obtained at least 5 minutes apart within 1 hr before the start of infusion (pre-dose) on Day 1. Single ECGs were obtained at 0.5, 1, 1.5, 2, 3, 4, 6, and 12 hrs after the start of infusion on Day 1 and Day 15, within 1 hr before the start of the morning infusion on Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, and 14, and in the morning on Day 16. All the 12-lead ECGs were measured using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. |
| Part 1: Number of Participants With Vital Signs of Potential Clinical Importance (PCI) | Up to Day 3 | The vital sign includes systolic blood pressure, diastolic blood pressure, heart rate, respiratory rate and temperature which were measured in a semi-supine position, where the participant had rested in the same position for at least 5 minutes. The number of participants with vital values, of PCI were reported. These were collected on Day 1 at pre-dose, 0.5 hr, 1 hr, 1.5 hr, 2, 3, 4, 6, 12 and 24 hr, Day 2 (36 hr) and Day 3 (48 hr) during Part 1 (single dose escalation phase) of the study. |
| Part 2: Number of Participants With Vital Signs of PCI | Up to Day 16 | The vitals for systolic, diastolic blood pressure, heart rate, respiratory rate and temperature were taken in a semi-supine position, where the participant had rested in the same position for atleast 5 minutes. The number of participants with vital values, of PCI were reported. These were collected from Day 1 to Day 16. Assessments were done within 1 hr before the start of infusion (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, and 12 hrs after the start of infusion on Days 1 and 15, within 1 hr before the start of the morning infusion and on Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, and 14, and in the morning on Day 16. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1:Dose Proportionality: Cmax | Day 1 (pre-dose, 0.5 hr, 1 hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr, 3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr, 48hr post-dose | Blood samples were collected at Day 1 (pre-dose, 0.5 hr, 1 hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr, 3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr, 48hr post-dose. The data for estimate slope for log dose, has been reported. |
| Part 2-AUC (0-inf) of GSK3342830 | Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 hr post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 hr post-dose at Day 15 | AUC (0-inf), was defined as AUC extrapolated from time zero to infinity Day 1 at pre-dose (15 minutes) and 0.5 hr, 1 hr (end of infusion), 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 hrs after start of infusion. Single pre-dose samples on mornings of Days 3, 6, 9, 12, and 13. Serial samples (Day 15) time points: pre-dose (15 minutes) and 0.5 hr, 1 (end of infusion), 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 hrs after start of infusion. The untransformed values for AUC(0-inf) have been presented. |
| Part 2-Cmax of GSK3342830 | Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 hr, post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 hr post-dose at Day 15 | Cmax was defined as the maximum concentration of drug GSK3342830, in plasma. It was collected at Day 1 at pre-dose (15 minutes) and 0.5 hr, 1 hr (end of infusion), 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 hrs after start of infusion. Single pre-dose samples on mornings of Days 3, 6, 9, 12, and 13. Serial samples (Day 15) time points: pre-dose (15 minutes) and 0.5 hr, 1 (end of infusion), 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 hrs after start of infusion. |
| Part 2-Tmax of GSK3342830 | Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 h post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 h post-dose at Day 15 | Tmax was defined as time required to achieve Cmax for drug GSK3342830, in plasma. It was collected at Day 1 at pre-dose (15 minutes) and 0.5 hr, 1 hr (end of infusion), 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 hrs after start of infusion. Single pre-dose samples on mornings of Days 3, 6, 9, 12, and 13. Serial samples (Day 15) time points: pre-dose (15 minutes) and 0.5 hr, 1 (end of infusion), 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 hrs after start of infusion. |
| Part 2-Terminal t1/2 of GSK3342830 in Plasma | Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 h post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 h post-dose at Day 15 | t ½ is defined as the time required by the drug to reduce to half its quantity. Blood samples were collected at Day 1 at pre-dose (15 minutes) and 0.5 hr, 1 hr (end of infusion), 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 hrs after start of infusion. Single pre-dose samples on mornings of Days 3, 6, 9, 12, and 13. Serial samples (Day 15) time points: pre-dose (15 minutes) and 0.5 hr, 1 (end of infusion), 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 hrs after start of infusion. |
| Part 2-Total CL of GSK3342830 in Plasma | Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 hr post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 hr post-dose at Day 15 | The systemic CL is a PK measure of volume of plasma from which the drug is removed per unit time. The blood samples of 3 mL were collected at Day 1 at pre-dose (15 minutes) and 0.5 hr, 1 hr (end of infusion), 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 hrs after start of infusion. Single pre-dose samples on mornings of Days 3, 6, 9, 12, and 13. Serial samples (Day 15) time points: pre-dose (15 minutes) and 0.5 hr, 1 (end of infusion), 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 hrs after start of infusion. |
| Part 2- Vss of Distribution of GSK3342830 in Plasma | Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 h post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 h post-dose at Day 15 | Vss reflects the actual blood and tissue volume into which a drug is distributed and the relative binding of drug to protein in these spaces. The blood samples of 3 mL were collected at Day 1 at pre-dose (15 minutes) and 0.5 hr, 1 hr (end of infusion), 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 hrs after start of infusion. Single pre-dose samples on mornings of Days 3, 6, 9, 12, and 13. Serial samples (Day 15) time points: pre-dose (15 minutes) and 0.5 hr, 1 (end of infusion), 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 hrs after start of infusion. |
| Part 2-Urinary Excretion Ratio Relative to Dose Feu (t1-t2) of GSK3342830 | Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 hr post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 hr post-dose at Day 15 | The Feu has been reported from 0 to 4, 4 to 8, 8 to 12, 12 to 24 and 24 to 48 hrs. These were collected in opaque bottles at pre-dose (within a 24-hr period before dosing, may begin on Day -1) and 0 to 4, 4 to 8, 8 to 12, 12 to 24, and 24 to 48 hrs post-dose. |
| Part 1-Area Under the Plasma Concentration (AUC) From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration Across All Treatments AUC(0-t) for GSK3342830 | Day 1 (pre-dose, 0.5 hr, 1 hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr, 3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr, 48 hr post-dose | AUC (0-t) is defined as AUC from time zero to the last quantifiable concentration after dosing. Blood samples were collected on Day 1 at indicated timepoints (pre-dose, 0.5 hr, 1hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr,3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr 24 hr, 36 hr and 48 hr post-dose. The Part 1 phase of the study comprised of single dosing of participants. Log untransformed values for AUC (0-t) have been presented. |
| Part 2-CLr of GSK3342830 in Urine | Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 h post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 h post-dose at Day 15 | The renal CLr is a PK measure of volume of plasma from which the drug is removed per unit time.These were collected in opaque bottles on Day 1 and Day 15 at (Pre-dose, 0 to 8 and 8 to 24 hrs post-dose). The untransformed values for CLr have been presented. |
| Part 2- Ae of GSK3342830 in Urine | Day 1 and Day 15 at (Pre-dose, 0 to 8 and 8 to 24 hrs post-dose) | Ae defines as the amount of drug GSK3342830, excreted in urine. These were collected in opaque bottles on Day 1 and Day 15 at (Pre-dose, 0 to 8 and 8 to 24 hrs post-dose). The untransformed values for Ae have been presented. |
| Part 2: AUC From Time Zero to Last Measurable Concentration AUC (0- Tau) | Day 1 (pre-dose, 0.5 hr, 1 hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr, 3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr, 48hr post-dose | It was defined as Area Under the Concentration-time Curve From Time Zero (Pre-dose) to the time of the last measureable concentration. Blood samples were collected on Day 1 at indicated timepoints pre-dose, 0.5 hr, 1hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr,3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr 24 hr, 36 hr and 48 hr post-dose. Log untransformed values for AUC (0 to tau) have been presented. |
| Part 2: Dose Proportionality: AUC (0-tau) | Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 hr, post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 hr post-dose at Day 15 | Blood samples were collected at Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 hr post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 hr post-dose at Day 15. Data cannot be summarized because only 1 dose level studied so dose proportionality analysis cannot be performed as no comparison can be conducted. |
| Part 2: Observed Accumulation Ratio (Ro) Based on AUC and Cmax of GSK3342830 After Administration of Repeat IV Doses, as Data Permit | Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 h post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 h post-dose at Day 15 | The accumulation ratio has been reported. Sampling was done at Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 h post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 h post-dose at Day 15. Data cannot be summarized because only 1 dose level studied so dose proportionality analysis cannot be performed as no comparison can be conducted. |
| Part 2: Steady-state Ratio (Rss) of GSK3342830 to Assess Time Invariance, as Data Permit | Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 h post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 h post-dose at Day 15 | Sampling was done at Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 h post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 h post-dose at Day 15. Since the study was terminated early, data is only available for one dose level for Part 2. Some subjects have only partial data and were not dosed on Day 15. |
| Part 2: Trough Plasma Concentrations at the End of the Dosing Interval (Ctau) to Assess the Achievement of Steady-state of GSK3342830 After Administration of Repeat IV Doses, as Data Permit | Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 h post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 h post-dose at Day 15 | Sampling was done at Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 h post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 h post-dose at Day 15. The untransformed values for Ctau have been presented. |
| Part 2- Trough Concentration (Ctau) | Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 h post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 h post-dose at Day 15 | Blood samples were collected on Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 h post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 h post-dose at Day 15. The untransformed values for Ctau have been presented. |
| Part 1-AUC Pre Dose to Infinite (Inf) Time (AUC [0-inf]) of GSK3342830 | Day 1 (pre-dose, 0.5 hr, 1 hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr, 3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr, 48hr post-dose | AUC (0-inf) is defined as AUC extrapolated from time zero to infinity. Blood samples were collected on Day 1 at indicated timepoints pre-dose, 0.5 hr, 1hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr,3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr 24 hr, 36 hr and 48 hr post-dose. This part 1 phase of the study comprised of single dosing of the participants. Log untransformed values for AUC (0-inf) have been presented. |
| Part 1-Maximum Plasma Concentration (Cmax) of GSK3342830 | Day 1 (pre-dose, 0.5 hr, 1 hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr, 3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr, 48 hr post-dose | Cmax was defined as the maximum concentration of drug GSK3342830, in plasma. Blood samples were collected on Day 1 at indicated timepoints pre-dose, 0.5 hr, 1hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr,3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr 24 hr, 36 hr and 48 hr post-dose. This part 1 phase of the study comprised of single dosing of the participants. Log untransformed values for Cmax have been presented. |
| Part 1-Time to Maximum Plasma Concentration (Tmax) of GSK3342830 | Day 1 (pre-dose, 0.5 hr, 1 hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr, 3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr, 48hr post-dose | Tmax was defined as time required to achieve Cmax for drug GSK3342830, in plasma. Blood samples were collected on Day 1 at indicated timepoints pre-dose, 0.5 hr, 1hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr,3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr 24 hr, 36 hr and 48 hr post-dose. This part 1 phase of the study comprised of single dosing of the participants. Log untransformed values for tmax have been presented. |
| Part 1-Terminal Elimination Half-life (t1/2) of GSK3342830 in Plasma | Day 1 (pre-dose, 0.5 hr, 1 hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr, 3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr, 48 hr post-dose | t ½ is defined as the time required by the drug to reduce to half its quantity. Blood samples were collected on Day 1 at indicated timepoints pre-dose, 0.5 hr, 1hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr,3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr 24 hr, 36 hr and 48 hr post-dose. This part 1 phase of the study comprised of single dosing of the participants. Log untransformed values for t1/2 have been presented. |
| Part 1-Total Systemic Clearance (CL) of GSK3342830 in Plasma | Day 1 (pre-dose, 0.5 hr, 1 hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr, 3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr, 48 hr post-dose | The systemic CL is a PK measure of volume of plasma from which the drug is removed per unit time. Blood samples were collected on Day 1 at indicated timepoints pre-dose, 0.5 hr, 1hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr,3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr 24 hr, 36 hr and 48 hr post-dose. This part 1 phase of the study comprised of single dosing of the participants. Log untransformed values for CL have been presented. |
| Part 1-Steady-state Volume (Vss) of Distribution of GSK3342830 in Plasma | Day 1 (pre-dose, 0.5 hr, 1 hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr, 3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr, 48 hr post-dose | Vss reflects the actual blood and tissue volume into which a drug is distributed and the relative binding of drug to protein in these spaces. Blood samples were collected on Day 1 at indicated timepoints pre-dose, 0.5 hr, 1hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr,3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr 24 hr, 36 hr and 48 hr post-dose. This part 1 phase of the study comprised of single dosing of the participants. Log untransformed values for Vss have been presented. |
| Part 1-Urinary Excretion Ratio Relative to Dose (Feu [t1-t2]) of GSK3342830 | Day 1 (pre-dose, 0.5 hr, 1 hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr, 3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr, 48 hr post-dose | Urine samples were collected at indicated timepoints pre-dose and post dose. The Feu has been reported from 0 to 4, 4 to 8, 8 to 12, 12 to 24 and 24 to 48 hrs. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates that data is not available. The standard deviation could not be calculated as only single participant was present. Log untransformed values for Feu (t1-t2) have been presented. |
| Part 1-Renal Clearance (CLr) of GSK3342830 in Urine | Day 1 (pre-dose, 0.5 hr, 1 hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr, 3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr, 48hr post-dose | The renal clearance (CLr) is a PK measure of volume of drug is removed per unit time. Urine samples were collected at indicated timepoints pre-dose and post dose. This part 1 phase of the study comprised of single dosing of the participants. Log untransformed values for CLr have been presented. |
| Part 1-Amount Excreted in Urine (Ae) of GSK3342830 in Urine | Day 1 (pre-dose, 0.5 hr, 1 hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr, 3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr, 48hr post-dose | Ae is defined as amount of drug GSK3342830, excreted in urine. Urine samples were collected pre-dose (within a 24-hr period before dosing, may begin on Day -1) and 0 to 4, 4 to 8, 8 to 12, 12 to 24, and 24 to 48 hrs post-dose. Log untransformed values for Ae have been presented. |
| Part 1:Dose Proportionality: AUC (0-t) | Day 1 (pre-dose, 0.5 hr, 1 hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr, 3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr, 48hr post-dose | Blood samples were collected at Day 1 (pre-dose, 0.5 hr, 1 hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr, 3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr, 48hr post-dose. Dose proportionality was assessed for AUC(0-inf) and Cmax after single dose administration. AUC(0-inf) was selected as the AUC exposure measure as it is the default AUC parameter for single dose administration and the observed data permitted its calculation. |
| Part 1:Dose Proportionality: AUC (0-inf) | Day 1 (pre-dose, 0.5 hr, 1 hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr, 3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr, 48hr post-dose | Blood samples were collected at Day 1 (pre-dose, 0.5 hr, 1 hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr, 3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr, 48 hr post-dose. The data for estimate slope for log dose, has been reported. |
Countries
Australia
Participant flow
Recruitment details
This is a first-time-in-human (FTIH), randomized, double-blind, placebo-controlled, dose-escalation study to determine the safety, tolerability & pharmacokinetic (PK) profile of GSK3342830 after administration of single (Part 1) & repeat (Part 2) IV doses in healthy adult participants (par.) & single IV dose in healthy adult Japanese par. (Part 3).
Pre-assignment details
A total of 62 par. were enrolled in the study. Part 1 comprised of 48 par. and 14 par. were enrolled in Part 2. No par. were enrolled in Part 3 as the study was terminated early per sponsor discretion.
Participants by arm
| Arm | Count |
|---|---|
| GSK3342830 250 mg Healthy adult participants in this cohort, were administered GSK3342830 dose in Part 1 as 250 mg, for 1 hr as a single IV infusion, on Day 1. | 6 |
| GSK3342830 500 mg Healthy adult participants in this cohort received an escalated dose GSK3342830 at 500 mg, for 1 hr, as a single IV infusion on Day 1. | 6 |
| GSK3342830 1000 mg The healthy adult participants in this cohort received an escalated dose GSK3342830 at 1000 mg, for 1 hr, as a single IV infusion on Day 1. | 6 |
| GSK3342830 2000 mg The healthy adult participants in this cohort received an escalated dose of GSK3342830 at 2000 mg, for 1 hr, as a single IV infusion on Day 1. | 6 |
| GSK3342830 4000 mg The healthy adult participants in this cohort received an escalated dose of GSK3342830 at 4000 mg, for 1 hr, as a single IV infusion on Day 1. | 6 |
| GSK3342830 6000 mg The healthy adult participants in this cohort received an escalated dose of GSK3342830 at 6000 mg, for 1 hr, as a single IV infusion on Day 1. | 6 |
| Placebo, Part 1 Healthy adult participants from each cohort received placebo in form of infusion for 1 hr, on Day 1. | 12 |
| GSK3342830 1000 mg TID Healthy adult participants in this repeat dose escalation cohort were administered GSK3342830 dose, in Part 2 as 1000 mg, as a single IV infusion on Day 1, TID IV infusions (approximately every 8 hrs) on Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, and 14, and a single IV infusion on Day 15. | 11 |
| Placebo, Part 2 Healthy adult participants in this repeat dose escalation cohort were administered with matching placebo to GSK3342830 1000 mg TID, Single IV infusion on Day 1, TID IV infusions (approximately every 8 hrs) on Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, and 14, and a single IV infusion on Day 15. | 3 |
| Total | 62 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Part 2 | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 5 | 0 |
Baseline characteristics
| Characteristic | GSK3342830 250 mg | GSK3342830 500 mg | GSK3342830 1000 mg | GSK3342830 2000 mg | GSK3342830 4000 mg | GSK3342830 6000 mg | Placebo, Part 1 | GSK3342830 1000 mg TID | Placebo, Part 2 | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 23.2 Years STANDARD_DEVIATION 3.54 | 22.8 Years STANDARD_DEVIATION 2.64 | 32.2 Years STANDARD_DEVIATION 10.57 | 25.5 Years STANDARD_DEVIATION 3.78 | 30.2 Years STANDARD_DEVIATION 7.7 | 21.0 Years STANDARD_DEVIATION 1.1 | 28.3 Years STANDARD_DEVIATION 5.68 | 27.1 Years STANDARD_DEVIATION 3.99 | 22.3 Years STANDARD_DEVIATION 1.53 | 26.4 Years STANDARD_DEVIATION 6.08 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 6 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 4 Participants |
| Race/Ethnicity, Customized Multiple | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 6 Participants | 5 Participants | 4 Participants | 5 Participants | 4 Participants | 6 Participants | 10 Participants | 10 Participants | 2 Participants | 52 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 12 Participants | 11 Participants | 3 Participants | 62 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 12 | 0 / 11 | 0 / 3 |
| other Total, other adverse events | 5 / 6 | 4 / 6 | 2 / 6 | 5 / 6 | 5 / 6 | 4 / 6 | 11 / 12 | 11 / 11 | 3 / 3 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 12 | 0 / 11 | 0 / 3 |
Outcome results
Primary
Part 1: Number of Participants Having Abnormal Urine Parameters (Using Dipstick Test) as a Measure of Safety
An aliquot of the urine samples from first morning void urine samples was collected to analyze specific gravity, pH, glucose, protein, blood and ketone bodies by dipstick method, microscopic examination (if blood or protein is abnormal), albumin to creatinine ration (ACR), neutrophil gelatinase associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1). Urine samples were analyzed after the end of the study to verify if a clinical signal is detected. Urine samples were collected on Day 1 of Part 1 (Single-dose escalation) of the study.
Time frame: Up to Day 2
Population: Safety population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GSK3342830 250 mg | Part 1: Number of Participants Having Abnormal Urine Parameters (Using Dipstick Test) as a Measure of Safety | 0 Participants |
| GSK3342830 500 mg | Part 1: Number of Participants Having Abnormal Urine Parameters (Using Dipstick Test) as a Measure of Safety | 0 Participants |
| GSK3342830 1000 mg | Part 1: Number of Participants Having Abnormal Urine Parameters (Using Dipstick Test) as a Measure of Safety | 0 Participants |
| GSK3342830 2000 mg | Part 1: Number of Participants Having Abnormal Urine Parameters (Using Dipstick Test) as a Measure of Safety | 0 Participants |
| GSK3342830 4000 mg | Part 1: Number of Participants Having Abnormal Urine Parameters (Using Dipstick Test) as a Measure of Safety | 0 Participants |
| GSK3342830 6000 mg | Part 1: Number of Participants Having Abnormal Urine Parameters (Using Dipstick Test) as a Measure of Safety | 0 Participants |
| Placebo, Part 1 | Part 1: Number of Participants Having Abnormal Urine Parameters (Using Dipstick Test) as a Measure of Safety | 0 Participants |
Primary
Part 1: Number of Participants With Abnormal Clinical Chemistry Parameters as a Measure of Safety-Grade 3 or Higher
Blood samples were collected and processed to measure the number of participants with abnormal blood urea nitrogen (BUN), creatinine, glucose, bicarbonate, sodium, potassium, chloride, calcium, aspartate aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT), alkaline phosphatase (ALP) levels, uric acid, total and direct bilirubin, total protein and albumin. These were collected on Day 1, during Part 1(single dose escalation) of the study. Participants with abnormalities Grade 3 or higher were reported.
Time frame: Day 2
Population: Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GSK3342830 250 mg | Part 1: Number of Participants With Abnormal Clinical Chemistry Parameters as a Measure of Safety-Grade 3 or Higher | 0 Participants |
| GSK3342830 500 mg | Part 1: Number of Participants With Abnormal Clinical Chemistry Parameters as a Measure of Safety-Grade 3 or Higher | 0 Participants |
| GSK3342830 1000 mg | Part 1: Number of Participants With Abnormal Clinical Chemistry Parameters as a Measure of Safety-Grade 3 or Higher | 0 Participants |
| GSK3342830 2000 mg | Part 1: Number of Participants With Abnormal Clinical Chemistry Parameters as a Measure of Safety-Grade 3 or Higher | 0 Participants |
| GSK3342830 4000 mg | Part 1: Number of Participants With Abnormal Clinical Chemistry Parameters as a Measure of Safety-Grade 3 or Higher | 0 Participants |
| GSK3342830 6000 mg | Part 1: Number of Participants With Abnormal Clinical Chemistry Parameters as a Measure of Safety-Grade 3 or Higher | 0 Participants |
| Placebo, Part 1 | Part 1: Number of Participants With Abnormal Clinical Chemistry Parameters as a Measure of Safety-Grade 3 or Higher | 0 Participants |
Primary
Part 1: Number of Participants With Abnormal Hematology Parameters as a Measure of Safety-Grade 3 or Higher
Blood samples were collected and processed to measure the number of participants with abnormal platelet counts, red blood cells (RBC) count, white blood cells (WBC) count (absolute), hemoglobin, hematocrit, reticulocytes, total iron, total iron binding capacity (TIBC), ferritin, RBC indices (mean corpuscle volume \[MCV\], mean corpuscle hemoglobin \[MCH\] and mean corpuscle hemoglobin concentration \[MCHC\]) and differential WBC count (neutrophils, lymphocytes, monocytes, eosinophil's, and basophils). Participants with abnormalities of Grade 3 or higher have been reported.
Time frame: Up to Day 2
Population: Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GSK3342830 250 mg | Part 1: Number of Participants With Abnormal Hematology Parameters as a Measure of Safety-Grade 3 or Higher | 0 Participants |
| GSK3342830 500 mg | Part 1: Number of Participants With Abnormal Hematology Parameters as a Measure of Safety-Grade 3 or Higher | 0 Participants |
| GSK3342830 1000 mg | Part 1: Number of Participants With Abnormal Hematology Parameters as a Measure of Safety-Grade 3 or Higher | 0 Participants |
| GSK3342830 2000 mg | Part 1: Number of Participants With Abnormal Hematology Parameters as a Measure of Safety-Grade 3 or Higher | 0 Participants |
| GSK3342830 4000 mg | Part 1: Number of Participants With Abnormal Hematology Parameters as a Measure of Safety-Grade 3 or Higher | 0 Participants |
| GSK3342830 6000 mg | Part 1: Number of Participants With Abnormal Hematology Parameters as a Measure of Safety-Grade 3 or Higher | 0 Participants |
| Placebo, Part 1 | Part 1: Number of Participants With Abnormal Hematology Parameters as a Measure of Safety-Grade 3 or Higher | 0 Participants |
Primary
Part 1: Number of Participants With Adverse Event (AE) and Serious Adverse Event (SAE)
An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, Requires hospitalization or prolongation of existing hospitalization, Results in disability/incapacity, Is a congenital anomaly/birth defect, medical judgement and is associated with liver injury or liver impartment. The number of participants with AEs and SAEs assessed in Part 1 (Single dose) of the study were reported.
Time frame: Up to Day 43
Population: Safety population comprised of all participants who received at least 1 dose of study drug and had at least one post-dose safety assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GSK3342830 250 mg | Part 1: Number of Participants With Adverse Event (AE) and Serious Adverse Event (SAE) | Any AE | 5 Participants |
| GSK3342830 250 mg | Part 1: Number of Participants With Adverse Event (AE) and Serious Adverse Event (SAE) | Any SAE | 0 Participants |
| GSK3342830 500 mg | Part 1: Number of Participants With Adverse Event (AE) and Serious Adverse Event (SAE) | Any AE | 4 Participants |
| GSK3342830 500 mg | Part 1: Number of Participants With Adverse Event (AE) and Serious Adverse Event (SAE) | Any SAE | 0 Participants |
| GSK3342830 1000 mg | Part 1: Number of Participants With Adverse Event (AE) and Serious Adverse Event (SAE) | Any AE | 6 Participants |
| GSK3342830 1000 mg | Part 1: Number of Participants With Adverse Event (AE) and Serious Adverse Event (SAE) | Any SAE | 0 Participants |
| GSK3342830 2000 mg | Part 1: Number of Participants With Adverse Event (AE) and Serious Adverse Event (SAE) | Any AE | 5 Participants |
| GSK3342830 2000 mg | Part 1: Number of Participants With Adverse Event (AE) and Serious Adverse Event (SAE) | Any SAE | 0 Participants |
| GSK3342830 4000 mg | Part 1: Number of Participants With Adverse Event (AE) and Serious Adverse Event (SAE) | Any AE | 5 Participants |
| GSK3342830 4000 mg | Part 1: Number of Participants With Adverse Event (AE) and Serious Adverse Event (SAE) | Any SAE | 0 Participants |
| GSK3342830 6000 mg | Part 1: Number of Participants With Adverse Event (AE) and Serious Adverse Event (SAE) | Any AE | 4 Participants |
| GSK3342830 6000 mg | Part 1: Number of Participants With Adverse Event (AE) and Serious Adverse Event (SAE) | Any SAE | 0 Participants |
| Placebo, Part 1 | Part 1: Number of Participants With Adverse Event (AE) and Serious Adverse Event (SAE) | Any AE | 11 Participants |
| Placebo, Part 1 | Part 1: Number of Participants With Adverse Event (AE) and Serious Adverse Event (SAE) | Any SAE | 0 Participants |
Primary
Part 1: Number of Participants With Electrocardiogram (ECG) Parameters of Potential Clinical Importance (PCI)
Triplicate 12-lead ECGs were obtained at least 5 minutes apart within 1 hr before dosing. Single ECGs were obtained at all other time points on Day 1 at 0.5 hr, 1 hr, 1.5 hr, 2, 3, 4, 6, 12 and 24 hr, Day 2 (36 hr) and Day 3 (48 hr) during Part 1 (single dose escalation phase) of the study. All the 12-lead ECGs were measured using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals.
Time frame: Up to Day 3
Population: Safety population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GSK3342830 250 mg | Part 1: Number of Participants With Electrocardiogram (ECG) Parameters of Potential Clinical Importance (PCI) | QT Interval | 1 Participants |
| GSK3342830 250 mg | Part 1: Number of Participants With Electrocardiogram (ECG) Parameters of Potential Clinical Importance (PCI) | Heart Rate | 0 Participants |
| GSK3342830 250 mg | Part 1: Number of Participants With Electrocardiogram (ECG) Parameters of Potential Clinical Importance (PCI) | RR Interval | 0 Participants |
| GSK3342830 250 mg | Part 1: Number of Participants With Electrocardiogram (ECG) Parameters of Potential Clinical Importance (PCI) | PR Interval | 0 Participants |
| GSK3342830 250 mg | Part 1: Number of Participants With Electrocardiogram (ECG) Parameters of Potential Clinical Importance (PCI) | QTc (Fridericia) | 1 Participants |
| GSK3342830 250 mg | Part 1: Number of Participants With Electrocardiogram (ECG) Parameters of Potential Clinical Importance (PCI) | QRS Duration | 0 Participants |
| GSK3342830 250 mg | Part 1: Number of Participants With Electrocardiogram (ECG) Parameters of Potential Clinical Importance (PCI) | QTc (Bazett) | 1 Participants |
| GSK3342830 500 mg | Part 1: Number of Participants With Electrocardiogram (ECG) Parameters of Potential Clinical Importance (PCI) | Heart Rate | 0 Participants |
| GSK3342830 500 mg | Part 1: Number of Participants With Electrocardiogram (ECG) Parameters of Potential Clinical Importance (PCI) | PR Interval | 1 Participants |
| GSK3342830 500 mg | Part 1: Number of Participants With Electrocardiogram (ECG) Parameters of Potential Clinical Importance (PCI) | QTc (Fridericia) | 0 Participants |
| GSK3342830 500 mg | Part 1: Number of Participants With Electrocardiogram (ECG) Parameters of Potential Clinical Importance (PCI) | QTc (Bazett) | 1 Participants |
| GSK3342830 500 mg | Part 1: Number of Participants With Electrocardiogram (ECG) Parameters of Potential Clinical Importance (PCI) | QT Interval | 2 Participants |
| GSK3342830 500 mg | Part 1: Number of Participants With Electrocardiogram (ECG) Parameters of Potential Clinical Importance (PCI) | QRS Duration | 0 Participants |
| GSK3342830 500 mg | Part 1: Number of Participants With Electrocardiogram (ECG) Parameters of Potential Clinical Importance (PCI) | RR Interval | 0 Participants |
| GSK3342830 1000 mg | Part 1: Number of Participants With Electrocardiogram (ECG) Parameters of Potential Clinical Importance (PCI) | QRS Duration | 1 Participants |
| GSK3342830 1000 mg | Part 1: Number of Participants With Electrocardiogram (ECG) Parameters of Potential Clinical Importance (PCI) | RR Interval | 0 Participants |
| GSK3342830 1000 mg | Part 1: Number of Participants With Electrocardiogram (ECG) Parameters of Potential Clinical Importance (PCI) | PR Interval | 0 Participants |
| GSK3342830 1000 mg | Part 1: Number of Participants With Electrocardiogram (ECG) Parameters of Potential Clinical Importance (PCI) | Heart Rate | 0 Participants |
| GSK3342830 1000 mg | Part 1: Number of Participants With Electrocardiogram (ECG) Parameters of Potential Clinical Importance (PCI) | QTc (Fridericia) | 1 Participants |
| GSK3342830 1000 mg | Part 1: Number of Participants With Electrocardiogram (ECG) Parameters of Potential Clinical Importance (PCI) | QT Interval | 1 Participants |
| GSK3342830 1000 mg | Part 1: Number of Participants With Electrocardiogram (ECG) Parameters of Potential Clinical Importance (PCI) | QTc (Bazett) | 1 Participants |
| GSK3342830 2000 mg | Part 1: Number of Participants With Electrocardiogram (ECG) Parameters of Potential Clinical Importance (PCI) | QT Interval | 0 Participants |
| GSK3342830 2000 mg | Part 1: Number of Participants With Electrocardiogram (ECG) Parameters of Potential Clinical Importance (PCI) | Heart Rate | 0 Participants |
| GSK3342830 2000 mg | Part 1: Number of Participants With Electrocardiogram (ECG) Parameters of Potential Clinical Importance (PCI) | PR Interval | 0 Participants |
| GSK3342830 2000 mg | Part 1: Number of Participants With Electrocardiogram (ECG) Parameters of Potential Clinical Importance (PCI) | QRS Duration | 3 Participants |
| GSK3342830 2000 mg | Part 1: Number of Participants With Electrocardiogram (ECG) Parameters of Potential Clinical Importance (PCI) | QTc (Bazett) | 1 Participants |
| GSK3342830 2000 mg | Part 1: Number of Participants With Electrocardiogram (ECG) Parameters of Potential Clinical Importance (PCI) | QTc (Fridericia) | 0 Participants |
| GSK3342830 2000 mg | Part 1: Number of Participants With Electrocardiogram (ECG) Parameters of Potential Clinical Importance (PCI) | RR Interval | 0 Participants |
| GSK3342830 4000 mg | Part 1: Number of Participants With Electrocardiogram (ECG) Parameters of Potential Clinical Importance (PCI) | RR Interval | 0 Participants |
| GSK3342830 4000 mg | Part 1: Number of Participants With Electrocardiogram (ECG) Parameters of Potential Clinical Importance (PCI) | Heart Rate | 0 Participants |
| GSK3342830 4000 mg | Part 1: Number of Participants With Electrocardiogram (ECG) Parameters of Potential Clinical Importance (PCI) | QT Interval | 0 Participants |
| GSK3342830 4000 mg | Part 1: Number of Participants With Electrocardiogram (ECG) Parameters of Potential Clinical Importance (PCI) | QRS Duration | 1 Participants |
| GSK3342830 4000 mg | Part 1: Number of Participants With Electrocardiogram (ECG) Parameters of Potential Clinical Importance (PCI) | PR Interval | 0 Participants |
| GSK3342830 4000 mg | Part 1: Number of Participants With Electrocardiogram (ECG) Parameters of Potential Clinical Importance (PCI) | QTc (Fridericia) | 1 Participants |
| GSK3342830 4000 mg | Part 1: Number of Participants With Electrocardiogram (ECG) Parameters of Potential Clinical Importance (PCI) | QTc (Bazett) | 2 Participants |
| GSK3342830 6000 mg | Part 1: Number of Participants With Electrocardiogram (ECG) Parameters of Potential Clinical Importance (PCI) | RR Interval | 0 Participants |
| GSK3342830 6000 mg | Part 1: Number of Participants With Electrocardiogram (ECG) Parameters of Potential Clinical Importance (PCI) | Heart Rate | 0 Participants |
| GSK3342830 6000 mg | Part 1: Number of Participants With Electrocardiogram (ECG) Parameters of Potential Clinical Importance (PCI) | PR Interval | 0 Participants |
| GSK3342830 6000 mg | Part 1: Number of Participants With Electrocardiogram (ECG) Parameters of Potential Clinical Importance (PCI) | QTc (Bazett) | 2 Participants |
| GSK3342830 6000 mg | Part 1: Number of Participants With Electrocardiogram (ECG) Parameters of Potential Clinical Importance (PCI) | QTc (Fridericia) | 0 Participants |
| GSK3342830 6000 mg | Part 1: Number of Participants With Electrocardiogram (ECG) Parameters of Potential Clinical Importance (PCI) | QT Interval | 1 Participants |
| GSK3342830 6000 mg | Part 1: Number of Participants With Electrocardiogram (ECG) Parameters of Potential Clinical Importance (PCI) | QRS Duration | 1 Participants |
| Placebo, Part 1 | Part 1: Number of Participants With Electrocardiogram (ECG) Parameters of Potential Clinical Importance (PCI) | QT Interval | 2 Participants |
| Placebo, Part 1 | Part 1: Number of Participants With Electrocardiogram (ECG) Parameters of Potential Clinical Importance (PCI) | QTc (Bazett) | 3 Participants |
| Placebo, Part 1 | Part 1: Number of Participants With Electrocardiogram (ECG) Parameters of Potential Clinical Importance (PCI) | PR Interval | 0 Participants |
| Placebo, Part 1 | Part 1: Number of Participants With Electrocardiogram (ECG) Parameters of Potential Clinical Importance (PCI) | QTc (Fridericia) | 1 Participants |
| Placebo, Part 1 | Part 1: Number of Participants With Electrocardiogram (ECG) Parameters of Potential Clinical Importance (PCI) | Heart Rate | 0 Participants |
| Placebo, Part 1 | Part 1: Number of Participants With Electrocardiogram (ECG) Parameters of Potential Clinical Importance (PCI) | RR Interval | 0 Participants |
| Placebo, Part 1 | Part 1: Number of Participants With Electrocardiogram (ECG) Parameters of Potential Clinical Importance (PCI) | QRS Duration | 2 Participants |
Primary
Part 1: Number of Participants With Vital Signs of Potential Clinical Importance (PCI)
The vital sign includes systolic blood pressure, diastolic blood pressure, heart rate, respiratory rate and temperature which were measured in a semi-supine position, where the participant had rested in the same position for at least 5 minutes. The number of participants with vital values, of PCI were reported. These were collected on Day 1 at pre-dose, 0.5 hr, 1 hr, 1.5 hr, 2, 3, 4, 6, 12 and 24 hr, Day 2 (36 hr) and Day 3 (48 hr) during Part 1 (single dose escalation phase) of the study.
Time frame: Up to Day 3
Population: Safety population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GSK3342830 250 mg | Part 1: Number of Participants With Vital Signs of Potential Clinical Importance (PCI) | Pulse rate | 0 Participants |
| GSK3342830 250 mg | Part 1: Number of Participants With Vital Signs of Potential Clinical Importance (PCI) | Systolic Blood Pressure | 1 Participants |
| GSK3342830 250 mg | Part 1: Number of Participants With Vital Signs of Potential Clinical Importance (PCI) | Temperature | 0 Participants |
| GSK3342830 250 mg | Part 1: Number of Participants With Vital Signs of Potential Clinical Importance (PCI) | Respiratory rate | 0 Participants |
| GSK3342830 250 mg | Part 1: Number of Participants With Vital Signs of Potential Clinical Importance (PCI) | Diastolic Blood Pressue | 0 Participants |
| GSK3342830 500 mg | Part 1: Number of Participants With Vital Signs of Potential Clinical Importance (PCI) | Systolic Blood Pressure | 0 Participants |
| GSK3342830 500 mg | Part 1: Number of Participants With Vital Signs of Potential Clinical Importance (PCI) | Diastolic Blood Pressue | 0 Participants |
| GSK3342830 500 mg | Part 1: Number of Participants With Vital Signs of Potential Clinical Importance (PCI) | Temperature | 0 Participants |
| GSK3342830 500 mg | Part 1: Number of Participants With Vital Signs of Potential Clinical Importance (PCI) | Respiratory rate | 0 Participants |
| GSK3342830 500 mg | Part 1: Number of Participants With Vital Signs of Potential Clinical Importance (PCI) | Pulse rate | 1 Participants |
| GSK3342830 1000 mg | Part 1: Number of Participants With Vital Signs of Potential Clinical Importance (PCI) | Temperature | 0 Participants |
| GSK3342830 1000 mg | Part 1: Number of Participants With Vital Signs of Potential Clinical Importance (PCI) | Diastolic Blood Pressue | 0 Participants |
| GSK3342830 1000 mg | Part 1: Number of Participants With Vital Signs of Potential Clinical Importance (PCI) | Pulse rate | 0 Participants |
| GSK3342830 1000 mg | Part 1: Number of Participants With Vital Signs of Potential Clinical Importance (PCI) | Systolic Blood Pressure | 0 Participants |
| GSK3342830 1000 mg | Part 1: Number of Participants With Vital Signs of Potential Clinical Importance (PCI) | Respiratory rate | 0 Participants |
| GSK3342830 2000 mg | Part 1: Number of Participants With Vital Signs of Potential Clinical Importance (PCI) | Diastolic Blood Pressue | 1 Participants |
| GSK3342830 2000 mg | Part 1: Number of Participants With Vital Signs of Potential Clinical Importance (PCI) | Temperature | 0 Participants |
| GSK3342830 2000 mg | Part 1: Number of Participants With Vital Signs of Potential Clinical Importance (PCI) | Respiratory rate | 0 Participants |
| GSK3342830 2000 mg | Part 1: Number of Participants With Vital Signs of Potential Clinical Importance (PCI) | Systolic Blood Pressure | 1 Participants |
| GSK3342830 2000 mg | Part 1: Number of Participants With Vital Signs of Potential Clinical Importance (PCI) | Pulse rate | 0 Participants |
| GSK3342830 4000 mg | Part 1: Number of Participants With Vital Signs of Potential Clinical Importance (PCI) | Systolic Blood Pressure | 0 Participants |
| GSK3342830 4000 mg | Part 1: Number of Participants With Vital Signs of Potential Clinical Importance (PCI) | Diastolic Blood Pressue | 0 Participants |
| GSK3342830 4000 mg | Part 1: Number of Participants With Vital Signs of Potential Clinical Importance (PCI) | Pulse rate | 0 Participants |
| GSK3342830 4000 mg | Part 1: Number of Participants With Vital Signs of Potential Clinical Importance (PCI) | Temperature | 0 Participants |
| GSK3342830 4000 mg | Part 1: Number of Participants With Vital Signs of Potential Clinical Importance (PCI) | Respiratory rate | 0 Participants |
| GSK3342830 6000 mg | Part 1: Number of Participants With Vital Signs of Potential Clinical Importance (PCI) | Temperature | 0 Participants |
| GSK3342830 6000 mg | Part 1: Number of Participants With Vital Signs of Potential Clinical Importance (PCI) | Pulse rate | 0 Participants |
| GSK3342830 6000 mg | Part 1: Number of Participants With Vital Signs of Potential Clinical Importance (PCI) | Systolic Blood Pressure | 0 Participants |
| GSK3342830 6000 mg | Part 1: Number of Participants With Vital Signs of Potential Clinical Importance (PCI) | Respiratory rate | 0 Participants |
| GSK3342830 6000 mg | Part 1: Number of Participants With Vital Signs of Potential Clinical Importance (PCI) | Diastolic Blood Pressue | 0 Participants |
| Placebo, Part 1 | Part 1: Number of Participants With Vital Signs of Potential Clinical Importance (PCI) | Systolic Blood Pressure | 1 Participants |
| Placebo, Part 1 | Part 1: Number of Participants With Vital Signs of Potential Clinical Importance (PCI) | Pulse rate | 0 Participants |
| Placebo, Part 1 | Part 1: Number of Participants With Vital Signs of Potential Clinical Importance (PCI) | Respiratory rate | 0 Participants |
| Placebo, Part 1 | Part 1: Number of Participants With Vital Signs of Potential Clinical Importance (PCI) | Diastolic Blood Pressue | 1 Participants |
| Placebo, Part 1 | Part 1: Number of Participants With Vital Signs of Potential Clinical Importance (PCI) | Temperature | 0 Participants |
Primary
Part 2: Number of Participants Having Abnormal Urine Parameters (Using Dipstick Test) as a Measure of Safety
An aliquot of the urine samples from first morning void urine samples was collected to analyze specific gravity, pH, glucose, protein, blood and ketone bodies by dipstick method, microscopic examination (if blood or protein is abnormal), ACR, NGAL and KIM-1. These urine samples were analyzed after the end of the study to verify if a clinical signal is detected. The samples were collected on Day 2, 5, 10, and Day 15 of Part 2 (Repeat dose escalation) of the study.
Time frame: Day 2, 5, 10 and Day 15
Population: Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GSK3342830 250 mg | Part 2: Number of Participants Having Abnormal Urine Parameters (Using Dipstick Test) as a Measure of Safety | 0 Participants |
| GSK3342830 500 mg | Part 2: Number of Participants Having Abnormal Urine Parameters (Using Dipstick Test) as a Measure of Safety | 0 Participants |
Primary
Part 2: Number of Participants With Abnormal Clinical Chemistry Parameters as a Measure of Safety-Grade 3 or Higher
Blood samples were collected and processed to measure the number of participants with abnormal BUN, creat, glucose, bicarbonate, sodium, potassium, chloride, calcium, AST/SGOT, ALT/SGPT, ALP levels, uric acid, total and direct bilirubin, total protein and albumin. These were collected on Day 2, 5, 10 and Day 15 during Part 2 (repeat dose escalation), of the study. Participants with abnormalities Grade 3 or higher were reported.
Time frame: Up to Day 15
Population: Safety population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GSK3342830 250 mg | Part 2: Number of Participants With Abnormal Clinical Chemistry Parameters as a Measure of Safety-Grade 3 or Higher | Serum Glucose | 1 Participants |
| GSK3342830 250 mg | Part 2: Number of Participants With Abnormal Clinical Chemistry Parameters as a Measure of Safety-Grade 3 or Higher | Serum or Plasma ALT | 1 Participants |
| GSK3342830 250 mg | Part 2: Number of Participants With Abnormal Clinical Chemistry Parameters as a Measure of Safety-Grade 3 or Higher | Serum or Plasma albumin | 1 Participants |
| GSK3342830 250 mg | Part 2: Number of Participants With Abnormal Clinical Chemistry Parameters as a Measure of Safety-Grade 3 or Higher | Serum or Plasma ALP | 0 Participants |
| GSK3342830 250 mg | Part 2: Number of Participants With Abnormal Clinical Chemistry Parameters as a Measure of Safety-Grade 3 or Higher | Serum or Plasma AST | 2 Participants |
| GSK3342830 250 mg | Part 2: Number of Participants With Abnormal Clinical Chemistry Parameters as a Measure of Safety-Grade 3 or Higher | Serum or Plasma Calcium | 0 Participants |
| GSK3342830 250 mg | Part 2: Number of Participants With Abnormal Clinical Chemistry Parameters as a Measure of Safety-Grade 3 or Higher | Serum or Plasma Chloride | 0 Participants |
| GSK3342830 250 mg | Part 2: Number of Participants With Abnormal Clinical Chemistry Parameters as a Measure of Safety-Grade 3 or Higher | Serum or Plasma Creat | 0 Participants |
| GSK3342830 250 mg | Part 2: Number of Participants With Abnormal Clinical Chemistry Parameters as a Measure of Safety-Grade 3 or Higher | Serum or Plasma Direct Bilirubin | 2 Participants |
| GSK3342830 250 mg | Part 2: Number of Participants With Abnormal Clinical Chemistry Parameters as a Measure of Safety-Grade 3 or Higher | Serum or Plasma Potassium | 1 Participants |
| GSK3342830 250 mg | Part 2: Number of Participants With Abnormal Clinical Chemistry Parameters as a Measure of Safety-Grade 3 or Higher | Serum or Plasma Protein | 0 Participants |
| GSK3342830 250 mg | Part 2: Number of Participants With Abnormal Clinical Chemistry Parameters as a Measure of Safety-Grade 3 or Higher | Serum or Plasma Sodium | 1 Participants |
| GSK3342830 500 mg | Part 2: Number of Participants With Abnormal Clinical Chemistry Parameters as a Measure of Safety-Grade 3 or Higher | Serum or Plasma Protein | 0 Participants |
| GSK3342830 500 mg | Part 2: Number of Participants With Abnormal Clinical Chemistry Parameters as a Measure of Safety-Grade 3 or Higher | Serum Glucose | 0 Participants |
| GSK3342830 500 mg | Part 2: Number of Participants With Abnormal Clinical Chemistry Parameters as a Measure of Safety-Grade 3 or Higher | Serum or Plasma Chloride | 0 Participants |
| GSK3342830 500 mg | Part 2: Number of Participants With Abnormal Clinical Chemistry Parameters as a Measure of Safety-Grade 3 or Higher | Serum or Plasma ALT | 0 Participants |
| GSK3342830 500 mg | Part 2: Number of Participants With Abnormal Clinical Chemistry Parameters as a Measure of Safety-Grade 3 or Higher | Serum or Plasma Potassium | 0 Participants |
| GSK3342830 500 mg | Part 2: Number of Participants With Abnormal Clinical Chemistry Parameters as a Measure of Safety-Grade 3 or Higher | Serum or Plasma albumin | 0 Participants |
| GSK3342830 500 mg | Part 2: Number of Participants With Abnormal Clinical Chemistry Parameters as a Measure of Safety-Grade 3 or Higher | Serum or Plasma Creat | 0 Participants |
| GSK3342830 500 mg | Part 2: Number of Participants With Abnormal Clinical Chemistry Parameters as a Measure of Safety-Grade 3 or Higher | Serum or Plasma ALP | 0 Participants |
| GSK3342830 500 mg | Part 2: Number of Participants With Abnormal Clinical Chemistry Parameters as a Measure of Safety-Grade 3 or Higher | Serum or Plasma Sodium | 0 Participants |
| GSK3342830 500 mg | Part 2: Number of Participants With Abnormal Clinical Chemistry Parameters as a Measure of Safety-Grade 3 or Higher | Serum or Plasma AST | 0 Participants |
| GSK3342830 500 mg | Part 2: Number of Participants With Abnormal Clinical Chemistry Parameters as a Measure of Safety-Grade 3 or Higher | Serum or Plasma Direct Bilirubin | 0 Participants |
| GSK3342830 500 mg | Part 2: Number of Participants With Abnormal Clinical Chemistry Parameters as a Measure of Safety-Grade 3 or Higher | Serum or Plasma Calcium | 0 Participants |
Primary
Part 2: Number of Participants With Abnormal Hematology Parameters as a Measure of Safety-Grade 3 or Higher
Blood samples were collected and processed to measure the number of participants with abnormal platelet counts, RBC count, WBC count (absolute), hemoglobin, hematocrit, reticulocytes, total iron, TIBC, ferritin, RBC indices MCV, MCH and MCHC and differential WBC count (neutrophils, lymphocytes, monocytes, eosinophils, and basophils). These were collected on Day 2, 5, 10 and Day 15, during Part 2 of the study. Part 2 is repeat dose escalation. Participants with abnormalities of Grade 3 or higher have been reported.
Time frame: Up to Day 15
Population: Safety population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GSK3342830 250 mg | Part 2: Number of Participants With Abnormal Hematology Parameters as a Measure of Safety-Grade 3 or Higher | 0 Participants |
| GSK3342830 500 mg | Part 2: Number of Participants With Abnormal Hematology Parameters as a Measure of Safety-Grade 3 or Higher | 0 Participants |
Primary
Part 2: Number of Participants With AE and SAE
An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, Requires hospitalization or prolongation of existing hospitalization, Results in disability/incapacity, Is a congenital anomaly/birth defect, medical judgement and is associated with liver injury or liver impartment. The number of participants with AEs and SAEs assessed in Part 2 (Repeat dose) of the study were reported.
Time frame: Up to Day 56
Population: Safety population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GSK3342830 250 mg | Part 2: Number of Participants With AE and SAE | Any AE | 11 Participants |
| GSK3342830 250 mg | Part 2: Number of Participants With AE and SAE | Any SAE | 0 Participants |
| GSK3342830 500 mg | Part 2: Number of Participants With AE and SAE | Any AE | 3 Participants |
| GSK3342830 500 mg | Part 2: Number of Participants With AE and SAE | Any SAE | 0 Participants |
Primary
Part 2: Number of Participants With ECG Parameters of PCI
Triplicate 12-lead ECGs were obtained at least 5 minutes apart within 1 hr before the start of infusion (pre-dose) on Day 1. Single ECGs were obtained at 0.5, 1, 1.5, 2, 3, 4, 6, and 12 hrs after the start of infusion on Day 1 and Day 15, within 1 hr before the start of the morning infusion on Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, and 14, and in the morning on Day 16. All the 12-lead ECGs were measured using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals.
Time frame: Up to Day 16
Population: Safety population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GSK3342830 250 mg | Part 2: Number of Participants With ECG Parameters of PCI | QRS Duration | 0 Participants |
| GSK3342830 250 mg | Part 2: Number of Participants With ECG Parameters of PCI | QTc (Bazett) | 2 Participants |
| GSK3342830 250 mg | Part 2: Number of Participants With ECG Parameters of PCI | PR Interval | 1 Participants |
| GSK3342830 250 mg | Part 2: Number of Participants With ECG Parameters of PCI | QTc (Fridericia) | 1 Participants |
| GSK3342830 250 mg | Part 2: Number of Participants With ECG Parameters of PCI | QT Interval | 1 Participants |
| GSK3342830 250 mg | Part 2: Number of Participants With ECG Parameters of PCI | RR Interval | 0 Participants |
| GSK3342830 250 mg | Part 2: Number of Participants With ECG Parameters of PCI | Heart Rate | 0 Participants |
| GSK3342830 500 mg | Part 2: Number of Participants With ECG Parameters of PCI | RR Interval | 0 Participants |
| GSK3342830 500 mg | Part 2: Number of Participants With ECG Parameters of PCI | Heart Rate | 0 Participants |
| GSK3342830 500 mg | Part 2: Number of Participants With ECG Parameters of PCI | PR Interval | 0 Participants |
| GSK3342830 500 mg | Part 2: Number of Participants With ECG Parameters of PCI | QRS Duration | 0 Participants |
| GSK3342830 500 mg | Part 2: Number of Participants With ECG Parameters of PCI | QT Interval | 2 Participants |
| GSK3342830 500 mg | Part 2: Number of Participants With ECG Parameters of PCI | QTc (Bazett) | 1 Participants |
| GSK3342830 500 mg | Part 2: Number of Participants With ECG Parameters of PCI | QTc (Fridericia) | 1 Participants |
Primary
Part 2: Number of Participants With Vital Signs of PCI
The vitals for systolic, diastolic blood pressure, heart rate, respiratory rate and temperature were taken in a semi-supine position, where the participant had rested in the same position for atleast 5 minutes. The number of participants with vital values, of PCI were reported. These were collected from Day 1 to Day 16. Assessments were done within 1 hr before the start of infusion (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, and 12 hrs after the start of infusion on Days 1 and 15, within 1 hr before the start of the morning infusion and on Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, and 14, and in the morning on Day 16.
Time frame: Up to Day 16
Population: Safety population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GSK3342830 250 mg | Part 2: Number of Participants With Vital Signs of PCI | DBP | 0 Participants |
| GSK3342830 250 mg | Part 2: Number of Participants With Vital Signs of PCI | Temperature | 0 Participants |
| GSK3342830 250 mg | Part 2: Number of Participants With Vital Signs of PCI | Pulse rate | 1 Participants |
| GSK3342830 250 mg | Part 2: Number of Participants With Vital Signs of PCI | Respiratory rate | 0 Participants |
| GSK3342830 250 mg | Part 2: Number of Participants With Vital Signs of PCI | SBP | 0 Participants |
| GSK3342830 500 mg | Part 2: Number of Participants With Vital Signs of PCI | Respiratory rate | 0 Participants |
| GSK3342830 500 mg | Part 2: Number of Participants With Vital Signs of PCI | SBP | 0 Participants |
| GSK3342830 500 mg | Part 2: Number of Participants With Vital Signs of PCI | DBP | 1 Participants |
| GSK3342830 500 mg | Part 2: Number of Participants With Vital Signs of PCI | Pulse rate | 0 Participants |
| GSK3342830 500 mg | Part 2: Number of Participants With Vital Signs of PCI | Temperature | 0 Participants |
Secondary
Part 1-Amount Excreted in Urine (Ae) of GSK3342830 in Urine
Ae is defined as amount of drug GSK3342830, excreted in urine. Urine samples were collected pre-dose (within a 24-hr period before dosing, may begin on Day -1) and 0 to 4, 4 to 8, 8 to 12, 12 to 24, and 24 to 48 hrs post-dose. Log untransformed values for Ae have been presented.
Time frame: Day 1 (pre-dose, 0.5 hr, 1 hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr, 3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr, 48hr post-dose
Population: PK Parameter Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GSK3342830 250 mg | Part 1-Amount Excreted in Urine (Ae) of GSK3342830 in Urine | 239.6 Milligram | Standard Deviation 38.25 |
| GSK3342830 500 mg | Part 1-Amount Excreted in Urine (Ae) of GSK3342830 in Urine | 558.7 Milligram | Standard Deviation 260.49 |
| GSK3342830 1000 mg | Part 1-Amount Excreted in Urine (Ae) of GSK3342830 in Urine | 968.9 Milligram | Standard Deviation 216.28 |
| GSK3342830 2000 mg | Part 1-Amount Excreted in Urine (Ae) of GSK3342830 in Urine | 1816 Milligram | Standard Deviation 189.65 |
| GSK3342830 4000 mg | Part 1-Amount Excreted in Urine (Ae) of GSK3342830 in Urine | 3919 Milligram | Standard Deviation 117.58 |
| GSK3342830 6000 mg | Part 1-Amount Excreted in Urine (Ae) of GSK3342830 in Urine | 5999 Milligram | Standard Deviation 413.23 |
Secondary
Part 1-Area Under the Plasma Concentration (AUC) From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration Across All Treatments AUC(0-t) for GSK3342830
AUC (0-t) is defined as AUC from time zero to the last quantifiable concentration after dosing. Blood samples were collected on Day 1 at indicated timepoints (pre-dose, 0.5 hr, 1hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr,3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr 24 hr, 36 hr and 48 hr post-dose. The Part 1 phase of the study comprised of single dosing of participants. Log untransformed values for AUC (0-t) have been presented.
Time frame: Day 1 (pre-dose, 0.5 hr, 1 hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr, 3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr, 48 hr post-dose
Population: The Pharmacokinetic (PK) Parameter Population included all participants in the PK population for whom valid and evaluable PK parameters were derived. PK Population is defined as all participants who received at least 1 dose of GSK3342830 and have evaluable PK data for GSK3342830.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GSK3342830 250 mg | Part 1-Area Under the Plasma Concentration (AUC) From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration Across All Treatments AUC(0-t) for GSK3342830 | 40.24 hour *microgram per milliliter | Standard Deviation 5.9451 |
| GSK3342830 500 mg | Part 1-Area Under the Plasma Concentration (AUC) From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration Across All Treatments AUC(0-t) for GSK3342830 | 93.92 hour *microgram per milliliter | Standard Deviation 11.849 |
| GSK3342830 1000 mg | Part 1-Area Under the Plasma Concentration (AUC) From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration Across All Treatments AUC(0-t) for GSK3342830 | 171.3 hour *microgram per milliliter | Standard Deviation 28.299 |
| GSK3342830 2000 mg | Part 1-Area Under the Plasma Concentration (AUC) From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration Across All Treatments AUC(0-t) for GSK3342830 | 344.0 hour *microgram per milliliter | Standard Deviation 30.312 |
| GSK3342830 4000 mg | Part 1-Area Under the Plasma Concentration (AUC) From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration Across All Treatments AUC(0-t) for GSK3342830 | 672.9 hour *microgram per milliliter | Standard Deviation 99.383 |
| GSK3342830 6000 mg | Part 1-Area Under the Plasma Concentration (AUC) From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration Across All Treatments AUC(0-t) for GSK3342830 | 1039 hour *microgram per milliliter | Standard Deviation 134.97 |
Secondary
Part 1-AUC Pre Dose to Infinite (Inf) Time (AUC [0-inf]) of GSK3342830
AUC (0-inf) is defined as AUC extrapolated from time zero to infinity. Blood samples were collected on Day 1 at indicated timepoints pre-dose, 0.5 hr, 1hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr,3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr 24 hr, 36 hr and 48 hr post-dose. This part 1 phase of the study comprised of single dosing of the participants. Log untransformed values for AUC (0-inf) have been presented.
Time frame: Day 1 (pre-dose, 0.5 hr, 1 hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr, 3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr, 48hr post-dose
Population: PK Parameter Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GSK3342830 250 mg | Part 1-AUC Pre Dose to Infinite (Inf) Time (AUC [0-inf]) of GSK3342830 | 42.08 hour *microgram per milliliter | Standard Deviation 14.6 |
| GSK3342830 500 mg | Part 1-AUC Pre Dose to Infinite (Inf) Time (AUC [0-inf]) of GSK3342830 | 95.76 hour *microgram per milliliter | Standard Deviation 12.5 |
| GSK3342830 1000 mg | Part 1-AUC Pre Dose to Infinite (Inf) Time (AUC [0-inf]) of GSK3342830 | 172.5 hour *microgram per milliliter | Standard Deviation 15.9 |
| GSK3342830 2000 mg | Part 1-AUC Pre Dose to Infinite (Inf) Time (AUC [0-inf]) of GSK3342830 | 346.0 hour *microgram per milliliter | Standard Deviation 9.2 |
| GSK3342830 4000 mg | Part 1-AUC Pre Dose to Infinite (Inf) Time (AUC [0-inf]) of GSK3342830 | 671.6 hour *microgram per milliliter | Standard Deviation 14.5 |
| GSK3342830 6000 mg | Part 1-AUC Pre Dose to Infinite (Inf) Time (AUC [0-inf]) of GSK3342830 | 1038 hour *microgram per milliliter | Standard Deviation 12.6 |
Secondary
Part 1:Dose Proportionality: AUC (0-inf)
Blood samples were collected at Day 1 (pre-dose, 0.5 hr, 1 hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr, 3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr, 48 hr post-dose. The data for estimate slope for log dose, has been reported.
Time frame: Day 1 (pre-dose, 0.5 hr, 1 hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr, 3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr, 48hr post-dose
Population: PK Parameter Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GSK3342830 250 mg | Part 1:Dose Proportionality: AUC (0-inf) | 0.988 hour*microgram per milliliter | Standard Error 0.0198 |
Secondary
Part 1:Dose Proportionality: AUC (0-t)
Blood samples were collected at Day 1 (pre-dose, 0.5 hr, 1 hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr, 3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr, 48hr post-dose. Dose proportionality was assessed for AUC(0-inf) and Cmax after single dose administration. AUC(0-inf) was selected as the AUC exposure measure as it is the default AUC parameter for single dose administration and the observed data permitted its calculation.
Time frame: Day 1 (pre-dose, 0.5 hr, 1 hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr, 3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr, 48hr post-dose
Population: PK Parameter Population
Secondary
Part 1:Dose Proportionality: Cmax
Blood samples were collected at Day 1 (pre-dose, 0.5 hr, 1 hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr, 3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr, 48hr post-dose. The data for estimate slope for log dose, has been reported.
Time frame: Day 1 (pre-dose, 0.5 hr, 1 hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr, 3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr, 48hr post-dose
Population: PK Parameter Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GSK3342830 250 mg | Part 1:Dose Proportionality: Cmax | 0.968 microgram per milliliter | Standard Error 0.0384 |
Secondary
Part 1-Maximum Plasma Concentration (Cmax) of GSK3342830
Cmax was defined as the maximum concentration of drug GSK3342830, in plasma. Blood samples were collected on Day 1 at indicated timepoints pre-dose, 0.5 hr, 1hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr,3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr 24 hr, 36 hr and 48 hr post-dose. This part 1 phase of the study comprised of single dosing of the participants. Log untransformed values for Cmax have been presented.
Time frame: Day 1 (pre-dose, 0.5 hr, 1 hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr, 3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr, 48 hr post-dose
Population: PK Parameter Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GSK3342830 250 mg | Part 1-Maximum Plasma Concentration (Cmax) of GSK3342830 | 16.37 Microgram per milliliter | Standard Deviation 2.9161 |
| GSK3342830 500 mg | Part 1-Maximum Plasma Concentration (Cmax) of GSK3342830 | 35.09 Microgram per milliliter | Standard Deviation 5.8409 |
| GSK3342830 1000 mg | Part 1-Maximum Plasma Concentration (Cmax) of GSK3342830 | 71.11 Microgram per milliliter | Standard Deviation 11.109 |
| GSK3342830 2000 mg | Part 1-Maximum Plasma Concentration (Cmax) of GSK3342830 | 117.4 Microgram per milliliter | Standard Deviation 41.338 |
| GSK3342830 4000 mg | Part 1-Maximum Plasma Concentration (Cmax) of GSK3342830 | 242.4 Microgram per milliliter | Standard Deviation 31.907 |
| GSK3342830 6000 mg | Part 1-Maximum Plasma Concentration (Cmax) of GSK3342830 | 389.8 Microgram per milliliter | Standard Deviation 31.01 |
Secondary
Part 1-Renal Clearance (CLr) of GSK3342830 in Urine
The renal clearance (CLr) is a PK measure of volume of drug is removed per unit time. Urine samples were collected at indicated timepoints pre-dose and post dose. This part 1 phase of the study comprised of single dosing of the participants. Log untransformed values for CLr have been presented.
Time frame: Day 1 (pre-dose, 0.5 hr, 1 hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr, 3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr, 48hr post-dose
Population: PK Parameter Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GSK3342830 250 mg | Part 1-Renal Clearance (CLr) of GSK3342830 in Urine | 5.709 Liter per hour | Standard Deviation 0.97041 |
| GSK3342830 500 mg | Part 1-Renal Clearance (CLr) of GSK3342830 in Urine | 5.696 Liter per hour | Standard Deviation 1.9452 |
| GSK3342830 1000 mg | Part 1-Renal Clearance (CLr) of GSK3342830 in Urine | 5.771 Liter per hour | Standard Deviation 2.0146 |
| GSK3342830 2000 mg | Part 1-Renal Clearance (CLr) of GSK3342830 in Urine | 5.229 Liter per hour | Standard Deviation 0.32521 |
| GSK3342830 4000 mg | Part 1-Renal Clearance (CLr) of GSK3342830 in Urine | 5.867 Liter per hour | Standard Deviation 0.70267 |
| GSK3342830 6000 mg | Part 1-Renal Clearance (CLr) of GSK3342830 in Urine | 5.837 Liter per hour | Standard Deviation 0.98448 |
Secondary
Part 1-Steady-state Volume (Vss) of Distribution of GSK3342830 in Plasma
Vss reflects the actual blood and tissue volume into which a drug is distributed and the relative binding of drug to protein in these spaces. Blood samples were collected on Day 1 at indicated timepoints pre-dose, 0.5 hr, 1hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr,3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr 24 hr, 36 hr and 48 hr post-dose. This part 1 phase of the study comprised of single dosing of the participants. Log untransformed values for Vss have been presented.
Time frame: Day 1 (pre-dose, 0.5 hr, 1 hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr, 3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr, 48 hr post-dose
Population: PK Parameter Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GSK3342830 250 mg | Part 1-Steady-state Volume (Vss) of Distribution of GSK3342830 in Plasma | 14.65 Liter | Standard Deviation 2.6449 |
| GSK3342830 500 mg | Part 1-Steady-state Volume (Vss) of Distribution of GSK3342830 in Plasma | 13.98 Liter | Standard Deviation 2.2987 |
| GSK3342830 1000 mg | Part 1-Steady-state Volume (Vss) of Distribution of GSK3342830 in Plasma | 15.54 Liter | Standard Deviation 2.4329 |
| GSK3342830 2000 mg | Part 1-Steady-state Volume (Vss) of Distribution of GSK3342830 in Plasma | 19.87 Liter | Standard Deviation 11.115 |
| GSK3342830 4000 mg | Part 1-Steady-state Volume (Vss) of Distribution of GSK3342830 in Plasma | 16.63 Liter | Standard Deviation 1.2716 |
| GSK3342830 6000 mg | Part 1-Steady-state Volume (Vss) of Distribution of GSK3342830 in Plasma | 15.61 Liter | Standard Deviation 1.3961 |
Secondary
Part 1-Terminal Elimination Half-life (t1/2) of GSK3342830 in Plasma
t ½ is defined as the time required by the drug to reduce to half its quantity. Blood samples were collected on Day 1 at indicated timepoints pre-dose, 0.5 hr, 1hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr,3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr 24 hr, 36 hr and 48 hr post-dose. This part 1 phase of the study comprised of single dosing of the participants. Log untransformed values for t1/2 have been presented.
Time frame: Day 1 (pre-dose, 0.5 hr, 1 hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr, 3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr, 48 hr post-dose
Population: PK Parameter Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GSK3342830 250 mg | Part 1-Terminal Elimination Half-life (t1/2) of GSK3342830 in Plasma | 1.860 hour | Standard Deviation 0.1915 |
| GSK3342830 500 mg | Part 1-Terminal Elimination Half-life (t1/2) of GSK3342830 in Plasma | 2.139 hour | Standard Deviation 0.30026 |
| GSK3342830 1000 mg | Part 1-Terminal Elimination Half-life (t1/2) of GSK3342830 in Plasma | 2.295 hour | Standard Deviation 0.22578 |
| GSK3342830 2000 mg | Part 1-Terminal Elimination Half-life (t1/2) of GSK3342830 in Plasma | 2.596 hour | Standard Deviation 0.34939 |
| GSK3342830 4000 mg | Part 1-Terminal Elimination Half-life (t1/2) of GSK3342830 in Plasma | 2.465 hour | Standard Deviation 0.33519 |
| GSK3342830 6000 mg | Part 1-Terminal Elimination Half-life (t1/2) of GSK3342830 in Plasma | 2.461 hour | Standard Deviation 0.33327 |
Secondary
Part 1-Time to Maximum Plasma Concentration (Tmax) of GSK3342830
Tmax was defined as time required to achieve Cmax for drug GSK3342830, in plasma. Blood samples were collected on Day 1 at indicated timepoints pre-dose, 0.5 hr, 1hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr,3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr 24 hr, 36 hr and 48 hr post-dose. This part 1 phase of the study comprised of single dosing of the participants. Log untransformed values for tmax have been presented.
Time frame: Day 1 (pre-dose, 0.5 hr, 1 hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr, 3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr, 48hr post-dose
Population: PK Parameter Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GSK3342830 250 mg | Part 1-Time to Maximum Plasma Concentration (Tmax) of GSK3342830 | 1.042 hour | Standard Deviation 0.1021 |
| GSK3342830 500 mg | Part 1-Time to Maximum Plasma Concentration (Tmax) of GSK3342830 | 1.000 hour | Standard Deviation 0 |
| GSK3342830 1000 mg | Part 1-Time to Maximum Plasma Concentration (Tmax) of GSK3342830 | 1.000 hour | Standard Deviation 0 |
| GSK3342830 2000 mg | Part 1-Time to Maximum Plasma Concentration (Tmax) of GSK3342830 | 1.167 hour | Standard Deviation 0.4082 |
| GSK3342830 4000 mg | Part 1-Time to Maximum Plasma Concentration (Tmax) of GSK3342830 | 1.000 hour | Standard Deviation 0 |
| GSK3342830 6000 mg | Part 1-Time to Maximum Plasma Concentration (Tmax) of GSK3342830 | 1.000 hour | Standard Deviation 0 |
Secondary
Part 1-Total Systemic Clearance (CL) of GSK3342830 in Plasma
The systemic CL is a PK measure of volume of plasma from which the drug is removed per unit time. Blood samples were collected on Day 1 at indicated timepoints pre-dose, 0.5 hr, 1hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr,3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr 24 hr, 36 hr and 48 hr post-dose. This part 1 phase of the study comprised of single dosing of the participants. Log untransformed values for CL have been presented.
Time frame: Day 1 (pre-dose, 0.5 hr, 1 hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr, 3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr, 48 hr post-dose
Population: PK Parameter Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GSK3342830 250 mg | Part 1-Total Systemic Clearance (CL) of GSK3342830 in Plasma | 5.994 Liter per hour | Standard Deviation 0.88869 |
| GSK3342830 500 mg | Part 1-Total Systemic Clearance (CL) of GSK3342830 in Plasma | 5.255 Liter per hour | Standard Deviation 0.63134 |
| GSK3342830 1000 mg | Part 1-Total Systemic Clearance (CL) of GSK3342830 in Plasma | 5.857 Liter per hour | Standard Deviation 0.90413 |
| GSK3342830 2000 mg | Part 1-Total Systemic Clearance (CL) of GSK3342830 in Plasma | 5.801 Liter per hour | Standard Deviation 0.55138 |
| GSK3342830 4000 mg | Part 1-Total Systemic Clearance (CL) of GSK3342830 in Plasma | 6.007 Liter per hour | Standard Deviation 0.857 |
| GSK3342830 6000 mg | Part 1-Total Systemic Clearance (CL) of GSK3342830 in Plasma | 5.819 Liter per hour | Standard Deviation 0.70924 |
Secondary
Part 1-Urinary Excretion Ratio Relative to Dose (Feu [t1-t2]) of GSK3342830
Urine samples were collected at indicated timepoints pre-dose and post dose. The Feu has been reported from 0 to 4, 4 to 8, 8 to 12, 12 to 24 and 24 to 48 hrs. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates that data is not available. The standard deviation could not be calculated as only single participant was present. Log untransformed values for Feu (t1-t2) have been presented.
Time frame: Day 1 (pre-dose, 0.5 hr, 1 hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr, 3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr, 48 hr post-dose
Population: PK parameter population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK3342830 250 mg | Part 1-Urinary Excretion Ratio Relative to Dose (Feu [t1-t2]) of GSK3342830 | Feu (12-24) (n=6,6,6,6,6,6) | 2.173 Percentage of excretion ratio | Standard Deviation 1.0482 |
| GSK3342830 250 mg | Part 1-Urinary Excretion Ratio Relative to Dose (Feu [t1-t2]) of GSK3342830 | Feu (4-8) (n=6,6,6,6,6,6) | 21.38 Percentage of excretion ratio | Standard Deviation 6.2577 |
| GSK3342830 250 mg | Part 1-Urinary Excretion Ratio Relative to Dose (Feu [t1-t2]) of GSK3342830 | Feu (0-4) (n=6,6,6,6,6,6) | 68.66 Percentage of excretion ratio | Standard Deviation 10.456 |
| GSK3342830 250 mg | Part 1-Urinary Excretion Ratio Relative to Dose (Feu [t1-t2]) of GSK3342830 | Feu (24-48) (n=1,1,6,6,6,6) | 0.2132 Percentage of excretion ratio | — |
| GSK3342830 250 mg | Part 1-Urinary Excretion Ratio Relative to Dose (Feu [t1-t2]) of GSK3342830 | Feu (8-12) (n=6,6,6,6,6,6) | 3.612 Percentage of excretion ratio | Standard Deviation 0.48583 |
| GSK3342830 500 mg | Part 1-Urinary Excretion Ratio Relative to Dose (Feu [t1-t2]) of GSK3342830 | Feu (4-8) (n=6,6,6,6,6,6) | 21.52 Percentage of excretion ratio | Standard Deviation 2.7078 |
| GSK3342830 500 mg | Part 1-Urinary Excretion Ratio Relative to Dose (Feu [t1-t2]) of GSK3342830 | Feu (12-24) (n=6,6,6,6,6,6) | 2.557 Percentage of excretion ratio | Standard Deviation 0.68228 |
| GSK3342830 500 mg | Part 1-Urinary Excretion Ratio Relative to Dose (Feu [t1-t2]) of GSK3342830 | Feu (0-4) (n=6,6,6,6,6,6) | 83.01 Percentage of excretion ratio | Standard Deviation 49.11 |
| GSK3342830 500 mg | Part 1-Urinary Excretion Ratio Relative to Dose (Feu [t1-t2]) of GSK3342830 | Feu (24-48) (n=1,1,6,6,6,6) | 0.2371 Percentage of excretion ratio | — |
| GSK3342830 500 mg | Part 1-Urinary Excretion Ratio Relative to Dose (Feu [t1-t2]) of GSK3342830 | Feu (8-12) (n=6,6,6,6,6,6) | 4.627 Percentage of excretion ratio | Standard Deviation 1.0872 |
| GSK3342830 1000 mg | Part 1-Urinary Excretion Ratio Relative to Dose (Feu [t1-t2]) of GSK3342830 | Feu (4-8) (n=6,6,6,6,6,6) | 18.00 Percentage of excretion ratio | Standard Deviation 4.3264 |
| GSK3342830 1000 mg | Part 1-Urinary Excretion Ratio Relative to Dose (Feu [t1-t2]) of GSK3342830 | Feu (12-24) (n=6,6,6,6,6,6) | 2.039 Percentage of excretion ratio | Standard Deviation 0.8284 |
| GSK3342830 1000 mg | Part 1-Urinary Excretion Ratio Relative to Dose (Feu [t1-t2]) of GSK3342830 | Feu (24-48) (n=1,1,6,6,6,6) | 0.2036 Percentage of excretion ratio | Standard Deviation 0.038871 |
| GSK3342830 1000 mg | Part 1-Urinary Excretion Ratio Relative to Dose (Feu [t1-t2]) of GSK3342830 | Feu (8-12) (n=6,6,6,6,6,6) | 4.794 Percentage of excretion ratio | Standard Deviation 0.68561 |
| GSK3342830 1000 mg | Part 1-Urinary Excretion Ratio Relative to Dose (Feu [t1-t2]) of GSK3342830 | Feu (0-4) (n=6,6,6,6,6,6) | 71.85 Percentage of excretion ratio | Standard Deviation 23.591 |
| GSK3342830 2000 mg | Part 1-Urinary Excretion Ratio Relative to Dose (Feu [t1-t2]) of GSK3342830 | Feu (8-12) (n=6,6,6,6,6,6) | 6.861 Percentage of excretion ratio | Standard Deviation 3.7957 |
| GSK3342830 2000 mg | Part 1-Urinary Excretion Ratio Relative to Dose (Feu [t1-t2]) of GSK3342830 | Feu (0-4) (n=6,6,6,6,6,6) | 59.29 Percentage of excretion ratio | Standard Deviation 21.74 |
| GSK3342830 2000 mg | Part 1-Urinary Excretion Ratio Relative to Dose (Feu [t1-t2]) of GSK3342830 | Feu (4-8) (n=6,6,6,6,6,6) | 20.44 Percentage of excretion ratio | Standard Deviation 1.3961 |
| GSK3342830 2000 mg | Part 1-Urinary Excretion Ratio Relative to Dose (Feu [t1-t2]) of GSK3342830 | Feu (12-24) (n=6,6,6,6,6,6) | 3.967 Percentage of excretion ratio | Standard Deviation 4.3285 |
| GSK3342830 2000 mg | Part 1-Urinary Excretion Ratio Relative to Dose (Feu [t1-t2]) of GSK3342830 | Feu (24-48) (n=1,1,6,6,6,6) | 0.2245 Percentage of excretion ratio | Standard Deviation 0.067861 |
| GSK3342830 4000 mg | Part 1-Urinary Excretion Ratio Relative to Dose (Feu [t1-t2]) of GSK3342830 | Feu (12-24) (n=6,6,6,6,6,6) | 1.972 Percentage of excretion ratio | Standard Deviation 1.0979 |
| GSK3342830 4000 mg | Part 1-Urinary Excretion Ratio Relative to Dose (Feu [t1-t2]) of GSK3342830 | Feu (0-4) (n=6,6,6,6,6,6) | 68.39 Percentage of excretion ratio | Standard Deviation 5.8313 |
| GSK3342830 4000 mg | Part 1-Urinary Excretion Ratio Relative to Dose (Feu [t1-t2]) of GSK3342830 | Feu (24-48) (n=1,1,6,6,6,6) | 0.1720 Percentage of excretion ratio | Standard Deviation 0.069232 |
| GSK3342830 4000 mg | Part 1-Urinary Excretion Ratio Relative to Dose (Feu [t1-t2]) of GSK3342830 | Feu (4-8) (n=6,6,6,6,6,6) | 22.33 Percentage of excretion ratio | Standard Deviation 7.1655 |
| GSK3342830 4000 mg | Part 1-Urinary Excretion Ratio Relative to Dose (Feu [t1-t2]) of GSK3342830 | Feu (8-12) (n=6,6,6,6,6,6) | 5.102 Percentage of excretion ratio | Standard Deviation 1.5791 |
| GSK3342830 6000 mg | Part 1-Urinary Excretion Ratio Relative to Dose (Feu [t1-t2]) of GSK3342830 | Feu (0-4) (n=6,6,6,6,6,6) | 73.42 Percentage of excretion ratio | Standard Deviation 8.3037 |
| GSK3342830 6000 mg | Part 1-Urinary Excretion Ratio Relative to Dose (Feu [t1-t2]) of GSK3342830 | Feu (12-24) (n=6,6,6,6,6,6) | 1.941 Percentage of excretion ratio | Standard Deviation 0.91904 |
| GSK3342830 6000 mg | Part 1-Urinary Excretion Ratio Relative to Dose (Feu [t1-t2]) of GSK3342830 | Feu (4-8) (n=6,6,6,6,6,6) | 19.11 Percentage of excretion ratio | Standard Deviation 2.595 |
| GSK3342830 6000 mg | Part 1-Urinary Excretion Ratio Relative to Dose (Feu [t1-t2]) of GSK3342830 | Feu (24-48) (n=1,1,6,6,6,6) | 0.1809 Percentage of excretion ratio | Standard Deviation 0.057906 |
| GSK3342830 6000 mg | Part 1-Urinary Excretion Ratio Relative to Dose (Feu [t1-t2]) of GSK3342830 | Feu (8-12) (n=6,6,6,6,6,6) | 5.336 Percentage of excretion ratio | Standard Deviation 1.9488 |
Secondary
Part 2- Ae of GSK3342830 in Urine
Ae defines as the amount of drug GSK3342830, excreted in urine. These were collected in opaque bottles on Day 1 and Day 15 at (Pre-dose, 0 to 8 and 8 to 24 hrs post-dose). The untransformed values for Ae have been presented.
Time frame: Day 1 and Day 15 at (Pre-dose, 0 to 8 and 8 to 24 hrs post-dose)
Population: PK Parameter Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK3342830 250 mg | Part 2- Ae of GSK3342830 in Urine | Day 1 (n=11) | 952.4 milligram | Standard Deviation 61.274 |
| GSK3342830 250 mg | Part 2- Ae of GSK3342830 in Urine | Day 15 (n=6) | 964.9 milligram | Standard Deviation 223.3 |
Secondary
Part 2-AUC (0-inf) of GSK3342830
AUC (0-inf), was defined as AUC extrapolated from time zero to infinity Day 1 at pre-dose (15 minutes) and 0.5 hr, 1 hr (end of infusion), 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 hrs after start of infusion. Single pre-dose samples on mornings of Days 3, 6, 9, 12, and 13. Serial samples (Day 15) time points: pre-dose (15 minutes) and 0.5 hr, 1 (end of infusion), 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 hrs after start of infusion. The untransformed values for AUC(0-inf) have been presented.
Time frame: Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 hr post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 hr post-dose at Day 15
Population: PK Parameter Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GSK3342830 250 mg | Part 2-AUC (0-inf) of GSK3342830 | 156.5 hour *microgram per milliliter | Standard Deviation 24.756 |
Secondary
Part 2: AUC From Time Zero to Last Measurable Concentration AUC (0- Tau)
It was defined as Area Under the Concentration-time Curve From Time Zero (Pre-dose) to the time of the last measureable concentration. Blood samples were collected on Day 1 at indicated timepoints pre-dose, 0.5 hr, 1hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr,3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr 24 hr, 36 hr and 48 hr post-dose. Log untransformed values for AUC (0 to tau) have been presented.
Time frame: Day 1 (pre-dose, 0.5 hr, 1 hr, 1.25 hr, 1.5 hr, 2 hr, 3 hr, 3.5 hr, 4 hr, 4.5 hr, 5 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr, 48hr post-dose
Population: PK Parameter Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK3342830 250 mg | Part 2: AUC From Time Zero to Last Measurable Concentration AUC (0- Tau) | Day 1 (n=11) | 145.6 hour*microgram per milliliter | Standard Deviation 23.344 |
| GSK3342830 250 mg | Part 2: AUC From Time Zero to Last Measurable Concentration AUC (0- Tau) | Day 15 (n=6) | 156.1 hour*microgram per milliliter | Standard Deviation 14.612 |
Secondary
Part 2-CLr of GSK3342830 in Urine
The renal CLr is a PK measure of volume of plasma from which the drug is removed per unit time.These were collected in opaque bottles on Day 1 and Day 15 at (Pre-dose, 0 to 8 and 8 to 24 hrs post-dose). The untransformed values for CLr have been presented.
Time frame: Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 h post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 h post-dose at Day 15
Population: PK Parameter Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK3342830 250 mg | Part 2-CLr of GSK3342830 in Urine | Day 1 (n=11) | 6.261 Liter per hour | Standard Deviation 1.3406 |
| GSK3342830 250 mg | Part 2-CLr of GSK3342830 in Urine | Day 15 (n=6) | 6.174 Liter per hour | Standard Deviation 1.3504 |
Secondary
Part 2-Cmax of GSK3342830
Cmax was defined as the maximum concentration of drug GSK3342830, in plasma. It was collected at Day 1 at pre-dose (15 minutes) and 0.5 hr, 1 hr (end of infusion), 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 hrs after start of infusion. Single pre-dose samples on mornings of Days 3, 6, 9, 12, and 13. Serial samples (Day 15) time points: pre-dose (15 minutes) and 0.5 hr, 1 (end of infusion), 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 hrs after start of infusion.
Time frame: Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 hr, post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 hr post-dose at Day 15
Population: PK Parameter Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GSK3342830 250 mg | Part 2-Cmax of GSK3342830 | 60.25 microgram per milliliter | Standard Deviation 10.875 |
Secondary
Part 2: Dose Proportionality: AUC (0-tau)
Blood samples were collected at Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 hr post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 hr post-dose at Day 15. Data cannot be summarized because only 1 dose level studied so dose proportionality analysis cannot be performed as no comparison can be conducted.
Time frame: Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 hr, post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 hr post-dose at Day 15
Population: PK Parameter Population
Secondary
Part 2: Observed Accumulation Ratio (Ro) Based on AUC and Cmax of GSK3342830 After Administration of Repeat IV Doses, as Data Permit
The accumulation ratio has been reported. Sampling was done at Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 h post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 h post-dose at Day 15. Data cannot be summarized because only 1 dose level studied so dose proportionality analysis cannot be performed as no comparison can be conducted.
Time frame: Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 h post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 h post-dose at Day 15
Population: PK Parameter Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GSK3342830 250 mg | Part 2: Observed Accumulation Ratio (Ro) Based on AUC and Cmax of GSK3342830 After Administration of Repeat IV Doses, as Data Permit | 1.117 Ratio | Standard Deviation 0.16167 |
Secondary
Part 2: Steady-state Ratio (Rss) of GSK3342830 to Assess Time Invariance, as Data Permit
Sampling was done at Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 h post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 h post-dose at Day 15. Since the study was terminated early, data is only available for one dose level for Part 2. Some subjects have only partial data and were not dosed on Day 15.
Time frame: Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 h post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 h post-dose at Day 15
Population: PK Parameter Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GSK3342830 250 mg | Part 2: Steady-state Ratio (Rss) of GSK3342830 to Assess Time Invariance, as Data Permit | 1.033 Ratio | Standard Deviation 0.14336 |
Secondary
Part 2-Terminal t1/2 of GSK3342830 in Plasma
t ½ is defined as the time required by the drug to reduce to half its quantity. Blood samples were collected at Day 1 at pre-dose (15 minutes) and 0.5 hr, 1 hr (end of infusion), 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 hrs after start of infusion. Single pre-dose samples on mornings of Days 3, 6, 9, 12, and 13. Serial samples (Day 15) time points: pre-dose (15 minutes) and 0.5 hr, 1 (end of infusion), 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 hrs after start of infusion.
Time frame: Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 h post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 h post-dose at Day 15
Population: PK Parameter Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GSK3342830 250 mg | Part 2-Terminal t1/2 of GSK3342830 in Plasma | 2.171 hour | Standard Deviation 0.21459 |
Secondary
Part 2-Tmax of GSK3342830
Tmax was defined as time required to achieve Cmax for drug GSK3342830, in plasma. It was collected at Day 1 at pre-dose (15 minutes) and 0.5 hr, 1 hr (end of infusion), 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 hrs after start of infusion. Single pre-dose samples on mornings of Days 3, 6, 9, 12, and 13. Serial samples (Day 15) time points: pre-dose (15 minutes) and 0.5 hr, 1 (end of infusion), 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 hrs after start of infusion.
Time frame: Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 h post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 h post-dose at Day 15
Population: PK Parameter Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GSK3342830 250 mg | Part 2-Tmax of GSK3342830 | 1.023 hour | Standard Deviation 0.0754 |
Secondary
Part 2-Total CL of GSK3342830 in Plasma
The systemic CL is a PK measure of volume of plasma from which the drug is removed per unit time. The blood samples of 3 mL were collected at Day 1 at pre-dose (15 minutes) and 0.5 hr, 1 hr (end of infusion), 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 hrs after start of infusion. Single pre-dose samples on mornings of Days 3, 6, 9, 12, and 13. Serial samples (Day 15) time points: pre-dose (15 minutes) and 0.5 hr, 1 (end of infusion), 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 hrs after start of infusion.
Time frame: Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 hr post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 hr post-dose at Day 15
Population: PK Parameter Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GSK3342830 250 mg | Part 2-Total CL of GSK3342830 in Plasma | 6.552 Liter per hour | Standard Deviation 1.1567 |
Secondary
Part 2- Trough Concentration (Ctau)
Blood samples were collected on Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 h post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 h post-dose at Day 15. The untransformed values for Ctau have been presented.
Time frame: Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 h post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 h post-dose at Day 15
Population: PK Parameter Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK3342830 250 mg | Part 2- Trough Concentration (Ctau) | Day 1 (n=11) | 3.366 microgram per milliliter | Standard Deviation 0.82694 |
| GSK3342830 250 mg | Part 2- Trough Concentration (Ctau) | Day 15 (n=6) | 3.059 microgram per milliliter | Standard Deviation 0.55052 |
Secondary
Part 2: Trough Plasma Concentrations at the End of the Dosing Interval (Ctau) to Assess the Achievement of Steady-state of GSK3342830 After Administration of Repeat IV Doses, as Data Permit
Sampling was done at Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 h post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 h post-dose at Day 15. The untransformed values for Ctau have been presented.
Time frame: Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 h post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 h post-dose at Day 15
Population: PK Parameter Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK3342830 250 mg | Part 2: Trough Plasma Concentrations at the End of the Dosing Interval (Ctau) to Assess the Achievement of Steady-state of GSK3342830 After Administration of Repeat IV Doses, as Data Permit | Day 1 (n=11) | 3.366 microgram per milliliter | Standard Deviation 0.82694 |
| GSK3342830 250 mg | Part 2: Trough Plasma Concentrations at the End of the Dosing Interval (Ctau) to Assess the Achievement of Steady-state of GSK3342830 After Administration of Repeat IV Doses, as Data Permit | Day 15 (n=6) | 3.059 microgram per milliliter | Standard Deviation 0.55052 |
Secondary
Part 2-Urinary Excretion Ratio Relative to Dose Feu (t1-t2) of GSK3342830
The Feu has been reported from 0 to 4, 4 to 8, 8 to 12, 12 to 24 and 24 to 48 hrs. These were collected in opaque bottles at pre-dose (within a 24-hr period before dosing, may begin on Day -1) and 0 to 4, 4 to 8, 8 to 12, 12 to 24, and 24 to 48 hrs post-dose.
Time frame: Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 hr post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 hr post-dose at Day 15
Population: PK Parameter Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK3342830 250 mg | Part 2-Urinary Excretion Ratio Relative to Dose Feu (t1-t2) of GSK3342830 | Day 1 Feu (0-8), n=11 | 90.39 Percentage of excretion ratio | Standard Deviation 5.9551 |
| GSK3342830 250 mg | Part 2-Urinary Excretion Ratio Relative to Dose Feu (t1-t2) of GSK3342830 | Day 1 Feu (8-24), n= 11 | 4.855 Percentage of excretion ratio | Standard Deviation 1.399 |
| GSK3342830 250 mg | Part 2-Urinary Excretion Ratio Relative to Dose Feu (t1-t2) of GSK3342830 | Day 15, Feu (0-8), n=6 | 89.80 Percentage of excretion ratio | Standard Deviation 19.319 |
| GSK3342830 250 mg | Part 2-Urinary Excretion Ratio Relative to Dose Feu (t1-t2) of GSK3342830 | Day 15, Feu (8-24), n=6 | 4.530 Percentage of excretion ratio | Standard Deviation 2.9358 |
Secondary
Part 2- Vss of Distribution of GSK3342830 in Plasma
Vss reflects the actual blood and tissue volume into which a drug is distributed and the relative binding of drug to protein in these spaces. The blood samples of 3 mL were collected at Day 1 at pre-dose (15 minutes) and 0.5 hr, 1 hr (end of infusion), 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 hrs after start of infusion. Single pre-dose samples on mornings of Days 3, 6, 9, 12, and 13. Serial samples (Day 15) time points: pre-dose (15 minutes) and 0.5 hr, 1 (end of infusion), 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 hrs after start of infusion.
Time frame: Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 h post-dose at Day 1. Pre-dose on Day 3, 6, 9, 12, and 13. Pre-dose, and 0.5, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, and 8 h post-dose at Day 15
Population: PK Parameter Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GSK3342830 250 mg | Part 2- Vss of Distribution of GSK3342830 in Plasma | 17.04 Liter | Standard Deviation 3.2541 |