Hepatitis B
Conditions
Keywords
Single dose, Multiple ascending doses (MAD), Pharmacokinetics, Safety, GSK3389404, Tolerability
Brief summary
This study is a Phase 1, randomized, double-blind (Sponsor unblinded), placebo controlled, dose escalation study to determine the safety, tolerability and pharmacokinetics (PK) profile of GSK3389404 as single (Part 1) and multiple subcutaneous (SC) injections (Part 2) in healthy subjects. This study represents the first administration of GSK3389404 in humans to define the safety, tolerability and PK following single and multiple doses of GSK3389404 in healthy subjects.
Interventions
DRUGGSK3389404
GSK3389404 is supplied as solution for injection vial. Each vial contains 100 mg/mL of GSK3389404. It's physical appearance is clear colourless to slightly yellow solution.
DRUGMatching Placebo
Placebo is supplied as solution for injection vial. It's physical appearance is clear colourless solution.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. * The subject is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions and is likely to complete the study as planned. * Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and electrocardiograms (ECGs). There should be no evidence of cardiac, pulmonary, hepatic, biliary, gastrointestinal, or renal disorders, or cancer within the past 5 years (except localized or in situ cancer of the skin). A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or
Exclusion criteria
and are reported as outside of the normal reference range for healthy subjects may be included only if the Investigator considers the finding unlikely to introduce additional risk to the subject and will not interfere with the study procedures. * Male or female between 18 and 55 years of age, inclusive, at the time of signing the informed consent form (ICF). * Body weight \>50 kilograms (kg) (110 pounds \[lb\]) for men and \>45 kg (99 lb) women and a body mass index (BMI) between 18 to 30 kg/meter-squared, inclusive, will be allowed. * AST, ALT, ALP, bilirubin, and creatinine within the normal reference range. If outside the normal reference range, these values may be repeated once at the discretion of the Investigator or designee. * WBC count (including neutrophil counts), haemoglobin and platelets within the normal reference range. If outside the normal reference range, these values may be repeated once at the discretion of the Investigator or designee. * Females of Reproductive Potential (FRP) are not permitted. Eligible females must meet the following criteria: * Non-pregnant (as confirmed by a negative serum human chorionic gonadotrophin (hCG) test); AND * Non-lactating at screening and prior to dosing; AND * Non-reproductive potential as defined by at least one of the following conditions: Pre-menopausal females without reproductive potential defined by one of the following: Documented salpingectomy, Hysterectomy, Documented bilateral oophorectomy; Postmenopausal defined as 12 months of spontaneous amenorrhea; A blood sample with simultaneous follicle stimulating hormone (FSH) and estradiol levels may be conducted at the discretion of the Investigator or site to confirm non-reproductive potential. * Male subjects with female partners of child-bearing potential must agree to meet one of the contraception requirements from the time of first dose of study treatment until the last follow-up visit (Part 1 Day 60; Part 2 Day 113). * Vasectomy with documentation of azoospermia. * Male condom plus partner use of one of the contraceptive options below that meets the standard operating procedure (SOP) effectiveness criteria including a \<1% rate of failure per year, as stated in the product label: Contraceptive subdermal implant; Intrauterine device or intrauterine system; Combined estrogen and progestogen oral contraceptive; 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cl/F of GSK3389404 Following Dosing on Day 22 of Part 2 | Day 22 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 29, 36, 50, 71 and at Follow-up (Day 115) | Blood samples were collected to evaluate Cl/F of GSK3389404 on Day 22 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 29, 36, 50, 71 and at Follow-up (Day 113+- 2 days). |
| Change From Baseline in RR at the Indicated Time Points in Part 2 | Day 1 (pre-dose) and up to 115 days | Respiratory rate was taken at Baseline (Day 1, pre-dose) and at 1, 2, 4, 6, 8, 12, 24, 48 and 72 hour post Day 1 dose; on Days 8 and 15; Day 22 (pre-dose) and at 1, 4, 6, 12, 24, 48 and 72 hours post Day 22 dose; on Days 29, 36, 50, 71 and at Follow-up visit (Day 113+- 2 days). Baseline was defined as the last scheduled non-missing measurement taken prior to drug administration. Change from Baseline was calculated as value at indicated time point minus Baseline value. |
| Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Day 1 (pre-dose) and up to 115 days | Body temperature was taken at Baseline (Day 1, pre-dose) and at 1, 2, 4, 6, 8, 12, 24, 48 and 72 hour post Day 1 dose; on Days 8 and 15; Day 22 (pre-dose) and at 1, 4, 6, 12, 24, 48 and 72 hours post Day 22 dose; on Days 29, 36, 50, 71 and at Follow-up visit (Day 113+- 2 days). Baseline was defined as the last scheduled non-missing measurement taken prior to drug administration. Change from Baseline was calculated as value at indicated time point minus Baseline value. |
| Number of Participants With 12-lead Electrocardiogram (ECG) Findings in Part 1 | Day 1 (pre-dose) and up to 31 days | 12-lead ECGs were recorded at Baseline (Day 1, pre-dose) and at 1, 4, 8, 12, 24 and 48 hour post dose; and on Days 8 and 30. Measurements were obtained after resting for at least 5 minutes in a supine position. Baseline was defined as the last scheduled non-missing measurement taken prior to drug administration. Change from Baseline was calculated as value at indicated time point minus Baseline value. Number of participants with worst change from Baseline in ECG have been presented as clinically significant (CS) change or not a clinically significant (NCS) change. |
| Area Under the Plasma Concentration Curve (AUC) From Time Zero to Infinity [AUC (0-inf)], AUC From Time Zero to the Time of Last Quantifiable Concentration [AUC(0-t)], AUC From Time Zero to 24 Hours [AUC(0-24)] of GSK3389404 After Single Dose in Part 1 | Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 30 post-dose | Blood samples were collected to evaluate AUC (0-inf), AUC (0-t) and AUC (0-24) of GSK3389404 on Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 30 post-dose. Pharmacokinetic Concentration Population was defined as participants who underwent plasma PK sampling and had evaluable PK assay results post-dose. |
| Maximum Observed Concentration (Cmax), Observed Concentration at 24 Hours (C24) and at 168 Hours (C168) of GSK3389404 Following Single Dose in Part 1 | Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 30 post-dose | Blood samples were collected to evaluate Cmax, C24 and C168 of GSK3389404 on Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 30 post-dose. |
| Time to Maximum Observed Concentration (Tmax), Terminal Half-life (T1/2) and Lag Time (Tlag) of GSK3389404 Following Single Dose in Part 1 | Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 30 post-dose | Blood samples were collected to evaluate Tmax, T1/2 and Tlag of GSK3389404 on Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 30 post-dose. |
| Apparent SC Plasma Clearance (CL/F) of GSK3389404 Following Single Dose in Part 1 | Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 30 post-dose | Blood samples were collected to evaluate CL/F of GSK3389404 on Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 30 post-dose. |
| AUC (0-t), AUC(0-24), AUC From Time Zero to 168 Hours Post-dose [AUC(0-168)] and AUC (0-inf) of GSK3389404 Following Single Dose on Day 1 of Part 2 | Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 15 post-dose | Blood samples were collected to evaluate AUC (0-t), AUC (0-24), AUC (0-168) and AUC (0-inf) of GSK3389404 on Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 15 post-dose. |
| Cmax, C24 and C168 of GSK3389404 Following Single Dose on Day 1 of Part 2 | Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 15 post-dose | Blood samples were collected to evaluate Cmax, C24 and C168 of GSK3389404 on Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 15 post-dose. |
| Tmax, T1/2 and Tlag of GSK3389404 Following Single Dose on Day 1 of Part 2 | Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 15 post-dose | Blood samples were collected to evaluate Tmax, T1/2 and Tlag of GSK3389404 on Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 15 post-dose. |
| CL/F of GSK3389404 Following Single Dose on Day 1 of Part 2 | Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 15 post-dose | Blood samples were collected to evaluate CL/F of GSK3389404 on Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 15 post-dose. Only those participants with data available at the specified time points were analyzed. |
| AUC(0-24) and AUC From Time Zero to the End of the Dosing Interval [AUC(0-tau)] of GSK3389404 Following Dosing on Day 22 of Part 2 | Day 22 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 29, 36, 50, 71 and at Follow-up (Day 115) | Blood samples were collected to evaluate AUC (0-24) and AUC (0-tau) of GSK3389404 on Day 22 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 29, 36, 50, 71 and at Follow-up (Day 113+- 2 days ). |
| Observed Concentration at the End of the Dosing Interval (Ctau), C24 and Cmax of GSK3389404 Following Dosing on Day 22 of Part 2 | Day 22 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 29, 36, 50, 71 and at Follow-up (Day 115) | Blood samples were collected to evaluate Ctau, C24 and Cmax of GSK3389404 on Day 22 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 29, 36, 50, 71 and at Follow-up (Day 113+- 2 days ). |
| Tmax, T1/2 and Tlag of GSK3389404 Following Dosing on Day 22 of Part 2 | Day 22 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 29, 36, 50, 71 and at Follow-up (Day 115) | Blood samples were collected to evaluate Tmax, T1/2 and Tlag of GSK3389404 on Day 22 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 29, 36, 50, 71 and at Follow-up (Day 113+- 2 days). |
| Number of Participants With Any Non-serious Adverse Event (AE); Any Serious AE (SAE); Any AEs Leading to Discontinuation of Study Treatment (AELD) in Part 1 | Up to 62 days | An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment 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 or event associated with liver injury and impaired liver function were categorized as SAE. Participants who received any of the study treatment and had any AE or SAE or AELD were considered for analysis. Safety Population comprised of all participants who received at least 1 dose of study treatment. |
| Number of Participants With Any Non-serious AE; Any SAE; Any AELD in Part 2 | Up to 115 days | An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment 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 or event associated with liver injury and impaired liver function were categorized as SAE. Participants who received any of the study treatment and had any AE or SAE or AELD were considered for analysis. |
| Number of Participants With Laboratory Values of Potential Clinical Importance in Part 1 | Up to 62 days | Blood samples were collected for hematology, clinical chemistry, coagulation parameters and urinalysis. Abnormalities of potential clinical importance were evaluated as per Division of Acquired Immune Deficiency Syndrome \[DAIDS\] table for grading the severity of adult and pediatric adverse events. Laboratory abnormalities of DAIDS Grade 1 or higher were considered as of potential clinical importance and were summarized. |
| Number of Participants With Laboratory Values of Potential Clinical Importance in Part 2 | Up to 115 days | Blood samples were collected for hematology, clinical chemistry, coagulation parameters and urinalysis. Abnormalities of potential clinical importance were evaluated as per DAIDS table for grading the severity of adult and pediatric adverse events. Laboratory abnormalities of DAIDS Grade 1 or higher were considered as of potential clinical importance and were summarized. |
| Change From Baseline in Complement Factor Component 3 (C3) and C4 Levels in Part 1 | Day 1 (pre-dose) and up to 31 days | Blood samples were collected to evaluate complement factors (C3 and C4) levels. Latest pre-dose assessment at Day 1 was considered as Baseline value. Change from Baseline was calculated as difference between minimum level (lowest of the measurements for specimens collected) observed post-dose and pre-study drug administration. |
| Change From Baseline in Complement Split Product C5a Levels in Part 1 | Day 1 (pre-dose) and up to 31 days | Blood samples were collected to evaluate complement split product C5a levels. Latest pre-dose assessment at Day 1 was considered as Baseline value. Change from Baseline was calculated as difference between maximum level (highest of the measurements for specimens collected) observed post-dose and pre-study drug administration. |
| Change From Baseline in Complement Split Product Bb Levels in Part 1 | Day 1 (pre-dose) and up to 31 days | Blood samples were collected to evaluate complement split product Bb levels. Latest pre-dose assessment at Day 1 was considered as Baseline value. Change from Baseline was calculated as difference between maximum level (highest of the measurements for specimens collected) observed post-dose and pre-study drug administration |
| Change From Baseline in Complement Factor C3 and C4 Levels in Part 2 | Day 1 (pre-dose) and Day 22 | Blood samples were collected to evaluate complement factors (C3 and C4) levels. Latest pre-dose assessment at Day 1 or Day 22 was considered as Baseline value. Change from Baseline was calculated as difference between minimum level (lowest of the measurements for specimens collected each after Day 1 and Day 22 study drug administrations) observed post-dose and pre-study drug administration |
| Change From Baseline in Complement Factor C5a Levels in Part 2 | Day 1 (pre-dose) and Day 22 | Blood samples were collected to evaluate complement factors C5a levels. Latest pre-dose assessment at Day 1 or Day 22 was considered as Baseline value. Change from Baseline was calculated as difference between maximum level (lowest of the measurements for specimens collected each after Day 1 and Day 22 study drug administrations) observed post-dose and pre-study drug administration. |
| Change From Baseline in Complement Factor Bb Levels in Part 2 | Day 1 (pre-dose) and Day 22 | Blood samples were collected to evaluate complement factors C5a levels. Latest pre-dose assessment at Day 1 or Day 22 was considered as Baseline value. Change from Baseline was calculated as difference between maximum level (lowest of the measurements for specimens collected each after Day 1 and Day 22 study drug administrations) observed post-dose and pre-study drug administration. |
| Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | Day 1 (pre-dose) and up to 30 days | SBP and DBP were taken at Baseline (Day 1, pre-dose) and at 1, 2, 4, 8, 12, 24, 48 and 72 hour post dose; and on Days 8 and 30. Measurements were obtained after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the last scheduled non-missing measurement taken prior to drug administration. Change from Baseline was calculated as value at indicated time point minus Baseline value. |
| Change From Baseline in Pulse Rate (PR) at the Indicated Time Points in Part 1 | Day 1 (pre-dose) and up to 30 days | Pulse rate was taken at Baseline (Day 1, pre-dose) and at 1, 2, 4, 8, 12, 24, 48 and 72 hour post dose; and on Days 8 and 30. Measurements were obtained after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the last scheduled non-missing measurement taken prior to drug administration. Change from Baseline was calculated as value at indicated time point minus Baseline value. |
| Change From Baseline in Respiratory Rate (RR) at the Indicated Time Points in Part 1 | Day 1 (pre-dose) and up to 30 days | Respiratory rate was taken at Baseline (Day 1, pre-dose) and at 1, 2, 4, 8, 12, 24, 48 and 72 hour post dose; and on Days 8 and 30. Baseline was defined as the last scheduled non-missing measurement taken prior to drug administration. Change from Baseline was calculated as value at indicated time point minus Baseline value. |
| Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 | Day 1 (pre-dose) and up to 30 days | Temperature was taken at Baseline (Day 1, pre-dose) and at 1, 2, 4, 8, 12, 24, 48 and 72 hour post dose; and on Days 8 and 30. Baseline was defined as the last scheduled non-missing measurement taken prior to drug administration. Change from Baseline was calculated as value at indicated time point minus Baseline value. |
| Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | Day 1 (pre-dose) and up to 115 days | SBP and DBP were taken at Baseline (Day 1, pre-dose) and at 1, 2, 4, 6, 8, 12, 24, 48 and 72 hour post Day 1 dose; on Days 8 and 15; Day 22 (pre-dose) and at 1, 4, 6, 12, 24, 48 and 72 hours post Day 22 dose; on Days 29, 36, 50, 71 and at Follow-up visit (Day 113 +- 2 days). Measurements were obtained after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the last scheduled non-missing measurement taken prior to drug administration. Change from Baseline was calculated as value at indicated time point minus Baseline value. |
| Change From Baseline in PR at the Indicated Time Points in Part 2 | Day 1 (pre-dose) and up to 115 days | Pulse rate was taken at Baseline (Day 1, pre-dose) and at 1, 2, 4, 6, 8, 12, 24, 48 and 72 hour post Day 1 dose; on Days 8 and 15; Day 22 (pre-dose) and at 1, 4, 6, 12, 24, 48 and 72 hours post Day 22 dose; on Days 29, 36, 50, 71 and at Follow-up visit (Day 113+- 2 days). Measurements were obtained after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the last scheduled non-missing measurement taken prior to drug administration. Change from Baseline was calculated as value at indicated time point minus Baseline value. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dose Proportionality of GSK202007 for Dose Range 30 mg - 120 mg After Multiple Dose Administrations | Day 22 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 29, 36, 50, 71 and at Follow-up (Day 115) in Part 2 | Results of proportionality assessment using power model and ANOVA following multiple doses are presented. Slope estimates and 90% confidence interval are presented for Day 22 of Part 2. |
| Accumulation Ratio by AUC (RAUC), by Cmax (RCmax), by C24 (RC24) and by Ctau (RCtau) of GSK3389404 in Part 2 | Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 15 post-dose; Day 22 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 29, 36, 50, 71 and at Follow-up (Day 115) | For Part 2, the extent of accumulation of GSK3389404 was evaluated by comparing AUC (0-tau), Cmax, C24 and Ctau on Day 22 to AUC (0-168), Cmax, C24 and C168 on Day 1. For each dose level, a linear mixed effect model was fitted with the log transformed PK parameter as the dependent variable, day as a fixed effect and subject as a random effect. |
| Time Invariance (LI) of GSK3389404 in Part 2 | Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 15 post-dose; Day 22 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 29, 36, 50, 71 and at Follow-up (Day 115) | For Part 2, time invariance was evaluated by comparing AUC (0-tau) for Day 22 to AUC (0-inf) for Day 1. For each dose level, a linear mixed effect model was fitted with the log transformed PK parameter as the dependent variable, day as a fixed effect and subject as a random effect. Only those participants with data available at the specified time points were analyzed. |
| Trough Plasma Concentrations of GSK3389404 in Part 2 | Pre-dose on Days 8, 15, 22 and 29 | For Part 2, mean plasma GSK3389404 pre-dose values between Day 1 to Day 29 and Ctau were plotted against time to assess attainment of GSK3389404 steady state following multiple dose administration. Achievement of plasma GSK3389404 steady-state was assessed by calculating the 90% confidence interval (CI) of the slope of the linear regression of log (Ctau) versus time. NA indicates data was not available. |
| AUC (0-inf), AUC(0-t), AUC(0-24) of the Metabolite of GSK3389404 After Single Dose in Part 1 | Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 30 post-dose | Blood samples were collected to evaluate AUC (0-inf), AUC (0-t) and AUC (0-24) of metabolite of GSK3389404 on Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 30 post-dose. |
| Cmax, C24 and C168 of the Metabolite of GSK3389404 Following Single Dose in Part 1 | Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 30 post-dose | Blood samples were collected to evaluate Cmax, C24 and C168 of the metabolite of GSK3389404 on Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 30 post-dose. |
| Tmax, T1/2 and Tlag of the Metabolite of GSK3389404 Following Single Dose in Part 1 | Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 30 post-dose | Blood samples were collected to evaluate Tmax, T1/2 and Tlag of the metabolite of GSK3389404 on Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 30 post-dose. |
| AUC (0-t), AUC(0-24), AUC(0-168) and AUC (0-inf) of the Metabolite of GSK3389404 Following Single Dose on Day 1 of Part 2 | Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 15 post-dose | Blood samples were collected to evaluate AUC (0-t), AUC (0-24), AUC (0-168) and AUC (0-inf) of the metabolite of GSK3389404 on Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 15 post-dose. |
| Cmax, C24 and C168 of the Metabolite of GSK3389404 Following Single Dose on Day 1 of Part 2 | Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 15 post-dose | Blood samples were collected to evaluate Cmax, C24 and C168 of the metabolite of GSK3389404 on Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 15 post-dose. |
| Tmax, T1/2 and Tlag of the Metabolite of GSK3389404 Following Single Dose on Day 1 of Part 2 | Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 15 post-dose | Blood samples were collected to evaluate Tmax, T1/2 and Tlag of the metabolite of GSK3389404 on Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 15 post-dose. |
| AUC(0-24) and AUC(0-tau) of the Metabolite of GSK3389404 Following Dosing of GSK3389404 on Day 22 of Part 2 | Day 22 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 29, 36, 50, 71 and at Follow-up (Day 115) | Blood samples were collected to evaluate AUC (0-24) and AUC (0-tau) of the metabolite of GSK3389404 on Day 22 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 29, 36, 50, 71 and at Follow-up (Day 113+- 2 days). |
| Ctau, C24 and Cmax of the Metabolite of GSK3389404 Following Dosing of GSK3389404 on Day 22 of Part 2 | Day 22 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 29, 36, 50, 71 and at Follow-up (Day 115) | Blood samples were collected to evaluate Ctau, C24 and Cmax of the metabolite of GSK3389404 on Day 22 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 29, 36, 50, 71 and at Follow-up (Day 113+- 2 days). |
| Tmax, T1/2 and Tlag of the Metabolite of GSK3389404 Following Dosing on Day 22 of Part 2 | Day 22 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 29, 36, 50, 71 and at Follow-up (Day 115) | Blood samples were collected to evaluate Tmax, T1/2 and Tlag of the metabolite of GSK3389404 on Day 22 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 29, 36, 50, 71 and at Follow-up (Day 113+- 2 days). |
| Dose Proportionality of GSK202007 for Dose Range 10 mg - 120 mg After Single Dose Administrations | Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 30 post-dose; Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 15 post-dose in Part 2. | Results of dose proportionality assessment using power model and analysis of variance (ANOVA) following single dose administariton (Part 1 and Day 1 in Part 2) are presented. Slope estimates and 90% confidence interval are presented for combined data of Day 1 of Part 1 and 2. |
Countries
United Kingdom
Participant flow
Recruitment details
This was a Phase 1, randomized, double-blind (sponsor un-blinded), placebo-controlled, dose escalation study to determine the safety, tolerability, and pharmacokinetic (PK) profile of GSK3389404 as single and multiple subcutaneous (SC) injections in healthy participants. This study was conducted at 2 centers in London, United Kingdom.
Pre-assignment details
The study was conducted in 2 Parts: Single-Ascending Dose (Part 1) and Multiple-Ascending Dose (Part 2). In Part 1, total of 32 participants were enrolled and all of them were randomized to receive the study treatment. In Part 2, a total of 24 participants were enrolled and all of them were randomized to receive the study treatment.
Participants by arm
| Arm | Count |
|---|---|
| Part 1: Placebo Participant received a single dose of subcutaneous (injection under the skin) injection of placebo matching with GSK3389404 10 milligram (mg) or 30 mg, or 60 mg or 120 mg. | 8 |
| Part 1: GSK3389404 10 mg Participants received a single dose of GSK3389404 10 mg by subcutaneous injection on Day 1 of Part 1. | 6 |
| Part 1: GSK3389404 30 mg Participants received a single dose of GSK3389404 30 mg by subcutaneous injection on Day 1 of Part 1. | 6 |
| Part 1: GSK3389404 60 mg Participants received a single dose of GSK3389404 60 mg by subcutaneous injection on Day 1 of Part 1. | 6 |
| Part 1: GSK3389404 120 mg Participants received a single dose of GSK3389404 120 mg by subcutaneous injection on Day 1 of Part 1. | 6 |
| Part 2: Placebo Participant received a single dose of subcutaneous injection of placebo matching with GSK3389404 30 mg or 60 mg or 120 mg once weekly (QW) for 4 weeks in Part 2. | 6 |
| Part 2: GSK3389404 30 mg Participants received a single dose of GSK3389404 30 mg by subcutaneous injection QW for 4 weeks in Part 2. | 6 |
| Part 2: GSK3389404 60 mg Participants received a single dose of GSK3389404 60 mg by subcutaneous injection QW for 4 weeks in Part 2. | 6 |
| Part 2: GSK3389404 120 mg Participants received a single dose of GSK3389404 120 mg by subcutaneous injection QW for 4 weeks in Part 2. | 6 |
| Total | 56 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Multiple-Ascending Dose(Part 2-115 Days) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Part 2: GSK3389404 120 mg | Total | Part 1: Placebo | Part 1: GSK3389404 10 mg | Part 1: GSK3389404 30 mg | Part 1: GSK3389404 60 mg | Part 1: GSK3389404 120 mg | Part 2: Placebo | Part 2: GSK3389404 30 mg | Part 2: GSK3389404 60 mg |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 38.5 Years STANDARD_DEVIATION 12.23 | 32.5 Years STANDARD_DEVIATION 10.03 | 28.1 Years STANDARD_DEVIATION 8.22 | 27.5 Years STANDARD_DEVIATION 3.78 | 37.5 Years STANDARD_DEVIATION 12.44 | 32.8 Years STANDARD_DEVIATION 7.41 | 37.8 Years STANDARD_DEVIATION 13.41 | 38.0 Years STANDARD_DEVIATION 11.78 | 32.2 Years STANDARD_DEVIATION 6.91 | 40.5 Years STANDARD_DEVIATION 11.13 |
| Race/Ethnicity, Customized Race/Ethnicity, Customized African American/African heritage | 0 Participants | 4 Participants | 0 Participants | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race/Ethnicity, Customized Asian-Central/South Asian heritage | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Race/Ethnicity, Customized Asian-South East Asian heritage | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race/Ethnicity, Customized Caribbean | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race/Ethnicity, Customized Caribbean British | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race/Ethnicity, Customized White-White/Caucasian/European heritage | 6 Participants | 45 Participants | 8 Participants | 3 Participants | 4 Participants | 6 Participants | 6 Participants | 4 Participants | 5 Participants | 3 Participants |
| Sex: Female, Male Female | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Sex: Female, Male Male | 6 Participants | 54 Participants | 8 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 4 / 8 | 3 / 6 | 2 / 6 | 3 / 6 | 5 / 6 | 3 / 6 | 5 / 6 | 2 / 6 | 4 / 6 |
| serious Total, serious adverse events | 0 / 8 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Apparent SC Plasma Clearance (CL/F) of GSK3389404 Following Single Dose in Part 1
Blood samples were collected to evaluate CL/F of GSK3389404 on Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 30 post-dose.
Time frame: Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 30 post-dose
Population: Pharmacokinetic Concentration Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Placebo | Apparent SC Plasma Clearance (CL/F) of GSK3389404 Following Single Dose in Part 1 | 16.8 Liter per hour | Standard Deviation 4.2805 |
| Part 1: GSK3389404 10 mg | Apparent SC Plasma Clearance (CL/F) of GSK3389404 Following Single Dose in Part 1 | 15.8 Liter per hour | Standard Deviation 4.671 |
| Part 1: GSK3389404 30 mg | Apparent SC Plasma Clearance (CL/F) of GSK3389404 Following Single Dose in Part 1 | 13.6 Liter per hour | Standard Deviation 3.6934 |
| Part 1: GSK3389404 60 mg | Apparent SC Plasma Clearance (CL/F) of GSK3389404 Following Single Dose in Part 1 | 16.2 Liter per hour | Standard Deviation 4.705 |
Primary
Area Under the Plasma Concentration Curve (AUC) From Time Zero to Infinity [AUC (0-inf)], AUC From Time Zero to the Time of Last Quantifiable Concentration [AUC(0-t)], AUC From Time Zero to 24 Hours [AUC(0-24)] of GSK3389404 After Single Dose in Part 1
Blood samples were collected to evaluate AUC (0-inf), AUC (0-t) and AUC (0-24) of GSK3389404 on Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 30 post-dose. Pharmacokinetic Concentration Population was defined as participants who underwent plasma PK sampling and had evaluable PK assay results post-dose.
Time frame: Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 30 post-dose
Population: Pharmacokinetic Concentration Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Placebo | Area Under the Plasma Concentration Curve (AUC) From Time Zero to Infinity [AUC (0-inf)], AUC From Time Zero to the Time of Last Quantifiable Concentration [AUC(0-t)], AUC From Time Zero to 24 Hours [AUC(0-24)] of GSK3389404 After Single Dose in Part 1 | AUC (0-t) | 484 Nanogram*hour per milliliter(ng*hour/mL) | Standard Deviation 80.962 |
| Part 1: Placebo | Area Under the Plasma Concentration Curve (AUC) From Time Zero to Infinity [AUC (0-inf)], AUC From Time Zero to the Time of Last Quantifiable Concentration [AUC(0-t)], AUC From Time Zero to 24 Hours [AUC(0-24)] of GSK3389404 After Single Dose in Part 1 | AUC (0-inf) | 632 Nanogram*hour per milliliter(ng*hour/mL) | Standard Deviation 171.59 |
| Part 1: Placebo | Area Under the Plasma Concentration Curve (AUC) From Time Zero to Infinity [AUC (0-inf)], AUC From Time Zero to the Time of Last Quantifiable Concentration [AUC(0-t)], AUC From Time Zero to 24 Hours [AUC(0-24)] of GSK3389404 After Single Dose in Part 1 | AUC (0-24) | 592 Nanogram*hour per milliliter(ng*hour/mL) | Standard Deviation 105.91 |
| Part 1: GSK3389404 10 mg | Area Under the Plasma Concentration Curve (AUC) From Time Zero to Infinity [AUC (0-inf)], AUC From Time Zero to the Time of Last Quantifiable Concentration [AUC(0-t)], AUC From Time Zero to 24 Hours [AUC(0-24)] of GSK3389404 After Single Dose in Part 1 | AUC (0-t) | 1770 Nanogram*hour per milliliter(ng*hour/mL) | Standard Deviation 961.03 |
| Part 1: GSK3389404 10 mg | Area Under the Plasma Concentration Curve (AUC) From Time Zero to Infinity [AUC (0-inf)], AUC From Time Zero to the Time of Last Quantifiable Concentration [AUC(0-t)], AUC From Time Zero to 24 Hours [AUC(0-24)] of GSK3389404 After Single Dose in Part 1 | AUC (0-inf) | 2080 Nanogram*hour per milliliter(ng*hour/mL) | Standard Deviation 801.85 |
| Part 1: GSK3389404 10 mg | Area Under the Plasma Concentration Curve (AUC) From Time Zero to Infinity [AUC (0-inf)], AUC From Time Zero to the Time of Last Quantifiable Concentration [AUC(0-t)], AUC From Time Zero to 24 Hours [AUC(0-24)] of GSK3389404 After Single Dose in Part 1 | AUC (0-24) | 1970 Nanogram*hour per milliliter(ng*hour/mL) | Standard Deviation 855.08 |
| Part 1: GSK3389404 30 mg | Area Under the Plasma Concentration Curve (AUC) From Time Zero to Infinity [AUC (0-inf)], AUC From Time Zero to the Time of Last Quantifiable Concentration [AUC(0-t)], AUC From Time Zero to 24 Hours [AUC(0-24)] of GSK3389404 After Single Dose in Part 1 | AUC (0-t) | 3710 Nanogram*hour per milliliter(ng*hour/mL) | Standard Deviation 1485.6 |
| Part 1: GSK3389404 30 mg | Area Under the Plasma Concentration Curve (AUC) From Time Zero to Infinity [AUC (0-inf)], AUC From Time Zero to the Time of Last Quantifiable Concentration [AUC(0-t)], AUC From Time Zero to 24 Hours [AUC(0-24)] of GSK3389404 After Single Dose in Part 1 | AUC (0-inf) | 4750 Nanogram*hour per milliliter(ng*hour/mL) | Standard Deviation 1450.8 |
| Part 1: GSK3389404 30 mg | Area Under the Plasma Concentration Curve (AUC) From Time Zero to Infinity [AUC (0-inf)], AUC From Time Zero to the Time of Last Quantifiable Concentration [AUC(0-t)], AUC From Time Zero to 24 Hours [AUC(0-24)] of GSK3389404 After Single Dose in Part 1 | AUC (0-24) | 4330 Nanogram*hour per milliliter(ng*hour/mL) | Standard Deviation 1313.5 |
| Part 1: GSK3389404 60 mg | Area Under the Plasma Concentration Curve (AUC) From Time Zero to Infinity [AUC (0-inf)], AUC From Time Zero to the Time of Last Quantifiable Concentration [AUC(0-t)], AUC From Time Zero to 24 Hours [AUC(0-24)] of GSK3389404 After Single Dose in Part 1 | AUC (0-t) | 7440 Nanogram*hour per milliliter(ng*hour/mL) | Standard Deviation 2844.8 |
| Part 1: GSK3389404 60 mg | Area Under the Plasma Concentration Curve (AUC) From Time Zero to Infinity [AUC (0-inf)], AUC From Time Zero to the Time of Last Quantifiable Concentration [AUC(0-t)], AUC From Time Zero to 24 Hours [AUC(0-24)] of GSK3389404 After Single Dose in Part 1 | AUC (0-24) | 7950 Nanogram*hour per milliliter(ng*hour/mL) | Standard Deviation 3264.9 |
| Part 1: GSK3389404 60 mg | Area Under the Plasma Concentration Curve (AUC) From Time Zero to Infinity [AUC (0-inf)], AUC From Time Zero to the Time of Last Quantifiable Concentration [AUC(0-t)], AUC From Time Zero to 24 Hours [AUC(0-24)] of GSK3389404 After Single Dose in Part 1 | AUC (0-inf) | 8150 Nanogram*hour per milliliter(ng*hour/mL) | Standard Deviation 3204.5 |
Primary
AUC(0-24) and AUC From Time Zero to the End of the Dosing Interval [AUC(0-tau)] of GSK3389404 Following Dosing on Day 22 of Part 2
Blood samples were collected to evaluate AUC (0-24) and AUC (0-tau) of GSK3389404 on Day 22 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 29, 36, 50, 71 and at Follow-up (Day 113+- 2 days ).
Time frame: Day 22 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 29, 36, 50, 71 and at Follow-up (Day 115)
Population: Pharmacokinetic Concentration Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Placebo | AUC(0-24) and AUC From Time Zero to the End of the Dosing Interval [AUC(0-tau)] of GSK3389404 Following Dosing on Day 22 of Part 2 | AUC (0-24) | 1486 ng*hour/mL | Standard Deviation 364.92 |
| Part 1: Placebo | AUC(0-24) and AUC From Time Zero to the End of the Dosing Interval [AUC(0-tau)] of GSK3389404 Following Dosing on Day 22 of Part 2 | AUC (0-tau) | 1598 ng*hour/mL | Standard Deviation 565.02 |
| Part 1: GSK3389404 10 mg | AUC(0-24) and AUC From Time Zero to the End of the Dosing Interval [AUC(0-tau)] of GSK3389404 Following Dosing on Day 22 of Part 2 | AUC (0-24) | 3973 ng*hour/mL | Standard Deviation 906.81 |
| Part 1: GSK3389404 10 mg | AUC(0-24) and AUC From Time Zero to the End of the Dosing Interval [AUC(0-tau)] of GSK3389404 Following Dosing on Day 22 of Part 2 | AUC (0-tau) | 4052 ng*hour/mL | Standard Deviation 873.65 |
| Part 1: GSK3389404 30 mg | AUC(0-24) and AUC From Time Zero to the End of the Dosing Interval [AUC(0-tau)] of GSK3389404 Following Dosing on Day 22 of Part 2 | AUC (0-24) | 8918 ng*hour/mL | Standard Deviation 3447.7 |
| Part 1: GSK3389404 30 mg | AUC(0-24) and AUC From Time Zero to the End of the Dosing Interval [AUC(0-tau)] of GSK3389404 Following Dosing on Day 22 of Part 2 | AUC (0-tau) | 9047 ng*hour/mL | Standard Deviation 3361.3 |
Primary
AUC (0-t), AUC(0-24), AUC From Time Zero to 168 Hours Post-dose [AUC(0-168)] and AUC (0-inf) of GSK3389404 Following Single Dose on Day 1 of Part 2
Blood samples were collected to evaluate AUC (0-t), AUC (0-24), AUC (0-168) and AUC (0-inf) of GSK3389404 on Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 15 post-dose.
Time frame: Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 15 post-dose
Population: Pharmacokinetic Concentration Population. Only data available at the specified time points was analyzed. (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Placebo | AUC (0-t), AUC(0-24), AUC From Time Zero to 168 Hours Post-dose [AUC(0-168)] and AUC (0-inf) of GSK3389404 Following Single Dose on Day 1 of Part 2 | AUC (0-168), n=6, 5, 6 | 1420 ng*hour/mL | Standard Deviation 291.72 |
| Part 1: Placebo | AUC (0-t), AUC(0-24), AUC From Time Zero to 168 Hours Post-dose [AUC(0-168)] and AUC (0-inf) of GSK3389404 Following Single Dose on Day 1 of Part 2 | AUC (0-t), n=6, 6, 6 | 1300 ng*hour/mL | Standard Deviation 286.51 |
| Part 1: Placebo | AUC (0-t), AUC(0-24), AUC From Time Zero to 168 Hours Post-dose [AUC(0-168)] and AUC (0-inf) of GSK3389404 Following Single Dose on Day 1 of Part 2 | AUC (0-inf), n=6, 5, 6 | 1420 ng*hour/mL | Standard Deviation 291.72 |
| Part 1: Placebo | AUC (0-t), AUC(0-24), AUC From Time Zero to 168 Hours Post-dose [AUC(0-168)] and AUC (0-inf) of GSK3389404 Following Single Dose on Day 1 of Part 2 | AUC (0-24), n=6, 5, 6 | 1410 ng*hour/mL | Standard Deviation 292.51 |
| Part 1: GSK3389404 10 mg | AUC (0-t), AUC(0-24), AUC From Time Zero to 168 Hours Post-dose [AUC(0-168)] and AUC (0-inf) of GSK3389404 Following Single Dose on Day 1 of Part 2 | AUC (0-168), n=6, 5, 6 | 5080 ng*hour/mL | Standard Deviation 1332.6 |
| Part 1: GSK3389404 10 mg | AUC (0-t), AUC(0-24), AUC From Time Zero to 168 Hours Post-dose [AUC(0-168)] and AUC (0-inf) of GSK3389404 Following Single Dose on Day 1 of Part 2 | AUC (0-24), n=6, 5, 6 | 4940 ng*hour/mL | Standard Deviation 1131.6 |
| Part 1: GSK3389404 10 mg | AUC (0-t), AUC(0-24), AUC From Time Zero to 168 Hours Post-dose [AUC(0-168)] and AUC (0-inf) of GSK3389404 Following Single Dose on Day 1 of Part 2 | AUC (0-inf), n=6, 5, 6 | 5080 ng*hour/mL | Standard Deviation 1328.9 |
| Part 1: GSK3389404 10 mg | AUC (0-t), AUC(0-24), AUC From Time Zero to 168 Hours Post-dose [AUC(0-168)] and AUC (0-inf) of GSK3389404 Following Single Dose on Day 1 of Part 2 | AUC (0-t), n=6, 6, 6 | 4150 ng*hour/mL | Standard Deviation 1103.1 |
| Part 1: GSK3389404 30 mg | AUC (0-t), AUC(0-24), AUC From Time Zero to 168 Hours Post-dose [AUC(0-168)] and AUC (0-inf) of GSK3389404 Following Single Dose on Day 1 of Part 2 | AUC (0-inf), n=6, 5, 6 | 8480 ng*hour/mL | Standard Deviation 3249.8 |
| Part 1: GSK3389404 30 mg | AUC (0-t), AUC(0-24), AUC From Time Zero to 168 Hours Post-dose [AUC(0-168)] and AUC (0-inf) of GSK3389404 Following Single Dose on Day 1 of Part 2 | AUC (0-t), n=6, 6, 6 | 7970 ng*hour/mL | Standard Deviation 3082.7 |
| Part 1: GSK3389404 30 mg | AUC (0-t), AUC(0-24), AUC From Time Zero to 168 Hours Post-dose [AUC(0-168)] and AUC (0-inf) of GSK3389404 Following Single Dose on Day 1 of Part 2 | AUC (0-24), n=6, 5, 6 | 8330 ng*hour/mL | Standard Deviation 3363.3 |
| Part 1: GSK3389404 30 mg | AUC (0-t), AUC(0-24), AUC From Time Zero to 168 Hours Post-dose [AUC(0-168)] and AUC (0-inf) of GSK3389404 Following Single Dose on Day 1 of Part 2 | AUC (0-168), n=6, 5, 6 | 8480 ng*hour/mL | Standard Deviation 3249.8 |
Primary
Change From Baseline in Body Temperature at the Indicated Time Points in Part 1
Temperature was taken at Baseline (Day 1, pre-dose) and at 1, 2, 4, 8, 12, 24, 48 and 72 hour post dose; and on Days 8 and 30. Baseline was defined as the last scheduled non-missing measurement taken prior to drug administration. Change from Baseline was calculated as value at indicated time point minus Baseline value.
Time frame: Day 1 (pre-dose) and up to 30 days
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Placebo | Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 | Temperature, 24 hour | -0.01 Degree Celsius | Standard Deviation 0.29 |
| Part 1: Placebo | Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 | Temperature, 72 hour | 0.06 Degree Celsius | Standard Deviation 0.22 |
| Part 1: Placebo | Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 | Temperature, 2 hour | 0.04 Degree Celsius | Standard Deviation 0.288 |
| Part 1: Placebo | Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 | Temperature, 48 hour | 0.00 Degree Celsius | Standard Deviation 0.434 |
| Part 1: Placebo | Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 | Temperature, Day 8 | 0.00 Degree Celsius | Standard Deviation 0.233 |
| Part 1: Placebo | Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 | Temperature, 8 hour | 0.24 Degree Celsius | Standard Deviation 0.297 |
| Part 1: Placebo | Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 | Temperature, Day 30 | -0.04 Degree Celsius | Standard Deviation 0.177 |
| Part 1: Placebo | Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 | Temperature, 12 hour | 0.18 Degree Celsius | Standard Deviation 0.255 |
| Part 1: Placebo | Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 | Temperature, 1 hour | 0.06 Degree Celsius | Standard Deviation 0.185 |
| Part 1: Placebo | Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 | Temperature, 4 hour | 0.14 Degree Celsius | Standard Deviation 0.213 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 | Temperature, 1 hour | 0.00 Degree Celsius | Standard Deviation 0.237 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 | Temperature, 4 hour | 0.08 Degree Celsius | Standard Deviation 0.319 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 | Temperature, 8 hour | -0.02 Degree Celsius | Standard Deviation 0.279 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 | Temperature, 2 hour | -0.02 Degree Celsius | Standard Deviation 0.147 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 | Temperature, 12 hour | 0.03 Degree Celsius | Standard Deviation 0.234 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 | Temperature, Day 30 | -0.07 Degree Celsius | Standard Deviation 0.216 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 | Temperature, 48 hour | -0.10 Degree Celsius | Standard Deviation 0.21 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 | Temperature, Day 8 | -0.08 Degree Celsius | Standard Deviation 0.319 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 | Temperature, 24 hour | -0.10 Degree Celsius | Standard Deviation 0.167 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 | Temperature, 72 hour | -0.07 Degree Celsius | Standard Deviation 0.25 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 | Temperature, 72 hour | 0.07 Degree Celsius | Standard Deviation 0.225 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 | Temperature, 8 hour | 0.20 Degree Celsius | Standard Deviation 0.126 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 | Temperature, 48 hour | 0.03 Degree Celsius | Standard Deviation 0.121 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 | Temperature, Day 8 | 0.00 Degree Celsius | Standard Deviation 0.2 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 | Temperature, 1 hour | 0.05 Degree Celsius | Standard Deviation 0.122 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 | Temperature, 2 hour | 0.02 Degree Celsius | Standard Deviation 0.172 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 | Temperature, 4 hour | 0.05 Degree Celsius | Standard Deviation 0.217 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 | Temperature, 12 hour | -0.03 Degree Celsius | Standard Deviation 0.137 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 | Temperature, 24 hour | -0.05 Degree Celsius | Standard Deviation 0.152 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 | Temperature, Day 30 | 0.00 Degree Celsius | Standard Deviation 0.19 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 | Temperature, Day 30 | -0.07 Degree Celsius | Standard Deviation 0.225 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 | Temperature, 48 hour | 0.02 Degree Celsius | Standard Deviation 0.248 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 | Temperature, 24 hour | 0.07 Degree Celsius | Standard Deviation 0.197 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 | Temperature, 12 hour | 0.12 Degree Celsius | Standard Deviation 0.204 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 | Temperature, Day 8 | -0.20 Degree Celsius | Standard Deviation 0.228 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 | Temperature, 72 hour | 0.07 Degree Celsius | Standard Deviation 0.175 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 | Temperature, 2 hour | -0.15 Degree Celsius | Standard Deviation 0.243 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 | Temperature, 4 hour | -0.02 Degree Celsius | Standard Deviation 0.264 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 | Temperature, 8 hour | 0.18 Degree Celsius | Standard Deviation 0.147 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 | Temperature, 1 hour | 0.10 Degree Celsius | Standard Deviation 0.276 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 | Temperature, 8 hour | 0.23 Degree Celsius | Standard Deviation 0.288 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 | Temperature, 12 hour | 0.08 Degree Celsius | Standard Deviation 0.232 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 | Temperature, 1 hour | 0.10 Degree Celsius | Standard Deviation 0.2 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 | Temperature, Day 8 | 0.05 Degree Celsius | Standard Deviation 0.138 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 | Temperature, 24 hour | -0.03 Degree Celsius | Standard Deviation 0.35 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 | Temperature, 48 hour | -0.10 Degree Celsius | Standard Deviation 0.276 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 | Temperature, 4 hour | 0.08 Degree Celsius | Standard Deviation 0.194 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 | Temperature, 72 hour | -0.03 Degree Celsius | Standard Deviation 0.197 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 | Temperature, 2 hour | 0.05 Degree Celsius | Standard Deviation 0.243 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 1 | Temperature, Day 30 | -0.12 Degree Celsius | Standard Deviation 0.436 |
Primary
Change From Baseline in Body Temperature at the Indicated Time Points in Part 2
Body temperature was taken at Baseline (Day 1, pre-dose) and at 1, 2, 4, 6, 8, 12, 24, 48 and 72 hour post Day 1 dose; on Days 8 and 15; Day 22 (pre-dose) and at 1, 4, 6, 12, 24, 48 and 72 hours post Day 22 dose; on Days 29, 36, 50, 71 and at Follow-up visit (Day 113+- 2 days). Baseline was defined as the last scheduled non-missing measurement taken prior to drug administration. Change from Baseline was calculated as value at indicated time point minus Baseline value.
Time frame: Day 1 (pre-dose) and up to 115 days
Population: Safety Population. Only data available at the specified time points was analyzed. (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Placebo | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 50, n=6, 6, 6, 5 | 0.02 Degree Celsius | Standard Deviation 0.325 |
| Part 1: Placebo | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 2, 24 hour, n=6, 6, 6, 6 | 0.05 Degree Celsius | Standard Deviation 0.321 |
| Part 1: Placebo | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 24, 48 hour, n=6, 6, 6, 6 | 0.12 Degree Celsius | Standard Deviation 0.417 |
| Part 1: Placebo | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 23, 24 hour, n=6, 6, 6, 6 | 0.18 Degree Celsius | Standard Deviation 0.366 |
| Part 1: Placebo | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 22, 12 hour, n=6, 6, 6, 6 | 0.22 Degree Celsius | Standard Deviation 0.366 |
| Part 1: Placebo | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 3, 48 hour, n=6, 6, 6, 6 | 0.05 Degree Celsius | Standard Deviation 0.442 |
| Part 1: Placebo | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 22, 6 hour, n=6, 6, 6, 6 | 0.22 Degree Celsius | Standard Deviation 0.306 |
| Part 1: Placebo | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Follow-up, n=6, 6, 6, 5 | -0.18 Degree Celsius | Standard Deviation 0.479 |
| Part 1: Placebo | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 36, n=6, 6, 6, 5 | 0.22 Degree Celsius | Standard Deviation 0.271 |
| Part 1: Placebo | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 4, 72 hour, n=6, 6, 6, 6 | -0.05 Degree Celsius | Standard Deviation 0.362 |
| Part 1: Placebo | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 1, 1 hour, n=6, 6, 6, 6 | 0.27 Degree Celsius | Standard Deviation 0.388 |
| Part 1: Placebo | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 1, 2 hour, n=6, 6, 6, 6 | 0.20 Degree Celsius | Standard Deviation 0.167 |
| Part 1: Placebo | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 1, 8 hour, n=6, 6, 6, 6 | 0.20 Degree Celsius | Standard Deviation 0.228 |
| Part 1: Placebo | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 8, n=6, 6, 6, 6 | 0.02 Degree Celsius | Standard Deviation 0.436 |
| Part 1: Placebo | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 22, 4 hour, n=6, 6, 6, 6 | 0.38 Degree Celsius | Standard Deviation 0.422 |
| Part 1: Placebo | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 29, n=6, 6, 6, 6 | -0.38 Degree Celsius | Standard Deviation 0.366 |
| Part 1: Placebo | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 15, n=6, 6, 6, 6 | -0.23 Degree Celsius | Standard Deviation 0.446 |
| Part 1: Placebo | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 1, 6 hour, n=6, 6, 6, 6 | 0.28 Degree Celsius | Standard Deviation 0.325 |
| Part 1: Placebo | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 1, 4 hour, n=6, 6, 6, 6 | 0.40 Degree Celsius | Standard Deviation 0.11 |
| Part 1: Placebo | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 1, 12 hour, n=6, 6, 6, 6 | 0.22 Degree Celsius | Standard Deviation 0.147 |
| Part 1: Placebo | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 22, pre-dose, n=6, 6, 6, 6 | 0.08 Degree Celsius | Standard Deviation 0.488 |
| Part 1: Placebo | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 22, 8 hour, n=6, 6, 6, 6 | 0.25 Degree Celsius | Standard Deviation 0.217 |
| Part 1: Placebo | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 71, n=6, 6, 6, 5 | -0.18 Degree Celsius | Standard Deviation 0.286 |
| Part 1: Placebo | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 25, 72 hour, n=6, 6, 6, 6 | 0.10 Degree Celsius | Standard Deviation 0.276 |
| Part 1: Placebo | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 22, 1 hour, n=6, 6, 6, 6 | 0.15 Degree Celsius | Standard Deviation 0.266 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Follow-up, n=6, 6, 6, 5 | 0.08 Degree Celsius | Standard Deviation 0.397 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 24, 48 hour, n=6, 6, 6, 6 | 0.00 Degree Celsius | Standard Deviation 0.352 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 22, 4 hour, n=6, 6, 6, 6 | 0.13 Degree Celsius | Standard Deviation 0.513 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 22, 6 hour, n=6, 6, 6, 6 | 0.28 Degree Celsius | Standard Deviation 0.248 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 23, 24 hour, n=6, 6, 6, 6 | 0.15 Degree Celsius | Standard Deviation 0.536 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 22, 8 hour, n=6, 6, 6, 6 | 0.23 Degree Celsius | Standard Deviation 0.367 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 1, 6 hour, n=6, 6, 6, 6 | 0.38 Degree Celsius | Standard Deviation 0.454 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 22, 12 hour, n=6, 6, 6, 6 | 0.08 Degree Celsius | Standard Deviation 0.299 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 1, 8 hour, n=6, 6, 6, 6 | 0.43 Degree Celsius | Standard Deviation 0.408 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 1, 1 hour, n=6, 6, 6, 6 | 0.15 Degree Celsius | Standard Deviation 0.288 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 50, n=6, 6, 6, 5 | -0.07 Degree Celsius | Standard Deviation 0.48 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 1, 12 hour, n=6, 6, 6, 6 | 0.50 Degree Celsius | Standard Deviation 0.369 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 1, 4 hour, n=6, 6, 6, 6 | 0.35 Degree Celsius | Standard Deviation 0.308 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 2, 24 hour, n=6, 6, 6, 6 | -0.10 Degree Celsius | Standard Deviation 0.379 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 8, n=6, 6, 6, 6 | 0.05 Degree Celsius | Standard Deviation 0.235 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 36, n=6, 6, 6, 5 | 0.03 Degree Celsius | Standard Deviation 0.35 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 3, 48 hour, n=6, 6, 6, 6 | 0.15 Degree Celsius | Standard Deviation 0.489 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 4, 72 hour, n=6, 6, 6, 6 | 0.28 Degree Celsius | Standard Deviation 0.595 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 29, n=6, 6, 6, 6 | -0.05 Degree Celsius | Standard Deviation 0.187 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 1, 2 hour, n=6, 6, 6, 6 | -0.02 Degree Celsius | Standard Deviation 0.256 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 15, n=6, 6, 6, 6 | 0.08 Degree Celsius | Standard Deviation 0.376 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 22, 1 hour, n=6, 6, 6, 6 | -0.15 Degree Celsius | Standard Deviation 0.315 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 25, 72 hour, n=6, 6, 6, 6 | 0.20 Degree Celsius | Standard Deviation 0.562 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 22, pre-dose, n=6, 6, 6, 6 | -0.02 Degree Celsius | Standard Deviation 0.331 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 71, n=6, 6, 6, 5 | -0.13 Degree Celsius | Standard Deviation 0.378 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 1, 12 hour, n=6, 6, 6, 6 | -0.15 Degree Celsius | Standard Deviation 0.295 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 1, 4 hour, n=6, 6, 6, 6 | 0.02 Degree Celsius | Standard Deviation 0.117 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 23, 24 hour, n=6, 6, 6, 6 | -0.13 Degree Celsius | Standard Deviation 0.216 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 1, 1 hour, n=6, 6, 6, 6 | -0.05 Degree Celsius | Standard Deviation 0.176 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 1, 2 hour, n=6, 6, 6, 6 | 0.05 Degree Celsius | Standard Deviation 0.187 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 1, 6 hour, n=6, 6, 6, 6 | 0.10 Degree Celsius | Standard Deviation 0.237 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 1, 8 hour, n=6, 6, 6, 6 | -0.13 Degree Celsius | Standard Deviation 0.32 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 2, 24 hour, n=6, 6, 6, 6 | -0.18 Degree Celsius | Standard Deviation 0.223 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 3, 48 hour, n=6, 6, 6, 6 | -0.22 Degree Celsius | Standard Deviation 0.204 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 4, 72 hour, n=6, 6, 6, 6 | 0.30 Degree Celsius | Standard Deviation 0.21 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 8, n=6, 6, 6, 6 | 0.10 Degree Celsius | Standard Deviation 0.283 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 15, n=6, 6, 6, 6 | -0.05 Degree Celsius | Standard Deviation 0.197 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 22, pre-dose, n=6, 6, 6, 6 | -0.22 Degree Celsius | Standard Deviation 0.183 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 22, 1 hour, n=6, 6, 6, 6 | -0.07 Degree Celsius | Standard Deviation 0.175 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 22, 4 hour, n=6, 6, 6, 6 | 0.07 Degree Celsius | Standard Deviation 0.242 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 22, 6 hour, n=6, 6, 6, 6 | 0.17 Degree Celsius | Standard Deviation 0.163 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 22, 8 hour, n=6, 6, 6, 6 | -0.05 Degree Celsius | Standard Deviation 0.243 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 22, 12 hour, n=6, 6, 6, 6 | 0.27 Degree Celsius | Standard Deviation 0.344 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 24, 48 hour, n=6, 6, 6, 6 | -0.08 Degree Celsius | Standard Deviation 0.098 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 25, 72 hour, n=6, 6, 6, 6 | 0.12 Degree Celsius | Standard Deviation 0.445 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 29, n=6, 6, 6, 6 | -0.15 Degree Celsius | Standard Deviation 0.266 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 36, n=6, 6, 6, 5 | -0.20 Degree Celsius | Standard Deviation 0.385 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 50, n=6, 6, 6, 5 | -0.37 Degree Celsius | Standard Deviation 0.121 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 71, n=6, 6, 6, 5 | -0.53 Degree Celsius | Standard Deviation 0.28 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Follow-up, n=6, 6, 6, 5 | -0.12 Degree Celsius | Standard Deviation 0.293 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 24, 48 hour, n=6, 6, 6, 6 | -0.13 Degree Celsius | Standard Deviation 0.432 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 22, pre-dose, n=6, 6, 6, 6 | -0.23 Degree Celsius | Standard Deviation 0.082 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 15, n=6, 6, 6, 6 | -0.12 Degree Celsius | Standard Deviation 0.366 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Follow-up, n=6, 6, 6, 5 | -0.02 Degree Celsius | Standard Deviation 0.259 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 25, 72 hour, n=6, 6, 6, 6 | -0.20 Degree Celsius | Standard Deviation 0.276 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 8, n=6, 6, 6, 6 | -0.20 Degree Celsius | Standard Deviation 0.424 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 4, 72 hour, n=6, 6, 6, 6 | -0.02 Degree Celsius | Standard Deviation 0.417 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 71, n=6, 6, 6, 5 | -0.34 Degree Celsius | Standard Deviation 0.305 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 29, n=6, 6, 6, 6 | -0.23 Degree Celsius | Standard Deviation 0.25 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 3, 48 hour, n=6, 6, 6, 6 | -0.32 Degree Celsius | Standard Deviation 0.313 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 2, 24 hour, n=6, 6, 6, 6 | -0.15 Degree Celsius | Standard Deviation 0.138 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 1, 1 hour, n=6, 6, 6, 6 | 0.02 Degree Celsius | Standard Deviation 0.44 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 36, n=6, 6, 6, 5 | -0.16 Degree Celsius | Standard Deviation 0.378 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 1, 12 hour, n=6, 6, 6, 6 | 0.20 Degree Celsius | Standard Deviation 0.39 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 1, 8 hour, n=6, 6, 6, 6 | 0.33 Degree Celsius | Standard Deviation 0.557 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 1, 6 hour, n=6, 6, 6, 6 | 0.20 Degree Celsius | Standard Deviation 0.358 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 50, n=6, 6, 6, 5 | 0.04 Degree Celsius | Standard Deviation 0.416 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 1, 4 hour, n=6, 6, 6, 6 | 0.15 Degree Celsius | Standard Deviation 0.432 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 22, 12 hour, n=6, 6, 6, 6 | 0.22 Degree Celsius | Standard Deviation 0.147 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 22, 8 hour, n=6, 6, 6, 6 | -0.02 Degree Celsius | Standard Deviation 0.214 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 22, 6 hour, n=6, 6, 6, 6 | -0.02 Degree Celsius | Standard Deviation 0.293 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 23, 24 hour, n=6, 6, 6, 6 | -0.12 Degree Celsius | Standard Deviation 0.279 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 22, 4 hour, n=6, 6, 6, 6 | -0.18 Degree Celsius | Standard Deviation 0.366 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 22, 1 hour, n=6, 6, 6, 6 | -0.20 Degree Celsius | Standard Deviation 0.303 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Body Temperature at the Indicated Time Points in Part 2 | Temperature, Day 1, 2 hour, n=6, 6, 6, 6 | -0.02 Degree Celsius | Standard Deviation 0.24 |
Primary
Change From Baseline in Complement Factor Bb Levels in Part 2
Blood samples were collected to evaluate complement factors C5a levels. Latest pre-dose assessment at Day 1 or Day 22 was considered as Baseline value. Change from Baseline was calculated as difference between maximum level (lowest of the measurements for specimens collected each after Day 1 and Day 22 study drug administrations) observed post-dose and pre-study drug administration.
Time frame: Day 1 (pre-dose) and Day 22
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Placebo | Change From Baseline in Complement Factor Bb Levels in Part 2 | Bb, Day 1 | 0.4217 mg/L | Standard Deviation 0.62669 |
| Part 1: Placebo | Change From Baseline in Complement Factor Bb Levels in Part 2 | Bb, Day 22 | 1.4003 mg/L | Standard Deviation 0.5658 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Complement Factor Bb Levels in Part 2 | Bb, Day 22 | 1.3447 mg/L | Standard Deviation 0.75517 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Complement Factor Bb Levels in Part 2 | Bb, Day 1 | 0.5033 mg/L | Standard Deviation 0.76727 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Complement Factor Bb Levels in Part 2 | Bb, Day 22 | 0.6833 mg/L | Standard Deviation 0.57597 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Complement Factor Bb Levels in Part 2 | Bb, Day 1 | 0.9700 mg/L | Standard Deviation 0.60554 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Complement Factor Bb Levels in Part 2 | Bb, Day 1 | 1.2667 mg/L | Standard Deviation 0.55623 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Complement Factor Bb Levels in Part 2 | Bb, Day 22 | 1.7340 mg/L | Standard Deviation 1.05781 |
Primary
Change From Baseline in Complement Factor C3 and C4 Levels in Part 2
Blood samples were collected to evaluate complement factors (C3 and C4) levels. Latest pre-dose assessment at Day 1 or Day 22 was considered as Baseline value. Change from Baseline was calculated as difference between minimum level (lowest of the measurements for specimens collected each after Day 1 and Day 22 study drug administrations) observed post-dose and pre-study drug administration
Time frame: Day 1 (pre-dose) and Day 22
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Placebo | Change From Baseline in Complement Factor C3 and C4 Levels in Part 2 | C3, Day 22 | -0.1143 G/L | Standard Deviation 0.07139 |
| Part 1: Placebo | Change From Baseline in Complement Factor C3 and C4 Levels in Part 2 | C4, Day 22 | -0.0397 G/L | Standard Deviation 0.02043 |
| Part 1: Placebo | Change From Baseline in Complement Factor C3 and C4 Levels in Part 2 | C3, Day 1 | -0.0495 G/L | Standard Deviation 0.06661 |
| Part 1: Placebo | Change From Baseline in Complement Factor C3 and C4 Levels in Part 2 | C4, Day 1 | -0.0190 G/L | Standard Deviation 0.01192 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Complement Factor C3 and C4 Levels in Part 2 | C4, Day 1 | -0.0132 G/L | Standard Deviation 0.03511 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Complement Factor C3 and C4 Levels in Part 2 | C4, Day 22 | -0.0405 G/L | Standard Deviation 0.03661 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Complement Factor C3 and C4 Levels in Part 2 | C3, Day 22 | -0.1013 G/L | Standard Deviation 0.06017 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Complement Factor C3 and C4 Levels in Part 2 | C3, Day 1 | -0.0333 G/L | Standard Deviation 0.05961 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Complement Factor C3 and C4 Levels in Part 2 | C3, Day 1 | -0.0783 G/L | Standard Deviation 0.04025 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Complement Factor C3 and C4 Levels in Part 2 | C4, Day 1 | -0.0470 G/L | Standard Deviation 0.02674 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Complement Factor C3 and C4 Levels in Part 2 | C3, Day 22 | -0.0840 G/L | Standard Deviation 0.02521 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Complement Factor C3 and C4 Levels in Part 2 | C4, Day 22 | -0.0390 G/L | Standard Deviation 0.0198 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Complement Factor C3 and C4 Levels in Part 2 | C3, Day 22 | -0.1702 G/L | Standard Deviation 0.07908 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Complement Factor C3 and C4 Levels in Part 2 | C4, Day 1 | -0.0135 G/L | Standard Deviation 0.01271 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Complement Factor C3 and C4 Levels in Part 2 | C4, Day 22 | -0.0443 G/L | Standard Deviation 0.02805 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Complement Factor C3 and C4 Levels in Part 2 | C3, Day 1 | -0.0293 G/L | Standard Deviation 0.05722 |
Primary
Change From Baseline in Complement Factor C5a Levels in Part 2
Blood samples were collected to evaluate complement factors C5a levels. Latest pre-dose assessment at Day 1 or Day 22 was considered as Baseline value. Change from Baseline was calculated as difference between maximum level (lowest of the measurements for specimens collected each after Day 1 and Day 22 study drug administrations) observed post-dose and pre-study drug administration.
Time frame: Day 1 (pre-dose) and Day 22
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Placebo | Change From Baseline in Complement Factor C5a Levels in Part 2 | C5a, Day 22 | 9.083 ug/L | Standard Deviation 4.2002 |
| Part 1: Placebo | Change From Baseline in Complement Factor C5a Levels in Part 2 | C5a, Day 1 | 3.000 ug/L | Standard Deviation 4.2895 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Complement Factor C5a Levels in Part 2 | C5a, Day 1 | -1.167 ug/L | Standard Deviation 5.8963 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Complement Factor C5a Levels in Part 2 | C5a, Day 22 | 9.667 ug/L | Standard Deviation 10.5862 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Complement Factor C5a Levels in Part 2 | C5a, Day 1 | 2.750 ug/L | Standard Deviation 4.1563 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Complement Factor C5a Levels in Part 2 | C5a, Day 22 | 7.333 ug/L | Standard Deviation 2.3805 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Complement Factor C5a Levels in Part 2 | C5a, Day 22 | 13.667 ug/L | Standard Deviation 9.9029 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Complement Factor C5a Levels in Part 2 | C5a, Day 1 | 11.083 ug/L | Standard Deviation 6.3907 |
Primary
Change From Baseline in Complement Factor Component 3 (C3) and C4 Levels in Part 1
Blood samples were collected to evaluate complement factors (C3 and C4) levels. Latest pre-dose assessment at Day 1 was considered as Baseline value. Change from Baseline was calculated as difference between minimum level (lowest of the measurements for specimens collected) observed post-dose and pre-study drug administration.
Time frame: Day 1 (pre-dose) and up to 31 days
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Placebo | Change From Baseline in Complement Factor Component 3 (C3) and C4 Levels in Part 1 | C4 | -0.0320 Gram per liter (g/L) | Standard Deviation 0.04107 |
| Part 1: Placebo | Change From Baseline in Complement Factor Component 3 (C3) and C4 Levels in Part 1 | C3 | -0.0811 Gram per liter (g/L) | Standard Deviation 0.09367 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Complement Factor Component 3 (C3) and C4 Levels in Part 1 | C4 | -0.0123 Gram per liter (g/L) | Standard Deviation 0.01768 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Complement Factor Component 3 (C3) and C4 Levels in Part 1 | C3 | -0.0142 Gram per liter (g/L) | Standard Deviation 0.04549 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Complement Factor Component 3 (C3) and C4 Levels in Part 1 | C3 | -0.1580 Gram per liter (g/L) | Standard Deviation 0.12739 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Complement Factor Component 3 (C3) and C4 Levels in Part 1 | C4 | -0.0600 Gram per liter (g/L) | Standard Deviation 0.04544 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Complement Factor Component 3 (C3) and C4 Levels in Part 1 | C4 | -0.0212 Gram per liter (g/L) | Standard Deviation 0.01987 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Complement Factor Component 3 (C3) and C4 Levels in Part 1 | C3 | -0.0900 Gram per liter (g/L) | Standard Deviation 0.07452 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Complement Factor Component 3 (C3) and C4 Levels in Part 1 | C3 | -0.0412 Gram per liter (g/L) | Standard Deviation 0.06432 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Complement Factor Component 3 (C3) and C4 Levels in Part 1 | C4 | -0.0250 Gram per liter (g/L) | Standard Deviation 0.01979 |
Primary
Change From Baseline in Complement Split Product Bb Levels in Part 1
Blood samples were collected to evaluate complement split product Bb levels. Latest pre-dose assessment at Day 1 was considered as Baseline value. Change from Baseline was calculated as difference between maximum level (highest of the measurements for specimens collected) observed post-dose and pre-study drug administration
Time frame: Day 1 (pre-dose) and up to 31 days
Population: Safety Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Placebo | Change From Baseline in Complement Split Product Bb Levels in Part 1 | 0.8788 mg per liter (mg/L) | Standard Deviation 1.01171 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Complement Split Product Bb Levels in Part 1 | 1.5517 mg per liter (mg/L) | Standard Deviation 1.26063 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Complement Split Product Bb Levels in Part 1 | 0.6900 mg per liter (mg/L) | Standard Deviation 0.48187 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Complement Split Product Bb Levels in Part 1 | 1.2900 mg per liter (mg/L) | Standard Deviation 1.69068 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Complement Split Product Bb Levels in Part 1 | 0.3350 mg per liter (mg/L) | Standard Deviation 0.78899 |
Primary
Change From Baseline in Complement Split Product C5a Levels in Part 1
Blood samples were collected to evaluate complement split product C5a levels. Latest pre-dose assessment at Day 1 was considered as Baseline value. Change from Baseline was calculated as difference between maximum level (highest of the measurements for specimens collected) observed post-dose and pre-study drug administration.
Time frame: Day 1 (pre-dose) and up to 31 days
Population: Safety Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Placebo | Change From Baseline in Complement Split Product C5a Levels in Part 1 | 7.895 Microgram per liter (ug/L) | Standard Deviation 4.636 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Complement Split Product C5a Levels in Part 1 | 7.755 Microgram per liter (ug/L) | Standard Deviation 8.8013 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Complement Split Product C5a Levels in Part 1 | 2.590 Microgram per liter (ug/L) | Standard Deviation 1.9653 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Complement Split Product C5a Levels in Part 1 | 5.102 Microgram per liter (ug/L) | Standard Deviation 18.7596 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Complement Split Product C5a Levels in Part 1 | 1.485 Microgram per liter (ug/L) | Standard Deviation 2.5368 |
Primary
Change From Baseline in PR at the Indicated Time Points in Part 2
Pulse rate was taken at Baseline (Day 1, pre-dose) and at 1, 2, 4, 6, 8, 12, 24, 48 and 72 hour post Day 1 dose; on Days 8 and 15; Day 22 (pre-dose) and at 1, 4, 6, 12, 24, 48 and 72 hours post Day 22 dose; on Days 29, 36, 50, 71 and at Follow-up visit (Day 113+- 2 days). Measurements were obtained after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the last scheduled non-missing measurement taken prior to drug administration. Change from Baseline was calculated as value at indicated time point minus Baseline value.
Time frame: Day 1 (pre-dose) and up to 115 days
Population: Safety Population. Only data available at the specified time points was analyzed. (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Placebo | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 1, 2 hour, n=6, 6, 6, 6 | 0.4 bpm | Standard Deviation 4.57 |
| Part 1: Placebo | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 22, 1 hour, n=6, 6, 6, 6 | 1.4 bpm | Standard Deviation 4.84 |
| Part 1: Placebo | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Follow-up, n=6, 6, 6, 5 | 6.1 bpm | Standard Deviation 6.79 |
| Part 1: Placebo | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 22, 4 hour, n=6, 6, 6, 6 | 6.0 bpm | Standard Deviation 4.01 |
| Part 1: Placebo | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 1, 4 hour, n=6, 6, 6, 6 | 4.7 bpm | Standard Deviation 4.13 |
| Part 1: Placebo | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 23, 24 hour, n=6, 6, 6, 6 | 3.6 bpm | Standard Deviation 3.46 |
| Part 1: Placebo | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 22, 6 hour, n=6, 6, 6, 6 | 7.2 bpm | Standard Deviation 3.75 |
| Part 1: Placebo | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 22, 8 hour, n=6, 6, 6, 6 | 2.2 bpm | Standard Deviation 6.26 |
| Part 1: Placebo | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 22, 12 hour, n=6, 6, 6, 6 | 6.4 bpm | Standard Deviation 4.03 |
| Part 1: Placebo | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 8, n=6, 6, 6, 6 | 0.5 bpm | Standard Deviation 3.11 |
| Part 1: Placebo | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 71, n=6, 6, 6, 5 | 6.1 bpm | Standard Deviation 2.74 |
| Part 1: Placebo | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 1, 6 hour, n=6, 6, 6, 6 | 6.4 bpm | Standard Deviation 2.38 |
| Part 1: Placebo | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 1, 8 hour, n=6, 6, 6, 6 | 0.4 bpm | Standard Deviation 1.83 |
| Part 1: Placebo | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 36, n=6, 6, 6, 5 | 4.1 bpm | Standard Deviation 6.54 |
| Part 1: Placebo | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 50, n=6, 6, 6, 5 | 9.9 bpm | Standard Deviation 4.85 |
| Part 1: Placebo | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 1, 12 hour, n=6, 6, 6, 6 | 4.0 bpm | Standard Deviation 3.29 |
| Part 1: Placebo | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 2, 24 hour, n=6, 6, 6, 6 | 0.6 bpm | Standard Deviation 4.62 |
| Part 1: Placebo | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 1, 1 hour, n=6, 6, 6, 6 | -1.5 bpm | Standard Deviation 7.15 |
| Part 1: Placebo | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 3, 48 hour, n=6, 6, 6, 6 | 3.8 bpm | Standard Deviation 4.9 |
| Part 1: Placebo | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 29, n=6, 6, 6, 6 | 8.4 bpm | Standard Deviation 4.76 |
| Part 1: Placebo | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 4, 72 hour, n=6, 6, 6, 6 | 10.1 bpm | Standard Deviation 8.83 |
| Part 1: Placebo | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 25, 72 hour, n=6, 6, 6, 6 | 8.7 bpm | Standard Deviation 10.05 |
| Part 1: Placebo | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 15, n=6, 6, 6, 6 | -0.2 bpm | Standard Deviation 10.22 |
| Part 1: Placebo | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 22, pre-dose, n=6, 6, 6, 6 | 2.7 bpm | Standard Deviation 6.8 |
| Part 1: Placebo | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 24, 48 hour, n=6, 6, 6, 6 | 4.1 bpm | Standard Deviation 2.88 |
| Part 1: GSK3389404 10 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 25, 72 hour, n=6, 6, 6, 6 | 7.1 bpm | Standard Deviation 5.05 |
| Part 1: GSK3389404 10 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 8, n=6, 6, 6, 6 | 1.6 bpm | Standard Deviation 8.2 |
| Part 1: GSK3389404 10 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 22, 1 hour, n=6, 6, 6, 6 | -3.1 bpm | Standard Deviation 4.22 |
| Part 1: GSK3389404 10 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 36, n=6, 6, 6, 5 | 5.4 bpm | Standard Deviation 7.51 |
| Part 1: GSK3389404 10 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 23, 24 hour, n=6, 6, 6, 6 | 0.0 bpm | Standard Deviation 4.92 |
| Part 1: GSK3389404 10 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 29, n=6, 6, 6, 6 | 6.9 bpm | Standard Deviation 8.33 |
| Part 1: GSK3389404 10 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 22, 4 hour, n=6, 6, 6, 6 | 4.3 bpm | Standard Deviation 5.87 |
| Part 1: GSK3389404 10 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 1, 12 hour, n=6, 6, 6, 6 | 7.2 bpm | Standard Deviation 7.13 |
| Part 1: GSK3389404 10 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 2, 24 hour, n=6, 6, 6, 6 | -2.4 bpm | Standard Deviation 4.84 |
| Part 1: GSK3389404 10 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 24, 48 hour, n=6, 6, 6, 6 | -1.0 bpm | Standard Deviation 4.85 |
| Part 1: GSK3389404 10 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 22, 6 hour, n=6, 6, 6, 6 | 3.8 bpm | Standard Deviation 1.81 |
| Part 1: GSK3389404 10 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 22, 12 hour, n=6, 6, 6, 6 | 5.4 bpm | Standard Deviation 4.64 |
| Part 1: GSK3389404 10 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 22, pre-dose, n=6, 6, 6, 6 | 8.0 bpm | Standard Deviation 14.84 |
| Part 1: GSK3389404 10 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 22, 8 hour, n=6, 6, 6, 6 | -1.6 bpm | Standard Deviation 5.59 |
| Part 1: GSK3389404 10 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 1, 4 hour, n=6, 6, 6, 6 | 4.6 bpm | Standard Deviation 5.99 |
| Part 1: GSK3389404 10 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 3, 48 hour, n=6, 6, 6, 6 | 4.3 bpm | Standard Deviation 9.58 |
| Part 1: GSK3389404 10 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 1, 1 hour, n=6, 6, 6, 6 | 0.5 bpm | Standard Deviation 3.8 |
| Part 1: GSK3389404 10 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 15, n=6, 6, 6, 6 | 4.9 bpm | Standard Deviation 12.25 |
| Part 1: GSK3389404 10 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 71, n=6, 6, 6, 5 | 5.1 bpm | Standard Deviation 7.39 |
| Part 1: GSK3389404 10 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 1, 6 hour, n=6, 6, 6, 6 | 5.8 bpm | Standard Deviation 7.12 |
| Part 1: GSK3389404 10 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Follow-up, n=6, 6, 6, 5 | 2.7 bpm | Standard Deviation 5.08 |
| Part 1: GSK3389404 10 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 50, n=6, 6, 6, 5 | 1.1 bpm | Standard Deviation 2.09 |
| Part 1: GSK3389404 10 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 4, 72 hour, n=6, 6, 6, 6 | 5.7 bpm | Standard Deviation 5.3 |
| Part 1: GSK3389404 10 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 1, 8 hour, n=6, 6, 6, 6 | 3.5 bpm | Standard Deviation 5.39 |
| Part 1: GSK3389404 10 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 1, 2 hour, n=6, 6, 6, 6 | -1.6 bpm | Standard Deviation 6.79 |
| Part 1: GSK3389404 30 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 4, 72 hour, n=6, 6, 6, 6 | 10.8 bpm | Standard Deviation 8.06 |
| Part 1: GSK3389404 30 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 22, 6 hour, n=6, 6, 6, 6 | 8.6 bpm | Standard Deviation 3.98 |
| Part 1: GSK3389404 30 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 1, 1 hour, n=6, 6, 6, 6 | 0.3 bpm | Standard Deviation 1.54 |
| Part 1: GSK3389404 30 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 1, 2 hour, n=6, 6, 6, 6 | 2.9 bpm | Standard Deviation 4.17 |
| Part 1: GSK3389404 30 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 1, 4 hour, n=6, 6, 6, 6 | 6.6 bpm | Standard Deviation 3.75 |
| Part 1: GSK3389404 30 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 1, 6 hour, n=6, 6, 6, 6 | 7.9 bpm | Standard Deviation 3.27 |
| Part 1: GSK3389404 30 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 1, 8 hour, n=6, 6, 6, 6 | 7.8 bpm | Standard Deviation 6.99 |
| Part 1: GSK3389404 30 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 1, 12 hour, n=6, 6, 6, 6 | 7.8 bpm | Standard Deviation 6.09 |
| Part 1: GSK3389404 30 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 2, 24 hour, n=6, 6, 6, 6 | 2.4 bpm | Standard Deviation 3.33 |
| Part 1: GSK3389404 30 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 3, 48 hour, n=6, 6, 6, 6 | 6.2 bpm | Standard Deviation 5.7 |
| Part 1: GSK3389404 30 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 8, n=6, 6, 6, 6 | 7.1 bpm | Standard Deviation 6.86 |
| Part 1: GSK3389404 30 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 15, n=6, 6, 6, 6 | 2.4 bpm | Standard Deviation 3.52 |
| Part 1: GSK3389404 30 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 22, pre-dose, n=6, 6, 6, 6 | 1.5 bpm | Standard Deviation 1.59 |
| Part 1: GSK3389404 30 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 22, 1 hour, n=6, 6, 6, 6 | 2.2 bpm | Standard Deviation 3.35 |
| Part 1: GSK3389404 30 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 22, 4 hour, n=6, 6, 6, 6 | 11.5 bpm | Standard Deviation 10.74 |
| Part 1: GSK3389404 30 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 22, 8 hour, n=6, 6, 6, 6 | 5.7 bpm | Standard Deviation 3.61 |
| Part 1: GSK3389404 30 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 22, 12 hour, n=6, 6, 6, 6 | 9.3 bpm | Standard Deviation 4.47 |
| Part 1: GSK3389404 30 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 23, 24 hour, n=6, 6, 6, 6 | 4.6 bpm | Standard Deviation 6.63 |
| Part 1: GSK3389404 30 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 24, 48 hour, n=6, 6, 6, 6 | 3.6 bpm | Standard Deviation 3.79 |
| Part 1: GSK3389404 30 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 25, 72 hour, n=6, 6, 6, 6 | 7.0 bpm | Standard Deviation 4.94 |
| Part 1: GSK3389404 30 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 29, n=6, 6, 6, 6 | 5.0 bpm | Standard Deviation 1.14 |
| Part 1: GSK3389404 30 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 36, n=6, 6, 6, 5 | 3.8 bpm | Standard Deviation 6.1 |
| Part 1: GSK3389404 30 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 50, n=6, 6, 6, 5 | 2.2 bpm | Standard Deviation 6.51 |
| Part 1: GSK3389404 30 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 71, n=6, 6, 6, 5 | 6.0 bpm | Standard Deviation 2.04 |
| Part 1: GSK3389404 30 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Follow-up, n=6, 6, 6, 5 | 6.0 bpm | Standard Deviation 4.23 |
| Part 1: GSK3389404 60 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 15, n=6, 6, 6, 6 | -5.7 bpm | Standard Deviation 6.04 |
| Part 1: GSK3389404 60 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 1, 1 hour, n=6, 6, 6, 6 | -2.4 bpm | Standard Deviation 2.09 |
| Part 1: GSK3389404 60 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 24, 48 hour, n=6, 6, 6, 6 | 2.9 bpm | Standard Deviation 9.4 |
| Part 1: GSK3389404 60 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 8, n=6, 6, 6, 6 | -1.6 bpm | Standard Deviation 2.55 |
| Part 1: GSK3389404 60 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 4, 72 hour, n=6, 6, 6, 6 | 4.0 bpm | Standard Deviation 7.05 |
| Part 1: GSK3389404 60 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Follow-up, n=6, 6, 6, 5 | 2.0 bpm | Standard Deviation 5.71 |
| Part 1: GSK3389404 60 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 25, 72 hour, n=6, 6, 6, 6 | 4.3 bpm | Standard Deviation 7.77 |
| Part 1: GSK3389404 60 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 3, 48 hour, n=6, 6, 6, 6 | -0.1 bpm | Standard Deviation 2.93 |
| Part 1: GSK3389404 60 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 1, 12 hour, n=6, 6, 6, 6 | 3.9 bpm | Standard Deviation 4.59 |
| Part 1: GSK3389404 60 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 71, n=6, 6, 6, 5 | -1.9 bpm | Standard Deviation 6.93 |
| Part 1: GSK3389404 60 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 29, n=6, 6, 6, 6 | -0.6 bpm | Standard Deviation 7.41 |
| Part 1: GSK3389404 60 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 2, 24 hour, n=6, 6, 6, 6 | -1.1 bpm | Standard Deviation 2.39 |
| Part 1: GSK3389404 60 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 36, n=6, 6, 6, 5 | -3.2 bpm | Standard Deviation 13.57 |
| Part 1: GSK3389404 60 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 1, 8 hour, n=6, 6, 6, 6 | 0.5 bpm | Standard Deviation 3.91 |
| Part 1: GSK3389404 60 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 1, 6 hour, n=6, 6, 6, 6 | 6.6 bpm | Standard Deviation 3.93 |
| Part 1: GSK3389404 60 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 1, 2 hour, n=6, 6, 6, 6 | -1.1 bpm | Standard Deviation 3.81 |
| Part 1: GSK3389404 60 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 22, 8 hour, n=6, 6, 6, 6 | -2.1 bpm | Standard Deviation 5.06 |
| Part 1: GSK3389404 60 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 22, 6 hour, n=6, 6, 6, 6 | 2.4 bpm | Standard Deviation 5.99 |
| Part 1: GSK3389404 60 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 50, n=6, 6, 6, 5 | -7.0 bpm | Standard Deviation 6.34 |
| Part 1: GSK3389404 60 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 22, 12 hour, n=6, 6, 6, 6 | 7.9 bpm | Standard Deviation 7.02 |
| Part 1: GSK3389404 60 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 22, 4 hour, n=6, 6, 6, 6 | 2.6 bpm | Standard Deviation 6.63 |
| Part 1: GSK3389404 60 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 22, 1 hour, n=6, 6, 6, 6 | -3.2 bpm | Standard Deviation 7.19 |
| Part 1: GSK3389404 60 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 1, 4 hour, n=6, 6, 6, 6 | 2.4 bpm | Standard Deviation 2.79 |
| Part 1: GSK3389404 60 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 23, 24 hour, n=6, 6, 6, 6 | 0.7 bpm | Standard Deviation 7.64 |
| Part 1: GSK3389404 60 mg | Change From Baseline in PR at the Indicated Time Points in Part 2 | PR, Day 22, pre-dose, n=6, 6, 6, 6 | -2.9 bpm | Standard Deviation 4.51 |
Primary
Change From Baseline in Pulse Rate (PR) at the Indicated Time Points in Part 1
Pulse rate was taken at Baseline (Day 1, pre-dose) and at 1, 2, 4, 8, 12, 24, 48 and 72 hour post dose; and on Days 8 and 30. Measurements were obtained after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the last scheduled non-missing measurement taken prior to drug administration. Change from Baseline was calculated as value at indicated time point minus Baseline value.
Time frame: Day 1 (pre-dose) and up to 30 days
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Placebo | Change From Baseline in Pulse Rate (PR) at the Indicated Time Points in Part 1 | PR, 1 hour | 0.2 Beats per minute (bpm) | Standard Deviation 3.2 |
| Part 1: Placebo | Change From Baseline in Pulse Rate (PR) at the Indicated Time Points in Part 1 | PR, 48 hour | 1.8 Beats per minute (bpm) | Standard Deviation 10.74 |
| Part 1: Placebo | Change From Baseline in Pulse Rate (PR) at the Indicated Time Points in Part 1 | PR, 72 hour | 3.7 Beats per minute (bpm) | Standard Deviation 4.85 |
| Part 1: Placebo | Change From Baseline in Pulse Rate (PR) at the Indicated Time Points in Part 1 | PR, 24 hour | -1.9 Beats per minute (bpm) | Standard Deviation 4.49 |
| Part 1: Placebo | Change From Baseline in Pulse Rate (PR) at the Indicated Time Points in Part 1 | PR, 12 hour | 6.9 Beats per minute (bpm) | Standard Deviation 12.49 |
| Part 1: Placebo | Change From Baseline in Pulse Rate (PR) at the Indicated Time Points in Part 1 | PR, 8 hour | 1.5 Beats per minute (bpm) | Standard Deviation 4.46 |
| Part 1: Placebo | Change From Baseline in Pulse Rate (PR) at the Indicated Time Points in Part 1 | PR, Day 8 | 3.5 Beats per minute (bpm) | Standard Deviation 5.55 |
| Part 1: Placebo | Change From Baseline in Pulse Rate (PR) at the Indicated Time Points in Part 1 | PR, 4 hour | 0.4 Beats per minute (bpm) | Standard Deviation 5.83 |
| Part 1: Placebo | Change From Baseline in Pulse Rate (PR) at the Indicated Time Points in Part 1 | PR, 2 hour | 1.6 Beats per minute (bpm) | Standard Deviation 3.68 |
| Part 1: Placebo | Change From Baseline in Pulse Rate (PR) at the Indicated Time Points in Part 1 | PR, Day 30 | 2.0 Beats per minute (bpm) | Standard Deviation 6.53 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Pulse Rate (PR) at the Indicated Time Points in Part 1 | PR, 1 hour | 0.3 Beats per minute (bpm) | Standard Deviation 5.49 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Pulse Rate (PR) at the Indicated Time Points in Part 1 | PR, 2 hour | 4.0 Beats per minute (bpm) | Standard Deviation 12.68 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Pulse Rate (PR) at the Indicated Time Points in Part 1 | PR, 4 hour | -0.5 Beats per minute (bpm) | Standard Deviation 7.68 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Pulse Rate (PR) at the Indicated Time Points in Part 1 | PR, 8 hour | 1.2 Beats per minute (bpm) | Standard Deviation 4.5 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Pulse Rate (PR) at the Indicated Time Points in Part 1 | PR, 12 hour | 1.6 Beats per minute (bpm) | Standard Deviation 5.04 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Pulse Rate (PR) at the Indicated Time Points in Part 1 | PR, 24 hour | -1.6 Beats per minute (bpm) | Standard Deviation 9.89 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Pulse Rate (PR) at the Indicated Time Points in Part 1 | PR, 48 hour | 0.2 Beats per minute (bpm) | Standard Deviation 9.79 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Pulse Rate (PR) at the Indicated Time Points in Part 1 | PR, 72 hour | 1.0 Beats per minute (bpm) | Standard Deviation 5.26 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Pulse Rate (PR) at the Indicated Time Points in Part 1 | PR, Day 8 | 0.4 Beats per minute (bpm) | Standard Deviation 6.34 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Pulse Rate (PR) at the Indicated Time Points in Part 1 | PR, Day 30 | 4.3 Beats per minute (bpm) | Standard Deviation 11.94 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Pulse Rate (PR) at the Indicated Time Points in Part 1 | PR, 8 hour | 1.9 Beats per minute (bpm) | Standard Deviation 2.63 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Pulse Rate (PR) at the Indicated Time Points in Part 1 | PR, Day 30 | 0.2 Beats per minute (bpm) | Standard Deviation 5.36 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Pulse Rate (PR) at the Indicated Time Points in Part 1 | PR, 12 hour | 2.3 Beats per minute (bpm) | Standard Deviation 4.19 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Pulse Rate (PR) at the Indicated Time Points in Part 1 | PR, 1 hour | -2.0 Beats per minute (bpm) | Standard Deviation 3.19 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Pulse Rate (PR) at the Indicated Time Points in Part 1 | PR, 4 hour | -1.9 Beats per minute (bpm) | Standard Deviation 3.24 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Pulse Rate (PR) at the Indicated Time Points in Part 1 | PR, 2 hour | 2.3 Beats per minute (bpm) | Standard Deviation 4.54 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Pulse Rate (PR) at the Indicated Time Points in Part 1 | PR, Day 8 | 1.4 Beats per minute (bpm) | Standard Deviation 2.58 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Pulse Rate (PR) at the Indicated Time Points in Part 1 | PR, 24 hour | 1.4 Beats per minute (bpm) | Standard Deviation 7.17 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Pulse Rate (PR) at the Indicated Time Points in Part 1 | PR, 72 hour | 4.0 Beats per minute (bpm) | Standard Deviation 3.47 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Pulse Rate (PR) at the Indicated Time Points in Part 1 | PR, 48 hour | 1.4 Beats per minute (bpm) | Standard Deviation 4.46 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Pulse Rate (PR) at the Indicated Time Points in Part 1 | PR, Day 8 | 6.0 Beats per minute (bpm) | Standard Deviation 7.36 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Pulse Rate (PR) at the Indicated Time Points in Part 1 | PR, 1 hour | 1.5 Beats per minute (bpm) | Standard Deviation 5.43 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Pulse Rate (PR) at the Indicated Time Points in Part 1 | PR, 8 hour | 4.8 Beats per minute (bpm) | Standard Deviation 5.89 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Pulse Rate (PR) at the Indicated Time Points in Part 1 | PR, 48 hour | 2.3 Beats per minute (bpm) | Standard Deviation 5.1 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Pulse Rate (PR) at the Indicated Time Points in Part 1 | PR, 2 hour | 3.8 Beats per minute (bpm) | Standard Deviation 6 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Pulse Rate (PR) at the Indicated Time Points in Part 1 | PR, 72 hour | 5.3 Beats per minute (bpm) | Standard Deviation 5.39 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Pulse Rate (PR) at the Indicated Time Points in Part 1 | PR, Day 30 | 6.3 Beats per minute (bpm) | Standard Deviation 6.19 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Pulse Rate (PR) at the Indicated Time Points in Part 1 | PR, 12 hour | 8.6 Beats per minute (bpm) | Standard Deviation 8.12 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Pulse Rate (PR) at the Indicated Time Points in Part 1 | PR, 4 hour | 0.2 Beats per minute (bpm) | Standard Deviation 5.53 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Pulse Rate (PR) at the Indicated Time Points in Part 1 | PR, 24 hour | -1.3 Beats per minute (bpm) | Standard Deviation 5.49 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Pulse Rate (PR) at the Indicated Time Points in Part 1 | PR, 48 hour | -0.6 Beats per minute (bpm) | Standard Deviation 6.61 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Pulse Rate (PR) at the Indicated Time Points in Part 1 | PR, 72 hour | 0.3 Beats per minute (bpm) | Standard Deviation 9.9 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Pulse Rate (PR) at the Indicated Time Points in Part 1 | PR, 8 hour | 1.3 Beats per minute (bpm) | Standard Deviation 6.76 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Pulse Rate (PR) at the Indicated Time Points in Part 1 | PR, 12 hour | -0.7 Beats per minute (bpm) | Standard Deviation 8.35 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Pulse Rate (PR) at the Indicated Time Points in Part 1 | PR, 2 hour | -2.3 Beats per minute (bpm) | Standard Deviation 8.82 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Pulse Rate (PR) at the Indicated Time Points in Part 1 | PR, Day 30 | -1.1 Beats per minute (bpm) | Standard Deviation 9.67 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Pulse Rate (PR) at the Indicated Time Points in Part 1 | PR, 4 hour | 0.7 Beats per minute (bpm) | Standard Deviation 9.37 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Pulse Rate (PR) at the Indicated Time Points in Part 1 | PR, 24 hour | -0.9 Beats per minute (bpm) | Standard Deviation 10.07 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Pulse Rate (PR) at the Indicated Time Points in Part 1 | PR, 1 hour | -3.2 Beats per minute (bpm) | Standard Deviation 6.63 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Pulse Rate (PR) at the Indicated Time Points in Part 1 | PR, Day 8 | 1.5 Beats per minute (bpm) | Standard Deviation 9.03 |
Primary
Change From Baseline in Respiratory Rate (RR) at the Indicated Time Points in Part 1
Respiratory rate was taken at Baseline (Day 1, pre-dose) and at 1, 2, 4, 8, 12, 24, 48 and 72 hour post dose; and on Days 8 and 30. Baseline was defined as the last scheduled non-missing measurement taken prior to drug administration. Change from Baseline was calculated as value at indicated time point minus Baseline value.
Time frame: Day 1 (pre-dose) and up to 30 days
Population: Safety Population. Only data available at the specified time points was analyzed. (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Placebo | Change From Baseline in Respiratory Rate (RR) at the Indicated Time Points in Part 1 | RR, 12 hour, n=8, 6, 6, 6, 6 | -0.3 Breaths per minute | Standard Deviation 2.19 |
| Part 1: Placebo | Change From Baseline in Respiratory Rate (RR) at the Indicated Time Points in Part 1 | RR, 8 hour, n=8, 6, 6, 6, 6 | -0.1 Breaths per minute | Standard Deviation 2.95 |
| Part 1: Placebo | Change From Baseline in Respiratory Rate (RR) at the Indicated Time Points in Part 1 | RR, 4 hour, n=8, 6, 6, 5, 6 | -0.8 Breaths per minute | Standard Deviation 3.01 |
| Part 1: Placebo | Change From Baseline in Respiratory Rate (RR) at the Indicated Time Points in Part 1 | RR, 2 hour, n=8, 6, 6, 6, 6 | -0.3 Breaths per minute | Standard Deviation 2.38 |
| Part 1: Placebo | Change From Baseline in Respiratory Rate (RR) at the Indicated Time Points in Part 1 | RR, 1 hour, n=8, 6, 6, 6, 6 | -0.5 Breaths per minute | Standard Deviation 2.14 |
| Part 1: Placebo | Change From Baseline in Respiratory Rate (RR) at the Indicated Time Points in Part 1 | RR, Day 30, n=8, 6, 6, 6, 6 | 1.0 Breaths per minute | Standard Deviation 1.69 |
| Part 1: Placebo | Change From Baseline in Respiratory Rate (RR) at the Indicated Time Points in Part 1 | RR, Day 8, n=8, 6, 6, 6, 6 | -0.6 Breaths per minute | Standard Deviation 3.2 |
| Part 1: Placebo | Change From Baseline in Respiratory Rate (RR) at the Indicated Time Points in Part 1 | RR, 24 hour, n=8, 6, 6, 6, 6 | -0.6 Breaths per minute | Standard Deviation 2.62 |
| Part 1: Placebo | Change From Baseline in Respiratory Rate (RR) at the Indicated Time Points in Part 1 | RR, 72 hour, n=8, 6, 6, 6, 6 | -0.5 Breaths per minute | Standard Deviation 3.07 |
| Part 1: Placebo | Change From Baseline in Respiratory Rate (RR) at the Indicated Time Points in Part 1 | RR, 48 hour, n=8, 6, 6, 6, 6 | -0.5 Breaths per minute | Standard Deviation 3.12 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Respiratory Rate (RR) at the Indicated Time Points in Part 1 | RR, Day 30, n=8, 6, 6, 6, 6 | 0.0 Breaths per minute | Standard Deviation 1.41 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Respiratory Rate (RR) at the Indicated Time Points in Part 1 | RR, 4 hour, n=8, 6, 6, 5, 6 | -0.2 Breaths per minute | Standard Deviation 2.14 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Respiratory Rate (RR) at the Indicated Time Points in Part 1 | RR, 8 hour, n=8, 6, 6, 6, 6 | -0.5 Breaths per minute | Standard Deviation 1.87 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Respiratory Rate (RR) at the Indicated Time Points in Part 1 | RR, 12 hour, n=8, 6, 6, 6, 6 | 0.8 Breaths per minute | Standard Deviation 1.6 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Respiratory Rate (RR) at the Indicated Time Points in Part 1 | RR, 24 hour, n=8, 6, 6, 6, 6 | -0.3 Breaths per minute | Standard Deviation 2.94 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Respiratory Rate (RR) at the Indicated Time Points in Part 1 | RR, 48 hour, n=8, 6, 6, 6, 6 | -0.8 Breaths per minute | Standard Deviation 2.32 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Respiratory Rate (RR) at the Indicated Time Points in Part 1 | RR, 72 hour, n=8, 6, 6, 6, 6 | 0.7 Breaths per minute | Standard Deviation 3.44 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Respiratory Rate (RR) at the Indicated Time Points in Part 1 | RR, Day 8, n=8, 6, 6, 6, 6 | -1.3 Breaths per minute | Standard Deviation 1.51 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Respiratory Rate (RR) at the Indicated Time Points in Part 1 | RR, 1 hour, n=8, 6, 6, 6, 6 | -1.3 Breaths per minute | Standard Deviation 1.86 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Respiratory Rate (RR) at the Indicated Time Points in Part 1 | RR, 2 hour, n=8, 6, 6, 6, 6 | 0.3 Breaths per minute | Standard Deviation 3.14 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Respiratory Rate (RR) at the Indicated Time Points in Part 1 | RR, 1 hour, n=8, 6, 6, 6, 6 | 0.8 Breaths per minute | Standard Deviation 3.54 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Respiratory Rate (RR) at the Indicated Time Points in Part 1 | RR, 48 hour, n=8, 6, 6, 6, 6 | -2.0 Breaths per minute | Standard Deviation 3.74 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Respiratory Rate (RR) at the Indicated Time Points in Part 1 | RR, 8 hour, n=8, 6, 6, 6, 6 | -1.0 Breaths per minute | Standard Deviation 3.79 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Respiratory Rate (RR) at the Indicated Time Points in Part 1 | RR, Day 8, n=8, 6, 6, 6, 6 | -1.5 Breaths per minute | Standard Deviation 4.72 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Respiratory Rate (RR) at the Indicated Time Points in Part 1 | RR, 4 hour, n=8, 6, 6, 5, 6 | 0.0 Breaths per minute | Standard Deviation 2.9 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Respiratory Rate (RR) at the Indicated Time Points in Part 1 | RR, 2 hour, n=8, 6, 6, 6, 6 | -2.7 Breaths per minute | Standard Deviation 2.66 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Respiratory Rate (RR) at the Indicated Time Points in Part 1 | RR, 12 hour, n=8, 6, 6, 6, 6 | -0.5 Breaths per minute | Standard Deviation 2.59 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Respiratory Rate (RR) at the Indicated Time Points in Part 1 | RR, 72 hour, n=8, 6, 6, 6, 6 | 0.0 Breaths per minute | Standard Deviation 3.52 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Respiratory Rate (RR) at the Indicated Time Points in Part 1 | RR, Day 30, n=8, 6, 6, 6, 6 | -0.7 Breaths per minute | Standard Deviation 3.44 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Respiratory Rate (RR) at the Indicated Time Points in Part 1 | RR, 24 hour, n=8, 6, 6, 6, 6 | -2.2 Breaths per minute | Standard Deviation 3.54 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Respiratory Rate (RR) at the Indicated Time Points in Part 1 | RR, Day 30, n=8, 6, 6, 6, 6 | -0.7 Breaths per minute | Standard Deviation 3.5 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Respiratory Rate (RR) at the Indicated Time Points in Part 1 | RR, 1 hour, n=8, 6, 6, 6, 6 | 1.5 Breaths per minute | Standard Deviation 2.59 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Respiratory Rate (RR) at the Indicated Time Points in Part 1 | RR, 12 hour, n=8, 6, 6, 6, 6 | 0.0 Breaths per minute | Standard Deviation 3.1 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Respiratory Rate (RR) at the Indicated Time Points in Part 1 | RR, 4 hour, n=8, 6, 6, 5, 6 | 0.4 Breaths per minute | Standard Deviation 5.5 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Respiratory Rate (RR) at the Indicated Time Points in Part 1 | RR, 2 hour, n=8, 6, 6, 6, 6 | 1.0 Breaths per minute | Standard Deviation 4.15 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Respiratory Rate (RR) at the Indicated Time Points in Part 1 | RR, Day 8, n=8, 6, 6, 6, 6 | 1.0 Breaths per minute | Standard Deviation 2.97 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Respiratory Rate (RR) at the Indicated Time Points in Part 1 | RR, 48 hour, n=8, 6, 6, 6, 6 | 3.0 Breaths per minute | Standard Deviation 3.29 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Respiratory Rate (RR) at the Indicated Time Points in Part 1 | RR, 72 hour, n=8, 6, 6, 6, 6 | 0.8 Breaths per minute | Standard Deviation 3.66 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Respiratory Rate (RR) at the Indicated Time Points in Part 1 | RR, 8 hour, n=8, 6, 6, 6, 6 | -1.2 Breaths per minute | Standard Deviation 3.87 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Respiratory Rate (RR) at the Indicated Time Points in Part 1 | RR, 24 hour, n=8, 6, 6, 6, 6 | 0.5 Breaths per minute | Standard Deviation 1.52 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Respiratory Rate (RR) at the Indicated Time Points in Part 1 | RR, 1 hour, n=8, 6, 6, 6, 6 | 0.7 Breaths per minute | Standard Deviation 3.67 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Respiratory Rate (RR) at the Indicated Time Points in Part 1 | RR, 24 hour, n=8, 6, 6, 6, 6 | -0.7 Breaths per minute | Standard Deviation 1.75 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Respiratory Rate (RR) at the Indicated Time Points in Part 1 | RR, 48 hour, n=8, 6, 6, 6, 6 | 1.7 Breaths per minute | Standard Deviation 1.63 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Respiratory Rate (RR) at the Indicated Time Points in Part 1 | RR, 72 hour, n=8, 6, 6, 6, 6 | -1.7 Breaths per minute | Standard Deviation 2.25 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Respiratory Rate (RR) at the Indicated Time Points in Part 1 | RR, 12 hour, n=8, 6, 6, 6, 6 | 0.0 Breaths per minute | Standard Deviation 1.41 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Respiratory Rate (RR) at the Indicated Time Points in Part 1 | RR, Day 8, n=8, 6, 6, 6, 6 | -1.0 Breaths per minute | Standard Deviation 2.68 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Respiratory Rate (RR) at the Indicated Time Points in Part 1 | RR, 8 hour, n=8, 6, 6, 6, 6 | -2.2 Breaths per minute | Standard Deviation 1.83 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Respiratory Rate (RR) at the Indicated Time Points in Part 1 | RR, Day 30, n=8, 6, 6, 6, 6 | -0.3 Breaths per minute | Standard Deviation 2.25 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Respiratory Rate (RR) at the Indicated Time Points in Part 1 | RR, 2 hour, n=8, 6, 6, 6, 6 | -1.7 Breaths per minute | Standard Deviation 1.63 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Respiratory Rate (RR) at the Indicated Time Points in Part 1 | RR, 4 hour, n=8, 6, 6, 5, 6 | 0.2 Breaths per minute | Standard Deviation 3.31 |
Primary
Change From Baseline in RR at the Indicated Time Points in Part 2
Respiratory rate was taken at Baseline (Day 1, pre-dose) and at 1, 2, 4, 6, 8, 12, 24, 48 and 72 hour post Day 1 dose; on Days 8 and 15; Day 22 (pre-dose) and at 1, 4, 6, 12, 24, 48 and 72 hours post Day 22 dose; on Days 29, 36, 50, 71 and at Follow-up visit (Day 113+- 2 days). Baseline was defined as the last scheduled non-missing measurement taken prior to drug administration. Change from Baseline was calculated as value at indicated time point minus Baseline value.
Time frame: Day 1 (pre-dose) and up to 115 days
Population: Safety Population. Only data available at the specified time points was analyzed. (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Placebo | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 1, 4 hour, n=6, 6, 6, 6 | 0.0 Breaths per minute | Standard Deviation 3.35 |
| Part 1: Placebo | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 4, 72 hour, n=6, 6, 6, 6 | 0.8 Breaths per minute | Standard Deviation 2.71 |
| Part 1: Placebo | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 1, 2 hour, n=6, 6, 6, 6 | -0.3 Breaths per minute | Standard Deviation 1.97 |
| Part 1: Placebo | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 1, 8 hour, n=6, 6, 6, 6 | -0.7 Breaths per minute | Standard Deviation 2.73 |
| Part 1: Placebo | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 3, 48 hour, n=6, 6, 6, 6 | -1.0 Breaths per minute | Standard Deviation 2.1 |
| Part 1: Placebo | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 50, n=6, 6, 6, 5 | 0.5 Breaths per minute | Standard Deviation 3.56 |
| Part 1: Placebo | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 1, 12 hour, n=6, 6, 6, 6 | 2.0 Breaths per minute | Standard Deviation 3.79 |
| Part 1: Placebo | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 22, 8 hour, n=6, 6, 6, 6 | 1.7 Breaths per minute | Standard Deviation 1.97 |
| Part 1: Placebo | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 22, 12 hour, n=6, 6, 6, 6 | 2.3 Breaths per minute | Standard Deviation 3.2 |
| Part 1: Placebo | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 24, 48 hour, n=6, 6, 6, 6 | 1.0 Breaths per minute | Standard Deviation 3.03 |
| Part 1: Placebo | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 2, 24 hour, n=6, 6, 6, 6 | 0.7 Breaths per minute | Standard Deviation 2.42 |
| Part 1: Placebo | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 22, 4 hour, n=6, 6, 6, 6 | -0.7 Breaths per minute | Standard Deviation 1.63 |
| Part 1: Placebo | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 36, n=6, 6, 6, 5 | 0.0 Breaths per minute | Standard Deviation 3.1 |
| Part 1: Placebo | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Follow-up, n=6, 6, 6, 5 | -1.7 Breaths per minute | Standard Deviation 1.51 |
| Part 1: Placebo | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 23, 24 hour, n=6, 6, 6, 6 | 0.7 Breaths per minute | Standard Deviation 3.5 |
| Part 1: Placebo | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 25, 72 hour, n=6, 6, 6, 6 | 1.0 Breaths per minute | Standard Deviation 2.76 |
| Part 1: Placebo | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 22, 6 hour, n=6, 6, 6, 6 | 1.0 Breaths per minute | Standard Deviation 2.1 |
| Part 1: Placebo | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 8, n=6, 6, 6, 6 | 1.3 Breaths per minute | Standard Deviation 1.63 |
| Part 1: Placebo | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 22, 1 hour, n=6, 6, 6, 6 | 0.7 Breaths per minute | Standard Deviation 3.27 |
| Part 1: Placebo | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 71, n=6, 6, 6, 5 | 0.2 Breaths per minute | Standard Deviation 2.4 |
| Part 1: Placebo | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 29, n=6, 6, 6, 6 | 0.7 Breaths per minute | Standard Deviation 1.63 |
| Part 1: Placebo | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 15, n=6, 6, 6, 6 | 0.7 Breaths per minute | Standard Deviation 1.63 |
| Part 1: Placebo | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 1, 6 hour, n=6, 6, 6, 6 | -0.3 Breaths per minute | Standard Deviation 2.66 |
| Part 1: Placebo | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 1, 1 hour, n=6, 6, 6, 6 | -0.3 Breaths per minute | Standard Deviation 1.97 |
| Part 1: Placebo | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 22, pre-dose, n=6, 6, 6, 6 | 0.0 Breaths per minute | Standard Deviation 1.79 |
| Part 1: GSK3389404 10 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 24, 48 hour, n=6, 6, 6, 6 | 1.7 Breaths per minute | Standard Deviation 2.94 |
| Part 1: GSK3389404 10 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 22, pre-dose, n=6, 6, 6, 6 | 0.7 Breaths per minute | Standard Deviation 2.42 |
| Part 1: GSK3389404 10 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 1, 1 hour, n=6, 6, 6, 6 | 0.7 Breaths per minute | Standard Deviation 2.73 |
| Part 1: GSK3389404 10 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 23, 24 hour, n=6, 6, 6, 6 | 1.3 Breaths per minute | Standard Deviation 2.73 |
| Part 1: GSK3389404 10 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 22, 6 hour, n=6, 6, 6, 6 | 2.3 Breaths per minute | Standard Deviation 3.88 |
| Part 1: GSK3389404 10 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 22, 12 hour, n=6, 6, 6, 6 | 4.3 Breaths per minute | Standard Deviation 3.2 |
| Part 1: GSK3389404 10 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 1, 8 hour, n=6, 6, 6, 6 | 1.3 Breaths per minute | Standard Deviation 3.01 |
| Part 1: GSK3389404 10 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 1, 2 hour, n=6, 6, 6, 6 | -0.3 Breaths per minute | Standard Deviation 2.34 |
| Part 1: GSK3389404 10 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 3, 48 hour, n=6, 6, 6, 6 | -0.3 Breaths per minute | Standard Deviation 2.34 |
| Part 1: GSK3389404 10 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 71, n=6, 6, 6, 5 | 1.3 Breaths per minute | Standard Deviation 1.03 |
| Part 1: GSK3389404 10 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 1, 4 hour, n=6, 6, 6, 6 | 1.0 Breaths per minute | Standard Deviation 3.52 |
| Part 1: GSK3389404 10 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Follow-up, n=6, 6, 6, 5 | -1.0 Breaths per minute | Standard Deviation 1.67 |
| Part 1: GSK3389404 10 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 1, 6 hour, n=6, 6, 6, 6 | 1.3 Breaths per minute | Standard Deviation 4.13 |
| Part 1: GSK3389404 10 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 50, n=6, 6, 6, 5 | 1.0 Breaths per minute | Standard Deviation 3.74 |
| Part 1: GSK3389404 10 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 22, 1 hour, n=6, 6, 6, 6 | 0.3 Breaths per minute | Standard Deviation 3.88 |
| Part 1: GSK3389404 10 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 1, 12 hour, n=6, 6, 6, 6 | 1.7 Breaths per minute | Standard Deviation 2.66 |
| Part 1: GSK3389404 10 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 22, 4 hour, n=6, 6, 6, 6 | 1.8 Breaths per minute | Standard Deviation 4.02 |
| Part 1: GSK3389404 10 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 36, n=6, 6, 6, 5 | 0.7 Breaths per minute | Standard Deviation 3.27 |
| Part 1: GSK3389404 10 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 22, 8 hour, n=6, 6, 6, 6 | 2.7 Breaths per minute | Standard Deviation 3.5 |
| Part 1: GSK3389404 10 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 2, 24 hour, n=6, 6, 6, 6 | 1.0 Breaths per minute | Standard Deviation 2.1 |
| Part 1: GSK3389404 10 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 4, 72 hour, n=6, 6, 6, 6 | 1.3 Breaths per minute | Standard Deviation 3.67 |
| Part 1: GSK3389404 10 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 29, n=6, 6, 6, 6 | 1.3 Breaths per minute | Standard Deviation 2.73 |
| Part 1: GSK3389404 10 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 8, n=6, 6, 6, 6 | -0.3 Breaths per minute | Standard Deviation 3.88 |
| Part 1: GSK3389404 10 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 25, 72 hour, n=6, 6, 6, 6 | 2.7 Breaths per minute | Standard Deviation 2.42 |
| Part 1: GSK3389404 10 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 15, n=6, 6, 6, 6 | 1.5 Breaths per minute | Standard Deviation 1.76 |
| Part 1: GSK3389404 30 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 22, 6 hour, n=6, 6, 6, 6 | 3.0 Breaths per minute | Standard Deviation 2.76 |
| Part 1: GSK3389404 30 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 22, 8 hour, n=6, 6, 6, 6 | -0.7 Breaths per minute | Standard Deviation 2.07 |
| Part 1: GSK3389404 30 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 1, 1 hour, n=6, 6, 6, 6 | 0.0 Breaths per minute | Standard Deviation 1.26 |
| Part 1: GSK3389404 30 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 1, 2 hour, n=6, 6, 6, 6 | 0.7 Breaths per minute | Standard Deviation 1.63 |
| Part 1: GSK3389404 30 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 1, 4 hour, n=6, 6, 6, 6 | -0.7 Breaths per minute | Standard Deviation 2.42 |
| Part 1: GSK3389404 30 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 1, 6 hour, n=6, 6, 6, 6 | 2.0 Breaths per minute | Standard Deviation 2.53 |
| Part 1: GSK3389404 30 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 1, 8 hour, n=6, 6, 6, 6 | 0.7 Breaths per minute | Standard Deviation 2.42 |
| Part 1: GSK3389404 30 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 1, 12 hour, n=6, 6, 6, 6 | 3.3 Breaths per minute | Standard Deviation 2.42 |
| Part 1: GSK3389404 30 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 2, 24 hour, n=6, 6, 6, 6 | -1.7 Breaths per minute | Standard Deviation 1.51 |
| Part 1: GSK3389404 30 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 3, 48 hour, n=6, 6, 6, 6 | -1.0 Breaths per minute | Standard Deviation 2.76 |
| Part 1: GSK3389404 30 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 4, 72 hour, n=6, 6, 6, 6 | 0.3 Breaths per minute | Standard Deviation 3.44 |
| Part 1: GSK3389404 30 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 8, n=6, 6, 6, 6 | 1.3 Breaths per minute | Standard Deviation 3.72 |
| Part 1: GSK3389404 30 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 15, n=6, 6, 6, 6 | 0.7 Breaths per minute | Standard Deviation 2.42 |
| Part 1: GSK3389404 30 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 22, pre-dose, n=6, 6, 6, 6 | -1.0 Breaths per minute | Standard Deviation 2.45 |
| Part 1: GSK3389404 30 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 22, 1 hour, n=6, 6, 6, 6 | -0.3 Breaths per minute | Standard Deviation 3.88 |
| Part 1: GSK3389404 30 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 22, 4 hour, n=6, 6, 6, 6 | -1.0 Breaths per minute | Standard Deviation 3.74 |
| Part 1: GSK3389404 30 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 29, n=6, 6, 6, 6 | -1.0 Breaths per minute | Standard Deviation 1.67 |
| Part 1: GSK3389404 30 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 22, 12 hour, n=6, 6, 6, 6 | 1.0 Breaths per minute | Standard Deviation 2.1 |
| Part 1: GSK3389404 30 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 23, 24 hour, n=6, 6, 6, 6 | -0.3 Breaths per minute | Standard Deviation 2.94 |
| Part 1: GSK3389404 30 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 24, 48 hour, n=6, 6, 6, 6 | -0.3 Breaths per minute | Standard Deviation 2.66 |
| Part 1: GSK3389404 30 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 25, 72 hour, n=6, 6, 6, 6 | -0.7 Breaths per minute | Standard Deviation 3.01 |
| Part 1: GSK3389404 30 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 36, n=6, 6, 6, 5 | 0.0 Breaths per minute | Standard Deviation 3.35 |
| Part 1: GSK3389404 30 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 50, n=6, 6, 6, 5 | -0.7 Breaths per minute | Standard Deviation 3.27 |
| Part 1: GSK3389404 30 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 71, n=6, 6, 6, 5 | 0.0 Breaths per minute | Standard Deviation 4 |
| Part 1: GSK3389404 30 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Follow-up, n=6, 6, 6, 5 | -0.7 Breaths per minute | Standard Deviation 3.5 |
| Part 1: GSK3389404 60 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 22, pre-dose, n=6, 6, 6, 6 | -0.5 Breaths per minute | Standard Deviation 1.97 |
| Part 1: GSK3389404 60 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 15, n=6, 6, 6, 6 | -0.8 Breaths per minute | Standard Deviation 3.13 |
| Part 1: GSK3389404 60 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Follow-up, n=6, 6, 6, 5 | 0.6 Breaths per minute | Standard Deviation 2.61 |
| Part 1: GSK3389404 60 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 24, 48 hour, n=6, 6, 6, 6 | -0.5 Breaths per minute | Standard Deviation 2.66 |
| Part 1: GSK3389404 60 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 71, n=6, 6, 6, 5 | 0.6 Breaths per minute | Standard Deviation 1.34 |
| Part 1: GSK3389404 60 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 25, 72 hour, n=6, 6, 6, 6 | -1.5 Breaths per minute | Standard Deviation 1.22 |
| Part 1: GSK3389404 60 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 8, n=6, 6, 6, 6 | -0.8 Breaths per minute | Standard Deviation 3.13 |
| Part 1: GSK3389404 60 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 4, 72 hour, n=6, 6, 6, 6 | -0.2 Breaths per minute | Standard Deviation 1.33 |
| Part 1: GSK3389404 60 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 29, n=6, 6, 6, 6 | -0.2 Breaths per minute | Standard Deviation 1.33 |
| Part 1: GSK3389404 60 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 2, 24 hour, n=6, 6, 6, 6 | -0.5 Breaths per minute | Standard Deviation 0.84 |
| Part 1: GSK3389404 60 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 1, 12 hour, n=6, 6, 6, 6 | 0.5 Breaths per minute | Standard Deviation 2.95 |
| Part 1: GSK3389404 60 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 1, 1 hour, n=6, 6, 6, 6 | 0.5 Breaths per minute | Standard Deviation 1.97 |
| Part 1: GSK3389404 60 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 36, n=6, 6, 6, 5 | -1.0 Breaths per minute | Standard Deviation 1.73 |
| Part 1: GSK3389404 60 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 1, 8 hour, n=6, 6, 6, 6 | 0.8 Breaths per minute | Standard Deviation 1.83 |
| Part 1: GSK3389404 60 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 1, 6 hour, n=6, 6, 6, 6 | -0.5 Breaths per minute | Standard Deviation 0.84 |
| Part 1: GSK3389404 60 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 3, 48 hour, n=6, 6, 6, 6 | -0.8 Breaths per minute | Standard Deviation 1.6 |
| Part 1: GSK3389404 60 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 50, n=6, 6, 6, 5 | -0.2 Breaths per minute | Standard Deviation 1.48 |
| Part 1: GSK3389404 60 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 22, 8 hour, n=6, 6, 6, 6 | -0.8 Breaths per minute | Standard Deviation 1.83 |
| Part 1: GSK3389404 60 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 22, 6 hour, n=6, 6, 6, 6 | 0.2 Breaths per minute | Standard Deviation 2.56 |
| Part 1: GSK3389404 60 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 1, 4 hour, n=6, 6, 6, 6 | -0.5 Breaths per minute | Standard Deviation 0.84 |
| Part 1: GSK3389404 60 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 22, 12 hour, n=6, 6, 6, 6 | -1.5 Breaths per minute | Standard Deviation 2.35 |
| Part 1: GSK3389404 60 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 22, 4 hour, n=6, 6, 6, 6 | 0.8 Breaths per minute | Standard Deviation 0.98 |
| Part 1: GSK3389404 60 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 22, 1 hour, n=6, 6, 6, 6 | 0.5 Breaths per minute | Standard Deviation 1.52 |
| Part 1: GSK3389404 60 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 1, 2 hour, n=6, 6, 6, 6 | 0.5 Breaths per minute | Standard Deviation 1.22 |
| Part 1: GSK3389404 60 mg | Change From Baseline in RR at the Indicated Time Points in Part 2 | RR, Day 23, 24 hour, n=6, 6, 6, 6 | -0.5 Breaths per minute | Standard Deviation 0.84 |
Primary
Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2
SBP and DBP were taken at Baseline (Day 1, pre-dose) and at 1, 2, 4, 6, 8, 12, 24, 48 and 72 hour post Day 1 dose; on Days 8 and 15; Day 22 (pre-dose) and at 1, 4, 6, 12, 24, 48 and 72 hours post Day 22 dose; on Days 29, 36, 50, 71 and at Follow-up visit (Day 113 +- 2 days). Measurements were obtained after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the last scheduled non-missing measurement taken prior to drug administration. Change from Baseline was calculated as value at indicated time point minus Baseline value.
Time frame: Day 1 (pre-dose) and up to 115 days
Population: Safety Population. Only data available at the specified time points was analyzed. (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Placebo | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 1, 1 hour, n=6, 6, 6, 6 | 0.5 mmHg | Standard Deviation 4.75 |
| Part 1: Placebo | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 71, n=6, 6, 6, 5 | 3.2 mmHg | Standard Deviation 6.27 |
| Part 1: Placebo | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 36, n=6, 6, 6, 5 | -0.8 mmHg | Standard Deviation 8.1 |
| Part 1: Placebo | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 29, n=6, 6, 6, 6 | 0.6 mmHg | Standard Deviation 9.06 |
| Part 1: Placebo | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 25, 72 hour, n=6, 6, 6, 6 | 1.3 mmHg | Standard Deviation 6.71 |
| Part 1: Placebo | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 15, n=6, 6, 6, 6 | 2.9 mmHg | Standard Deviation 11.22 |
| Part 1: Placebo | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 23, 24 hour, n=6, 6, 6, 6 | 0.8 mmHg | Standard Deviation 8.5 |
| Part 1: Placebo | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 24, 48 hour, n=6, 6, 6, 6 | -0.6 mmHg | Standard Deviation 5.84 |
| Part 1: Placebo | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 23, 24 hour, n=6, 6, 6, 6 | 0.7 mmHg | Standard Deviation 8.59 |
| Part 1: Placebo | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 22, pre-dose, n=6, 6, 6, 6 | 1.0 mmHg | Standard Deviation 7.07 |
| Part 1: Placebo | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 8, n=6, 6, 6, 6 | 1.6 mmHg | Standard Deviation 7.61 |
| Part 1: Placebo | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 22, 12 hour, n=6, 6, 6, 6 | -0.1 mmHg | Standard Deviation 7.8 |
| Part 1: Placebo | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 22, 8 hour, n=6, 6, 6, 6 | -0.3 mmHg | Standard Deviation 5.82 |
| Part 1: Placebo | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 22, 1 hour, n=6, 6, 6, 6 | 2.6 mmHg | Standard Deviation 6.79 |
| Part 1: Placebo | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 1, 6 hour, n=6, 6, 6, 6 | -5.3 mmHg | Standard Deviation 5.51 |
| Part 1: Placebo | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 22, 6 hour, n=6, 6, 6, 6 | -4.5 mmHg | Standard Deviation 6.22 |
| Part 1: Placebo | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 22, 4 hour, n=6, 6, 6, 6 | -4.0 mmHg | Standard Deviation 7.53 |
| Part 1: Placebo | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 22, 12 hour, n=6, 6, 6, 6 | 4.9 mmHg | Standard Deviation 6.14 |
| Part 1: Placebo | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 22, 8 hour, n=6, 6, 6, 6 | -0.3 mmHg | Standard Deviation 5.73 |
| Part 1: Placebo | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 22, 6 hour, n=6, 6, 6, 6 | -2.4 mmHg | Standard Deviation 7.57 |
| Part 1: Placebo | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 36, n=6, 6, 6, 5 | -2.8 mmHg | Standard Deviation 9.99 |
| Part 1: Placebo | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 1, 8 hour, n=6, 6, 6, 6 | -0.2 mmHg | Standard Deviation 6.66 |
| Part 1: Placebo | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 22, 4 hour, n=6, 6, 6, 6 | -0.3 mmHg | Standard Deviation 6.11 |
| Part 1: Placebo | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 22, 1 hour, n=6, 6, 6, 6 | 1.7 mmHg | Standard Deviation 6.34 |
| Part 1: Placebo | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 50, n=6, 6, 6, 5 | 5.8 mmHg | Standard Deviation 3.93 |
| Part 1: Placebo | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 29, n=6, 6, 6, 6 | 0.3 mmHg | Standard Deviation 6.24 |
| Part 1: Placebo | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 22, pre-dose, n=6, 6, 6, 6 | -1.1 mmHg | Standard Deviation 9.18 |
| Part 1: Placebo | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 3, 48 hour, n=6, 6, 6, 6 | -0.2 mmHg | Standard Deviation 5.41 |
| Part 1: Placebo | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 15, n=6, 6, 6, 6 | 3.5 mmHg | Standard Deviation 10.88 |
| Part 1: Placebo | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 8, n=6, 6, 6, 6 | -0.7 mmHg | Standard Deviation 7.45 |
| Part 1: Placebo | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 4, 72 hour, n=6, 6, 6, 6 | 3.9 mmHg | Standard Deviation 4.96 |
| Part 1: Placebo | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 3, 48 hour, n=6, 6, 6, 6 | 0.7 mmHg | Standard Deviation 8.69 |
| Part 1: Placebo | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 71, n=6, 6, 6, 5 | 1.1 mmHg | Standard Deviation 7.49 |
| Part 1: Placebo | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 2, 24 hour, n=6, 6, 6, 6 | 3.0 mmHg | Standard Deviation 6.25 |
| Part 1: Placebo | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 1, 12 hour, n=6, 6, 6, 6 | -0.1 mmHg | Standard Deviation 6.39 |
| Part 1: Placebo | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 1, 2 hour, n=6, 6, 6, 6 | 2.1 mmHg | Standard Deviation 5.56 |
| Part 1: Placebo | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Follow-up, n=6, 6, 6, 5 | 4.8 mmHg | Standard Deviation 8.05 |
| Part 1: Placebo | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 1, 8 hour, n=6, 6, 6, 6 | 0.3 mmHg | Standard Deviation 3.26 |
| Part 1: Placebo | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 1, 6 hour, n=6, 6, 6, 6 | -3.6 mmHg | Standard Deviation 6.23 |
| Part 1: Placebo | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 1, 4 hour, n=6, 6, 6, 6 | -2.1 mmHg | Standard Deviation 5.54 |
| Part 1: Placebo | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 25, 72 hour, n=6, 6, 6, 6 | 1.2 mmHg | Standard Deviation 5.37 |
| Part 1: Placebo | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 24, 48 hour, n=6, 6, 6, 6 | 0.3 mmHg | Standard Deviation 3.79 |
| Part 1: Placebo | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 1, 4 hour, n=6, 6, 6, 6 | -2.6 mmHg | Standard Deviation 6.36 |
| Part 1: Placebo | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 4, 72 hour, n=6, 6, 6, 6 | 1.6 mmHg | Standard Deviation 5.77 |
| Part 1: Placebo | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 1, 2 hour, n=6, 6, 6, 6 | 0.7 mmHg | Standard Deviation 5.95 |
| Part 1: Placebo | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 1, 12 hour, n=6, 6, 6, 6 | -4.4 mmHg | Standard Deviation 7.17 |
| Part 1: Placebo | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 50, n=6, 6, 6, 5 | 8.1 mmHg | Standard Deviation 6.28 |
| Part 1: Placebo | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 1, 1 hour, n=6, 6, 6, 6 | 1.2 mmHg | Standard Deviation 5.55 |
| Part 1: Placebo | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Follow-up, n=6, 6, 6, 5 | 3.7 mmHg | Standard Deviation 6.38 |
| Part 1: Placebo | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 2, 24 hour, n=6, 6, 6, 6 | 2.6 mmHg | Standard Deviation 6.29 |
| Part 1: GSK3389404 10 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 2, 24 hour, n=6, 6, 6, 6 | 0.9 mmHg | Standard Deviation 3.36 |
| Part 1: GSK3389404 10 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 1, 1 hour, n=6, 6, 6, 6 | 5.7 mmHg | Standard Deviation 4.83 |
| Part 1: GSK3389404 10 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 3, 48 hour, n=6, 6, 6, 6 | 2.6 mmHg | Standard Deviation 5.55 |
| Part 1: GSK3389404 10 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 4, 72 hour, n=6, 6, 6, 6 | -6.1 mmHg | Standard Deviation 6.56 |
| Part 1: GSK3389404 10 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 8, n=6, 6, 6, 6 | 1.9 mmHg | Standard Deviation 5.59 |
| Part 1: GSK3389404 10 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 23, 24 hour, n=6, 6, 6, 6 | -4.2 mmHg | Standard Deviation 6.14 |
| Part 1: GSK3389404 10 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 25, 72 hour, n=6, 6, 6, 6 | 0.7 mmHg | Standard Deviation 3.88 |
| Part 1: GSK3389404 10 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 50, n=6, 6, 6, 5 | 9.7 mmHg | Standard Deviation 7.9 |
| Part 1: GSK3389404 10 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 8, n=6, 6, 6, 6 | -1.7 mmHg | Standard Deviation 6.25 |
| Part 1: GSK3389404 10 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 1, 2 hour, n=6, 6, 6, 6 | -0.1 mmHg | Standard Deviation 4.83 |
| Part 1: GSK3389404 10 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 1, 4 hour, n=6, 6, 6, 6 | -5.1 mmHg | Standard Deviation 6.25 |
| Part 1: GSK3389404 10 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 1, 6 hour, n=6, 6, 6, 6 | -2.6 mmHg | Standard Deviation 6.9 |
| Part 1: GSK3389404 10 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 1, 8 hour, n=6, 6, 6, 6 | 1.4 mmHg | Standard Deviation 4.12 |
| Part 1: GSK3389404 10 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 1, 12 hour, n=6, 6, 6, 6 | -2.6 mmHg | Standard Deviation 4.49 |
| Part 1: GSK3389404 10 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 15, n=6, 6, 6, 6 | 5.5 mmHg | Standard Deviation 3.6 |
| Part 1: GSK3389404 10 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 22, pre-dose, n=6, 6, 6, 6 | -3.8 mmHg | Standard Deviation 4.91 |
| Part 1: GSK3389404 10 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 22, 1 hour, n=6, 6, 6, 6 | -0.8 mmHg | Standard Deviation 7.56 |
| Part 1: GSK3389404 10 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 22, 4 hour, n=6, 6, 6, 6 | -0.3 mmHg | Standard Deviation 6.34 |
| Part 1: GSK3389404 10 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 22, 6 hour, n=6, 6, 6, 6 | 0.1 mmHg | Standard Deviation 5.44 |
| Part 1: GSK3389404 10 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 22, 8 hour, n=6, 6, 6, 6 | -2.8 mmHg | Standard Deviation 6.29 |
| Part 1: GSK3389404 10 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 22, 12 hour, n=6, 6, 6, 6 | -2.9 mmHg | Standard Deviation 3.01 |
| Part 1: GSK3389404 10 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 24, 48 hour, n=6, 6, 6, 6 | -2.8 mmHg | Standard Deviation 5.32 |
| Part 1: GSK3389404 10 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 29, n=6, 6, 6, 6 | 5.7 mmHg | Standard Deviation 7.45 |
| Part 1: GSK3389404 10 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 36, n=6, 6, 6, 5 | 4.3 mmHg | Standard Deviation 7.05 |
| Part 1: GSK3389404 10 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 71, n=6, 6, 6, 5 | 8.9 mmHg | Standard Deviation 6.31 |
| Part 1: GSK3389404 10 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Follow-up, n=6, 6, 6, 5 | 2.2 mmHg | Standard Deviation 6.54 |
| Part 1: GSK3389404 10 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 1, 1 hour, n=6, 6, 6, 6 | 3.4 mmHg | Standard Deviation 6.83 |
| Part 1: GSK3389404 10 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 1, 2 hour, n=6, 6, 6, 6 | 0.5 mmHg | Standard Deviation 2.99 |
| Part 1: GSK3389404 10 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 1, 4 hour, n=6, 6, 6, 6 | -2.6 mmHg | Standard Deviation 2.16 |
| Part 1: GSK3389404 10 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 1, 6 hour, n=6, 6, 6, 6 | -0.9 mmHg | Standard Deviation 3.71 |
| Part 1: GSK3389404 10 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 1, 8 hour, n=6, 6, 6, 6 | 0.6 mmHg | Standard Deviation 3.65 |
| Part 1: GSK3389404 10 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 1, 12 hour, n=6, 6, 6, 6 | -0.4 mmHg | Standard Deviation 5.32 |
| Part 1: GSK3389404 10 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 2, 24 hour, n=6, 6, 6, 6 | -0.1 mmHg | Standard Deviation 4.35 |
| Part 1: GSK3389404 10 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 3, 48 hour, n=6, 6, 6, 6 | 1.5 mmHg | Standard Deviation 6.13 |
| Part 1: GSK3389404 10 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 4, 72 hour, n=6, 6, 6, 6 | -3.7 mmHg | Standard Deviation 6.64 |
| Part 1: GSK3389404 10 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 15, n=6, 6, 6, 6 | 4.6 mmHg | Standard Deviation 7.93 |
| Part 1: GSK3389404 10 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 22, pre-dose, n=6, 6, 6, 6 | -4.6 mmHg | Standard Deviation 5.69 |
| Part 1: GSK3389404 10 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 22, 1 hour, n=6, 6, 6, 6 | -4.6 mmHg | Standard Deviation 4.41 |
| Part 1: GSK3389404 10 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 22, 4 hour, n=6, 6, 6, 6 | -2.0 mmHg | Standard Deviation 4.7 |
| Part 1: GSK3389404 10 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 22, 6 hour, n=6, 6, 6, 6 | -2.7 mmHg | Standard Deviation 2.55 |
| Part 1: GSK3389404 10 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 22, 8 hour, n=6, 6, 6, 6 | -5.9 mmHg | Standard Deviation 2.98 |
| Part 1: GSK3389404 10 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 22, 12 hour, n=6, 6, 6, 6 | 0.1 mmHg | Standard Deviation 3.22 |
| Part 1: GSK3389404 10 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 23, 24 hour, n=6, 6, 6, 6 | -5.7 mmHg | Standard Deviation 3.77 |
| Part 1: GSK3389404 10 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 24, 48 hour, n=6, 6, 6, 6 | -7.4 mmHg | Standard Deviation 4.48 |
| Part 1: GSK3389404 10 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 25, 72 hour, n=6, 6, 6, 6 | -1.0 mmHg | Standard Deviation 3.48 |
| Part 1: GSK3389404 10 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 29, n=6, 6, 6, 6 | 6.8 mmHg | Standard Deviation 7.69 |
| Part 1: GSK3389404 10 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 36, n=6, 6, 6, 5 | 4.2 mmHg | Standard Deviation 7.35 |
| Part 1: GSK3389404 10 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 50, n=6, 6, 6, 5 | 3.9 mmHg | Standard Deviation 4.47 |
| Part 1: GSK3389404 10 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 71, n=6, 6, 6, 5 | 4.9 mmHg | Standard Deviation 7.81 |
| Part 1: GSK3389404 10 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Follow-up, n=6, 6, 6, 5 | -2.1 mmHg | Standard Deviation 7.16 |
| Part 1: GSK3389404 30 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 1, 8 hour, n=6, 6, 6, 6 | 0.4 mmHg | Standard Deviation 10.56 |
| Part 1: GSK3389404 30 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Follow-up, n=6, 6, 6, 5 | 4.3 mmHg | Standard Deviation 3.85 |
| Part 1: GSK3389404 30 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 1, 12 hour, n=6, 6, 6, 6 | -7.7 mmHg | Standard Deviation 5.97 |
| Part 1: GSK3389404 30 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Follow-up, n=6, 6, 6, 5 | 10.0 mmHg | Standard Deviation 5.98 |
| Part 1: GSK3389404 30 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 1, 1 hour, n=6, 6, 6, 6 | 1.1 mmHg | Standard Deviation 5.35 |
| Part 1: GSK3389404 30 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 1, 8 hour, n=6, 6, 6, 6 | -3.0 mmHg | Standard Deviation 8.63 |
| Part 1: GSK3389404 30 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 24, 48 hour, n=6, 6, 6, 6 | -0.8 mmHg | Standard Deviation 5.02 |
| Part 1: GSK3389404 30 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 1, 2 hour, n=6, 6, 6, 6 | -0.6 mmHg | Standard Deviation 3.38 |
| Part 1: GSK3389404 30 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 1, 6 hour, n=6, 6, 6, 6 | -3.5 mmHg | Standard Deviation 5.03 |
| Part 1: GSK3389404 30 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 1, 4 hour, n=6, 6, 6, 6 | -4.6 mmHg | Standard Deviation 6.57 |
| Part 1: GSK3389404 30 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 3, 48 hour, n=6, 6, 6, 6 | -4.8 mmHg | Standard Deviation 5.24 |
| Part 1: GSK3389404 30 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 1, 6 hour, n=6, 6, 6, 6 | -1.6 mmHg | Standard Deviation 6.54 |
| Part 1: GSK3389404 30 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 1, 2 hour, n=6, 6, 6, 6 | -0.8 mmHg | Standard Deviation 6.74 |
| Part 1: GSK3389404 30 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 71, n=6, 6, 6, 5 | 4.1 mmHg | Standard Deviation 7.42 |
| Part 1: GSK3389404 30 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 2, 24 hour, n=6, 6, 6, 6 | -3.0 mmHg | Standard Deviation 4.87 |
| Part 1: GSK3389404 30 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 1, 12 hour, n=6, 6, 6, 6 | -2.9 mmHg | Standard Deviation 7.54 |
| Part 1: GSK3389404 30 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 1, 1 hour, n=6, 6, 6, 6 | -1.8 mmHg | Standard Deviation 3.49 |
| Part 1: GSK3389404 30 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 2, 24 hour, n=6, 6, 6, 6 | 0.4 mmHg | Standard Deviation 4.95 |
| Part 1: GSK3389404 30 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 3, 48 hour, n=6, 6, 6, 6 | -2.4 mmHg | Standard Deviation 6.34 |
| Part 1: GSK3389404 30 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 25, 72 hour, n=6, 6, 6, 6 | 4.4 mmHg | Standard Deviation 5.69 |
| Part 1: GSK3389404 30 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 29, n=6, 6, 6, 6 | -1.0 mmHg | Standard Deviation 4.68 |
| Part 1: GSK3389404 30 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 4, 72 hour, n=6, 6, 6, 6 | 0.2 mmHg | Standard Deviation 7.29 |
| Part 1: GSK3389404 30 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 22, 8 hour, n=6, 6, 6, 6 | -5.4 mmHg | Standard Deviation 6.27 |
| Part 1: GSK3389404 30 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 8, n=6, 6, 6, 6 | -4.4 mmHg | Standard Deviation 5.97 |
| Part 1: GSK3389404 30 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 15, n=6, 6, 6, 6 | -2.3 mmHg | Standard Deviation 6.47 |
| Part 1: GSK3389404 30 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 22, pre-dose, n=6, 6, 6, 6 | -4.0 mmHg | Standard Deviation 2.6 |
| Part 1: GSK3389404 30 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 1, 4 hour, n=6, 6, 6, 6 | -4.6 mmHg | Standard Deviation 5.86 |
| Part 1: GSK3389404 30 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 22, 1 hour, n=6, 6, 6, 6 | -1.6 mmHg | Standard Deviation 2.2 |
| Part 1: GSK3389404 30 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 25, 72 hour, n=6, 6, 6, 6 | 0.4 mmHg | Standard Deviation 2.83 |
| Part 1: GSK3389404 30 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 36, n=6, 6, 6, 5 | 0.7 mmHg | Standard Deviation 6.11 |
| Part 1: GSK3389404 30 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 22, 4 hour, n=6, 6, 6, 6 | -4.2 mmHg | Standard Deviation 5.24 |
| Part 1: GSK3389404 30 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 22, 6 hour, n=6, 6, 6, 6 | -6.1 mmHg | Standard Deviation 7.77 |
| Part 1: GSK3389404 30 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 22, 8 hour, n=6, 6, 6, 6 | -4.4 mmHg | Standard Deviation 7.14 |
| Part 1: GSK3389404 30 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 8, n=6, 6, 6, 6 | -2.6 mmHg | Standard Deviation 3.82 |
| Part 1: GSK3389404 30 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 22, 4 hour, n=6, 6, 6, 6 | -4.8 mmHg | Standard Deviation 6.46 |
| Part 1: GSK3389404 30 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 22, 1 hour, n=6, 6, 6, 6 | -2.3 mmHg | Standard Deviation 6.39 |
| Part 1: GSK3389404 30 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 50, n=6, 6, 6, 5 | -0.7 mmHg | Standard Deviation 7.2 |
| Part 1: GSK3389404 30 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 22, 6 hour, n=6, 6, 6, 6 | -9.3 mmHg | Standard Deviation 8.96 |
| Part 1: GSK3389404 30 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 22, 12 hour, n=6, 6, 6, 6 | -5.2 mmHg | Standard Deviation 8.57 |
| Part 1: GSK3389404 30 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 22, pre-dose, n=6, 6, 6, 6 | -3.1 mmHg | Standard Deviation 1.66 |
| Part 1: GSK3389404 30 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 22, 12 hour, n=6, 6, 6, 6 | -7.0 mmHg | Standard Deviation 9.15 |
| Part 1: GSK3389404 30 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 23, 24 hour, n=6, 6, 6, 6 | -4.5 mmHg | Standard Deviation 4 |
| Part 1: GSK3389404 30 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 15, n=6, 6, 6, 6 | 2.6 mmHg | Standard Deviation 6.7 |
| Part 1: GSK3389404 30 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 4, 72 hour, n=6, 6, 6, 6 | -1.9 mmHg | Standard Deviation 3.09 |
| Part 1: GSK3389404 30 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 24, 48 hour, n=6, 6, 6, 6 | -1.7 mmHg | Standard Deviation 4.3 |
| Part 1: GSK3389404 30 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 29, n=6, 6, 6, 6 | 1.1 mmHg | Standard Deviation 4.7 |
| Part 1: GSK3389404 30 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 23, 24 hour, n=6, 6, 6, 6 | -1.2 mmHg | Standard Deviation 5.67 |
| Part 1: GSK3389404 30 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 71, n=6, 6, 6, 5 | 2.4 mmHg | Standard Deviation 3.94 |
| Part 1: GSK3389404 30 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 36, n=6, 6, 6, 5 | 1.7 mmHg | Standard Deviation 4.67 |
| Part 1: GSK3389404 30 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 50, n=6, 6, 6, 5 | 2.9 mmHg | Standard Deviation 4.39 |
| Part 1: GSK3389404 60 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 22, pre-dose, n=6, 6, 6, 6 | -2.2 mmHg | Standard Deviation 2.37 |
| Part 1: GSK3389404 60 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 23, 24 hour, n=6, 6, 6, 6 | 4.9 mmHg | Standard Deviation 6.35 |
| Part 1: GSK3389404 60 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 71, n=6, 6, 6, 5 | 4.0 mmHg | Standard Deviation 2.22 |
| Part 1: GSK3389404 60 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 1, 12 hour, n=6, 6, 6, 6 | -4.4 mmHg | Standard Deviation 4.75 |
| Part 1: GSK3389404 60 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 3, 48 hour, n=6, 6, 6, 6 | -2.6 mmHg | Standard Deviation 4.76 |
| Part 1: GSK3389404 60 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 22, pre-dose, n=6, 6, 6, 6 | -1.1 mmHg | Standard Deviation 5.65 |
| Part 1: GSK3389404 60 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Follow-up, n=6, 6, 6, 5 | 7.7 mmHg | Standard Deviation 1.75 |
| Part 1: GSK3389404 60 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 25, 72 hour, n=6, 6, 6, 6 | 0.1 mmHg | Standard Deviation 5 |
| Part 1: GSK3389404 60 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 8, n=6, 6, 6, 6 | -3.0 mmHg | Standard Deviation 5.66 |
| Part 1: GSK3389404 60 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 4, 72 hour, n=6, 6, 6, 6 | -0.1 mmHg | Standard Deviation 4.13 |
| Part 1: GSK3389404 60 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 1, 1 hour, n=6, 6, 6, 6 | 5.3 mmHg | Standard Deviation 4.17 |
| Part 1: GSK3389404 60 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 22, 1 hour, n=6, 6, 6, 6 | 3.2 mmHg | Standard Deviation 7.34 |
| Part 1: GSK3389404 60 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 22, 12 hour, n=6, 6, 6, 6 | 5.2 mmHg | Standard Deviation 4.07 |
| Part 1: GSK3389404 60 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 50, n=6, 6, 6, 5 | 2.5 mmHg | Standard Deviation 2.32 |
| Part 1: GSK3389404 60 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 1, 2 hour, n=6, 6, 6, 6 | 3.9 mmHg | Standard Deviation 8.89 |
| Part 1: GSK3389404 60 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 22, 12 hour, n=6, 6, 6, 6 | -2.6 mmHg | Standard Deviation 4.15 |
| Part 1: GSK3389404 60 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 24, 48 hour, n=6, 6, 6, 6 | 2.8 mmHg | Standard Deviation 5.29 |
| Part 1: GSK3389404 60 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 22, 4 hour, n=6, 6, 6, 6 | 2.5 mmHg | Standard Deviation 4.99 |
| Part 1: GSK3389404 60 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 1, 2 hour, n=6, 6, 6, 6 | -1.6 mmHg | Standard Deviation 3.47 |
| Part 1: GSK3389404 60 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 22, 8 hour, n=6, 6, 6, 6 | -1.2 mmHg | Standard Deviation 2.55 |
| Part 1: GSK3389404 60 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 1, 4 hour, n=6, 6, 6, 6 | -8.0 mmHg | Standard Deviation 3.69 |
| Part 1: GSK3389404 60 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 1, 6 hour, n=6, 6, 6, 6 | 5.4 mmHg | Standard Deviation 6.67 |
| Part 1: GSK3389404 60 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 15, n=6, 6, 6, 6 | -3.1 mmHg | Standard Deviation 3.82 |
| Part 1: GSK3389404 60 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 22, 6 hour, n=6, 6, 6, 6 | 1.3 mmHg | Standard Deviation 5.49 |
| Part 1: GSK3389404 60 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 36, n=6, 6, 6, 5 | 2.6 mmHg | Standard Deviation 5.09 |
| Part 1: GSK3389404 60 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 1, 8 hour, n=6, 6, 6, 6 | 5.8 mmHg | Standard Deviation 6.37 |
| Part 1: GSK3389404 60 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 1, 1 hour, n=6, 6, 6, 6 | -2.4 mmHg | Standard Deviation 4.26 |
| Part 1: GSK3389404 60 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 25, 72 hour, n=6, 6, 6, 6 | 5.0 mmHg | Standard Deviation 3.87 |
| Part 1: GSK3389404 60 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Follow-up, n=6, 6, 6, 5 | 11.5 mmHg | Standard Deviation 5.29 |
| Part 1: GSK3389404 60 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 1, 12 hour, n=6, 6, 6, 6 | 5.8 mmHg | Standard Deviation 4.11 |
| Part 1: GSK3389404 60 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 22, 8 hour, n=6, 6, 6, 6 | 0.6 mmHg | Standard Deviation 4.57 |
| Part 1: GSK3389404 60 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 1, 8 hour, n=6, 6, 6, 6 | -4.1 mmHg | Standard Deviation 3.51 |
| Part 1: GSK3389404 60 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 22, 1 hour, n=6, 6, 6, 6 | -1.8 mmHg | Standard Deviation 3.44 |
| Part 1: GSK3389404 60 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 2, 24 hour, n=6, 6, 6, 6 | 2.4 mmHg | Standard Deviation 2.83 |
| Part 1: GSK3389404 60 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 36, n=6, 6, 6, 5 | 3.2 mmHg | Standard Deviation 3.89 |
| Part 1: GSK3389404 60 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 71, n=6, 6, 6, 5 | 7.4 mmHg | Standard Deviation 5.34 |
| Part 1: GSK3389404 60 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 23, 24 hour, n=6, 6, 6, 6 | -0.6 mmHg | Standard Deviation 4.08 |
| Part 1: GSK3389404 60 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 3, 48 hour, n=6, 6, 6, 6 | 5.0 mmHg | Standard Deviation 4.38 |
| Part 1: GSK3389404 60 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 29, n=6, 6, 6, 6 | -2.9 mmHg | Standard Deviation 4.3 |
| Part 1: GSK3389404 60 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 22, 4 hour, n=6, 6, 6, 6 | -3.4 mmHg | Standard Deviation 4.48 |
| Part 1: GSK3389404 60 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 2, 24 hour, n=6, 6, 6, 6 | -2.1 mmHg | Standard Deviation 2.1 |
| Part 1: GSK3389404 60 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 4, 72 hour, n=6, 6, 6, 6 | 7.5 mmHg | Standard Deviation 3.32 |
| Part 1: GSK3389404 60 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 50, n=6, 6, 6, 5 | -0.1 mmHg | Standard Deviation 6.22 |
| Part 1: GSK3389404 60 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 8, n=6, 6, 6, 6 | 2.8 mmHg | Standard Deviation 7.24 |
| Part 1: GSK3389404 60 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 24, 48 hour, n=6, 6, 6, 6 | -0.9 mmHg | Standard Deviation 8.38 |
| Part 1: GSK3389404 60 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 29, n=6, 6, 6, 6 | 1.9 mmHg | Standard Deviation 5.57 |
| Part 1: GSK3389404 60 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 22, 6 hour, n=6, 6, 6, 6 | -4.2 mmHg | Standard Deviation 6.42 |
| Part 1: GSK3389404 60 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 15, n=6, 6, 6, 6 | 1.5 mmHg | Standard Deviation 5.47 |
| Part 1: GSK3389404 60 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | SBP, Day 1, 4 hour, n=6, 6, 6, 6 | 0.4 mmHg | Standard Deviation 4.28 |
| Part 1: GSK3389404 60 mg | Change From Baseline in SBP and DBP at the Indicated Time Points in Part 2 | DBP, Day 1, 6 hour, n=6, 6, 6, 6 | -5.1 mmHg | Standard Deviation 3.37 |
Primary
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1
SBP and DBP were taken at Baseline (Day 1, pre-dose) and at 1, 2, 4, 8, 12, 24, 48 and 72 hour post dose; and on Days 8 and 30. Measurements were obtained after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the last scheduled non-missing measurement taken prior to drug administration. Change from Baseline was calculated as value at indicated time point minus Baseline value.
Time frame: Day 1 (pre-dose) and up to 30 days
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | DBP, 24 hour | -2.8 Millimeter of mercury (mmHg) | Standard Deviation 4.29 |
| Part 1: Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | SBP, Day 30 | 2.7 Millimeter of mercury (mmHg) | Standard Deviation 8.17 |
| Part 1: Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | DBP, Day 8 | -3.1 Millimeter of mercury (mmHg) | Standard Deviation 5.07 |
| Part 1: Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | DBP, 8 hour | -5.6 Millimeter of mercury (mmHg) | Standard Deviation 3.66 |
| Part 1: Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | SBP, 48 hour | -0.4 Millimeter of mercury (mmHg) | Standard Deviation 6.84 |
| Part 1: Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | DBP, 48 hour | -2.7 Millimeter of mercury (mmHg) | Standard Deviation 4.59 |
| Part 1: Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | SBP, 8 hour | -1.6 Millimeter of mercury (mmHg) | Standard Deviation 6.27 |
| Part 1: Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | DBP, 1 hour | -4.1 Millimeter of mercury (mmHg) | Standard Deviation 6.53 |
| Part 1: Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | DBP, 72 hour | -1.9 Millimeter of mercury (mmHg) | Standard Deviation 4.38 |
| Part 1: Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | SBP, 24 hour | -4.0 Millimeter of mercury (mmHg) | Standard Deviation 6.4 |
| Part 1: Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | SBP, 1 hour | -2.0 Millimeter of mercury (mmHg) | Standard Deviation 7.65 |
| Part 1: Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | DBP, 12 hour | -3.2 Millimeter of mercury (mmHg) | Standard Deviation 7.5 |
| Part 1: Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | SBP, 12 hour | 1.6 Millimeter of mercury (mmHg) | Standard Deviation 10.73 |
| Part 1: Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | SBP, 4 hour | -1.5 Millimeter of mercury (mmHg) | Standard Deviation 4.58 |
| Part 1: Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | SBP, 2 hour | -0.7 Millimeter of mercury (mmHg) | Standard Deviation 5.63 |
| Part 1: Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | DBP, Day 30 | -1.7 Millimeter of mercury (mmHg) | Standard Deviation 6.28 |
| Part 1: Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | DBP, 2 hour | -4.1 Millimeter of mercury (mmHg) | Standard Deviation 2.46 |
| Part 1: Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | DBP, 4 hour | -1.8 Millimeter of mercury (mmHg) | Standard Deviation 3.64 |
| Part 1: Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | SBP, Day 8 | -0.3 Millimeter of mercury (mmHg) | Standard Deviation 7.41 |
| Part 1: Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | SBP, 72 hour | -1.4 Millimeter of mercury (mmHg) | Standard Deviation 5.08 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | SBP, 8 hour | -4.6 Millimeter of mercury (mmHg) | Standard Deviation 11.61 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | SBP, 72 hour | -2.8 Millimeter of mercury (mmHg) | Standard Deviation 8.29 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | DBP, Day 30 | 0.5 Millimeter of mercury (mmHg) | Standard Deviation 7.36 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | SBP, 1 hour | -4.0 Millimeter of mercury (mmHg) | Standard Deviation 3.85 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | SBP, 2 hour | 0.3 Millimeter of mercury (mmHg) | Standard Deviation 5.89 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | DBP, 8 hour | -5.4 Millimeter of mercury (mmHg) | Standard Deviation 8.78 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | DBP, 12 hour | -5.8 Millimeter of mercury (mmHg) | Standard Deviation 10.3 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | DBP, 24 hour | -4.3 Millimeter of mercury (mmHg) | Standard Deviation 7.53 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | DBP, 2 hour | -3.1 Millimeter of mercury (mmHg) | Standard Deviation 4.29 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | DBP, 48 hour | -3.3 Millimeter of mercury (mmHg) | Standard Deviation 6.22 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | DBP, 72 hour | -2.2 Millimeter of mercury (mmHg) | Standard Deviation 5.71 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | DBP, Day 8 | -3.4 Millimeter of mercury (mmHg) | Standard Deviation 4.6 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | SBP, 12 hour | -5.5 Millimeter of mercury (mmHg) | Standard Deviation 10.15 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | SBP, 24 hour | -4.8 Millimeter of mercury (mmHg) | Standard Deviation 6.42 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | SBP, 4 hour | -5.5 Millimeter of mercury (mmHg) | Standard Deviation 6.42 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | SBP, 48 hour | -6.8 Millimeter of mercury (mmHg) | Standard Deviation 5.48 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | DBP, 4 hour | -5.6 Millimeter of mercury (mmHg) | Standard Deviation 7.39 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | SBP, Day 8 | -4.8 Millimeter of mercury (mmHg) | Standard Deviation 4.87 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | SBP, Day 30 | -1.7 Millimeter of mercury (mmHg) | Standard Deviation 8.21 |
| Part 1: GSK3389404 10 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | DBP, 1 hour | -4.4 Millimeter of mercury (mmHg) | Standard Deviation 4.38 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | SBP, 12 hour | 0.8 Millimeter of mercury (mmHg) | Standard Deviation 4.58 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | SBP, 1 hour | -0.8 Millimeter of mercury (mmHg) | Standard Deviation 8.55 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | SBP, Day 8 | -2.7 Millimeter of mercury (mmHg) | Standard Deviation 5.98 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | SBP, 4 hour | -0.9 Millimeter of mercury (mmHg) | Standard Deviation 4.32 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | SBP, 24 hour | 3.1 Millimeter of mercury (mmHg) | Standard Deviation 8.3 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | DBP, Day 30 | -5.1 Millimeter of mercury (mmHg) | Standard Deviation 6.92 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | DBP, 8 hour | -4.0 Millimeter of mercury (mmHg) | Standard Deviation 7.93 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | SBP, 48 hour | -5.0 Millimeter of mercury (mmHg) | Standard Deviation 3.89 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | SBP, Day 30 | -0.1 Millimeter of mercury (mmHg) | Standard Deviation 6.84 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | SBP, 2 hour | 2.2 Millimeter of mercury (mmHg) | Standard Deviation 8.08 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | DBP, 2 hour | -4.8 Millimeter of mercury (mmHg) | Standard Deviation 3.87 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | DBP, 4 hour | -0.6 Millimeter of mercury (mmHg) | Standard Deviation 7.39 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | DBP, 72 hour | 1.0 Millimeter of mercury (mmHg) | Standard Deviation 7.08 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | DBP, 1 hour | -3.8 Millimeter of mercury (mmHg) | Standard Deviation 7.36 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | DBP, 48 hour | -3.0 Millimeter of mercury (mmHg) | Standard Deviation 6.87 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | DBP, 24 hour | 0.2 Millimeter of mercury (mmHg) | Standard Deviation 9.2 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | DBP, Day 8 | -4.6 Millimeter of mercury (mmHg) | Standard Deviation 4.53 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | SBP, 72 hour | 4.6 Millimeter of mercury (mmHg) | Standard Deviation 9.89 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | SBP, 8 hour | -2.3 Millimeter of mercury (mmHg) | Standard Deviation 5.31 |
| Part 1: GSK3389404 30 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | DBP, 12 hour | -3.8 Millimeter of mercury (mmHg) | Standard Deviation 4.01 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | SBP, 12 hour | -1.5 Millimeter of mercury (mmHg) | Standard Deviation 7.04 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | DBP, 1 hour | 1.5 Millimeter of mercury (mmHg) | Standard Deviation 4.96 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | DBP, 2 hour | 0.6 Millimeter of mercury (mmHg) | Standard Deviation 3.64 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | DBP, 4 hour | -0.8 Millimeter of mercury (mmHg) | Standard Deviation 5.05 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | DBP, 12 hour | -1.5 Millimeter of mercury (mmHg) | Standard Deviation 4.37 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | DBP, 24 hour | 0.1 Millimeter of mercury (mmHg) | Standard Deviation 4 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | DBP, 48 hour | -1.3 Millimeter of mercury (mmHg) | Standard Deviation 4.78 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | DBP, 72 hour | 0.5 Millimeter of mercury (mmHg) | Standard Deviation 1.25 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | SBP, 1 hour | 1.8 Millimeter of mercury (mmHg) | Standard Deviation 6.22 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | SBP, 8 hour | 1.2 Millimeter of mercury (mmHg) | Standard Deviation 5.61 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | SBP, 48 hour | -1.7 Millimeter of mercury (mmHg) | Standard Deviation 4.07 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | SBP, 72 hour | 0.6 Millimeter of mercury (mmHg) | Standard Deviation 4.24 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | DBP, 8 hour | -0.7 Millimeter of mercury (mmHg) | Standard Deviation 4.43 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | DBP, Day 8 | 0.3 Millimeter of mercury (mmHg) | Standard Deviation 7.33 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | DBP, Day 30 | 2.1 Millimeter of mercury (mmHg) | Standard Deviation 7.26 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | SBP, 2 hour | 2.1 Millimeter of mercury (mmHg) | Standard Deviation 5.51 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | SBP, 4 hour | -4.6 Millimeter of mercury (mmHg) | Standard Deviation 7.68 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | SBP, 24 hour | -0.6 Millimeter of mercury (mmHg) | Standard Deviation 6.39 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | SBP, Day 8 | 0.5 Millimeter of mercury (mmHg) | Standard Deviation 6.61 |
| Part 1: GSK3389404 60 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | SBP, Day 30 | -0.9 Millimeter of mercury (mmHg) | Standard Deviation 4.75 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | DBP, 8 hour | -1.3 Millimeter of mercury (mmHg) | Standard Deviation 4.34 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | SBP, Day 8 | 0.5 Millimeter of mercury (mmHg) | Standard Deviation 3.48 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | DBP, 1 hour | 2.3 Millimeter of mercury (mmHg) | Standard Deviation 4.51 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | SBP, 4 hour | 0.3 Millimeter of mercury (mmHg) | Standard Deviation 5.94 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | SBP, 48 hour | -2.1 Millimeter of mercury (mmHg) | Standard Deviation 4.03 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | SBP, 24 hour | -0.9 Millimeter of mercury (mmHg) | Standard Deviation 2.69 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | SBP, 8 hour | 4.1 Millimeter of mercury (mmHg) | Standard Deviation 4.19 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | DBP, 72 hour | -2.7 Millimeter of mercury (mmHg) | Standard Deviation 3.19 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | SBP, 12 hour | 2.2 Millimeter of mercury (mmHg) | Standard Deviation 3.54 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | DBP, 48 hour | -1.4 Millimeter of mercury (mmHg) | Standard Deviation 2.5 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | SBP, Day 30 | 5.9 Millimeter of mercury (mmHg) | Standard Deviation 3.5 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | DBP, 24 hour | -2.6 Millimeter of mercury (mmHg) | Standard Deviation 4.11 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | DBP, 12 hour | -1.4 Millimeter of mercury (mmHg) | Standard Deviation 4.34 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | DBP, 4 hour | -0.4 Millimeter of mercury (mmHg) | Standard Deviation 5.42 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | DBP, 2 hour | -1.9 Millimeter of mercury (mmHg) | Standard Deviation 1.86 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | SBP, 1 hour | 0.2 Millimeter of mercury (mmHg) | Standard Deviation 6.18 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | DBP, Day 30 | -0.3 Millimeter of mercury (mmHg) | Standard Deviation 4.32 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | SBP, 72 hour | -1.5 Millimeter of mercury (mmHg) | Standard Deviation 2.95 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | SBP, 2 hour | 4.9 Millimeter of mercury (mmHg) | Standard Deviation 3.67 |
| Part 1: GSK3389404 120 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points in Part 1 | DBP, Day 8 | -2.0 Millimeter of mercury (mmHg) | Standard Deviation 2.91 |
Primary
Cl/F of GSK3389404 Following Dosing on Day 22 of Part 2
Blood samples were collected to evaluate Cl/F of GSK3389404 on Day 22 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 29, 36, 50, 71 and at Follow-up (Day 113+- 2 days).
Time frame: Day 22 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 29, 36, 50, 71 and at Follow-up (Day 115)
Population: Pharmacokinetic Concentration Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Placebo | Cl/F of GSK3389404 Following Dosing on Day 22 of Part 2 | 20.50 Liter per hour | Standard Deviation 6.3906 |
| Part 1: GSK3389404 10 mg | Cl/F of GSK3389404 Following Dosing on Day 22 of Part 2 | 15.48 Liter per hour | Standard Deviation 3.6973 |
| Part 1: GSK3389404 30 mg | Cl/F of GSK3389404 Following Dosing on Day 22 of Part 2 | 14.39 Liter per hour | Standard Deviation 3.7029 |
Primary
CL/F of GSK3389404 Following Single Dose on Day 1 of Part 2
Blood samples were collected to evaluate CL/F of GSK3389404 on Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 15 post-dose. Only those participants with data available at the specified time points were analyzed.
Time frame: Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 15 post-dose
Population: Pharmacokinetic Concentration Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Placebo | CL/F of GSK3389404 Following Single Dose on Day 1 of Part 2 | 22.1 Liter per hour | Standard Deviation 5.9872 |
| Part 1: GSK3389404 10 mg | CL/F of GSK3389404 Following Single Dose on Day 1 of Part 2 | 12.5 Liter per hour | Standard Deviation 3.412 |
| Part 1: GSK3389404 30 mg | CL/F of GSK3389404 Following Single Dose on Day 1 of Part 2 | 15.6 Liter per hour | Standard Deviation 4.7861 |
Primary
Cmax, C24 and C168 of GSK3389404 Following Single Dose on Day 1 of Part 2
Blood samples were collected to evaluate Cmax, C24 and C168 of GSK3389404 on Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 15 post-dose.
Time frame: Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 15 post-dose
Population: Pharmacokinetic Concentration Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Placebo | Cmax, C24 and C168 of GSK3389404 Following Single Dose on Day 1 of Part 2 | C168 | 0.00 ng/mL | Standard Deviation 0 |
| Part 1: Placebo | Cmax, C24 and C168 of GSK3389404 Following Single Dose on Day 1 of Part 2 | Cmax | 236 ng/mL | Standard Deviation 64.551 |
| Part 1: Placebo | Cmax, C24 and C168 of GSK3389404 Following Single Dose on Day 1 of Part 2 | C24 | 0.00 ng/mL | Standard Deviation 0 |
| Part 1: GSK3389404 10 mg | Cmax, C24 and C168 of GSK3389404 Following Single Dose on Day 1 of Part 2 | C24 | 2.58 ng/mL | Standard Deviation 6.3278 |
| Part 1: GSK3389404 10 mg | Cmax, C24 and C168 of GSK3389404 Following Single Dose on Day 1 of Part 2 | C168 | 0.00 ng/mL | Standard Deviation 0 |
| Part 1: GSK3389404 10 mg | Cmax, C24 and C168 of GSK3389404 Following Single Dose on Day 1 of Part 2 | Cmax | 723 ng/mL | Standard Deviation 216.01 |
| Part 1: GSK3389404 30 mg | Cmax, C24 and C168 of GSK3389404 Following Single Dose on Day 1 of Part 2 | Cmax | 1280 ng/mL | Standard Deviation 633.56 |
| Part 1: GSK3389404 30 mg | Cmax, C24 and C168 of GSK3389404 Following Single Dose on Day 1 of Part 2 | C168 | 0.00 ng/mL | Standard Deviation 0 |
| Part 1: GSK3389404 30 mg | Cmax, C24 and C168 of GSK3389404 Following Single Dose on Day 1 of Part 2 | C24 | 16.7 ng/mL | Standard Deviation 20.848 |
Primary
Maximum Observed Concentration (Cmax), Observed Concentration at 24 Hours (C24) and at 168 Hours (C168) of GSK3389404 Following Single Dose in Part 1
Blood samples were collected to evaluate Cmax, C24 and C168 of GSK3389404 on Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 30 post-dose.
Time frame: Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 30 post-dose
Population: Pharmacokinetic Concentration Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Placebo | Maximum Observed Concentration (Cmax), Observed Concentration at 24 Hours (C24) and at 168 Hours (C168) of GSK3389404 Following Single Dose in Part 1 | Cmax | 92.5 ng/mL | Standard Deviation 23.622 |
| Part 1: Placebo | Maximum Observed Concentration (Cmax), Observed Concentration at 24 Hours (C24) and at 168 Hours (C168) of GSK3389404 Following Single Dose in Part 1 | C168 | 0.00 ng/mL | Standard Deviation 0 |
| Part 1: Placebo | Maximum Observed Concentration (Cmax), Observed Concentration at 24 Hours (C24) and at 168 Hours (C168) of GSK3389404 Following Single Dose in Part 1 | C24 | 0.00 ng/mL | Standard Deviation 0 |
| Part 1: GSK3389404 10 mg | Maximum Observed Concentration (Cmax), Observed Concentration at 24 Hours (C24) and at 168 Hours (C168) of GSK3389404 Following Single Dose in Part 1 | Cmax | 350 ng/mL | Standard Deviation 257.48 |
| Part 1: GSK3389404 10 mg | Maximum Observed Concentration (Cmax), Observed Concentration at 24 Hours (C24) and at 168 Hours (C168) of GSK3389404 Following Single Dose in Part 1 | C168 | 0.00 ng/mL | Standard Deviation 0 |
| Part 1: GSK3389404 10 mg | Maximum Observed Concentration (Cmax), Observed Concentration at 24 Hours (C24) and at 168 Hours (C168) of GSK3389404 Following Single Dose in Part 1 | C24 | 0.00 ng/mL | Standard Deviation 0 |
| Part 1: GSK3389404 30 mg | Maximum Observed Concentration (Cmax), Observed Concentration at 24 Hours (C24) and at 168 Hours (C168) of GSK3389404 Following Single Dose in Part 1 | C24 | 3.33 ng/mL | Standard Deviation 8.165 |
| Part 1: GSK3389404 30 mg | Maximum Observed Concentration (Cmax), Observed Concentration at 24 Hours (C24) and at 168 Hours (C168) of GSK3389404 Following Single Dose in Part 1 | Cmax | 584 ng/mL | Standard Deviation 366.96 |
| Part 1: GSK3389404 30 mg | Maximum Observed Concentration (Cmax), Observed Concentration at 24 Hours (C24) and at 168 Hours (C168) of GSK3389404 Following Single Dose in Part 1 | C168 | 0.00 ng/mL | Standard Deviation 0 |
| Part 1: GSK3389404 60 mg | Maximum Observed Concentration (Cmax), Observed Concentration at 24 Hours (C24) and at 168 Hours (C168) of GSK3389404 Following Single Dose in Part 1 | Cmax | 889 ng/mL | Standard Deviation 496.73 |
| Part 1: GSK3389404 60 mg | Maximum Observed Concentration (Cmax), Observed Concentration at 24 Hours (C24) and at 168 Hours (C168) of GSK3389404 Following Single Dose in Part 1 | C168 | 0.00 ng/mL | Standard Deviation 0 |
| Part 1: GSK3389404 60 mg | Maximum Observed Concentration (Cmax), Observed Concentration at 24 Hours (C24) and at 168 Hours (C168) of GSK3389404 Following Single Dose in Part 1 | C24 | 18.7 ng/mL | Standard Deviation 17.781 |
Primary
Number of Participants With 12-lead Electrocardiogram (ECG) Findings in Part 1
12-lead ECGs were recorded at Baseline (Day 1, pre-dose) and at 1, 4, 8, 12, 24 and 48 hour post dose; and on Days 8 and 30. Measurements were obtained after resting for at least 5 minutes in a supine position. Baseline was defined as the last scheduled non-missing measurement taken prior to drug administration. Change from Baseline was calculated as value at indicated time point minus Baseline value. Number of participants with worst change from Baseline in ECG have been presented as clinically significant (CS) change or not a clinically significant (NCS) change.
Time frame: Day 1 (pre-dose) and up to 31 days
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Placebo | Number of Participants With 12-lead Electrocardiogram (ECG) Findings in Part 1 | CS | 0 Participants |
| Part 1: Placebo | Number of Participants With 12-lead Electrocardiogram (ECG) Findings in Part 1 | NCS | 2 Participants |
| Part 1: GSK3389404 10 mg | Number of Participants With 12-lead Electrocardiogram (ECG) Findings in Part 1 | NCS | 0 Participants |
| Part 1: GSK3389404 10 mg | Number of Participants With 12-lead Electrocardiogram (ECG) Findings in Part 1 | CS | 0 Participants |
| Part 1: GSK3389404 30 mg | Number of Participants With 12-lead Electrocardiogram (ECG) Findings in Part 1 | NCS | 1 Participants |
| Part 1: GSK3389404 30 mg | Number of Participants With 12-lead Electrocardiogram (ECG) Findings in Part 1 | CS | 0 Participants |
| Part 1: GSK3389404 60 mg | Number of Participants With 12-lead Electrocardiogram (ECG) Findings in Part 1 | CS | 0 Participants |
| Part 1: GSK3389404 60 mg | Number of Participants With 12-lead Electrocardiogram (ECG) Findings in Part 1 | NCS | 1 Participants |
| Part 1: GSK3389404 120 mg | Number of Participants With 12-lead Electrocardiogram (ECG) Findings in Part 1 | NCS | 3 Participants |
| Part 1: GSK3389404 120 mg | Number of Participants With 12-lead Electrocardiogram (ECG) Findings in Part 1 | CS | 0 Participants |
Primary
Number of Participants With Any Non-serious Adverse Event (AE); Any Serious AE (SAE); Any AEs Leading to Discontinuation of Study Treatment (AELD) in Part 1
An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment 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 or event associated with liver injury and impaired liver function were categorized as SAE. Participants who received any of the study treatment and had any AE or SAE or AELD were considered for analysis. Safety Population comprised of all participants who received at least 1 dose of study treatment.
Time frame: Up to 62 days
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Placebo | Number of Participants With Any Non-serious Adverse Event (AE); Any Serious AE (SAE); Any AEs Leading to Discontinuation of Study Treatment (AELD) in Part 1 | Any non-serious AE | 4 Participants |
| Part 1: Placebo | Number of Participants With Any Non-serious Adverse Event (AE); Any Serious AE (SAE); Any AEs Leading to Discontinuation of Study Treatment (AELD) in Part 1 | AELD | 0 Participants |
| Part 1: Placebo | Number of Participants With Any Non-serious Adverse Event (AE); Any Serious AE (SAE); Any AEs Leading to Discontinuation of Study Treatment (AELD) in Part 1 | Any SAE | 0 Participants |
| Part 1: GSK3389404 10 mg | Number of Participants With Any Non-serious Adverse Event (AE); Any Serious AE (SAE); Any AEs Leading to Discontinuation of Study Treatment (AELD) in Part 1 | Any SAE | 0 Participants |
| Part 1: GSK3389404 10 mg | Number of Participants With Any Non-serious Adverse Event (AE); Any Serious AE (SAE); Any AEs Leading to Discontinuation of Study Treatment (AELD) in Part 1 | Any non-serious AE | 3 Participants |
| Part 1: GSK3389404 10 mg | Number of Participants With Any Non-serious Adverse Event (AE); Any Serious AE (SAE); Any AEs Leading to Discontinuation of Study Treatment (AELD) in Part 1 | AELD | 0 Participants |
| Part 1: GSK3389404 30 mg | Number of Participants With Any Non-serious Adverse Event (AE); Any Serious AE (SAE); Any AEs Leading to Discontinuation of Study Treatment (AELD) in Part 1 | AELD | 0 Participants |
| Part 1: GSK3389404 30 mg | Number of Participants With Any Non-serious Adverse Event (AE); Any Serious AE (SAE); Any AEs Leading to Discontinuation of Study Treatment (AELD) in Part 1 | Any non-serious AE | 2 Participants |
| Part 1: GSK3389404 30 mg | Number of Participants With Any Non-serious Adverse Event (AE); Any Serious AE (SAE); Any AEs Leading to Discontinuation of Study Treatment (AELD) in Part 1 | Any SAE | 0 Participants |
| Part 1: GSK3389404 60 mg | Number of Participants With Any Non-serious Adverse Event (AE); Any Serious AE (SAE); Any AEs Leading to Discontinuation of Study Treatment (AELD) in Part 1 | AELD | 0 Participants |
| Part 1: GSK3389404 60 mg | Number of Participants With Any Non-serious Adverse Event (AE); Any Serious AE (SAE); Any AEs Leading to Discontinuation of Study Treatment (AELD) in Part 1 | Any non-serious AE | 3 Participants |
| Part 1: GSK3389404 60 mg | Number of Participants With Any Non-serious Adverse Event (AE); Any Serious AE (SAE); Any AEs Leading to Discontinuation of Study Treatment (AELD) in Part 1 | Any SAE | 0 Participants |
| Part 1: GSK3389404 120 mg | Number of Participants With Any Non-serious Adverse Event (AE); Any Serious AE (SAE); Any AEs Leading to Discontinuation of Study Treatment (AELD) in Part 1 | Any SAE | 0 Participants |
| Part 1: GSK3389404 120 mg | Number of Participants With Any Non-serious Adverse Event (AE); Any Serious AE (SAE); Any AEs Leading to Discontinuation of Study Treatment (AELD) in Part 1 | AELD | 0 Participants |
| Part 1: GSK3389404 120 mg | Number of Participants With Any Non-serious Adverse Event (AE); Any Serious AE (SAE); Any AEs Leading to Discontinuation of Study Treatment (AELD) in Part 1 | Any non-serious AE | 5 Participants |
Primary
Number of Participants With Any Non-serious AE; Any SAE; Any AELD in Part 2
An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment 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 or event associated with liver injury and impaired liver function were categorized as SAE. Participants who received any of the study treatment and had any AE or SAE or AELD were considered for analysis.
Time frame: Up to 115 days
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Placebo | Number of Participants With Any Non-serious AE; Any SAE; Any AELD in Part 2 | Any non-serious AE | 3 Participants |
| Part 1: Placebo | Number of Participants With Any Non-serious AE; Any SAE; Any AELD in Part 2 | Any SAE | 0 Participants |
| Part 1: Placebo | Number of Participants With Any Non-serious AE; Any SAE; Any AELD in Part 2 | AELD | 0 Participants |
| Part 1: GSK3389404 10 mg | Number of Participants With Any Non-serious AE; Any SAE; Any AELD in Part 2 | Any SAE | 0 Participants |
| Part 1: GSK3389404 10 mg | Number of Participants With Any Non-serious AE; Any SAE; Any AELD in Part 2 | Any non-serious AE | 5 Participants |
| Part 1: GSK3389404 10 mg | Number of Participants With Any Non-serious AE; Any SAE; Any AELD in Part 2 | AELD | 0 Participants |
| Part 1: GSK3389404 30 mg | Number of Participants With Any Non-serious AE; Any SAE; Any AELD in Part 2 | Any non-serious AE | 2 Participants |
| Part 1: GSK3389404 30 mg | Number of Participants With Any Non-serious AE; Any SAE; Any AELD in Part 2 | Any SAE | 0 Participants |
| Part 1: GSK3389404 30 mg | Number of Participants With Any Non-serious AE; Any SAE; Any AELD in Part 2 | AELD | 0 Participants |
| Part 1: GSK3389404 60 mg | Number of Participants With Any Non-serious AE; Any SAE; Any AELD in Part 2 | Any SAE | 0 Participants |
| Part 1: GSK3389404 60 mg | Number of Participants With Any Non-serious AE; Any SAE; Any AELD in Part 2 | AELD | 0 Participants |
| Part 1: GSK3389404 60 mg | Number of Participants With Any Non-serious AE; Any SAE; Any AELD in Part 2 | Any non-serious AE | 4 Participants |
Primary
Number of Participants With Laboratory Values of Potential Clinical Importance in Part 1
Blood samples were collected for hematology, clinical chemistry, coagulation parameters and urinalysis. Abnormalities of potential clinical importance were evaluated as per Division of Acquired Immune Deficiency Syndrome \[DAIDS\] table for grading the severity of adult and pediatric adverse events. Laboratory abnormalities of DAIDS Grade 1 or higher were considered as of potential clinical importance and were summarized.
Time frame: Up to 62 days
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Placebo | Number of Participants With Laboratory Values of Potential Clinical Importance in Part 1 | 5 Participants |
| Part 1: GSK3389404 10 mg | Number of Participants With Laboratory Values of Potential Clinical Importance in Part 1 | 3 Participants |
| Part 1: GSK3389404 30 mg | Number of Participants With Laboratory Values of Potential Clinical Importance in Part 1 | 2 Participants |
| Part 1: GSK3389404 60 mg | Number of Participants With Laboratory Values of Potential Clinical Importance in Part 1 | 4 Participants |
| Part 1: GSK3389404 120 mg | Number of Participants With Laboratory Values of Potential Clinical Importance in Part 1 | 3 Participants |
Primary
Number of Participants With Laboratory Values of Potential Clinical Importance in Part 2
Blood samples were collected for hematology, clinical chemistry, coagulation parameters and urinalysis. Abnormalities of potential clinical importance were evaluated as per DAIDS table for grading the severity of adult and pediatric adverse events. Laboratory abnormalities of DAIDS Grade 1 or higher were considered as of potential clinical importance and were summarized.
Time frame: Up to 115 days
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Placebo | Number of Participants With Laboratory Values of Potential Clinical Importance in Part 2 | 3 Participants |
| Part 1: GSK3389404 10 mg | Number of Participants With Laboratory Values of Potential Clinical Importance in Part 2 | 2 Participants |
| Part 1: GSK3389404 30 mg | Number of Participants With Laboratory Values of Potential Clinical Importance in Part 2 | 5 Participants |
| Part 1: GSK3389404 60 mg | Number of Participants With Laboratory Values of Potential Clinical Importance in Part 2 | 3 Participants |
Primary
Observed Concentration at the End of the Dosing Interval (Ctau), C24 and Cmax of GSK3389404 Following Dosing on Day 22 of Part 2
Blood samples were collected to evaluate Ctau, C24 and Cmax of GSK3389404 on Day 22 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 29, 36, 50, 71 and at Follow-up (Day 113+- 2 days ).
Time frame: Day 22 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 29, 36, 50, 71 and at Follow-up (Day 115)
Population: Pharmacokinetic Concentration Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Placebo | Observed Concentration at the End of the Dosing Interval (Ctau), C24 and Cmax of GSK3389404 Following Dosing on Day 22 of Part 2 | C24 | 0.000 ng/mL | Standard Deviation 0 |
| Part 1: Placebo | Observed Concentration at the End of the Dosing Interval (Ctau), C24 and Cmax of GSK3389404 Following Dosing on Day 22 of Part 2 | Ctau | 0.000 ng/mL | Standard Deviation 0 |
| Part 1: Placebo | Observed Concentration at the End of the Dosing Interval (Ctau), C24 and Cmax of GSK3389404 Following Dosing on Day 22 of Part 2 | Cmax | 197.7 ng/mL | Standard Deviation 39.657 |
| Part 1: GSK3389404 10 mg | Observed Concentration at the End of the Dosing Interval (Ctau), C24 and Cmax of GSK3389404 Following Dosing on Day 22 of Part 2 | C24 | 4.767 ng/mL | Standard Deviation 7.4115 |
| Part 1: GSK3389404 10 mg | Observed Concentration at the End of the Dosing Interval (Ctau), C24 and Cmax of GSK3389404 Following Dosing on Day 22 of Part 2 | Ctau | 0.000 ng/mL | Standard Deviation 0 |
| Part 1: GSK3389404 10 mg | Observed Concentration at the End of the Dosing Interval (Ctau), C24 and Cmax of GSK3389404 Following Dosing on Day 22 of Part 2 | Cmax | 614.8 ng/mL | Standard Deviation 211.25 |
| Part 1: GSK3389404 30 mg | Observed Concentration at the End of the Dosing Interval (Ctau), C24 and Cmax of GSK3389404 Following Dosing on Day 22 of Part 2 | Ctau | 0.000 ng/mL | Standard Deviation 0 |
| Part 1: GSK3389404 30 mg | Observed Concentration at the End of the Dosing Interval (Ctau), C24 and Cmax of GSK3389404 Following Dosing on Day 22 of Part 2 | Cmax | 1257 ng/mL | Standard Deviation 799.88 |
| Part 1: GSK3389404 30 mg | Observed Concentration at the End of the Dosing Interval (Ctau), C24 and Cmax of GSK3389404 Following Dosing on Day 22 of Part 2 | C24 | 15.60 ng/mL | Standard Deviation 18.278 |
Primary
Time to Maximum Observed Concentration (Tmax), Terminal Half-life (T1/2) and Lag Time (Tlag) of GSK3389404 Following Single Dose in Part 1
Blood samples were collected to evaluate Tmax, T1/2 and Tlag of GSK3389404 on Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 30 post-dose.
Time frame: Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 30 post-dose
Population: Pharmacokinetic Concentration Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Placebo | Time to Maximum Observed Concentration (Tmax), Terminal Half-life (T1/2) and Lag Time (Tlag) of GSK3389404 Following Single Dose in Part 1 | Tlag | 0.00 Hour | Standard Deviation 0 |
| Part 1: Placebo | Time to Maximum Observed Concentration (Tmax), Terminal Half-life (T1/2) and Lag Time (Tlag) of GSK3389404 Following Single Dose in Part 1 | Tmax | 1.60 Hour | Standard Deviation 1.2 |
| Part 1: Placebo | Time to Maximum Observed Concentration (Tmax), Terminal Half-life (T1/2) and Lag Time (Tlag) of GSK3389404 Following Single Dose in Part 1 | T1/2 | 4.55 Hour | Standard Deviation 3.3937 |
| Part 1: GSK3389404 10 mg | Time to Maximum Observed Concentration (Tmax), Terminal Half-life (T1/2) and Lag Time (Tlag) of GSK3389404 Following Single Dose in Part 1 | Tmax | 1.74 Hour | Standard Deviation 0.48 |
| Part 1: GSK3389404 10 mg | Time to Maximum Observed Concentration (Tmax), Terminal Half-life (T1/2) and Lag Time (Tlag) of GSK3389404 Following Single Dose in Part 1 | T1/2 | 4.67 Hour | Standard Deviation 3.553 |
| Part 1: GSK3389404 10 mg | Time to Maximum Observed Concentration (Tmax), Terminal Half-life (T1/2) and Lag Time (Tlag) of GSK3389404 Following Single Dose in Part 1 | Tlag | 0.00 Hour | Standard Deviation 0 |
| Part 1: GSK3389404 30 mg | Time to Maximum Observed Concentration (Tmax), Terminal Half-life (T1/2) and Lag Time (Tlag) of GSK3389404 Following Single Dose in Part 1 | Tlag | 0.00 Hour | Standard Deviation 0 |
| Part 1: GSK3389404 30 mg | Time to Maximum Observed Concentration (Tmax), Terminal Half-life (T1/2) and Lag Time (Tlag) of GSK3389404 Following Single Dose in Part 1 | T1/2 | 6.07 Hour | Standard Deviation 3.9531 |
| Part 1: GSK3389404 30 mg | Time to Maximum Observed Concentration (Tmax), Terminal Half-life (T1/2) and Lag Time (Tlag) of GSK3389404 Following Single Dose in Part 1 | Tmax | 2.67 Hour | Standard Deviation 1.37 |
| Part 1: GSK3389404 60 mg | Time to Maximum Observed Concentration (Tmax), Terminal Half-life (T1/2) and Lag Time (Tlag) of GSK3389404 Following Single Dose in Part 1 | Tlag | 0.00 Hour | Standard Deviation 0 |
| Part 1: GSK3389404 60 mg | Time to Maximum Observed Concentration (Tmax), Terminal Half-life (T1/2) and Lag Time (Tlag) of GSK3389404 Following Single Dose in Part 1 | T1/2 | 4.27 Hour | Standard Deviation 1.2281 |
| Part 1: GSK3389404 60 mg | Time to Maximum Observed Concentration (Tmax), Terminal Half-life (T1/2) and Lag Time (Tlag) of GSK3389404 Following Single Dose in Part 1 | Tmax | 3.83 Hour | Standard Deviation 0.41 |
Primary
Tmax, T1/2 and Tlag of GSK3389404 Following Dosing on Day 22 of Part 2
Blood samples were collected to evaluate Tmax, T1/2 and Tlag of GSK3389404 on Day 22 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 29, 36, 50, 71 and at Follow-up (Day 113+- 2 days).
Time frame: Day 22 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 29, 36, 50, 71 and at Follow-up (Day 115)
Population: Pharmacokinetic Concentration Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Placebo | Tmax, T1/2 and Tlag of GSK3389404 Following Dosing on Day 22 of Part 2 | Tlag | 0.00 Hour | Standard Deviation 0 |
| Part 1: Placebo | Tmax, T1/2 and Tlag of GSK3389404 Following Dosing on Day 22 of Part 2 | Tmax | 2.17 Hour | Standard Deviation 0.98 |
| Part 1: Placebo | Tmax, T1/2 and Tlag of GSK3389404 Following Dosing on Day 22 of Part 2 | T1/2 | 4.768 Hour | Standard Deviation 3.2072 |
| Part 1: GSK3389404 10 mg | Tmax, T1/2 and Tlag of GSK3389404 Following Dosing on Day 22 of Part 2 | Tlag | 0.00 Hour | Standard Deviation 0 |
| Part 1: GSK3389404 10 mg | Tmax, T1/2 and Tlag of GSK3389404 Following Dosing on Day 22 of Part 2 | Tmax | 2.26 Hour | Standard Deviation 0.88 |
| Part 1: GSK3389404 10 mg | Tmax, T1/2 and Tlag of GSK3389404 Following Dosing on Day 22 of Part 2 | T1/2 | 3.450 Hour | Standard Deviation 1.6049 |
| Part 1: GSK3389404 30 mg | Tmax, T1/2 and Tlag of GSK3389404 Following Dosing on Day 22 of Part 2 | Tlag | 0.00 Hour | Standard Deviation 0 |
| Part 1: GSK3389404 30 mg | Tmax, T1/2 and Tlag of GSK3389404 Following Dosing on Day 22 of Part 2 | Tmax | 2.67 Hour | Standard Deviation 1.03 |
| Part 1: GSK3389404 30 mg | Tmax, T1/2 and Tlag of GSK3389404 Following Dosing on Day 22 of Part 2 | T1/2 | 3.585 Hour | Standard Deviation 1.2332 |
Primary
Tmax, T1/2 and Tlag of GSK3389404 Following Single Dose on Day 1 of Part 2
Blood samples were collected to evaluate Tmax, T1/2 and Tlag of GSK3389404 on Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 15 post-dose.
Time frame: Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 15 post-dose
Population: Pharmacokinetic Concentration Population. Only data available at the specified time points was analyzed. (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Placebo | Tmax, T1/2 and Tlag of GSK3389404 Following Single Dose on Day 1 of Part 2 | T1/2, n=6, 5, 6 | 3.14 Hour | Standard Deviation 1.0621 |
| Part 1: Placebo | Tmax, T1/2 and Tlag of GSK3389404 Following Single Dose on Day 1 of Part 2 | Tmax, n=6, 6, 6 | 2.33 Hour | Standard Deviation 1.03 |
| Part 1: Placebo | Tmax, T1/2 and Tlag of GSK3389404 Following Single Dose on Day 1 of Part 2 | Tlag, n=6, 6, 6 | 0.00 Hour | Standard Deviation 0 |
| Part 1: GSK3389404 10 mg | Tmax, T1/2 and Tlag of GSK3389404 Following Single Dose on Day 1 of Part 2 | T1/2, n=6, 5, 6 | 3.47 Hour | Standard Deviation 1.8907 |
| Part 1: GSK3389404 10 mg | Tmax, T1/2 and Tlag of GSK3389404 Following Single Dose on Day 1 of Part 2 | Tmax, n=6, 6, 6 | 2.01 Hour | Standard Deviation 0.02 |
| Part 1: GSK3389404 10 mg | Tmax, T1/2 and Tlag of GSK3389404 Following Single Dose on Day 1 of Part 2 | Tlag, n=6, 6, 6 | 0.00 Hour | Standard Deviation 0 |
| Part 1: GSK3389404 30 mg | Tmax, T1/2 and Tlag of GSK3389404 Following Single Dose on Day 1 of Part 2 | Tmax, n=6, 6, 6 | 2.42 Hour | Standard Deviation 0.92 |
| Part 1: GSK3389404 30 mg | Tmax, T1/2 and Tlag of GSK3389404 Following Single Dose on Day 1 of Part 2 | Tlag, n=6, 6, 6 | 0.00 Hour | Standard Deviation 0 |
| Part 1: GSK3389404 30 mg | Tmax, T1/2 and Tlag of GSK3389404 Following Single Dose on Day 1 of Part 2 | T1/2, n=6, 5, 6 | 4.04 Hour | Standard Deviation 1.7867 |
Secondary
Accumulation Ratio by AUC (RAUC), by Cmax (RCmax), by C24 (RC24) and by Ctau (RCtau) of GSK3389404 in Part 2
For Part 2, the extent of accumulation of GSK3389404 was evaluated by comparing AUC (0-tau), Cmax, C24 and Ctau on Day 22 to AUC (0-168), Cmax, C24 and C168 on Day 1. For each dose level, a linear mixed effect model was fitted with the log transformed PK parameter as the dependent variable, day as a fixed effect and subject as a random effect.
Time frame: Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 15 post-dose; Day 22 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 29, 36, 50, 71 and at Follow-up (Day 115)
Population: Pharmacokinetic Concentration Population. Only data available at the specified time points was analyzed. (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Placebo | Accumulation Ratio by AUC (RAUC), by Cmax (RCmax), by C24 (RC24) and by Ctau (RCtau) of GSK3389404 in Part 2 | RAUC, n=6, 5, 6 | 1.115 Ratio | Standard Deviation 0.24879 |
| Part 1: Placebo | Accumulation Ratio by AUC (RAUC), by Cmax (RCmax), by C24 (RC24) and by Ctau (RCtau) of GSK3389404 in Part 2 | RCmax, n=6, 6, 6 | 0.8683 Ratio | Standard Deviation 0.16676 |
| Part 1: GSK3389404 10 mg | Accumulation Ratio by AUC (RAUC), by Cmax (RCmax), by C24 (RC24) and by Ctau (RCtau) of GSK3389404 in Part 2 | RCmax, n=6, 6, 6 | 0.8518 Ratio | Standard Deviation 0.18537 |
| Part 1: GSK3389404 10 mg | Accumulation Ratio by AUC (RAUC), by Cmax (RCmax), by C24 (RC24) and by Ctau (RCtau) of GSK3389404 in Part 2 | RAUC, n=6, 5, 6 | 0.8596 Ratio | Standard Deviation 0.099034 |
| Part 1: GSK3389404 10 mg | Accumulation Ratio by AUC (RAUC), by Cmax (RCmax), by C24 (RC24) and by Ctau (RCtau) of GSK3389404 in Part 2 | RC24, n=0, 1, 3 | 0.8580 Ratio | — |
| Part 1: GSK3389404 30 mg | Accumulation Ratio by AUC (RAUC), by Cmax (RCmax), by C24 (RC24) and by Ctau (RCtau) of GSK3389404 in Part 2 | RCmax, n=6, 6, 6 | 0.9920 Ratio | Standard Deviation 0.32054 |
| Part 1: GSK3389404 30 mg | Accumulation Ratio by AUC (RAUC), by Cmax (RCmax), by C24 (RC24) and by Ctau (RCtau) of GSK3389404 in Part 2 | RC24, n=0, 1, 3 | 0.5890 Ratio | Standard Deviation 0.51139 |
| Part 1: GSK3389404 30 mg | Accumulation Ratio by AUC (RAUC), by Cmax (RCmax), by C24 (RC24) and by Ctau (RCtau) of GSK3389404 in Part 2 | RAUC, n=6, 5, 6 | 1.094 Ratio | Standard Deviation 0.24035 |
Secondary
AUC(0-24) and AUC(0-tau) of the Metabolite of GSK3389404 Following Dosing of GSK3389404 on Day 22 of Part 2
Blood samples were collected to evaluate AUC (0-24) and AUC (0-tau) of the metabolite of GSK3389404 on Day 22 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 29, 36, 50, 71 and at Follow-up (Day 113+- 2 days).
Time frame: Day 22 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 29, 36, 50, 71 and at Follow-up (Day 115)
Population: Pharmacokinetic Concentration Population. Based on emerging PK results during the course of the study, it was observed that metabolite plasma concentrations were not quantifiable in any PK sample. Hence, PK parameters could not be estimated for metabolite.
| Arm | Measure | Group | Value |
|---|---|---|---|
| Unknown | AUC(0-24) and AUC(0-tau) of the Metabolite of GSK3389404 Following Dosing of GSK3389404 on Day 22 of Part 2 | AUC (0-24) | — |
| Unknown | AUC(0-24) and AUC(0-tau) of the Metabolite of GSK3389404 Following Dosing of GSK3389404 on Day 22 of Part 2 | AUC (0-tau) | — |
Secondary
AUC (0-inf), AUC(0-t), AUC(0-24) of the Metabolite of GSK3389404 After Single Dose in Part 1
Blood samples were collected to evaluate AUC (0-inf), AUC (0-t) and AUC (0-24) of metabolite of GSK3389404 on Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 30 post-dose.
Time frame: Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 30 post-dose
Population: Pharmacokinetic Concentration Population. Based on emerging PK results during the course of the study, it was observed that metabolite plasma concentrations were not quantifiable in any PK sample. Hence, PK parameters could not be estimated for metabolite.
| Arm | Measure | Group | Value |
|---|---|---|---|
| Unknown | AUC (0-inf), AUC(0-t), AUC(0-24) of the Metabolite of GSK3389404 After Single Dose in Part 1 | AUC (0-inf) | — |
| Unknown | AUC (0-inf), AUC(0-t), AUC(0-24) of the Metabolite of GSK3389404 After Single Dose in Part 1 | AUC (0-t) | — |
| Unknown | AUC (0-inf), AUC(0-t), AUC(0-24) of the Metabolite of GSK3389404 After Single Dose in Part 1 | AUC (0-24) | — |
Secondary
AUC (0-t), AUC(0-24), AUC(0-168) and AUC (0-inf) of the Metabolite of GSK3389404 Following Single Dose on Day 1 of Part 2
Blood samples were collected to evaluate AUC (0-t), AUC (0-24), AUC (0-168) and AUC (0-inf) of the metabolite of GSK3389404 on Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 15 post-dose.
Time frame: Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 15 post-dose
Population: Pharmacokinetic Concentration Population. Based on emerging PK results during the course of the study, it was observed that metabolite plasma concentrations were not quantifiable in any PK sample. Hence, PK parameters could not be estimated for metabolite.
| Arm | Measure | Group | Value |
|---|---|---|---|
| Unknown | AUC (0-t), AUC(0-24), AUC(0-168) and AUC (0-inf) of the Metabolite of GSK3389404 Following Single Dose on Day 1 of Part 2 | AUC (0-t) | — |
| Unknown | AUC (0-t), AUC(0-24), AUC(0-168) and AUC (0-inf) of the Metabolite of GSK3389404 Following Single Dose on Day 1 of Part 2 | AUC (0-24) | — |
| Unknown | AUC (0-t), AUC(0-24), AUC(0-168) and AUC (0-inf) of the Metabolite of GSK3389404 Following Single Dose on Day 1 of Part 2 | AUC (0-168) | — |
| Unknown | AUC (0-t), AUC(0-24), AUC(0-168) and AUC (0-inf) of the Metabolite of GSK3389404 Following Single Dose on Day 1 of Part 2 | AUC (0-inf) | — |
Secondary
Cmax, C24 and C168 of the Metabolite of GSK3389404 Following Single Dose in Part 1
Blood samples were collected to evaluate Cmax, C24 and C168 of the metabolite of GSK3389404 on Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 30 post-dose.
Time frame: Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 30 post-dose
Population: Pharmacokinetic Concentration Population. Based on emerging PK results during the course of the study, it was observed that metabolite plasma concentrations were not quantifiable in any PK sample. Hence, PK parameters could not be estimated for metabolite.
| Arm | Measure | Group | Value |
|---|---|---|---|
| Unknown | Cmax, C24 and C168 of the Metabolite of GSK3389404 Following Single Dose in Part 1 | Cmax | — |
| Unknown | Cmax, C24 and C168 of the Metabolite of GSK3389404 Following Single Dose in Part 1 | C24 | — |
| Unknown | Cmax, C24 and C168 of the Metabolite of GSK3389404 Following Single Dose in Part 1 | C168 | — |
Secondary
Cmax, C24 and C168 of the Metabolite of GSK3389404 Following Single Dose on Day 1 of Part 2
Blood samples were collected to evaluate Cmax, C24 and C168 of the metabolite of GSK3389404 on Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 15 post-dose.
Time frame: Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 15 post-dose
Population: Pharmacokinetic Concentration Population. Based on emerging PK results during the course of the study, it was observed that metabolite plasma concentrations were not quantifiable in any PK sample. Hence, PK parameters could not be estimated for metabolite.
| Arm | Measure | Group | Value |
|---|---|---|---|
| Unknown | Cmax, C24 and C168 of the Metabolite of GSK3389404 Following Single Dose on Day 1 of Part 2 | Cmax | — |
| Unknown | Cmax, C24 and C168 of the Metabolite of GSK3389404 Following Single Dose on Day 1 of Part 2 | C24 | — |
| Unknown | Cmax, C24 and C168 of the Metabolite of GSK3389404 Following Single Dose on Day 1 of Part 2 | C168 | — |
Secondary
Ctau, C24 and Cmax of the Metabolite of GSK3389404 Following Dosing of GSK3389404 on Day 22 of Part 2
Blood samples were collected to evaluate Ctau, C24 and Cmax of the metabolite of GSK3389404 on Day 22 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 29, 36, 50, 71 and at Follow-up (Day 113+- 2 days).
Time frame: Day 22 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 29, 36, 50, 71 and at Follow-up (Day 115)
Population: Pharmacokinetic Concentration Population. Based on emerging PK results during the course of the study, it was observed that metabolite plasma concentrations were not quantifiable in any PK sample. Hence, PK parameters could not be estimated for metabolite.
| Arm | Measure | Group | Value |
|---|---|---|---|
| Unknown | Ctau, C24 and Cmax of the Metabolite of GSK3389404 Following Dosing of GSK3389404 on Day 22 of Part 2 | Ctau | — |
| Unknown | Ctau, C24 and Cmax of the Metabolite of GSK3389404 Following Dosing of GSK3389404 on Day 22 of Part 2 | C24 | — |
| Unknown | Ctau, C24 and Cmax of the Metabolite of GSK3389404 Following Dosing of GSK3389404 on Day 22 of Part 2 | Cmax | — |
Secondary
Dose Proportionality of GSK202007 for Dose Range 10 mg - 120 mg After Single Dose Administrations
Results of dose proportionality assessment using power model and analysis of variance (ANOVA) following single dose administariton (Part 1 and Day 1 in Part 2) are presented. Slope estimates and 90% confidence interval are presented for combined data of Day 1 of Part 1 and 2.
Time frame: Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 30 post-dose; Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 15 post-dose in Part 2.
Population: Pharmacokinetic Concentration Population (combined for Part 1 and 2). Only data available at the specified time points was analyzed. (represented by n=X in the category titles).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: Placebo | Dose Proportionality of GSK202007 for Dose Range 10 mg - 120 mg After Single Dose Administrations | AUC (0-24), n=40 | 1.08 ratio |
| Part 1: Placebo | Dose Proportionality of GSK202007 for Dose Range 10 mg - 120 mg After Single Dose Administrations | AUC (0-inf), n=40 | 1.07 ratio |
| Part 1: Placebo | Dose Proportionality of GSK202007 for Dose Range 10 mg - 120 mg After Single Dose Administrations | Cmax, n=41 | 0.975 ratio |
Secondary
Dose Proportionality of GSK202007 for Dose Range 30 mg - 120 mg After Multiple Dose Administrations
Results of proportionality assessment using power model and ANOVA following multiple doses are presented. Slope estimates and 90% confidence interval are presented for Day 22 of Part 2.
Time frame: Day 22 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 29, 36, 50, 71 and at Follow-up (Day 115) in Part 2
Population: Pharmacokinetic Concentration Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: Placebo | Dose Proportionality of GSK202007 for Dose Range 30 mg - 120 mg After Multiple Dose Administrations | AUC (0-tau) | 1.25 ratio |
| Part 1: Placebo | Dose Proportionality of GSK202007 for Dose Range 30 mg - 120 mg After Multiple Dose Administrations | Cmax | 1.25 ratio |
Secondary
Time Invariance (LI) of GSK3389404 in Part 2
For Part 2, time invariance was evaluated by comparing AUC (0-tau) for Day 22 to AUC (0-inf) for Day 1. For each dose level, a linear mixed effect model was fitted with the log transformed PK parameter as the dependent variable, day as a fixed effect and subject as a random effect. Only those participants with data available at the specified time points were analyzed.
Time frame: Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 15 post-dose; Day 22 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 29, 36, 50, 71 and at Follow-up (Day 115)
Population: Pharmacokinetic Concentration Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Placebo | Time Invariance (LI) of GSK3389404 in Part 2 | 1.115 Ratio | Standard Deviation 0.24879 |
| Part 1: GSK3389404 10 mg | Time Invariance (LI) of GSK3389404 in Part 2 | 0.8598 Ratio | Standard Deviation 0.098644 |
| Part 1: GSK3389404 30 mg | Time Invariance (LI) of GSK3389404 in Part 2 | 1.094 Ratio | Standard Deviation 0.24035 |
Secondary
Tmax, T1/2 and Tlag of the Metabolite of GSK3389404 Following Dosing on Day 22 of Part 2
Blood samples were collected to evaluate Tmax, T1/2 and Tlag of the metabolite of GSK3389404 on Day 22 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 29, 36, 50, 71 and at Follow-up (Day 113+- 2 days).
Time frame: Day 22 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 29, 36, 50, 71 and at Follow-up (Day 115)
Population: Pharmacokinetic Concentration Population. Based on emerging PK results during the course of the study, it was observed that metabolite plasma concentrations were not quantifiable in any PK sample. Hence, PK parameters could not be estimated for metabolite.
| Arm | Measure | Group | Value |
|---|---|---|---|
| Unknown | Tmax, T1/2 and Tlag of the Metabolite of GSK3389404 Following Dosing on Day 22 of Part 2 | Tmax | — |
| Unknown | Tmax, T1/2 and Tlag of the Metabolite of GSK3389404 Following Dosing on Day 22 of Part 2 | T1/2 | — |
| Unknown | Tmax, T1/2 and Tlag of the Metabolite of GSK3389404 Following Dosing on Day 22 of Part 2 | Tlag | — |
Secondary
Tmax, T1/2 and Tlag of the Metabolite of GSK3389404 Following Single Dose in Part 1
Blood samples were collected to evaluate Tmax, T1/2 and Tlag of the metabolite of GSK3389404 on Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 30 post-dose.
Time frame: Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 30 post-dose
Population: Pharmacokinetic Concentration Population. Based on emerging PK results during the course of the study, it was observed that metabolite plasma concentrations were not quantifiable in any PK sample. Hence, PK parameters could not be estimated for metabolite.
| Arm | Measure | Group | Value |
|---|---|---|---|
| Unknown | Tmax, T1/2 and Tlag of the Metabolite of GSK3389404 Following Single Dose in Part 1 | Tmax | — |
| Unknown | Tmax, T1/2 and Tlag of the Metabolite of GSK3389404 Following Single Dose in Part 1 | T1/2 | — |
| Unknown | Tmax, T1/2 and Tlag of the Metabolite of GSK3389404 Following Single Dose in Part 1 | Tlag | — |
Secondary
Tmax, T1/2 and Tlag of the Metabolite of GSK3389404 Following Single Dose on Day 1 of Part 2
Blood samples were collected to evaluate Tmax, T1/2 and Tlag of the metabolite of GSK3389404 on Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 15 post-dose.
Time frame: Day 1 (pre-dose) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose; and on Days 8 and 15 post-dose
Population: Pharmacokinetic Concentration Population. Based on emerging PK results during the course of the study, it was observed that metabolite plasma concentrations were not quantifiable in any PK sample. Hence, PK parameters could not be estimated for metabolite.
| Arm | Measure | Group | Value |
|---|---|---|---|
| Unknown | Tmax, T1/2 and Tlag of the Metabolite of GSK3389404 Following Single Dose on Day 1 of Part 2 | Tmax | — |
| Unknown | Tmax, T1/2 and Tlag of the Metabolite of GSK3389404 Following Single Dose on Day 1 of Part 2 | T1/2 | — |
| Unknown | Tmax, T1/2 and Tlag of the Metabolite of GSK3389404 Following Single Dose on Day 1 of Part 2 | Tlag | — |
Secondary
Trough Plasma Concentrations of GSK3389404 in Part 2
For Part 2, mean plasma GSK3389404 pre-dose values between Day 1 to Day 29 and Ctau were plotted against time to assess attainment of GSK3389404 steady state following multiple dose administration. Achievement of plasma GSK3389404 steady-state was assessed by calculating the 90% confidence interval (CI) of the slope of the linear regression of log (Ctau) versus time. NA indicates data was not available.
Time frame: Pre-dose on Days 8, 15, 22 and 29
Population: Pharmacokinetic Concentration Population
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Part 1: Placebo | Trough Plasma Concentrations of GSK3389404 in Part 2 | Day 8 | NA Ratio |
| Part 1: Placebo | Trough Plasma Concentrations of GSK3389404 in Part 2 | Day 15 | NA Ratio |
| Part 1: Placebo | Trough Plasma Concentrations of GSK3389404 in Part 2 | Day 22 | NA Ratio |
| Part 1: Placebo | Trough Plasma Concentrations of GSK3389404 in Part 2 | Day 29 | NA Ratio |
| Part 1: GSK3389404 10 mg | Trough Plasma Concentrations of GSK3389404 in Part 2 | Day 29 | NA Ratio |
| Part 1: GSK3389404 10 mg | Trough Plasma Concentrations of GSK3389404 in Part 2 | Day 8 | NA Ratio |
| Part 1: GSK3389404 10 mg | Trough Plasma Concentrations of GSK3389404 in Part 2 | Day 22 | NA Ratio |
| Part 1: GSK3389404 10 mg | Trough Plasma Concentrations of GSK3389404 in Part 2 | Day 15 | NA Ratio |
| Part 1: GSK3389404 30 mg | Trough Plasma Concentrations of GSK3389404 in Part 2 | Day 29 | NA Ratio |
| Part 1: GSK3389404 30 mg | Trough Plasma Concentrations of GSK3389404 in Part 2 | Day 15 | NA Ratio |
| Part 1: GSK3389404 30 mg | Trough Plasma Concentrations of GSK3389404 in Part 2 | Day 22 | NA Ratio |
| Part 1: GSK3389404 30 mg | Trough Plasma Concentrations of GSK3389404 in Part 2 | Day 8 | NA Ratio |