Tuberculosis
Conditions
Keywords
ascending dose, Pharmacokinetics, GSK3036656, FTIH, Safety
Brief summary
GSK3036656 is being developed by GSK for the treatment of tuberculosis (TB). This is the FTIH study for GSK3036656 to evaluate the safety, tolerability and PK of single ascending and repeat oral doses of GSK3036656 in healthy adult subjects. The results of this study are intended to be used to identify appropriate and well-tolerated doses of GSK3036656 to be used in further studies. A food effect assessment will also be undertaken to investigate the influence of food on the PK of GSK3036656. The study will be conducted in two parts: Part A (single dose) and Part B (repeat dose). Up to two cohorts will be included in Part A. 9 healthy adult subjects will be included in each cohort. Each cohort will participate in up to 4 treatment (dosing) periods including a food effect treatment period. During each treatment period, GSK3036656 will be administered to 6 subjects and placebo will be administered to 3 subjects. The starting dose in Part A will be 5 milligrams (mg), and the maximum dose will be 1500 mg. The two cohorts in Part A will be dosed sequentially (i.e., dosing in Cohort 2 starts after dosing in Cohort 1 is completed). Initially, there will be a 14 day wash out period for individual subjects between each dose level. Study progression to Part B from Part A will be based on an acceptable safety, tolerability and PK profile in Part A. Part B will comprise up to 4 cohorts (Cohorts 3, 4, 5, and 6) each containing 10 (8 active: 2 placebo) healthy adult subjects to examine the safety, tolerability and PK of a repeated daily dose of GSK3036656 over a period of up to 14 days. Appropriate doses and dose regimens for Part B will be selected based on available safety, tolerability and PK data from Part A and/or any preceding repeat dose cohorts from Part B. Dividing the total daily dose into 2 or 3 smaller doses may be done in both Part A and Part B. Up to 18 subjects will be enrolled into Part A and up to 40 subjects will be enrolled into Part B. The total duration of the study for each subject recruited into Part A and Part B will be approximately 12 weeks and 8 weeks, respectively.
Interventions
DRUGGSK3036656
GSK3036656 is available as capsules (for oral administration) containing 5 mg, 25 mg or 100 mg of GSK3036656 as free base equivalent.
DRUGPlacebo
Placebo is a matching capsule containing Avicel PH (Suitable for Pharmaceutical Use) 102, for oral administration.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
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 the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. * A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or
Exclusion criteria
, outside the reference range for the population being studied, may be included only if the investigator in consultation with the medical monitor, if required, agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. * Body weight \>=60 kilograms (kg) and body mass index (BMI) within the range 19 to 29.9 kg/meter\^2 inclusive. * Male * Female subjects of non-child bearing potential are eligible to participate. Non-child bearing potential is defined as: * Pre-menopausal females with one of the following: documented tubal ligation; documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion or documented bilateral salpingectomy; hysterectomy; documented bilateral oophorectomy. * Postmenopausal defined as 12 months of spontaneous amenorrhea. Post-menopausal status will be confirmed by a simultaneous follicle stimulating hormone (FSH) and estradiol levels test. * Male subjects with female partners of child bearing potential must comply with the following contraception requirements from the time of first dose of study medication until 90 days after the last dose of study treatment (i.e. one sperm cycle). * Vasectomy with documentation of azoospermia. * Male condom plus partner use of one of the contraceptive options as follows: contraceptive subdermal implant; intrauterine device or intrauterine system; highly effective oral contraceptive, either combined or progestogen alone (provided it is associated with inhibition of ovulation); injectable progestogen; contraceptive vaginal ring; percutaneous contraceptive patches. * These allowed methods of contraception are only effective when used consistently, correctly and in accordance with the product label. The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception. * The subject is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| t1/2 of GSK3036656 Following Repeated Dose Administration for Part B | Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14. | Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14. The actual date and time of each blood sample collection was recorded. Results presented are for Day 14. |
| Number of Participants With Hematology Parameters of PCI for Part B | Up to 8 weeks | Blood samples were collected for the assessment of hematology parameters platelet count, red blood cell count, hemoglobin, hematocrit, reticulocytes, mean corpuscle volume, mean corpuscular hemoglobin, neutrophils, lymphocytes, monocytes, basophils and eosinophils. Only categories with PCI values have been presented. |
| Number of Participants With Abnormal Urinalysis Parameters for Part A | Up to 72 hours post-dose | Urinalysis included dipstick urine test which was used to screen for glucose, ketones, occult blood and protein up to 72 hours post dose. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters of urine glucose, ketones, occult blood and protein can be read as negative, trace, trace-intact, trace-lysed,1+ and 2+ indicating proportional concentrations in the urine sample. Only categories with non-negative values have been presented. Only those participants with data available the indicated time points were analyzed. |
| Urine Potential of Hydrogen (pH) Analysis by Dipstick Method for Part A | Up to 72 hours post-dose | Urinary pH measurement is a routine part of urinalysis. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 - 6.0). Urine samples were collected for the measurement of urine pH by method up to 72 hours in Part A. Only those participants with data available at the indicated time points were analyzed. |
| Number of Participants With Abnormal Urinalysis Parameters for Part B | Up to 8 weeks | Urinalysis included dipstick urine test which was used to screen for glucose, ketones, occult blood and protein up to 14 days post dose The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters of urine glucose, ketones, occult blood and protein can be read as negative, trace, trace-intact, trace-lysed, 1+ and 2+ indicating proportional concentrations in the urine sample. Only categories with non-negative values have been presented. Only those participants available at the specified time points were analyzed represented by n=x in the category titles. Period 1 = Cohort 1 in Part B, Period 2 = Cohort 2 in Part B. |
| Urine pH Analysis by Dipstick Method for Part B | Up to 8 weeks | Urinary pH measurement is a routine part of urinalysis. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 - 6.0). Urine samples were collected for the measurement of urine pH by method up to 8 weeks in Part B. Only those participants available at the specified time points were analyzed represented by n=x in the category titles. Period 1 = Cohort 1 in Part B, Period 2 = Cohort 2 in Part B. |
| Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-t]) Following Single Dose Administration of GSK3036656 for Part A | Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period | Blood samples for plasma PK analysis of GSK3036656 was collected into K3 Ethylenediaminetetraacetic acid (EDTA) tubes at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period. The actual date and time of each blood sample collection was recorded. PK population comprised of participants in the Safety population who administered at least one dose of active treatment and had at least one evaluable PK sample. |
| AUC From Time Zero Extrapolated to Infinite Time (AUC[0-infinity]) of GSK3036656 Following Single Dose Administration for Part A | Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period | Cmax will be derived from the PK samples collected at the indicated time points Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period. The actual date and time of each blood sample collection was recorded. |
| Maximum Observed Plasma Drug Concentration (Cmax) of GSK3036656 Following Single Dose Administration for Part A | Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period | Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period. The actual date and time of each blood sample collection was recorded. |
| Time to Maximum Observed Plasma Drug Concentration (Tmax) of GSK3036656 Following Single Dose Administration for Part A | Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period | Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period. The actual date and time of each blood sample collection was recorded. |
| Apparent Terminal Half-life (t1/2) of GSK3036656 Following Single Dose Administration for Part A | Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period | Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period. The actual date and time of each blood sample collection was recorded. |
| AUC[0-t] Following Repeated Dose Administration of GSK3036656 for Part B | Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 | Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1. The actual date and time of each blood sample collection was recorded. Results presented are for Day 1. |
| AUC From Time Zero During a Dosing Interval of Duration Tau (AUC[0-tau]) of GSK3036656 Following Repeated Dose Administration for Part B | Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14 | Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes at Pre-dose and at pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14The actual date and time of each blood sample collection was recorded. Results presented are for Day 14. |
| Cmax of GSK3036656 Following Repeated Dose Administration for Part B | Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1; at pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14; and at pre-dose on Days 12 and 13 | Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1; at pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14; and at pre-dose on Days 12 and 13. The actual date and time of each blood sample collection was recorded. |
| Tmax of GSK3036656 Following Repeat Dose Administration for Part B | Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1; at pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14; and at pre-dose on Days 12 and 13 | Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1; at pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14; and at pre-dose on Days 12 and 13. The actual date and time of each blood sample collection was recorded. |
| Number of Participants With Non-serious Adverse Events (nSAE) and Serious Adverse Events (SAEs) for Part A | Up to 12 weeks | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations judged by physician, such as important medical events that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in the above. Safety Population comprised of all randomized participants who received at least one dose of study medication. |
| Number of Participants With nSAE and SAEs for Part B | Up to 8 weeks | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations judged by physician, such as important medical events that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in the above. |
| Number of Participants With Abnormal Electrocardiogram (ECG) Findings for Part A | Up to 6 weeks | 12-lead ECGs were collected during the study using an ECG machine that automatically calculated the heart rate and measures PR, QRS, QT, and QT interval corrected for heart rate using Fridericia's formula (QTcF) intervals. At each time point at which triplicate ECGs were required, three individual ECG tracings were obtained as closely as possible in succession, but no more than 2 to 5 minutes apart. ECG findings were categorized as normal, abnormal not clinically significant (A-NCS) and abnormal clinically significant (A-CS). Only A-NCS and A-CS worst case post-Baseline values have been presented. Only those participants with data available at the indicated time point were analyzed. |
| Number of Subjects With Clinically Relevant Changes in ECG in Part B | Up to 8 weeks | 12-lead ECGs were collected during the study using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT interval and QTcF intervals. At each time point at which triplicate ECGs were required, three individual ECG tracings were obtained as closely as possible in succession, but no more than 2 to 5 minutes apart. ECG findings were categorized as normal, A-NCS and A-CS. Only A-NCS and A-CS worst case post-Baseline values have been presented. |
| Number of Participants With Abnormal Cardiac Telemetry Findings for Part A | 25 hours for each period | Continuous cardiac telemetry was performed from approximately 1 hour pre-dose to 24 hours post dosing . Number of participants who had abnormal findings upon cardiac telemetry assessment have been presented. |
| Number of Participants With Abnormal Cardiac Telemetry Findings for Part B | 25 hours for each period | Continuous cardiac telemetry was performed from approximately 1 hour pre-dose to 24 hours post dosing . Number of participants who had abnormal findings upon cardiac telemetry assessment have been presented. |
| Number of Participants With Vital Sign Parameters Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) of Potential Clinical Importance (PCI) for Part A | Up to 6 weeks | SBP and DBP were assessed in supine position with a completely automated device. Measurements were preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions (e.g., television, cell phones). The PCI range for SBP was less than 85 mmHg (lower) and greater than 160 mmHg (upper) while that for DBP was less than 45 mmHg (lower) and greater than 100 mmHg (upper). |
| Number of Participants With Vital Sign Parameters SBP and DBP of PCI for Part B | Up to 8 weeks | SBP and DBP were assessed in supine position with a completely automated device. Measurements were preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions (e.g., television, cell phones). The PCI range for SBP was less than 85 mmHg (lower) and greater than 160 mmHg (upper) while that for DBP was less than 45 mmHg (lower) and greater than 100 mmHg (upper). |
| Number of Participants With Vital Sign Parameter Heart Rate of PCI for Part A | Up to 6 weeks | Heart rate was assessed in supine position with a completely automated device. Measurements were preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions (e.g., television, cell phones). The PCI range for heart was less than 40 bpm (lower) and greater than 110 bpm (upper). |
| Number of Participants With Vital Sign Parameter Heart Rate of PCI for Part B | Up to 8 weeks | Heart rate was assessed in supine position with a completely automated device. Measurements were preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions (e.g., television, cell phones). The PCI range for heart was less than 40 bpm (lower) and greater than 110 bpm (upper). |
| Number of Participants With Vital Sign Parameter Temperature of PCI for Part A | Up to 6 weeks | Number of participants with temperature data of PCI have been presented. |
| Number of Participants With Vital Sign Parameter Temperature of PCI for Part B | Up to 8 weeks | Number of participants with temperature data of PCI have been presented. |
| Number of Participants With Clinical Chemistry Parameters of PCI for Part A | Up to 12 weeks | Blood samples were collected for the assessment of clinical chemistry parameters namely blood urea nitrogen (BUN), creatinine, glucose, cholesterol, potassium, sodium, calcium, aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase, triglycerides, total and direct bilirubin, total protein, albumin and troponin. Only categories with PCI values have been presented, therefore only AST is presented. |
| Number of Participants With Clinical Chemistry Parameters of PCI for Part B | Up to 8 weeks | Blood samples were collected for the assessment of clinical chemistry parameters namely BUN, creatinine, glucose, cholesterol, potassium, sodium, calcium, AST, ALT, alkaline phosphatase, triglycerides, total and direct bilirubin, total protein, albumin and troponin. Only categories with PCI values have been presented. |
| Number of Participants With Hematology Parameters of PCI for Part A | Up to 12 weeks | Blood samples were collected for the assessment of hematology parameters platelet count, red blood cell count, hemoglobin, hematocrit, reticulocytes, mean corpuscle volume, mean corpuscular hemoglobin, neutrophils, lymphocytes, monocytes, basophils and eosinophils. Only categories with PCI values have been presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC (0-infinity) of GSK3036656 Following Single Dose Administration in Fed Condition in Part A | Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period | Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period. The actual date and time of each blood sample collection was recorded. For the food effect assessment, the selected dose was given with a high fat meal. |
| Cmax of GSK3036656 Following Single Dose Administration in Fed Condition in Part A | Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period | Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period. The actual date and time of each blood sample collection was recorded. For the food effect assessment, the selected dose was given with a high fat meal. |
| t1/2 of GSK3036656 Following Single Dose Administration in Fed Condition in Part A | Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period | Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period. The actual date and time of each blood sample collection was recorded. For the food effect assessment, the selected dose was given with a high fat meal. |
| Tmax of GSK3036656 Following Single Dose Administration in Fed Condition in Part A | Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period | Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period. The actual date and time of each blood sample collection was recorded. For the food effect assessment, the selected dose was given with a high fat meal. |
| Observed Accumulation Ratio Based on AUC (AUC [Ro]) of GSK3036656 in Part B | Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1; at pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14 | AUC Ro was calculated as Day 14 AUC(0-tau)/Day 1 AUC(0-t), where t and tau= 24 hours. |
| Observed Accumulation Ratio Based on Cmax (RCmax) of GSK3036656 in Part B | Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1; at pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14 | Rcmax was calculated as Day 14 Cmax/Day 1 Cmax. Statistics has been presented on geometric least square means. |
| Steady State Ratio (Rss) of GSK3036656 in Part B | Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1; at pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14 | Rss was calculated as Day 14 AUC (0-tau)/Day 1 AUC (0-inf). It was not possible to calculate AUC(0-inf) on Day 1 for the repeat dosing period, therefore it was not possible to calculate the (Rss).Na indicates data was not available. |
| Trough Plasma Concentrations at the End of the Dosing Interval (Ctau) of GSK3036656 Following Repeat Dose Administrations in Part B | Day 1 (24 hours), Day 12 (Pre-dose ), Day 13 (Pre-dose ), Day 14 (Pre-dose), Day 14 (24 hours) | Blood samples for the analysis of Ctau were collected at Day 1 (24 hours), Day 12 (Pre-dose ), Day 13 (Pre-dose ), Day 14 (Pre-dose), Day 14 (24 hours). Ctau samples collected were used to assess attainment of steady state. Statistics has been presented on geometric least square means. |
| AUC (0-infinity) as a Measure of Dose Proportionality of GSK3036656 Following Single Dose Administrations for Part A | Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period | Blood samples for the analysis of AUC (0-infinity) were collected at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period. AUC(0-infinity) following single doses was used for assessment of dose proportionality. |
| AUC (0-t) as a Measure of Dose Proportionality of GSK3036656 Following Single Dose Administrations for Part A | Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period | Blood samples for the analysis of AUC (0-t) were collected at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period. AUC(0-t) following single doses was used for assessment of dose proportionality. |
| Cmax as a Measure of Dose Proportionality of GSK3036656 Following Single Dose Administrations for Part A | Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period | Blood samples for the analysis of Cmax were collected at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period. Cmax following single doses was used for assessment of dose proportionality. |
| AUC (0-tau) as a Measure of Dose Proportionality of GSK3036656 Following Repeat Dose Administrations for Part B | Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1; at pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14; and at pre-dose on Days 12 and 13 | Blood samples for the assessment of AUC (0-tau) were collected at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1; at pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14; and at pre-dose on Days 12 and 13. AUC (0-tau) following repeat doses was used for assessment of dose proportionality. |
| Cmax as a Measure of Dose Proportionality of GSK3036656 Following Repeat Dose Administrations for Part B | Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1; at pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14; and at pre-dose on Days 12 and 13 | Blood samples for the assessment of Cmax were collected at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1; at pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14; and at pre-dose on Days 12 and 13. Cmax following repeat doses was used for assessment of dose proportionality. |
| AUC (0-t) of GSK3036656 Following Single Dose Administration in Fed Condition in Part A | Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period | Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period. The actual date and time of each blood sample collection was recorded. For the food effect assessment, the selected dose was given with a high fat meal. |
Countries
United Kingdom
Participant flow
Recruitment details
This was a double blind, placebo-controlled study to evaluate the safety, tolerability and pharmacokinetics (PK) of single and repeat doses of GSK3036656 in healthy adult participants. The study was conducted at 1 center in United Kingdom from 02-April-2017 to 04-August-2017. Part A was a crossover design, Part B was a parallel group design..
Pre-assignment details
20 participants screened, 8 were screen failures (SF). 9 were randomized at the beginning of Part A. During Part A, 2 of the 3 participants who withdrew were replaced, hence 11 randomized. 30 participants screened, 7 were SF, 4 passed screening but were kept in reserve, hence 19 randomized in Part B.
Participants by arm
| Arm | Count |
|---|---|
| Part A - Placebo/15 mg/25 mg/5 mg (Fed) Participants received matching placebo to GSK3036656 5 mg followed by GSK3036656 15 mg followed by GSK3036656 25 mg followed by GSK3036656 5 mg (fed) capsules orally for 14 Days. | 3 |
| Part A - Placebo/15 mg/25 mg/Placebo Participants received matching placebo to GSK3036656 5 mg followed by GSK3036656 15 mg followed by GSK3036656 25 mg followed by matching placebo to GSK3036656 5 mg capsules orally for 14 Days. | 1 |
| Part A - 5 mg/Placebo/25 mg/5 mg (Fed) Participants received SK3036656 5 mg followed by matching placebo to GSK3036656 5 mg followed by GSK3036656 25 mg followed by GSK3036656 5 mg (fed) capsules orally for 14 Days. | 3 |
| Part A - 5 mg/Placebo/25 mg/Placebo Participants received SK3036656 5 mg followed by matching placebo to GSK3036656 5 mg followed by GSK3036656 25 mg followed by matching placebo to GSK3036656 5 mg capsules orally for 14 Days. | 1 |
| Part A - 5 mg/15 mg/Placebo/5 mg (Fed) Participants received GSK3036656 5 mg followed by GSK3036656 15 mg followed by matching placebo to GSK3036656 5 mg followed by GSK3036656 5 mg (fed) capsules orally for 14 Days. | 2 |
| Part A - 5 mg/15 mg/Placebo/Placebo Participants received GSK3036656 5 mg followed by GSK3036656 15 mg followed by matching placebo to GSK3036656 5 mg followed by matching placebo to GSK3036656 5 mg capsules orally for 14 Days. | 1 |
| Part B-Placebo Participants received matching placebo to active GSK3036656 5 mg / 15mg capsules orally once daily for 14 days. | 4 |
| Part B-Repeat GSK3036656 5 mg Participants received repeat dosing of GSK3036656 5 mg capsules orally once daily for 14 days. | 7 |
| Part B-Repeat GSK3036656 15 mg Participants received repeat dosing of GSK3036656 15 mg capsules orally once daily for 14 days. | 8 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Part A-Period 2 (14 Days) | Personal reasons | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part A-Period 3 (14 Days) | Reaction to ECG tabs causing a rash | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Part A - Placebo/15 mg/25 mg/5 mg (Fed) | Part A - Placebo/15 mg/25 mg/Placebo | Part A - 5 mg/Placebo/25 mg/5 mg (Fed) | Part A - 5 mg/Placebo/25 mg/Placebo | Part A - 5 mg/15 mg/Placebo/5 mg (Fed) | Part A - 5 mg/15 mg/Placebo/Placebo | Part B-Placebo | Part B-Repeat GSK3036656 5 mg | Part B-Repeat GSK3036656 15 mg | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 33.7 Years STANDARD_DEVIATION 5.03 | 25 Years | 26.3 Years STANDARD_DEVIATION 2.52 | 28.0 Years | 34.0 Years STANDARD_DEVIATION 1.41 | 50.0 Years | 30.3 Years STANDARD_DEVIATION 9.43 | 31.9 Years STANDARD_DEVIATION 6.26 | 35.1 Years STANDARD_DEVIATION 7.88 | 32.5 Years STANDARD_DEVIATION 7.39 |
| Race/Ethnicity, Customized American Indian/Alaskan Native | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian-South Asian Heritage | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Black/ African American | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Unknown | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized White-White/Caucasian/European Heritage | 1 Participants | 1 Participants | 3 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 5 Participants | 8 Participants | 23 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 3 Participants | 1 Participants | 3 Participants | 1 Participants | 2 Participants | 0 Participants | 4 Participants | 7 Participants | 8 Participants | 29 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 |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 5 | 0 / 4 | 0 / 7 | 0 / 8 |
| other Total, other adverse events | 1 / 9 | 1 / 6 | 1 / 6 | 3 / 6 | 1 / 5 | 0 / 4 | 2 / 7 | 1 / 8 |
| serious Total, serious adverse events | 0 / 9 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 5 | 0 / 4 | 0 / 7 | 0 / 8 |
Outcome results
Primary
Apparent Terminal Half-life (t1/2) of GSK3036656 Following Single Dose Administration for Part A
Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period. The actual date and time of each blood sample collection was recorded.
Time frame: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period
Population: PK Population for Part A
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A-Matching Placebo | Apparent Terminal Half-life (t1/2) of GSK3036656 Following Single Dose Administration for Part A | 38.3230 hours |
| Part A-GSK3036656 5 mg | Apparent Terminal Half-life (t1/2) of GSK3036656 Following Single Dose Administration for Part A | 28.4128 hours |
| Part A-GSK3036656 15 mg | Apparent Terminal Half-life (t1/2) of GSK3036656 Following Single Dose Administration for Part A | 47.9680 hours |
| Part A-GSK3036656 25 mg | Apparent Terminal Half-life (t1/2) of GSK3036656 Following Single Dose Administration for Part A | 32.4248 hours |
Primary
Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-t]) Following Single Dose Administration of GSK3036656 for Part A
Blood samples for plasma PK analysis of GSK3036656 was collected into K3 Ethylenediaminetetraacetic acid (EDTA) tubes at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period. The actual date and time of each blood sample collection was recorded. PK population comprised of participants in the Safety population who administered at least one dose of active treatment and had at least one evaluable PK sample.
Time frame: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period
Population: PK Population for Part A
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A-Matching Placebo | Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-t]) Following Single Dose Administration of GSK3036656 for Part A | 771.0468 hour*nanograms/milliliter | Geometric Coefficient of Variation 26 |
| Part A-GSK3036656 5 mg | Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-t]) Following Single Dose Administration of GSK3036656 for Part A | 3252.9152 hour*nanograms/milliliter | Geometric Coefficient of Variation 24.1 |
| Part A-GSK3036656 15 mg | Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-t]) Following Single Dose Administration of GSK3036656 for Part A | 5686.4151 hour*nanograms/milliliter | Geometric Coefficient of Variation 11.4 |
| Part A-GSK3036656 25 mg | Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-t]) Following Single Dose Administration of GSK3036656 for Part A | 782.7766 hour*nanograms/milliliter | Geometric Coefficient of Variation 18.1 |
Primary
AUC[0-t] Following Repeated Dose Administration of GSK3036656 for Part B
Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1. The actual date and time of each blood sample collection was recorded. Results presented are for Day 1.
Time frame: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1
Population: PK Population for Part B
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A-Matching Placebo | AUC[0-t] Following Repeated Dose Administration of GSK3036656 for Part B | 485.5625 hour*nanograms/milliliter | Geometric Coefficient of Variation 12.3 |
| Part A-GSK3036656 5 mg | AUC[0-t] Following Repeated Dose Administration of GSK3036656 for Part B | 1891.0416 hour*nanograms/milliliter | Geometric Coefficient of Variation 9.9 |
Primary
AUC From Time Zero During a Dosing Interval of Duration Tau (AUC[0-tau]) of GSK3036656 Following Repeated Dose Administration for Part B
Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes at Pre-dose and at pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14The actual date and time of each blood sample collection was recorded. Results presented are for Day 14.
Time frame: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14
Population: PK Population for Part B
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A-Matching Placebo | AUC From Time Zero During a Dosing Interval of Duration Tau (AUC[0-tau]) of GSK3036656 Following Repeated Dose Administration for Part B | 1392.2221 hour*nanograms/milliliter | Geometric Coefficient of Variation 12.5 |
| Part A-GSK3036656 5 mg | AUC From Time Zero During a Dosing Interval of Duration Tau (AUC[0-tau]) of GSK3036656 Following Repeated Dose Administration for Part B | 4461.2565 hour*nanograms/milliliter | Geometric Coefficient of Variation 23.7 |
Primary
AUC From Time Zero Extrapolated to Infinite Time (AUC[0-infinity]) of GSK3036656 Following Single Dose Administration for Part A
Cmax will be derived from the PK samples collected at the indicated time points Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period. The actual date and time of each blood sample collection was recorded.
Time frame: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period
Population: PK Population for Part A
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A-Matching Placebo | AUC From Time Zero Extrapolated to Infinite Time (AUC[0-infinity]) of GSK3036656 Following Single Dose Administration for Part A | 1404.5416 hour*nanograms/milliliter | Geometric Coefficient of Variation 29.9 |
| Part A-GSK3036656 5 mg | AUC From Time Zero Extrapolated to Infinite Time (AUC[0-infinity]) of GSK3036656 Following Single Dose Administration for Part A | 3796.1488 hour*nanograms/milliliter | Geometric Coefficient of Variation 19.8 |
| Part A-GSK3036656 15 mg | AUC From Time Zero Extrapolated to Infinite Time (AUC[0-infinity]) of GSK3036656 Following Single Dose Administration for Part A | 6557.7764 hour*nanograms/milliliter | Geometric Coefficient of Variation 13.8 |
| Part A-GSK3036656 25 mg | AUC From Time Zero Extrapolated to Infinite Time (AUC[0-infinity]) of GSK3036656 Following Single Dose Administration for Part A | 1450.7468 hour*nanograms/milliliter | Geometric Coefficient of Variation 9.4 |
Primary
Cmax of GSK3036656 Following Repeated Dose Administration for Part B
Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1; at pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14; and at pre-dose on Days 12 and 13. The actual date and time of each blood sample collection was recorded.
Time frame: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1; at pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14; and at pre-dose on Days 12 and 13
Population: PK Population for Part B
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-Matching Placebo | Cmax of GSK3036656 Following Repeated Dose Administration for Part B | Day 1 | 48.40 nanograms/milliliter | Geometric Coefficient of Variation 33.6 |
| Part A-Matching Placebo | Cmax of GSK3036656 Following Repeated Dose Administration for Part B | Day 14 | 97.04 nanograms/milliliter | Geometric Coefficient of Variation 19.8 |
| Part A-GSK3036656 5 mg | Cmax of GSK3036656 Following Repeated Dose Administration for Part B | Day 1 | 178.79 nanograms/milliliter | Geometric Coefficient of Variation 32.8 |
| Part A-GSK3036656 5 mg | Cmax of GSK3036656 Following Repeated Dose Administration for Part B | Day 14 | 309.55 nanograms/milliliter | Geometric Coefficient of Variation 20.2 |
Primary
Maximum Observed Plasma Drug Concentration (Cmax) of GSK3036656 Following Single Dose Administration for Part A
Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period. The actual date and time of each blood sample collection was recorded.
Time frame: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period
Population: PK Population for Part A
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A-Matching Placebo | Maximum Observed Plasma Drug Concentration (Cmax) of GSK3036656 Following Single Dose Administration for Part A | 49.06 nanograms/milliliter | Geometric Coefficient of Variation 30.5 |
| Part A-GSK3036656 5 mg | Maximum Observed Plasma Drug Concentration (Cmax) of GSK3036656 Following Single Dose Administration for Part A | 177.61 nanograms/milliliter | Geometric Coefficient of Variation 23.1 |
| Part A-GSK3036656 15 mg | Maximum Observed Plasma Drug Concentration (Cmax) of GSK3036656 Following Single Dose Administration for Part A | 207.38 nanograms/milliliter | Geometric Coefficient of Variation 18.5 |
| Part A-GSK3036656 25 mg | Maximum Observed Plasma Drug Concentration (Cmax) of GSK3036656 Following Single Dose Administration for Part A | 47.37 nanograms/milliliter | Geometric Coefficient of Variation 23.5 |
Primary
Number of Participants With Abnormal Cardiac Telemetry Findings for Part A
Continuous cardiac telemetry was performed from approximately 1 hour pre-dose to 24 hours post dosing . Number of participants who had abnormal findings upon cardiac telemetry assessment have been presented.
Time frame: 25 hours for each period
Population: Safety Population for Part A. For arm Part A-Matching Placebo 3 of the 9 placebo participants received placebo twice, therefore they had these measures done in 2 different treatment periods, so N=9 but number of units analyzed=12.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A-Matching Placebo | Number of Participants With Abnormal Cardiac Telemetry Findings for Part A | 0 Participants |
| Part A-GSK3036656 5 mg | Number of Participants With Abnormal Cardiac Telemetry Findings for Part A | 0 Participants |
| Part A-GSK3036656 15 mg | Number of Participants With Abnormal Cardiac Telemetry Findings for Part A | 0 Participants |
| Part A-GSK3036656 25 mg | Number of Participants With Abnormal Cardiac Telemetry Findings for Part A | 0 Participants |
| Part A-GSK3036656 5 mg (Fed) | Number of Participants With Abnormal Cardiac Telemetry Findings for Part A | 0 Participants |
Primary
Number of Participants With Abnormal Cardiac Telemetry Findings for Part B
Continuous cardiac telemetry was performed from approximately 1 hour pre-dose to 24 hours post dosing . Number of participants who had abnormal findings upon cardiac telemetry assessment have been presented.
Time frame: 25 hours for each period
Population: Safety Population for Part B
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A-Matching Placebo | Number of Participants With Abnormal Cardiac Telemetry Findings for Part B | 0 Participants |
| Part A-GSK3036656 5 mg | Number of Participants With Abnormal Cardiac Telemetry Findings for Part B | 0 Participants |
| Part A-GSK3036656 15 mg | Number of Participants With Abnormal Cardiac Telemetry Findings for Part B | 0 Participants |
Primary
Number of Participants With Abnormal Electrocardiogram (ECG) Findings for Part A
12-lead ECGs were collected during the study using an ECG machine that automatically calculated the heart rate and measures PR, QRS, QT, and QT interval corrected for heart rate using Fridericia's formula (QTcF) intervals. At each time point at which triplicate ECGs were required, three individual ECG tracings were obtained as closely as possible in succession, but no more than 2 to 5 minutes apart. ECG findings were categorized as normal, abnormal not clinically significant (A-NCS) and abnormal clinically significant (A-CS). Only A-NCS and A-CS worst case post-Baseline values have been presented. Only those participants with data available at the indicated time point were analyzed.
Time frame: Up to 6 weeks
Population: Safety Population for Part A. For arm Part A-Matching Placebo 3 of the 9 placebo participants received placebo twice, therefore they had these measures done in 2 different treatment periods, so N=9 but number of units analyzed=12.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A-Matching Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Findings for Part A | A-NCS | 2 Participants |
| Part A-Matching Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Findings for Part A | A-CS | 0 Participants |
| Part A-GSK3036656 5 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings for Part A | A-CS | 0 Participants |
| Part A-GSK3036656 5 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings for Part A | A-NCS | 1 Participants |
| Part A-GSK3036656 15 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings for Part A | A-NCS | 0 Participants |
| Part A-GSK3036656 15 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings for Part A | A-CS | 0 Participants |
| Part A-GSK3036656 25 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings for Part A | A-NCS | 0 Participants |
| Part A-GSK3036656 25 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings for Part A | A-CS | 0 Participants |
| Part A-GSK3036656 5 mg (Fed) | Number of Participants With Abnormal Electrocardiogram (ECG) Findings for Part A | A-CS | 0 Participants |
| Part A-GSK3036656 5 mg (Fed) | Number of Participants With Abnormal Electrocardiogram (ECG) Findings for Part A | A-NCS | 0 Participants |
Primary
Number of Participants With Abnormal Urinalysis Parameters for Part A
Urinalysis included dipstick urine test which was used to screen for glucose, ketones, occult blood and protein up to 72 hours post dose. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters of urine glucose, ketones, occult blood and protein can be read as negative, trace, trace-intact, trace-lysed,1+ and 2+ indicating proportional concentrations in the urine sample. Only categories with non-negative values have been presented. Only those participants with data available the indicated time points were analyzed.
Time frame: Up to 72 hours post-dose
Population: Safety Population for Part A. For arm Part A-Matching Placebo 3 of the 9 placebo participants received placebo twice, therefore they had these measures done in 2 different treatment periods, so N=9 but number of units analyzed=12.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A-Matching Placebo | Number of Participants With Abnormal Urinalysis Parameters for Part A | Day -1, Occult blood, 1+ | 0 Participants |
| Part A-Matching Placebo | Number of Participants With Abnormal Urinalysis Parameters for Part A | Day -1, Protein, Trace | 1 Participants |
| Part A-Matching Placebo | Number of Participants With Abnormal Urinalysis Parameters for Part A | Day -1, Ketone, Trace | 1 Participants |
| Part A-Matching Placebo | Number of Participants With Abnormal Urinalysis Parameters for Part A | 72 hours, Occult blood, trace-lysed | 0 Participants |
| Part A-Matching Placebo | Number of Participants With Abnormal Urinalysis Parameters for Part A | Day -1, Occult blood, trace-intact | 1 Participants |
| Part A-Matching Placebo | Number of Participants With Abnormal Urinalysis Parameters for Part A | 24 hours, Occult blood, 2+ | 0 Participants |
| Part A-Matching Placebo | Number of Participants With Abnormal Urinalysis Parameters for Part A | Day -1, Occult blood, trace-lysed | 1 Participants |
| Part A-Matching Placebo | Number of Participants With Abnormal Urinalysis Parameters for Part A | 24 hours, Occult blood, trace-intact | 1 Participants |
| Part A-Matching Placebo | Number of Participants With Abnormal Urinalysis Parameters for Part A | 72 hours, Occult blood, 1+ | 1 Participants |
| Part A-Matching Placebo | Number of Participants With Abnormal Urinalysis Parameters for Part A | 72 hours, Ketone, Trace | 0 Participants |
| Part A-Matching Placebo | Number of Participants With Abnormal Urinalysis Parameters for Part A | 24 hours, Occult blood, trace-lysed | 1 Participants |
| Part A-Matching Placebo | Number of Participants With Abnormal Urinalysis Parameters for Part A | 24 hours, Ketones, 2+ | 1 Participants |
| Part A-Matching Placebo | Number of Participants With Abnormal Urinalysis Parameters for Part A | 72 hours, Occult blood, trace-intact | 0 Participants |
| Part A-Matching Placebo | Number of Participants With Abnormal Urinalysis Parameters for Part A | 72 hours, Protein, Trace | 2 Participants |
| Part A-Matching Placebo | Number of Participants With Abnormal Urinalysis Parameters for Part A | Day -1, Occult blood, 2+ | 0 Participants |
| Part A-GSK3036656 5 mg | Number of Participants With Abnormal Urinalysis Parameters for Part A | Day -1, Ketone, Trace | 0 Participants |
| Part A-GSK3036656 5 mg | Number of Participants With Abnormal Urinalysis Parameters for Part A | 72 hours, Occult blood, 1+ | 0 Participants |
| Part A-GSK3036656 5 mg | Number of Participants With Abnormal Urinalysis Parameters for Part A | 24 hours, Occult blood, trace-lysed | 0 Participants |
| Part A-GSK3036656 5 mg | Number of Participants With Abnormal Urinalysis Parameters for Part A | Day -1, Occult blood, 1+ | 0 Participants |
| Part A-GSK3036656 5 mg | Number of Participants With Abnormal Urinalysis Parameters for Part A | 72 hours, Ketone, Trace | 0 Participants |
| Part A-GSK3036656 5 mg | Number of Participants With Abnormal Urinalysis Parameters for Part A | Day -1, Occult blood, 2+ | 0 Participants |
| Part A-GSK3036656 5 mg | Number of Participants With Abnormal Urinalysis Parameters for Part A | Day -1, Occult blood, trace-intact | 0 Participants |
| Part A-GSK3036656 5 mg | Number of Participants With Abnormal Urinalysis Parameters for Part A | 24 hours, Occult blood, trace-intact | 0 Participants |
| Part A-GSK3036656 5 mg | Number of Participants With Abnormal Urinalysis Parameters for Part A | 72 hours, Occult blood, trace-lysed | 0 Participants |
| Part A-GSK3036656 5 mg | Number of Participants With Abnormal Urinalysis Parameters for Part A | Day -1, Occult blood, trace-lysed | 0 Participants |
| Part A-GSK3036656 5 mg | Number of Participants With Abnormal Urinalysis Parameters for Part A | Day -1, Protein, Trace | 0 Participants |
| Part A-GSK3036656 5 mg | Number of Participants With Abnormal Urinalysis Parameters for Part A | 24 hours, Ketones, 2+ | 0 Participants |
| Part A-GSK3036656 5 mg | Number of Participants With Abnormal Urinalysis Parameters for Part A | 72 hours, Occult blood, trace-intact | 0 Participants |
| Part A-GSK3036656 5 mg | Number of Participants With Abnormal Urinalysis Parameters for Part A | 24 hours, Occult blood, 2+ | 0 Participants |
| Part A-GSK3036656 5 mg | Number of Participants With Abnormal Urinalysis Parameters for Part A | 72 hours, Protein, Trace | 0 Participants |
| Part A-GSK3036656 15 mg | Number of Participants With Abnormal Urinalysis Parameters for Part A | 72 hours, Occult blood, 1+ | 1 Participants |
| Part A-GSK3036656 15 mg | Number of Participants With Abnormal Urinalysis Parameters for Part A | Day -1, Protein, Trace | 2 Participants |
| Part A-GSK3036656 15 mg | Number of Participants With Abnormal Urinalysis Parameters for Part A | 72 hours, Protein, Trace | 0 Participants |
| Part A-GSK3036656 15 mg | Number of Participants With Abnormal Urinalysis Parameters for Part A | 72 hours, Occult blood, trace-intact | 0 Participants |
| Part A-GSK3036656 15 mg | Number of Participants With Abnormal Urinalysis Parameters for Part A | Day -1, Occult blood, 1+ | 0 Participants |
| Part A-GSK3036656 15 mg | Number of Participants With Abnormal Urinalysis Parameters for Part A | 24 hours, Occult blood, 2+ | 1 Participants |
| Part A-GSK3036656 15 mg | Number of Participants With Abnormal Urinalysis Parameters for Part A | 24 hours, Ketones, 2+ | 0 Participants |
| Part A-GSK3036656 15 mg | Number of Participants With Abnormal Urinalysis Parameters for Part A | 72 hours, Ketone, Trace | 1 Participants |
| Part A-GSK3036656 15 mg | Number of Participants With Abnormal Urinalysis Parameters for Part A | 24 hours, Occult blood, trace-intact | 0 Participants |
| Part A-GSK3036656 15 mg | Number of Participants With Abnormal Urinalysis Parameters for Part A | Day -1, Occult blood, trace-intact | 0 Participants |
| Part A-GSK3036656 15 mg | Number of Participants With Abnormal Urinalysis Parameters for Part A | 24 hours, Occult blood, trace-lysed | 0 Participants |
| Part A-GSK3036656 15 mg | Number of Participants With Abnormal Urinalysis Parameters for Part A | Day -1, Occult blood, trace-lysed | 0 Participants |
| Part A-GSK3036656 15 mg | Number of Participants With Abnormal Urinalysis Parameters for Part A | Day -1, Ketone, Trace | 1 Participants |
| Part A-GSK3036656 15 mg | Number of Participants With Abnormal Urinalysis Parameters for Part A | 72 hours, Occult blood, trace-lysed | 0 Participants |
| Part A-GSK3036656 15 mg | Number of Participants With Abnormal Urinalysis Parameters for Part A | Day -1, Occult blood, 2+ | 1 Participants |
| Part A-GSK3036656 25 mg | Number of Participants With Abnormal Urinalysis Parameters for Part A | 24 hours, Ketones, 2+ | 0 Participants |
| Part A-GSK3036656 25 mg | Number of Participants With Abnormal Urinalysis Parameters for Part A | 72 hours, Ketone, Trace | 0 Participants |
| Part A-GSK3036656 25 mg | Number of Participants With Abnormal Urinalysis Parameters for Part A | Day -1, Ketone, Trace | 0 Participants |
| Part A-GSK3036656 25 mg | Number of Participants With Abnormal Urinalysis Parameters for Part A | Day -1, Occult blood, 1+ | 0 Participants |
| Part A-GSK3036656 25 mg | Number of Participants With Abnormal Urinalysis Parameters for Part A | Day -1, Occult blood, 2+ | 0 Participants |
| Part A-GSK3036656 25 mg | Number of Participants With Abnormal Urinalysis Parameters for Part A | Day -1, Occult blood, trace-intact | 0 Participants |
| Part A-GSK3036656 25 mg | Number of Participants With Abnormal Urinalysis Parameters for Part A | Day -1, Occult blood, trace-lysed | 0 Participants |
| Part A-GSK3036656 25 mg | Number of Participants With Abnormal Urinalysis Parameters for Part A | Day -1, Protein, Trace | 0 Participants |
| Part A-GSK3036656 25 mg | Number of Participants With Abnormal Urinalysis Parameters for Part A | 24 hours, Occult blood, 2+ | 0 Participants |
| Part A-GSK3036656 25 mg | Number of Participants With Abnormal Urinalysis Parameters for Part A | 24 hours, Occult blood, trace-intact | 0 Participants |
| Part A-GSK3036656 25 mg | Number of Participants With Abnormal Urinalysis Parameters for Part A | 24 hours, Occult blood, trace-lysed | 0 Participants |
| Part A-GSK3036656 25 mg | Number of Participants With Abnormal Urinalysis Parameters for Part A | 72 hours, Occult blood, 1+ | 0 Participants |
| Part A-GSK3036656 25 mg | Number of Participants With Abnormal Urinalysis Parameters for Part A | 72 hours, Occult blood, trace-intact | 0 Participants |
| Part A-GSK3036656 25 mg | Number of Participants With Abnormal Urinalysis Parameters for Part A | 72 hours, Occult blood, trace-lysed | 1 Participants |
| Part A-GSK3036656 25 mg | Number of Participants With Abnormal Urinalysis Parameters for Part A | 72 hours, Protein, Trace | 0 Participants |
| Part A-GSK3036656 5 mg (Fed) | Number of Participants With Abnormal Urinalysis Parameters for Part A | Day -1, Occult blood, 1+ | 1 Participants |
| Part A-GSK3036656 5 mg (Fed) | Number of Participants With Abnormal Urinalysis Parameters for Part A | 72 hours, Occult blood, 1+ | 0 Participants |
| Part A-GSK3036656 5 mg (Fed) | Number of Participants With Abnormal Urinalysis Parameters for Part A | 24 hours, Ketones, 2+ | 0 Participants |
| Part A-GSK3036656 5 mg (Fed) | Number of Participants With Abnormal Urinalysis Parameters for Part A | Day -1, Protein, Trace | 1 Participants |
| Part A-GSK3036656 5 mg (Fed) | Number of Participants With Abnormal Urinalysis Parameters for Part A | Day -1, Ketone, Trace | 0 Participants |
| Part A-GSK3036656 5 mg (Fed) | Number of Participants With Abnormal Urinalysis Parameters for Part A | 72 hours, Occult blood, trace-intact | 1 Participants |
| Part A-GSK3036656 5 mg (Fed) | Number of Participants With Abnormal Urinalysis Parameters for Part A | Day -1, Occult blood, trace-lysed | 0 Participants |
| Part A-GSK3036656 5 mg (Fed) | Number of Participants With Abnormal Urinalysis Parameters for Part A | Day -1, Occult blood, trace-intact | 0 Participants |
| Part A-GSK3036656 5 mg (Fed) | Number of Participants With Abnormal Urinalysis Parameters for Part A | Day -1, Occult blood, 2+ | 0 Participants |
| Part A-GSK3036656 5 mg (Fed) | Number of Participants With Abnormal Urinalysis Parameters for Part A | 72 hours, Protein, Trace | 0 Participants |
| Part A-GSK3036656 5 mg (Fed) | Number of Participants With Abnormal Urinalysis Parameters for Part A | 72 hours, Occult blood, trace-lysed | 0 Participants |
| Part A-GSK3036656 5 mg (Fed) | Number of Participants With Abnormal Urinalysis Parameters for Part A | 72 hours, Ketone, Trace | 0 Participants |
| Part A-GSK3036656 5 mg (Fed) | Number of Participants With Abnormal Urinalysis Parameters for Part A | 24 hours, Occult blood, trace-lysed | 0 Participants |
| Part A-GSK3036656 5 mg (Fed) | Number of Participants With Abnormal Urinalysis Parameters for Part A | 24 hours, Occult blood, trace-intact | 0 Participants |
| Part A-GSK3036656 5 mg (Fed) | Number of Participants With Abnormal Urinalysis Parameters for Part A | 24 hours, Occult blood, 2+ | 0 Participants |
Primary
Number of Participants With Abnormal Urinalysis Parameters for Part B
Urinalysis included dipstick urine test which was used to screen for glucose, ketones, occult blood and protein up to 14 days post dose The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters of urine glucose, ketones, occult blood and protein can be read as negative, trace, trace-intact, trace-lysed, 1+ and 2+ indicating proportional concentrations in the urine sample. Only categories with non-negative values have been presented. Only those participants available at the specified time points were analyzed represented by n=x in the category titles. Period 1 = Cohort 1 in Part B, Period 2 = Cohort 2 in Part B.
Time frame: Up to 8 weeks
Population: Safety Population for Part B
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A-Matching Placebo | Number of Participants With Abnormal Urinalysis Parameters for Part B | Follow-up (week 8), Ketones, n=4,7,8 | 0 Participants |
| Part A-Matching Placebo | Number of Participants With Abnormal Urinalysis Parameters for Part B | Day -1, Ketones, Trace,n=2,7,0 | 0 Participants |
| Part A-Matching Placebo | Number of Participants With Abnormal Urinalysis Parameters for Part B | Day 6,Occult blood,Trace-intact,n=2,0,8 | 0 Participants |
| Part A-Matching Placebo | Number of Participants With Abnormal Urinalysis Parameters for Part B | Day 6,Occult blood,Trace-lysed,n=2,0,8 | 0 Participants |
| Part A-Matching Placebo | Number of Participants With Abnormal Urinalysis Parameters for Part B | Day -1, Occult blood,Trace-intact,n=2,7,0 | 1 Participants |
| Part A-Matching Placebo | Number of Participants With Abnormal Urinalysis Parameters for Part B | Day 10, Ketones, Trace,n=2,0,8 | 0 Participants |
| Part A-Matching Placebo | Number of Participants With Abnormal Urinalysis Parameters for Part B | Day 14, Protein, 2+,n=2,0,8 | 0 Participants |
| Part A-Matching Placebo | Number of Participants With Abnormal Urinalysis Parameters for Part B | Day 14, Ketones, Trace,n=2,7,0 | 0 Participants |
| Part A-Matching Placebo | Number of Participants With Abnormal Urinalysis Parameters for Part B | Follow up (week 8), Occult blood, n=4,7,8 | 1 Participants |
| Part A-Matching Placebo | Number of Participants With Abnormal Urinalysis Parameters for Part B | Follow-up(week 8),Occult blood,Trace-lysed,n=4,7,8 | 0 Participants |
| Part A-Matching Placebo | Number of Participants With Abnormal Urinalysis Parameters for Part B | Day 14, protein, 1+,n=2,7,0 | 0 Participants |
| Part A-Matching Placebo | Number of Participants With Abnormal Urinalysis Parameters for Part B | Day -1,Occult blood,Trace-intact,n=2,0,8 | 1 Participants |
| Part A-GSK3036656 5 mg | Number of Participants With Abnormal Urinalysis Parameters for Part B | Day 14, Ketones, Trace,n=2,7,0 | 1 Participants |
| Part A-GSK3036656 5 mg | Number of Participants With Abnormal Urinalysis Parameters for Part B | Day -1, Ketones, Trace,n=2,7,0 | 1 Participants |
| Part A-GSK3036656 5 mg | Number of Participants With Abnormal Urinalysis Parameters for Part B | Follow up (week 8), Occult blood, n=4,7,8 | 0 Participants |
| Part A-GSK3036656 5 mg | Number of Participants With Abnormal Urinalysis Parameters for Part B | Day 14, protein, 1+,n=2,7,0 | 1 Participants |
| Part A-GSK3036656 5 mg | Number of Participants With Abnormal Urinalysis Parameters for Part B | Follow-up (week 8), Ketones, n=4,7,8 | 0 Participants |
| Part A-GSK3036656 5 mg | Number of Participants With Abnormal Urinalysis Parameters for Part B | Follow-up(week 8),Occult blood,Trace-lysed,n=4,7,8 | 0 Participants |
| Part A-GSK3036656 5 mg | Number of Participants With Abnormal Urinalysis Parameters for Part B | Day -1, Occult blood,Trace-intact,n=2,7,0 | 0 Participants |
| Part A-GSK3036656 15 mg | Number of Participants With Abnormal Urinalysis Parameters for Part B | Follow-up(week 8),Occult blood,Trace-lysed,n=4,7,8 | 2 Participants |
| Part A-GSK3036656 15 mg | Number of Participants With Abnormal Urinalysis Parameters for Part B | Day -1,Occult blood,Trace-intact,n=2,0,8 | 2 Participants |
| Part A-GSK3036656 15 mg | Number of Participants With Abnormal Urinalysis Parameters for Part B | Day 6,Occult blood,Trace-intact,n=2,0,8 | 1 Participants |
| Part A-GSK3036656 15 mg | Number of Participants With Abnormal Urinalysis Parameters for Part B | Day 6,Occult blood,Trace-lysed,n=2,0,8 | 2 Participants |
| Part A-GSK3036656 15 mg | Number of Participants With Abnormal Urinalysis Parameters for Part B | Day 10, Ketones, Trace,n=2,0,8 | 1 Participants |
| Part A-GSK3036656 15 mg | Number of Participants With Abnormal Urinalysis Parameters for Part B | Day 14, Protein, 2+,n=2,0,8 | 1 Participants |
| Part A-GSK3036656 15 mg | Number of Participants With Abnormal Urinalysis Parameters for Part B | Follow-up (week 8), Ketones, n=4,7,8 | 1 Participants |
| Part A-GSK3036656 15 mg | Number of Participants With Abnormal Urinalysis Parameters for Part B | Follow up (week 8), Occult blood, n=4,7,8 | 1 Participants |
Primary
Number of Participants With Clinical Chemistry Parameters of PCI for Part A
Blood samples were collected for the assessment of clinical chemistry parameters namely blood urea nitrogen (BUN), creatinine, glucose, cholesterol, potassium, sodium, calcium, aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase, triglycerides, total and direct bilirubin, total protein, albumin and troponin. Only categories with PCI values have been presented, therefore only AST is presented.
Time frame: Up to 12 weeks
Population: Safety Population for Part A. For arm Part A-Matching Placebo 3 of the 9 placebo participants received placebo twice, therefore they had these measures done in 2 different treatment periods, so N=9 but number of units analyzed=12.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A-Matching Placebo | Number of Participants With Clinical Chemistry Parameters of PCI for Part A | 0 Participants |
| Part A-GSK3036656 5 mg | Number of Participants With Clinical Chemistry Parameters of PCI for Part A | 0 Participants |
| Part A-GSK3036656 15 mg | Number of Participants With Clinical Chemistry Parameters of PCI for Part A | 0 Participants |
| Part A-GSK3036656 25 mg | Number of Participants With Clinical Chemistry Parameters of PCI for Part A | 0 Participants |
| Part A-GSK3036656 5 mg (Fed) | Number of Participants With Clinical Chemistry Parameters of PCI for Part A | 1 Participants |
Primary
Number of Participants With Clinical Chemistry Parameters of PCI for Part B
Blood samples were collected for the assessment of clinical chemistry parameters namely BUN, creatinine, glucose, cholesterol, potassium, sodium, calcium, AST, ALT, alkaline phosphatase, triglycerides, total and direct bilirubin, total protein, albumin and troponin. Only categories with PCI values have been presented.
Time frame: Up to 8 weeks
Population: Safety Population for Part B
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A-Matching Placebo | Number of Participants With Clinical Chemistry Parameters of PCI for Part B | ALT | 0 Participants |
| Part A-Matching Placebo | Number of Participants With Clinical Chemistry Parameters of PCI for Part B | AST | 0 Participants |
| Part A-GSK3036656 5 mg | Number of Participants With Clinical Chemistry Parameters of PCI for Part B | AST | 1 Participants |
| Part A-GSK3036656 5 mg | Number of Participants With Clinical Chemistry Parameters of PCI for Part B | ALT | 1 Participants |
| Part A-GSK3036656 15 mg | Number of Participants With Clinical Chemistry Parameters of PCI for Part B | ALT | 0 Participants |
| Part A-GSK3036656 15 mg | Number of Participants With Clinical Chemistry Parameters of PCI for Part B | AST | 0 Participants |
Primary
Number of Participants With Hematology Parameters of PCI for Part A
Blood samples were collected for the assessment of hematology parameters platelet count, red blood cell count, hemoglobin, hematocrit, reticulocytes, mean corpuscle volume, mean corpuscular hemoglobin, neutrophils, lymphocytes, monocytes, basophils and eosinophils. Only categories with PCI values have been presented.
Time frame: Up to 12 weeks
Population: Safety Population for Part A. For arm Part A-Matching Placebo 3 of the 9 placebo participants received placebo twice, therefore they had these measures done in 2 different treatment periods, so N=9 but number of units analyzed=12.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A-Matching Placebo | Number of Participants With Hematology Parameters of PCI for Part A | 0 Participants |
| Part A-GSK3036656 5 mg | Number of Participants With Hematology Parameters of PCI for Part A | 0 Participants |
| Part A-GSK3036656 15 mg | Number of Participants With Hematology Parameters of PCI for Part A | 0 Participants |
| Part A-GSK3036656 25 mg | Number of Participants With Hematology Parameters of PCI for Part A | 0 Participants |
| Part A-GSK3036656 5 mg (Fed) | Number of Participants With Hematology Parameters of PCI for Part A | 0 Participants |
Primary
Number of Participants With Hematology Parameters of PCI for Part B
Blood samples were collected for the assessment of hematology parameters platelet count, red blood cell count, hemoglobin, hematocrit, reticulocytes, mean corpuscle volume, mean corpuscular hemoglobin, neutrophils, lymphocytes, monocytes, basophils and eosinophils. Only categories with PCI values have been presented.
Time frame: Up to 8 weeks
Population: Safety Population for Part B
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A-Matching Placebo | Number of Participants With Hematology Parameters of PCI for Part B | Neutrophils | 0 Participants |
| Part A-Matching Placebo | Number of Participants With Hematology Parameters of PCI for Part B | Leukocytes | 0 Participants |
| Part A-GSK3036656 5 mg | Number of Participants With Hematology Parameters of PCI for Part B | Leukocytes | 1 Participants |
| Part A-GSK3036656 5 mg | Number of Participants With Hematology Parameters of PCI for Part B | Neutrophils | 1 Participants |
| Part A-GSK3036656 15 mg | Number of Participants With Hematology Parameters of PCI for Part B | Leukocytes | 0 Participants |
| Part A-GSK3036656 15 mg | Number of Participants With Hematology Parameters of PCI for Part B | Neutrophils | 1 Participants |
Primary
Number of Participants With Non-serious Adverse Events (nSAE) and Serious Adverse Events (SAEs) for Part A
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations judged by physician, such as important medical events that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in the above. Safety Population comprised of all randomized participants who received at least one dose of study medication.
Time frame: Up to 12 weeks
Population: Safety Population for Part A
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A-Matching Placebo | Number of Participants With Non-serious Adverse Events (nSAE) and Serious Adverse Events (SAEs) for Part A | nSAE | 1 Participants |
| Part A-Matching Placebo | Number of Participants With Non-serious Adverse Events (nSAE) and Serious Adverse Events (SAEs) for Part A | SAE | 0 Participants |
| Part A-GSK3036656 5 mg | Number of Participants With Non-serious Adverse Events (nSAE) and Serious Adverse Events (SAEs) for Part A | nSAE | 1 Participants |
| Part A-GSK3036656 5 mg | Number of Participants With Non-serious Adverse Events (nSAE) and Serious Adverse Events (SAEs) for Part A | SAE | 0 Participants |
| Part A-GSK3036656 15 mg | Number of Participants With Non-serious Adverse Events (nSAE) and Serious Adverse Events (SAEs) for Part A | nSAE | 1 Participants |
| Part A-GSK3036656 15 mg | Number of Participants With Non-serious Adverse Events (nSAE) and Serious Adverse Events (SAEs) for Part A | SAE | 0 Participants |
| Part A-GSK3036656 25 mg | Number of Participants With Non-serious Adverse Events (nSAE) and Serious Adverse Events (SAEs) for Part A | SAE | 0 Participants |
| Part A-GSK3036656 25 mg | Number of Participants With Non-serious Adverse Events (nSAE) and Serious Adverse Events (SAEs) for Part A | nSAE | 3 Participants |
| Part A-GSK3036656 5 mg (Fed) | Number of Participants With Non-serious Adverse Events (nSAE) and Serious Adverse Events (SAEs) for Part A | nSAE | 1 Participants |
| Part A-GSK3036656 5 mg (Fed) | Number of Participants With Non-serious Adverse Events (nSAE) and Serious Adverse Events (SAEs) for Part A | SAE | 0 Participants |
Primary
Number of Participants With nSAE and SAEs for Part B
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations judged by physician, such as important medical events that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in the above.
Time frame: Up to 8 weeks
Population: Safety Population for Part B
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A-Matching Placebo | Number of Participants With nSAE and SAEs for Part B | nSAE | 0 Participants |
| Part A-Matching Placebo | Number of Participants With nSAE and SAEs for Part B | SAE | 0 Participants |
| Part A-GSK3036656 5 mg | Number of Participants With nSAE and SAEs for Part B | nSAE | 2 Participants |
| Part A-GSK3036656 5 mg | Number of Participants With nSAE and SAEs for Part B | SAE | 0 Participants |
| Part A-GSK3036656 15 mg | Number of Participants With nSAE and SAEs for Part B | nSAE | 1 Participants |
| Part A-GSK3036656 15 mg | Number of Participants With nSAE and SAEs for Part B | SAE | 0 Participants |
Primary
Number of Participants With Vital Sign Parameter Heart Rate of PCI for Part A
Heart rate was assessed in supine position with a completely automated device. Measurements were preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions (e.g., television, cell phones). The PCI range for heart was less than 40 bpm (lower) and greater than 110 bpm (upper).
Time frame: Up to 6 weeks
Population: Safety Population for Part A. For arm Part A-Matching Placebo 3 of the 9 placebo participants received placebo twice, therefore they had these measures done in 2 different treatment periods, so N=9 but number of units analyzed=12.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A-Matching Placebo | Number of Participants With Vital Sign Parameter Heart Rate of PCI for Part A | 0 Participants |
| Part A-GSK3036656 5 mg | Number of Participants With Vital Sign Parameter Heart Rate of PCI for Part A | 0 Participants |
| Part A-GSK3036656 15 mg | Number of Participants With Vital Sign Parameter Heart Rate of PCI for Part A | 0 Participants |
| Part A-GSK3036656 25 mg | Number of Participants With Vital Sign Parameter Heart Rate of PCI for Part A | 0 Participants |
| Part A-GSK3036656 5 mg (Fed) | Number of Participants With Vital Sign Parameter Heart Rate of PCI for Part A | 0 Participants |
Primary
Number of Participants With Vital Sign Parameter Heart Rate of PCI for Part B
Heart rate was assessed in supine position with a completely automated device. Measurements were preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions (e.g., television, cell phones). The PCI range for heart was less than 40 bpm (lower) and greater than 110 bpm (upper).
Time frame: Up to 8 weeks
Population: Safety Population for Part B
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A-Matching Placebo | Number of Participants With Vital Sign Parameter Heart Rate of PCI for Part B | 0 Participants |
| Part A-GSK3036656 5 mg | Number of Participants With Vital Sign Parameter Heart Rate of PCI for Part B | 0 Participants |
| Part A-GSK3036656 15 mg | Number of Participants With Vital Sign Parameter Heart Rate of PCI for Part B | 0 Participants |
Primary
Number of Participants With Vital Sign Parameters SBP and DBP of PCI for Part B
SBP and DBP were assessed in supine position with a completely automated device. Measurements were preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions (e.g., television, cell phones). The PCI range for SBP was less than 85 mmHg (lower) and greater than 160 mmHg (upper) while that for DBP was less than 45 mmHg (lower) and greater than 100 mmHg (upper).
Time frame: Up to 8 weeks
Population: Safety Population for Part B
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A-Matching Placebo | Number of Participants With Vital Sign Parameters SBP and DBP of PCI for Part B | DBP | 0 Participants |
| Part A-Matching Placebo | Number of Participants With Vital Sign Parameters SBP and DBP of PCI for Part B | SBP | 0 Participants |
| Part A-GSK3036656 5 mg | Number of Participants With Vital Sign Parameters SBP and DBP of PCI for Part B | SBP | 0 Participants |
| Part A-GSK3036656 5 mg | Number of Participants With Vital Sign Parameters SBP and DBP of PCI for Part B | DBP | 0 Participants |
| Part A-GSK3036656 15 mg | Number of Participants With Vital Sign Parameters SBP and DBP of PCI for Part B | SBP | 0 Participants |
| Part A-GSK3036656 15 mg | Number of Participants With Vital Sign Parameters SBP and DBP of PCI for Part B | DBP | 1 Participants |
Primary
Number of Participants With Vital Sign Parameters Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) of Potential Clinical Importance (PCI) for Part A
SBP and DBP were assessed in supine position with a completely automated device. Measurements were preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions (e.g., television, cell phones). The PCI range for SBP was less than 85 mmHg (lower) and greater than 160 mmHg (upper) while that for DBP was less than 45 mmHg (lower) and greater than 100 mmHg (upper).
Time frame: Up to 6 weeks
Population: Safety Population for Part A. For arm Part A-Matching Placebo 3 of the 9 placebo participants received placebo twice, therefore they had these measures done in 2 different treatment periods, so N=9 but number of units analyzed=12.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A-Matching Placebo | Number of Participants With Vital Sign Parameters Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) of Potential Clinical Importance (PCI) for Part A | DBP | 0 Participants |
| Part A-Matching Placebo | Number of Participants With Vital Sign Parameters Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) of Potential Clinical Importance (PCI) for Part A | SBP | 0 Participants |
| Part A-GSK3036656 5 mg | Number of Participants With Vital Sign Parameters Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) of Potential Clinical Importance (PCI) for Part A | DBP | 0 Participants |
| Part A-GSK3036656 5 mg | Number of Participants With Vital Sign Parameters Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) of Potential Clinical Importance (PCI) for Part A | SBP | 0 Participants |
| Part A-GSK3036656 15 mg | Number of Participants With Vital Sign Parameters Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) of Potential Clinical Importance (PCI) for Part A | DBP | 0 Participants |
| Part A-GSK3036656 15 mg | Number of Participants With Vital Sign Parameters Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) of Potential Clinical Importance (PCI) for Part A | SBP | 0 Participants |
| Part A-GSK3036656 25 mg | Number of Participants With Vital Sign Parameters Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) of Potential Clinical Importance (PCI) for Part A | SBP | 0 Participants |
| Part A-GSK3036656 25 mg | Number of Participants With Vital Sign Parameters Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) of Potential Clinical Importance (PCI) for Part A | DBP | 0 Participants |
| Part A-GSK3036656 5 mg (Fed) | Number of Participants With Vital Sign Parameters Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) of Potential Clinical Importance (PCI) for Part A | DBP | 0 Participants |
| Part A-GSK3036656 5 mg (Fed) | Number of Participants With Vital Sign Parameters Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) of Potential Clinical Importance (PCI) for Part A | SBP | 0 Participants |
Primary
Number of Participants With Vital Sign Parameter Temperature of PCI for Part A
Number of participants with temperature data of PCI have been presented.
Time frame: Up to 6 weeks
Population: Safety Population for Part A. For arm Part A-Matching Placebo 3 of the 9 placebo participants received placebo twice, therefore they had these measures done in 2 different treatment periods, so N=9 but number of units analyzed=12.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A-Matching Placebo | Number of Participants With Vital Sign Parameter Temperature of PCI for Part A | 0 Participants |
| Part A-GSK3036656 5 mg | Number of Participants With Vital Sign Parameter Temperature of PCI for Part A | 0 Participants |
| Part A-GSK3036656 15 mg | Number of Participants With Vital Sign Parameter Temperature of PCI for Part A | 0 Participants |
| Part A-GSK3036656 25 mg | Number of Participants With Vital Sign Parameter Temperature of PCI for Part A | 0 Participants |
| Part A-GSK3036656 5 mg (Fed) | Number of Participants With Vital Sign Parameter Temperature of PCI for Part A | 0 Participants |
Primary
Number of Participants With Vital Sign Parameter Temperature of PCI for Part B
Number of participants with temperature data of PCI have been presented.
Time frame: Up to 8 weeks
Population: Safety Population for Part B
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A-Matching Placebo | Number of Participants With Vital Sign Parameter Temperature of PCI for Part B | 0 Participants |
| Part A-GSK3036656 5 mg | Number of Participants With Vital Sign Parameter Temperature of PCI for Part B | 0 Participants |
| Part A-GSK3036656 15 mg | Number of Participants With Vital Sign Parameter Temperature of PCI for Part B | 0 Participants |
Primary
Number of Subjects With Clinically Relevant Changes in ECG in Part B
12-lead ECGs were collected during the study using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT interval and QTcF intervals. At each time point at which triplicate ECGs were required, three individual ECG tracings were obtained as closely as possible in succession, but no more than 2 to 5 minutes apart. ECG findings were categorized as normal, A-NCS and A-CS. Only A-NCS and A-CS worst case post-Baseline values have been presented.
Time frame: Up to 8 weeks
Population: Safety Population for Part A
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A-Matching Placebo | Number of Subjects With Clinically Relevant Changes in ECG in Part B | A-NCS | 1 Participants |
| Part A-Matching Placebo | Number of Subjects With Clinically Relevant Changes in ECG in Part B | A-CS | 0 Participants |
| Part A-GSK3036656 5 mg | Number of Subjects With Clinically Relevant Changes in ECG in Part B | A-NCS | 3 Participants |
| Part A-GSK3036656 5 mg | Number of Subjects With Clinically Relevant Changes in ECG in Part B | A-CS | 0 Participants |
| Part A-GSK3036656 15 mg | Number of Subjects With Clinically Relevant Changes in ECG in Part B | A-NCS | 3 Participants |
| Part A-GSK3036656 15 mg | Number of Subjects With Clinically Relevant Changes in ECG in Part B | A-CS | 0 Participants |
Primary
t1/2 of GSK3036656 Following Repeated Dose Administration for Part B
Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14. The actual date and time of each blood sample collection was recorded. Results presented are for Day 14.
Time frame: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14.
Population: PK Population for Part B
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A-Matching Placebo | t1/2 of GSK3036656 Following Repeated Dose Administration for Part B | 40.1802 hours |
| Part A-GSK3036656 5 mg | t1/2 of GSK3036656 Following Repeated Dose Administration for Part B | 34.5109 hours |
Primary
Time to Maximum Observed Plasma Drug Concentration (Tmax) of GSK3036656 Following Single Dose Administration for Part A
Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period. The actual date and time of each blood sample collection was recorded.
Time frame: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period
Population: PK Population for Part A
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A-Matching Placebo | Time to Maximum Observed Plasma Drug Concentration (Tmax) of GSK3036656 Following Single Dose Administration for Part A | 1.250 hours |
| Part A-GSK3036656 5 mg | Time to Maximum Observed Plasma Drug Concentration (Tmax) of GSK3036656 Following Single Dose Administration for Part A | 1.000 hours |
| Part A-GSK3036656 15 mg | Time to Maximum Observed Plasma Drug Concentration (Tmax) of GSK3036656 Following Single Dose Administration for Part A | 0.875 hours |
| Part A-GSK3036656 25 mg | Time to Maximum Observed Plasma Drug Concentration (Tmax) of GSK3036656 Following Single Dose Administration for Part A | 2.000 hours |
Primary
Tmax of GSK3036656 Following Repeat Dose Administration for Part B
Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1; at pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14; and at pre-dose on Days 12 and 13. The actual date and time of each blood sample collection was recorded.
Time frame: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1; at pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14; and at pre-dose on Days 12 and 13
Population: PK Population for Part B
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A-Matching Placebo | Tmax of GSK3036656 Following Repeat Dose Administration for Part B | Day 1 | 1.0000 hours |
| Part A-Matching Placebo | Tmax of GSK3036656 Following Repeat Dose Administration for Part B | Day 14 | 0.7500 hours |
| Part A-GSK3036656 5 mg | Tmax of GSK3036656 Following Repeat Dose Administration for Part B | Day 1 | 0.7500 hours |
| Part A-GSK3036656 5 mg | Tmax of GSK3036656 Following Repeat Dose Administration for Part B | Day 14 | 0.7500 hours |
Primary
Urine pH Analysis by Dipstick Method for Part B
Urinary pH measurement is a routine part of urinalysis. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 - 6.0). Urine samples were collected for the measurement of urine pH by method up to 8 weeks in Part B. Only those participants available at the specified time points were analyzed represented by n=x in the category titles. Period 1 = Cohort 1 in Part B, Period 2 = Cohort 2 in Part B.
Time frame: Up to 8 weeks
Population: Safety Population for Part B
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-Matching Placebo | Urine pH Analysis by Dipstick Method for Part B | pH, Period 1, Day -1, n=2, 7, 0 | 6.25 pH | Standard Deviation 0.354 |
| Part A-Matching Placebo | Urine pH Analysis by Dipstick Method for Part B | pH, Period 2, Day 10, n=2, 0, 8 | 6.00 pH | Standard Deviation 0 |
| Part A-Matching Placebo | Urine pH Analysis by Dipstick Method for Part B | pH, Follow-up (week 8), n=4, 7, 8 | 6.63 pH | Standard Deviation 0.75 |
| Part A-Matching Placebo | Urine pH Analysis by Dipstick Method for Part B | pH, Period 2, Day 14, n=2, 0, 8 | 6.00 pH | Standard Deviation 0 |
| Part A-Matching Placebo | Urine pH Analysis by Dipstick Method for Part B | pH, Period 1, Day 6, n=2, 7, 0 | 6.25 pH | Standard Deviation 0.354 |
| Part A-Matching Placebo | Urine pH Analysis by Dipstick Method for Part B | pH, Period 1, Day 14, n=2, 7, 0 | 6.75 pH | Standard Deviation 0.354 |
| Part A-Matching Placebo | Urine pH Analysis by Dipstick Method for Part B | pH, Period 1, Day 10, n=2, 7, 0 | 6.25 pH | Standard Deviation 0.354 |
| Part A-Matching Placebo | Urine pH Analysis by Dipstick Method for Part B | pH, Period 2, Day -1, n=2, 0, 8 | 6.50 pH | Standard Deviation 0.707 |
| Part A-Matching Placebo | Urine pH Analysis by Dipstick Method for Part B | pH, Period 1, Day 4, n= 2, 7, 0 | 6.25 pH | Standard Deviation 0.354 |
| Part A-Matching Placebo | Urine pH Analysis by Dipstick Method for Part B | pH, Period 2, Day 4, n=2, 0, 8 | 5.50 pH | Standard Deviation 0.707 |
| Part A-Matching Placebo | Urine pH Analysis by Dipstick Method for Part B | pH, Period 2, Day 6, n=2, 0, 8 | 6.50 pH | Standard Deviation 0 |
| Part A-GSK3036656 5 mg | Urine pH Analysis by Dipstick Method for Part B | pH, Period 1, Day -1, n=2, 7, 0 | 6.71 pH | Standard Deviation 0.906 |
| Part A-GSK3036656 5 mg | Urine pH Analysis by Dipstick Method for Part B | pH, Period 1, Day 6, n=2, 7, 0 | 6.43 pH | Standard Deviation 0.535 |
| Part A-GSK3036656 5 mg | Urine pH Analysis by Dipstick Method for Part B | pH, Period 1, Day 10, n=2, 7, 0 | 6.14 pH | Standard Deviation 0.244 |
| Part A-GSK3036656 5 mg | Urine pH Analysis by Dipstick Method for Part B | pH, Period 1, Day 14, n=2, 7, 0 | 7.00 pH | Standard Deviation 0.957 |
| Part A-GSK3036656 5 mg | Urine pH Analysis by Dipstick Method for Part B | pH, Follow-up (week 8), n=4, 7, 8 | 6.29 pH | Standard Deviation 0.488 |
| Part A-GSK3036656 5 mg | Urine pH Analysis by Dipstick Method for Part B | pH, Period 1, Day 4, n= 2, 7, 0 | 5.79 pH | Standard Deviation 0.393 |
| Part A-GSK3036656 15 mg | Urine pH Analysis by Dipstick Method for Part B | pH, Period 2, Day 6, n=2, 0, 8 | 6.69 pH | Standard Deviation 0.458 |
| Part A-GSK3036656 15 mg | Urine pH Analysis by Dipstick Method for Part B | pH, Follow-up (week 8), n=4, 7, 8 | 6.88 pH | Standard Deviation 0.744 |
| Part A-GSK3036656 15 mg | Urine pH Analysis by Dipstick Method for Part B | pH, Period 2, Day -1, n=2, 0, 8 | 6.81 pH | Standard Deviation 0.594 |
| Part A-GSK3036656 15 mg | Urine pH Analysis by Dipstick Method for Part B | pH, Period 2, Day 4, n=2, 0, 8 | 6.25 pH | Standard Deviation 0.378 |
| Part A-GSK3036656 15 mg | Urine pH Analysis by Dipstick Method for Part B | pH, Period 2, Day 14, n=2, 0, 8 | 6.38 pH | Standard Deviation 0.582 |
| Part A-GSK3036656 15 mg | Urine pH Analysis by Dipstick Method for Part B | pH, Period 2, Day 10, n=2, 0, 8 | 6.38 pH | Standard Deviation 0.354 |
Primary
Urine Potential of Hydrogen (pH) Analysis by Dipstick Method for Part A
Urinary pH measurement is a routine part of urinalysis. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 - 6.0). Urine samples were collected for the measurement of urine pH by method up to 72 hours in Part A. Only those participants with data available at the indicated time points were analyzed.
Time frame: Up to 72 hours post-dose
Population: Safety Population for Part A. For arm Part A-Matching Placebo 3 of the 9 placebo participants received placebo twice, therefore they had these measures done in 2 different treatment periods, so N=9 but number of units analyzed=12.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-Matching Placebo | Urine Potential of Hydrogen (pH) Analysis by Dipstick Method for Part A | pH at 24 hours | 6.04 pH | Standard Deviation 0.498 |
| Part A-Matching Placebo | Urine Potential of Hydrogen (pH) Analysis by Dipstick Method for Part A | pH at Day -1 | 6.08 pH | Standard Deviation 0.469 |
| Part A-Matching Placebo | Urine Potential of Hydrogen (pH) Analysis by Dipstick Method for Part A | pH at 72 hours | 6.46 pH | Standard Deviation 0.753 |
| Part A-GSK3036656 5 mg | Urine Potential of Hydrogen (pH) Analysis by Dipstick Method for Part A | pH at 24 hours | 6.50 pH | Standard Deviation 0.447 |
| Part A-GSK3036656 5 mg | Urine Potential of Hydrogen (pH) Analysis by Dipstick Method for Part A | pH at Day -1 | 6.00 pH | Standard Deviation 0.548 |
| Part A-GSK3036656 5 mg | Urine Potential of Hydrogen (pH) Analysis by Dipstick Method for Part A | pH at 72 hours | 6.00 pH | Standard Deviation 1.095 |
| Part A-GSK3036656 15 mg | Urine Potential of Hydrogen (pH) Analysis by Dipstick Method for Part A | pH at 72 hours | 5.92 pH | Standard Deviation 0.492 |
| Part A-GSK3036656 15 mg | Urine Potential of Hydrogen (pH) Analysis by Dipstick Method for Part A | pH at Day -1 | 5.50 pH | Standard Deviation 0.548 |
| Part A-GSK3036656 15 mg | Urine Potential of Hydrogen (pH) Analysis by Dipstick Method for Part A | pH at 24 hours | 5.83 pH | Standard Deviation 0.258 |
| Part A-GSK3036656 25 mg | Urine Potential of Hydrogen (pH) Analysis by Dipstick Method for Part A | pH at 24 hours | 6.08 pH | Standard Deviation 0.204 |
| Part A-GSK3036656 25 mg | Urine Potential of Hydrogen (pH) Analysis by Dipstick Method for Part A | pH at Day -1 | 5.92 pH | Standard Deviation 0.492 |
| Part A-GSK3036656 25 mg | Urine Potential of Hydrogen (pH) Analysis by Dipstick Method for Part A | pH at 72 hours | 6.42 pH | Standard Deviation 0.665 |
| Part A-GSK3036656 5 mg (Fed) | Urine Potential of Hydrogen (pH) Analysis by Dipstick Method for Part A | pH at 24 hours | 6.80 pH | Standard Deviation 1.095 |
| Part A-GSK3036656 5 mg (Fed) | Urine Potential of Hydrogen (pH) Analysis by Dipstick Method for Part A | pH at Day -1 | 6.70 pH | Standard Deviation 1.483 |
| Part A-GSK3036656 5 mg (Fed) | Urine Potential of Hydrogen (pH) Analysis by Dipstick Method for Part A | pH at 72 hours | 7.30 pH | Standard Deviation 0.671 |
Secondary
AUC (0-infinity) as a Measure of Dose Proportionality of GSK3036656 Following Single Dose Administrations for Part A
Blood samples for the analysis of AUC (0-infinity) were collected at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period. AUC(0-infinity) following single doses was used for assessment of dose proportionality.
Time frame: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period
Population: PK Population for Part A
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A-Matching Placebo | AUC (0-infinity) as a Measure of Dose Proportionality of GSK3036656 Following Single Dose Administrations for Part A | 1404.5416 hours*nanograms/milliliter | Geometric Coefficient of Variation 29.9 |
| Part A-GSK3036656 5 mg | AUC (0-infinity) as a Measure of Dose Proportionality of GSK3036656 Following Single Dose Administrations for Part A | 3796.1488 hours*nanograms/milliliter | Geometric Coefficient of Variation 19.8 |
| Part A-GSK3036656 15 mg | AUC (0-infinity) as a Measure of Dose Proportionality of GSK3036656 Following Single Dose Administrations for Part A | 6557.7764 hours*nanograms/milliliter | Geometric Coefficient of Variation 13.8 |
| Part A-GSK3036656 25 mg | AUC (0-infinity) as a Measure of Dose Proportionality of GSK3036656 Following Single Dose Administrations for Part A | 1450.7468 hours*nanograms/milliliter | Geometric Coefficient of Variation 9.4 |
90% CI: [0.82, 1.1]
Secondary
AUC (0-infinity) of GSK3036656 Following Single Dose Administration in Fed Condition in Part A
Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period. The actual date and time of each blood sample collection was recorded. For the food effect assessment, the selected dose was given with a high fat meal.
Time frame: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period
Population: PK Population for Part A
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A-Matching Placebo | AUC (0-infinity) of GSK3036656 Following Single Dose Administration in Fed Condition in Part A | 1404.5416 hours*nanograms/milliliter | Geometric Coefficient of Variation 29.9 |
| Part A-GSK3036656 5 mg | AUC (0-infinity) of GSK3036656 Following Single Dose Administration in Fed Condition in Part A | 3796.1488 hours*nanograms/milliliter | Geometric Coefficient of Variation 19.8 |
| Part A-GSK3036656 15 mg | AUC (0-infinity) of GSK3036656 Following Single Dose Administration in Fed Condition in Part A | 6557.7764 hours*nanograms/milliliter | Geometric Coefficient of Variation 13.8 |
| Part A-GSK3036656 25 mg | AUC (0-infinity) of GSK3036656 Following Single Dose Administration in Fed Condition in Part A | 1450.7468 hours*nanograms/milliliter | Geometric Coefficient of Variation 9.4 |
90% CI: [0.71, 1.26]
Secondary
AUC (0-t) as a Measure of Dose Proportionality of GSK3036656 Following Single Dose Administrations for Part A
Blood samples for the analysis of AUC (0-t) were collected at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period. AUC(0-t) following single doses was used for assessment of dose proportionality.
Time frame: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period
Population: PK Population for Part A
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A-Matching Placebo | AUC (0-t) as a Measure of Dose Proportionality of GSK3036656 Following Single Dose Administrations for Part A | 771.0468 hours*nanograms/milliliter | Geometric Coefficient of Variation 26 |
| Part A-GSK3036656 5 mg | AUC (0-t) as a Measure of Dose Proportionality of GSK3036656 Following Single Dose Administrations for Part A | 3252.9152 hours*nanograms/milliliter | Geometric Coefficient of Variation 24.1 |
| Part A-GSK3036656 15 mg | AUC (0-t) as a Measure of Dose Proportionality of GSK3036656 Following Single Dose Administrations for Part A | 5686.4151 hours*nanograms/milliliter | Geometric Coefficient of Variation 11.4 |
| Part A-GSK3036656 25 mg | AUC (0-t) as a Measure of Dose Proportionality of GSK3036656 Following Single Dose Administrations for Part A | 782.7766 hours*nanograms/milliliter | Geometric Coefficient of Variation 18.1 |
90% CI: [1.24, 1.39]
Secondary
AUC (0-tau) as a Measure of Dose Proportionality of GSK3036656 Following Repeat Dose Administrations for Part B
Blood samples for the assessment of AUC (0-tau) were collected at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1; at pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14; and at pre-dose on Days 12 and 13. AUC (0-tau) following repeat doses was used for assessment of dose proportionality.
Time frame: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1; at pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14; and at pre-dose on Days 12 and 13
Population: PK Population for Part B
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A-Matching Placebo | AUC (0-tau) as a Measure of Dose Proportionality of GSK3036656 Following Repeat Dose Administrations for Part B | 1392.2221 hours*nanograms/milliliter | Geometric Coefficient of Variation 12.5 |
| Part A-GSK3036656 5 mg | AUC (0-tau) as a Measure of Dose Proportionality of GSK3036656 Following Repeat Dose Administrations for Part B | 4461.2565 hours*nanograms/milliliter | Geometric Coefficient of Variation 23.7 |
90% CI: [1.15, 1.33]
90% CI: [0.9, 1.22]
Secondary
AUC (0-t) of GSK3036656 Following Single Dose Administration in Fed Condition in Part A
Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period. The actual date and time of each blood sample collection was recorded. For the food effect assessment, the selected dose was given with a high fat meal.
Time frame: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period
Population: PK Population for Part A
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A-Matching Placebo | AUC (0-t) of GSK3036656 Following Single Dose Administration in Fed Condition in Part A | 771.0468 hours*nanograms/milliliter | Geometric Coefficient of Variation 26 |
| Part A-GSK3036656 5 mg | AUC (0-t) of GSK3036656 Following Single Dose Administration in Fed Condition in Part A | 3252.9152 hours*nanograms/milliliter | Geometric Coefficient of Variation 24.1 |
| Part A-GSK3036656 15 mg | AUC (0-t) of GSK3036656 Following Single Dose Administration in Fed Condition in Part A | 5686.4151 hours*nanograms/milliliter | Geometric Coefficient of Variation 11.4 |
| Part A-GSK3036656 25 mg | AUC (0-t) of GSK3036656 Following Single Dose Administration in Fed Condition in Part A | 782.7766 hours*nanograms/milliliter | Geometric Coefficient of Variation 18.1 |
90% CI: [0.87, 1.34]
Secondary
Cmax as a Measure of Dose Proportionality of GSK3036656 Following Repeat Dose Administrations for Part B
Blood samples for the assessment of Cmax were collected at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1; at pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14; and at pre-dose on Days 12 and 13. Cmax following repeat doses was used for assessment of dose proportionality.
Time frame: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1; at pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14; and at pre-dose on Days 12 and 13
Population: PK Population for Part B
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-Matching Placebo | Cmax as a Measure of Dose Proportionality of GSK3036656 Following Repeat Dose Administrations for Part B | Day 1 | 48.40 nanograms/milliliter | Geometric Coefficient of Variation 33.6 |
| Part A-Matching Placebo | Cmax as a Measure of Dose Proportionality of GSK3036656 Following Repeat Dose Administrations for Part B | Day 14 | 97.04 nanograms/milliliter | Geometric Coefficient of Variation 19.8 |
| Part A-GSK3036656 5 mg | Cmax as a Measure of Dose Proportionality of GSK3036656 Following Repeat Dose Administrations for Part B | Day 1 | 178.79 nanograms/milliliter | Geometric Coefficient of Variation 32.8 |
| Part A-GSK3036656 5 mg | Cmax as a Measure of Dose Proportionality of GSK3036656 Following Repeat Dose Administrations for Part B | Day 14 | 309.55 nanograms/milliliter | Geometric Coefficient of Variation 20.2 |
90% CI: [0.92, 1.46]
90% CI: [0.89, 1.22]
Secondary
Cmax as a Measure of Dose Proportionality of GSK3036656 Following Single Dose Administrations for Part A
Blood samples for the analysis of Cmax were collected at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period. Cmax following single doses was used for assessment of dose proportionality.
Time frame: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period
Population: PK Population for Part A
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A-Matching Placebo | Cmax as a Measure of Dose Proportionality of GSK3036656 Following Single Dose Administrations for Part A | 49.06 hours*nanograms/milliliter | Geometric Coefficient of Variation 30.5 |
| Part A-GSK3036656 5 mg | Cmax as a Measure of Dose Proportionality of GSK3036656 Following Single Dose Administrations for Part A | 177.61 hours*nanograms/milliliter | Geometric Coefficient of Variation 23.1 |
| Part A-GSK3036656 15 mg | Cmax as a Measure of Dose Proportionality of GSK3036656 Following Single Dose Administrations for Part A | 207.38 hours*nanograms/milliliter | Geometric Coefficient of Variation 18.5 |
| Part A-GSK3036656 25 mg | Cmax as a Measure of Dose Proportionality of GSK3036656 Following Single Dose Administrations for Part A | 47.37 hours*nanograms/milliliter | Geometric Coefficient of Variation 23.5 |
90% CI: [0.81, 1.11]
Secondary
Cmax of GSK3036656 Following Single Dose Administration in Fed Condition in Part A
Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period. The actual date and time of each blood sample collection was recorded. For the food effect assessment, the selected dose was given with a high fat meal.
Time frame: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period
Population: PK Population for Part A
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A-Matching Placebo | Cmax of GSK3036656 Following Single Dose Administration in Fed Condition in Part A | 49.06 nanograms/milliliter | Geometric Coefficient of Variation 30.5 |
| Part A-GSK3036656 5 mg | Cmax of GSK3036656 Following Single Dose Administration in Fed Condition in Part A | 177.61 nanograms/milliliter | Geometric Coefficient of Variation 23.1 |
| Part A-GSK3036656 15 mg | Cmax of GSK3036656 Following Single Dose Administration in Fed Condition in Part A | 207.38 nanograms/milliliter | Geometric Coefficient of Variation 18.5 |
| Part A-GSK3036656 25 mg | Cmax of GSK3036656 Following Single Dose Administration in Fed Condition in Part A | 35.54 nanograms/milliliter | Geometric Coefficient of Variation 23.5 |
90% CI: [0.76, 1.23]
Secondary
Observed Accumulation Ratio Based on AUC (AUC [Ro]) of GSK3036656 in Part B
AUC Ro was calculated as Day 14 AUC(0-tau)/Day 1 AUC(0-t), where t and tau= 24 hours.
Time frame: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1; at pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14
Population: PK Population for Part B
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A-Matching Placebo | Observed Accumulation Ratio Based on AUC (AUC [Ro]) of GSK3036656 in Part B | 2.8672 Ratio of AUC | Geometric Coefficient of Variation 9.1 |
| Part A-GSK3036656 5 mg | Observed Accumulation Ratio Based on AUC (AUC [Ro]) of GSK3036656 in Part B | 2.3592 Ratio of AUC | Geometric Coefficient of Variation 21.6 |
Secondary
Observed Accumulation Ratio Based on Cmax (RCmax) of GSK3036656 in Part B
Rcmax was calculated as Day 14 Cmax/Day 1 Cmax. Statistics has been presented on geometric least square means.
Time frame: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1; at pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14
Population: PK Population for Part B
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A-Matching Placebo | Observed Accumulation Ratio Based on Cmax (RCmax) of GSK3036656 in Part B | 2.0052 Ratio of Cmax | Geometric Coefficient of Variation 24.3 |
| Part A-GSK3036656 5 mg | Observed Accumulation Ratio Based on Cmax (RCmax) of GSK3036656 in Part B | 1.7313 Ratio of Cmax | Geometric Coefficient of Variation 26.7 |
Secondary
Steady State Ratio (Rss) of GSK3036656 in Part B
Rss was calculated as Day 14 AUC (0-tau)/Day 1 AUC (0-inf). It was not possible to calculate AUC(0-inf) on Day 1 for the repeat dosing period, therefore it was not possible to calculate the (Rss).Na indicates data was not available.
Time frame: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1; at pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14
Population: PK Population for Part B
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part A-Matching Placebo | Steady State Ratio (Rss) of GSK3036656 in Part B | NA Ratio of AUC |
| Part A-GSK3036656 5 mg | Steady State Ratio (Rss) of GSK3036656 in Part B | NA Ratio of AUC |
Secondary
t1/2 of GSK3036656 Following Single Dose Administration in Fed Condition in Part A
Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period. The actual date and time of each blood sample collection was recorded. For the food effect assessment, the selected dose was given with a high fat meal.
Time frame: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period
Population: PK Population for Part A
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A-Matching Placebo | t1/2 of GSK3036656 Following Single Dose Administration in Fed Condition in Part A | 38.3230 hours |
| Part A-GSK3036656 5 mg | t1/2 of GSK3036656 Following Single Dose Administration in Fed Condition in Part A | 28.4128 hours |
| Part A-GSK3036656 15 mg | t1/2 of GSK3036656 Following Single Dose Administration in Fed Condition in Part A | 47.9680 hours |
| Part A-GSK3036656 25 mg | t1/2 of GSK3036656 Following Single Dose Administration in Fed Condition in Part A | 32.4248 hours |
90% CI: [0.64, 1.23]
Secondary
Tmax of GSK3036656 Following Single Dose Administration in Fed Condition in Part A
Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period. The actual date and time of each blood sample collection was recorded. For the food effect assessment, the selected dose was given with a high fat meal.
Time frame: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period
Population: PK Population for Part A
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A-Matching Placebo | Tmax of GSK3036656 Following Single Dose Administration in Fed Condition in Part A | 1.250 hours |
| Part A-GSK3036656 5 mg | Tmax of GSK3036656 Following Single Dose Administration in Fed Condition in Part A | 1.000 hours |
| Part A-GSK3036656 15 mg | Tmax of GSK3036656 Following Single Dose Administration in Fed Condition in Part A | 0.875 hours |
| Part A-GSK3036656 25 mg | Tmax of GSK3036656 Following Single Dose Administration in Fed Condition in Part A | 2.000 hours |
90% CI: [-0.5, 2.5]
Secondary
Trough Plasma Concentrations at the End of the Dosing Interval (Ctau) of GSK3036656 Following Repeat Dose Administrations in Part B
Blood samples for the analysis of Ctau were collected at Day 1 (24 hours), Day 12 (Pre-dose ), Day 13 (Pre-dose ), Day 14 (Pre-dose), Day 14 (24 hours). Ctau samples collected were used to assess attainment of steady state. Statistics has been presented on geometric least square means.
Time frame: Day 1 (24 hours), Day 12 (Pre-dose ), Day 13 (Pre-dose ), Day 14 (Pre-dose), Day 14 (24 hours)
Population: PK Population for Part B
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-Matching Placebo | Trough Plasma Concentrations at the End of the Dosing Interval (Ctau) of GSK3036656 Following Repeat Dose Administrations in Part B | Day 12, Pre-dose | 38.31 nanograms/milliliter | Geometric Coefficient of Variation 20.8 |
| Part A-Matching Placebo | Trough Plasma Concentrations at the End of the Dosing Interval (Ctau) of GSK3036656 Following Repeat Dose Administrations in Part B | Day 14, Pre-dose | 43.66 nanograms/milliliter | Geometric Coefficient of Variation 15.1 |
| Part A-Matching Placebo | Trough Plasma Concentrations at the End of the Dosing Interval (Ctau) of GSK3036656 Following Repeat Dose Administrations in Part B | Day 13, Pre-dose | 41.78 nanograms/milliliter | Geometric Coefficient of Variation 14.5 |
| Part A-Matching Placebo | Trough Plasma Concentrations at the End of the Dosing Interval (Ctau) of GSK3036656 Following Repeat Dose Administrations in Part B | Day 14, 24 hours | 44.34 nanograms/milliliter | Geometric Coefficient of Variation 14.8 |
| Part A-Matching Placebo | Trough Plasma Concentrations at the End of the Dosing Interval (Ctau) of GSK3036656 Following Repeat Dose Administrations in Part B | Day 1, 24 hours | 14.32 nanograms/milliliter | Geometric Coefficient of Variation 10.8 |
| Part A-GSK3036656 5 mg | Trough Plasma Concentrations at the End of the Dosing Interval (Ctau) of GSK3036656 Following Repeat Dose Administrations in Part B | Day 14, 24 hours | 139.25 nanograms/milliliter | Geometric Coefficient of Variation 28.2 |
| Part A-GSK3036656 5 mg | Trough Plasma Concentrations at the End of the Dosing Interval (Ctau) of GSK3036656 Following Repeat Dose Administrations in Part B | Day 1, 24 hours | 57.69 nanograms/milliliter | Geometric Coefficient of Variation 10.5 |
| Part A-GSK3036656 5 mg | Trough Plasma Concentrations at the End of the Dosing Interval (Ctau) of GSK3036656 Following Repeat Dose Administrations in Part B | Day 12, Pre-dose | 139.14 nanograms/milliliter | Geometric Coefficient of Variation 21.6 |
| Part A-GSK3036656 5 mg | Trough Plasma Concentrations at the End of the Dosing Interval (Ctau) of GSK3036656 Following Repeat Dose Administrations in Part B | Day 13, Pre-dose | 131.77 nanograms/milliliter | Geometric Coefficient of Variation 28.8 |
| Part A-GSK3036656 5 mg | Trough Plasma Concentrations at the End of the Dosing Interval (Ctau) of GSK3036656 Following Repeat Dose Administrations in Part B | Day 14, Pre-dose | 139.54 nanograms/milliliter | Geometric Coefficient of Variation 32.5 |
Comparison: Repeat GSK3036656 5mg Day 1-1490% CI: [1.09, 1.1]
Comparison: Repeat GSK3036656 15mg Day 1-1490% CI: [1.07, 1.08]