A Phase 1 interventional study of GSK3389404 and Matching Placebo in Hepatitis B, sponsored by GlaxoSmithKline. Completed at 2 sites in United Kingdom. Open to participants aged 18 Years to 55 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2019-07-16.
Sponsored by GlaxoSmithKline · Phase 1, Interventional, and Other
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.
1,656 studies on the registry are indexed under Hepatitis B; 196 are open to participants now.
This study's enrollment of 56 is below the median of 120 across 1,187 interventional studies indexed under Hepatitis B.
Browse Hepatitis B studies →GlaxoSmithKline is the lead sponsor of 3,562 studies on the registry; 117 are open to participants now.
Of its 258 completed or terminated interventional studies of FDA-regulated products, 232 (90%) have results posted.
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Females of Reproductive Potential (FRP) are not permitted. Eligible females must meet the following criteria:
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).
Exclusion Criteria:
Subjects will receive a single dose of GSK3389404 10 mg by subcutaneous injection on Day 1 of Part 1.
Drug: GSK3389404
Subjects will receive 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.
Drug: Matching Placebo
Subjects will receive a single dose of GSK3389404 30 mg by subcutaneous injection on Day 1 of Part 1.
Drug: GSK3389404
Subjects will receive a single dose of GSK3389404 60 mg by subcutaneous injection on Day 1 of Part 1.
Drug: GSK3389404
Subjects will receive a single dose of GSK3389404 120 mg by subcutaneous injection on Day 1 of Part 1.
Drug: GSK3389404
Subjects will receive a single dose of GSK3389404 30 mg by subcutaneous injection QW for 4 weeks in Part 2.
Drug: GSK3389404
Subjects will receive 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.
Drug: Matching Placebo
Subjects will receive a single dose of GSK3389404 60 mg by subcutaneous injection QW for 4 weeks in Part 2.
Drug: GSK3389404
Subjects will receive a single dose of GSK3389404 120 mg by subcutaneous injection QW for 4 weeks in Part 2.
Drug: GSK3389404
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.
Placebo is supplied as solution for injection vial. It's physical appearance is clear colourless solution.
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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)
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)
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)
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)
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.
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
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)
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)
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
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
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
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
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
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
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
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)
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)
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)
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.
| Milestone | 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 | Part 2: GSK3389404 120 mg |
|---|---|---|---|---|---|---|---|---|---|
| Started | 8 | 6 | 6 | 6 | 6 | 0 | 0 | 0 | 0 |
| Completed | 8 | 6 | 6 | 6 | 6 | 0 | 0 | 0 | 0 |
| Not completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Milestone | 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 | Part 2: GSK3389404 120 mg |
|---|---|---|---|---|---|---|---|---|---|
| Started | 0 | 0 | 0 | 0 | 0 | 6 | 6 | 6 | 6 |
| Completed | 0 | 0 | 0 | 0 | 0 | 6 | 6 | 6 | 5 |
| Not completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Withdrew: Withdrawal by subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 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.
| Participants | Part 1: Placebo | Part 1: GSK3389404 10 mg | Part 1: GSK3389404 30 mg | Part 1: GSK3389404 60 mg | Part 1: GSK3389404 120 mg |
|---|---|---|---|---|---|
| Any non-serious AE | 4 | 3 | 2 | 3 | 5 |
| Any SAE | 0 | 0 | 0 | 0 | 0 |
| AELD | 0 | 0 | 0 | 0 | 0 |
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.
| Participants | Part 2: Placebo | Part 2: GSK3389404 30 mg | Part 2: GSK3389404 60 mg | Part 2: GSK3389404 120 mg |
|---|---|---|---|---|
| Any non-serious AE | 3 | 5 | 2 | 4 |
| Any SAE | 0 | 0 | 0 | 0 |
| AELD | 0 | 0 | 0 | 0 |
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.
| Participants | Part 1: Placebo | Part 1: GSK3389404 10 mg | Part 1: GSK3389404 30 mg | Part 1: GSK3389404 60 mg | Part 1: GSK3389404 120 mg |
|---|---|---|---|---|---|
| Number of Participants With Laboratory Values of Potential Clinical Importance in Part 1 | 5 | 3 | 2 | 4 | 3 |
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.
| Participants | Part 2: Placebo | Part 2: GSK3389404 30 mg | Part 2: GSK3389404 60 mg | Part 2: GSK3389404 120 mg |
|---|---|---|---|---|
| Number of Participants With Laboratory Values of Potential Clinical Importance in Part 2 | 3 | 2 | 5 | 3 |
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.
| Gram per liter (g/L) | Part 1: Placebo | Part 1: GSK3389404 10 mg | Part 1: GSK3389404 30 mg | Part 1: GSK3389404 60 mg | Part 1: GSK3389404 120 mg |
|---|---|---|---|---|---|
| C3 | -0.0811 ± 0.09367 | -0.0142 ± 0.04549 | -0.1580 ± 0.12739 | -0.0900 ± 0.07452 | -0.0412 ± 0.06432 |
| C4 | -0.0320 ± 0.04107 | -0.0123 ± 0.01768 | -0.0600 ± 0.04544 | -0.0212 ± 0.01987 | -0.0250 ± 0.01979 |
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.
| Microgram per liter (ug/L) | Part 1: Placebo | Part 1: GSK3389404 10 mg | Part 1: GSK3389404 30 mg | Part 1: GSK3389404 60 mg | Part 1: GSK3389404 120 mg |
|---|---|---|---|---|---|
| Change From Baseline in Complement Split Product C5a Levels in Part 1 | 7.895 ± 4.6360 | 7.755 ± 8.8013 | 2.590 ± 1.9653 | 5.102 ± 18.7596 | 1.485 ± 2.5368 |
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
| mg per liter (mg/L) | Part 1: Placebo | Part 1: GSK3389404 10 mg | Part 1: GSK3389404 30 mg | Part 1: GSK3389404 60 mg | Part 1: GSK3389404 120 mg |
|---|---|---|---|---|---|
| Change From Baseline in Complement Split Product Bb Levels in Part 1 | 0.8788 ± 1.01171 | 1.5517 ± 1.26063 | 0.6900 ± 0.48187 | 1.2900 ± 1.69068 | 0.3350 ± 0.78899 |
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
| G/L | Part 2: Placebo | Part 2: GSK3389404 30 mg | Part 2: GSK3389404 60 mg | Part 2: GSK3389404 120 mg |
|---|---|---|---|---|
| C3, Day 1 | -0.0495 ± 0.06661 | -0.0333 ± 0.05961 | -0.0783 ± 0.04025 | -0.0293 ± 0.05722 |
| C3, Day 22 | -0.1143 ± 0.07139 | -0.1013 ± 0.06017 | -0.0840 ± 0.02521 | -0.1702 ± 0.07908 |
| C4, Day 1 | -0.0190 ± 0.01192 | -0.0132 ± 0.03511 | -0.0470 ± 0.02674 | -0.0135 ± 0.01271 |
| C4, Day 22 | -0.0397 ± 0.02043 | -0.0405 ± 0.03661 | -0.0390 ± 0.01980 | -0.0443 ± 0.02805 |
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.
| ug/L | Part 2: Placebo | Part 2: GSK3389404 30 mg | Part 2: GSK3389404 60 mg | Part 2: GSK3389404 120 mg |
|---|---|---|---|---|
| C5a, Day 1 | 3.000 ± 4.2895 | -1.167 ± 5.8963 | 2.750 ± 4.1563 | 11.083 ± 6.3907 |
| C5a, Day 22 | 9.083 ± 4.2002 | 9.667 ± 10.5862 | 7.333 ± 2.3805 | 13.667 ± 9.9029 |
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.
| mg/L | Part 2: Placebo | Part 2: GSK3389404 30 mg | Part 2: GSK3389404 60 mg | Part 2: GSK3389404 120 mg |
|---|---|---|---|---|
| Bb, Day 1 | 0.4217 ± 0.62669 | 0.5033 ± 0.76727 | 0.9700 ± 0.60554 | 1.2667 ± 0.55623 |
| Bb, Day 22 | 1.4003 ± 0.56580 | 1.3447 ± 0.75517 | 0.6833 ± 0.57597 | 1.7340 ± 1.05781 |
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.
| Millimeter of mercury (mmHg) | Part 1: Placebo | Part 1: GSK3389404 10 mg | Part 1: GSK3389404 30 mg | Part 1: GSK3389404 60 mg | Part 1: GSK3389404 120 mg |
|---|---|---|---|---|---|
| DBP, 1 hour | -4.1 ± 6.53 | -4.4 ± 4.38 | -3.8 ± 7.36 | 1.5 ± 4.96 | 2.3 ± 4.51 |
| DBP, 2 hour | -4.1 ± 2.46 | -3.1 ± 4.29 | -4.8 ± 3.87 | 0.6 ± 3.64 | -1.9 ± 1.86 |
| DBP, 4 hour | -1.8 ± 3.64 | -5.6 ± 7.39 | -0.6 ± 7.39 | -0.8 ± 5.05 | -0.4 ± 5.42 |
| DBP, 8 hour | -5.6 ± 3.66 | -5.4 ± 8.78 | -4.0 ± 7.93 | -0.7 ± 4.43 | -1.3 ± 4.34 |
| DBP, 12 hour | -3.2 ± 7.50 | -5.8 ± 10.30 | -3.8 ± 4.01 | -1.5 ± 4.37 | -1.4 ± 4.34 |
| DBP, 24 hour | -2.8 ± 4.29 | -4.3 ± 7.53 | 0.2 ± 9.20 | 0.1 ± 4.00 | -2.6 ± 4.11 |
| DBP, 48 hour | -2.7 ± 4.59 | -3.3 ± 6.22 | -3.0 ± 6.87 | -1.3 ± 4.78 | -1.4 ± 2.50 |
| DBP, 72 hour | -1.9 ± 4.38 | -2.2 ± 5.71 | 1.0 ± 7.08 | 0.5 ± 1.25 | -2.7 ± 3.19 |
| DBP, Day 8 | -3.1 ± 5.07 | -3.4 ± 4.60 | -4.6 ± 4.53 | 0.3 ± 7.33 | -2.0 ± 2.91 |
| DBP, Day 30 | -1.7 ± 6.28 | 0.5 ± 7.36 | -5.1 ± 6.92 | 2.1 ± 7.26 | -0.3 ± 4.32 |
| SBP, 1 hour | -2.0 ± 7.65 | -4.0 ± 3.85 | -0.8 ± 8.55 | 1.8 ± 6.22 | 0.2 ± 6.18 |
| SBP, 2 hour | -0.7 ± 5.63 | 0.3 ± 5.89 | 2.2 ± 8.08 | 2.1 ± 5.51 | 4.9 ± 3.67 |
| SBP, 4 hour | -1.5 ± 4.58 | -5.5 ± 6.42 | -0.9 ± 4.32 | -4.6 ± 7.68 | 0.3 ± 5.94 |
| SBP, 8 hour | -1.6 ± 6.27 | -4.6 ± 11.61 | -2.3 ± 5.31 | 1.2 ± 5.61 | 4.1 ± 4.19 |
| SBP, 12 hour | 1.6 ± 10.73 | -5.5 ± 10.15 | 0.8 ± 4.58 | -1.5 ± 7.04 | 2.2 ± 3.54 |
| SBP, 24 hour | -4.0 ± 6.40 | -4.8 ± 6.42 | 3.1 ± 8.30 | -0.6 ± 6.39 | -0.9 ± 2.69 |
| SBP, 48 hour | -0.4 ± 6.84 | -6.8 ± 5.48 | -5.0 ± 3.89 | -1.7 ± 4.07 | -2.1 ± 4.03 |
| SBP, 72 hour | -1.4 ± 5.08 | -2.8 ± 8.29 | 4.6 ± 9.89 | 0.6 ± 4.24 | -1.5 ± 2.95 |
| SBP, Day 8 | -0.3 ± 7.41 | -4.8 ± 4.87 | -2.7 ± 5.98 | 0.5 ± 6.61 | 0.5 ± 3.48 |
| SBP, Day 30 | 2.7 ± 8.17 | -1.7 ± 8.21 | -0.1 ± 6.84 | -0.9 ± 4.75 | 5.9 ± 3.50 |
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.
| Beats per minute (bpm) | Part 1: Placebo | Part 1: GSK3389404 10 mg | Part 1: GSK3389404 30 mg | Part 1: GSK3389404 60 mg | Part 1: GSK3389404 120 mg |
|---|---|---|---|---|---|
| PR, 1 hour | 0.2 ± 3.20 | 0.3 ± 5.49 | -2.0 ± 3.19 | 1.5 ± 5.43 | -3.2 ± 6.63 |
| PR, 2 hour | 1.6 ± 3.68 | 4.0 ± 12.68 | 2.3 ± 4.54 | 3.8 ± 6.00 | -2.3 ± 8.82 |
| PR, 4 hour | 0.4 ± 5.83 | -0.5 ± 7.68 | -1.9 ± 3.24 | 0.2 ± 5.53 | 0.7 ± 9.37 |
| PR, 8 hour | 1.5 ± 4.46 | 1.2 ± 4.50 | 1.9 ± 2.63 | 4.8 ± 5.89 | 1.3 ± 6.76 |
| PR, 12 hour | 6.9 ± 12.49 | 1.6 ± 5.04 | 2.3 ± 4.19 | 8.6 ± 8.12 | -0.7 ± 8.35 |
| PR, 24 hour | -1.9 ± 4.49 | -1.6 ± 9.89 | 1.4 ± 7.17 | -1.3 ± 5.49 | -0.9 ± 10.07 |
| PR, 48 hour | 1.8 ± 10.74 | 0.2 ± 9.79 | 1.4 ± 4.46 | 2.3 ± 5.10 | -0.6 ± 6.61 |
| PR, 72 hour | 3.7 ± 4.85 | 1.0 ± 5.26 | 4.0 ± 3.47 | 5.3 ± 5.39 | 0.3 ± 9.90 |
| PR, Day 8 | 3.5 ± 5.55 | 0.4 ± 6.34 | 1.4 ± 2.58 | 6.0 ± 7.36 | 1.5 ± 9.03 |
| PR, Day 30 | 2.0 ± 6.53 | 4.3 ± 11.94 | 0.2 ± 5.36 | 6.3 ± 6.19 | -1.1 ± 9.67 |
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.
| Breaths per minute | Part 1: Placebo | Part 1: GSK3389404 10 mg | Part 1: GSK3389404 30 mg | Part 1: GSK3389404 60 mg | Part 1: GSK3389404 120 mg |
|---|---|---|---|---|---|
| RR, 1 hour, n=8, 6, 6, 6, 6 | -0.5 ± 2.14 | -1.3 ± 1.86 | 0.8 ± 3.54 | 1.5 ± 2.59 | 0.7 ± 3.67 |
| RR, 2 hour, n=8, 6, 6, 6, 6 | -0.3 ± 2.38 | 0.3 ± 3.14 | -2.7 ± 2.66 | 1.0 ± 4.15 | -1.7 ± 1.63 |
| RR, 4 hour, n=8, 6, 6, 5, 6 | -0.8 ± 3.01 | -0.2 ± 2.14 | 0.0 ± 2.90 | 0.4 ± 5.50 | 0.2 ± 3.31 |
| RR, 8 hour, n=8, 6, 6, 6, 6 | -0.1 ± 2.95 | -0.5 ± 1.87 | -1.0 ± 3.79 | -1.2 ± 3.87 | -2.2 ± 1.83 |
| RR, 12 hour, n=8, 6, 6, 6, 6 | -0.3 ± 2.19 | 0.8 ± 1.60 | -0.5 ± 2.59 | 0.0 ± 3.10 | 0.0 ± 1.41 |
| RR, 24 hour, n=8, 6, 6, 6, 6 | -0.6 ± 2.62 | -0.3 ± 2.94 | -2.2 ± 3.54 | 0.5 ± 1.52 | -0.7 ± 1.75 |
| RR, 48 hour, n=8, 6, 6, 6, 6 | -0.5 ± 3.12 | -0.8 ± 2.32 | -2.0 ± 3.74 | 3.0 ± 3.29 | 1.7 ± 1.63 |
| RR, 72 hour, n=8, 6, 6, 6, 6 | -0.5 ± 3.07 | 0.7 ± 3.44 | 0.0 ± 3.52 | 0.8 ± 3.66 | -1.7 ± 2.25 |
| RR, Day 8, n=8, 6, 6, 6, 6 | -0.6 ± 3.20 | -1.3 ± 1.51 | -1.5 ± 4.72 | 1.0 ± 2.97 | -1.0 ± 2.68 |
| RR, Day 30, n=8, 6, 6, 6, 6 | 1.0 ± 1.69 | 0.0 ± 1.41 | -0.7 ± 3.44 | -0.7 ± 3.50 | -0.3 ± 2.25 |
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.
| Degree Celsius | Part 1: Placebo | Part 1: GSK3389404 10 mg | Part 1: GSK3389404 30 mg | Part 1: GSK3389404 60 mg | Part 1: GSK3389404 120 mg |
|---|---|---|---|---|---|
| Temperature, 1 hour | 0.06 ± 0.185 | 0.00 ± 0.237 | 0.05 ± 0.122 | 0.10 ± 0.276 | 0.10 ± 0.200 |
| Temperature, 2 hour | 0.04 ± 0.288 | -0.02 ± 0.147 | 0.02 ± 0.172 | -0.15 ± 0.243 | 0.05 ± 0.243 |
| Temperature, 4 hour | 0.14 ± 0.213 | 0.08 ± 0.319 | 0.05 ± 0.217 | -0.02 ± 0.264 | 0.08 ± 0.194 |
| Temperature, 8 hour | 0.24 ± 0.297 | -0.02 ± 0.279 | 0.20 ± 0.126 | 0.18 ± 0.147 | 0.23 ± 0.288 |
| Temperature, 12 hour | 0.18 ± 0.255 | 0.03 ± 0.234 | -0.03 ± 0.137 | 0.12 ± 0.204 | 0.08 ± 0.232 |
| Temperature, 24 hour | -0.01 ± 0.290 | -0.10 ± 0.167 | -0.05 ± 0.152 | 0.07 ± 0.197 | -0.03 ± 0.350 |
| Temperature, 48 hour | 0.00 ± 0.434 | -0.10 ± 0.210 | 0.03 ± 0.121 | 0.02 ± 0.248 | -0.10 ± 0.276 |
| Temperature, 72 hour | 0.06 ± 0.220 | -0.07 ± 0.250 | 0.07 ± 0.225 | 0.07 ± 0.175 | -0.03 ± 0.197 |
| Temperature, Day 8 | 0.00 ± 0.233 | -0.08 ± 0.319 | 0.00 ± 0.200 | -0.20 ± 0.228 | 0.05 ± 0.138 |
| Temperature, Day 30 | -0.04 ± 0.177 | -0.07 ± 0.216 | 0.00 ± 0.190 | -0.07 ± 0.225 | -0.12 ± 0.436 |
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.
| mmHg | Part 2: Placebo | Part 2: GSK3389404 30 mg | Part 2: GSK3389404 60 mg | Part 2: GSK3389404 120 mg |
|---|---|---|---|---|
| DBP, Day 1, 1 hour, n=6, 6, 6, 6 | 0.5 ± 4.75 | 5.7 ± 4.83 | -1.8 ± 3.49 | -2.4 ± 4.26 |
| DBP, Day 1, 2 hour, n=6, 6, 6, 6 | 2.1 ± 5.56 | -0.1 ± 4.83 | -0.8 ± 6.74 | -1.6 ± 3.47 |
| DBP, Day 1, 4 hour, n=6, 6, 6, 6 | -2.1 ± 5.54 | -5.1 ± 6.25 | -4.6 ± 5.86 | -8.0 ± 3.69 |
| DBP, Day 1, 6 hour, n=6, 6, 6, 6 | -5.3 ± 5.51 | -2.6 ± 6.90 | -3.5 ± 5.03 | -5.1 ± 3.37 |
| DBP, Day 1, 8 hour, n=6, 6, 6, 6 | -0.2 ± 6.66 | 1.4 ± 4.12 | -3.0 ± 8.63 | -4.1 ± 3.51 |
| DBP, Day 1, 12 hour, n=6, 6, 6, 6 | -4.4 ± 7.17 | -2.6 ± 4.49 | -7.7 ± 5.97 | -4.4 ± 4.75 |
| DBP, Day 2, 24 hour, n=6, 6, 6, 6 | 2.6 ± 6.29 | 0.9 ± 3.36 | -3.0 ± 4.87 | -2.1 ± 2.10 |
| DBP, Day 3, 48 hour, n=6, 6, 6, 6 | -0.2 ± 5.41 | 2.6 ± 5.55 | -4.8 ± 5.24 | -2.6 ± 4.76 |
| DBP, Day 4, 72 hour, n=6, 6, 6, 6 | 1.6 ± 5.77 | -6.1 ± 6.56 | -1.9 ± 3.09 | -0.1 ± 4.13 |
| DBP, Day 8, n=6, 6, 6, 6 | 1.6 ± 7.61 | 1.9 ± 5.59 | -2.6 ± 3.82 | -3.0 ± 5.66 |
| DBP, Day 15, n=6, 6, 6, 6 | 2.9 ± 11.22 | 5.5 ± 3.60 | 2.6 ± 6.70 | -3.1 ± 3.82 |
| DBP, Day 22, pre-dose, n=6, 6, 6, 6 | 1.0 ± 7.07 | -3.8 ± 4.91 | -3.1 ± 1.66 | -2.2 ± 2.37 |
| DBP, Day 22, 1 hour, n=6, 6, 6, 6 | 2.6 ± 6.79 | -0.8 ± 7.56 | -2.3 ± 6.39 | -1.8 ± 3.44 |
| DBP, Day 22, 4 hour, n=6, 6, 6, 6 | -4.0 ± 7.53 | -0.3 ± 6.34 | -4.8 ± 6.46 | -3.4 ± 4.48 |
| DBP, Day 22, 6 hour, n=6, 6, 6, 6 | -4.5 ± 6.22 | 0.1 ± 5.44 | -9.3 ± 8.96 | -4.2 ± 6.42 |
| DBP, Day 22, 8 hour, n=6, 6, 6, 6 | -0.3 ± 5.82 | -2.8 ± 6.29 | -4.4 ± 7.14 | -1.2 ± 2.55 |
| DBP, Day 22, 12 hour, n=6, 6, 6, 6 | -0.1 ± 7.80 | -2.9 ± 3.01 | -7.0 ± 9.15 | -2.6 ± 4.15 |
| DBP, Day 23, 24 hour, n=6, 6, 6, 6 | 0.7 ± 8.59 | -4.2 ± 6.14 | -4.5 ± 4.00 | -0.6 ± 4.08 |
| DBP, Day 24, 48 hour, n=6, 6, 6, 6 | -0.6 ± 5.84 | -2.8 ± 5.32 | -1.7 ± 4.30 | -0.9 ± 8.38 |
| DBP, Day 25, 72 hour, n=6, 6, 6, 6 | 1.3 ± 6.71 | 0.7 ± 3.88 | 0.4 ± 2.83 | 0.1 ± 5.00 |
| DBP, Day 29, n=6, 6, 6, 6 | 0.6 ± 9.06 | 5.7 ± 7.45 | 1.1 ± 4.70 | -2.9 ± 4.30 |
| DBP, Day 36, n=6, 6, 6, 5 | -0.8 ± 8.10 | 4.3 ± 7.05 | 1.7 ± 4.67 | 2.6 ± 5.09 |
| DBP, Day 50, n=6, 6, 6, 5 | 5.8 ± 3.93 | 9.7 ± 7.90 | 2.9 ± 4.39 | -0.1 ± 6.22 |
| DBP, Day 71, n=6, 6, 6, 5 | 3.2 ± 6.27 | 8.9 ± 6.31 | 2.4 ± 3.94 | 4.0 ± 2.22 |
| DBP, Follow-up, n=6, 6, 6, 5 | 3.7 ± 6.38 | 2.2 ± 6.54 | 4.3 ± 3.85 | 7.7 ± 1.75 |
| SBP, Day 1, 1 hour, n=6, 6, 6, 6 | 1.2 ± 5.55 | 3.4 ± 6.83 | 1.1 ± 5.35 | 5.3 ± 4.17 |
| SBP, Day 1, 2 hour, n=6, 6, 6, 6 | 0.7 ± 5.95 | 0.5 ± 2.99 | -0.6 ± 3.38 | 3.9 ± 8.89 |
| SBP, Day 1, 4 hour, n=6, 6, 6, 6 | -2.6 ± 6.36 | -2.6 ± 2.16 | -4.6 ± 6.57 | 0.4 ± 4.28 |
| SBP, Day 1, 6 hour, n=6, 6, 6, 6 | -3.6 ± 6.23 | -0.9 ± 3.71 | -1.6 ± 6.54 | 5.4 ± 6.67 |
| SBP, Day 1, 8 hour, n=6, 6, 6, 6 | 0.3 ± 3.26 | 0.6 ± 3.65 | 0.4 ± 10.56 | 5.8 ± 6.37 |
| SBP, Day 1, 12 hour, n=6, 6, 6, 6 | -0.1 ± 6.39 | -0.4 ± 5.32 | -2.9 ± 7.54 | 5.8 ± 4.11 |
| SBP, Day 2, 24 hour, n=6, 6, 6, 6 | 3.0 ± 6.25 | -0.1 ± 4.35 | 0.4 ± 4.95 | 2.4 ± 2.83 |
| SBP, Day 3, 48 hour, n=6, 6, 6, 6 | 0.7 ± 8.69 | 1.5 ± 6.13 | -2.4 ± 6.34 | 5.0 ± 4.38 |
| SBP, Day 4, 72 hour, n=6, 6, 6, 6 | 3.9 ± 4.96 | -3.7 ± 6.64 | 0.2 ± 7.29 | 7.5 ± 3.32 |
| SBP, Day 8, n=6, 6, 6, 6 | -0.7 ± 7.45 | -1.7 ± 6.25 | -4.4 ± 5.97 | 2.8 ± 7.24 |
| SBP, Day 15, n=6, 6, 6, 6 | 3.5 ± 10.88 | 4.6 ± 7.93 | -2.3 ± 6.47 | 1.5 ± 5.47 |
| SBP, Day 22, pre-dose, n=6, 6, 6, 6 | -1.1 ± 9.18 | -4.6 ± 5.69 | -4.0 ± 2.60 | -1.1 ± 5.65 |
| SBP, Day 22, 1 hour, n=6, 6, 6, 6 | 1.7 ± 6.34 | -4.6 ± 4.41 | -1.6 ± 2.20 | 3.2 ± 7.34 |
| SBP, Day 22, 4 hour, n=6, 6, 6, 6 | -0.3 ± 6.11 | -2.0 ± 4.70 | -4.2 ± 5.24 | 2.5 ± 4.99 |
| SBP, Day 22, 6 hour, n=6, 6, 6, 6 | -2.4 ± 7.57 | -2.7 ± 2.55 | -6.1 ± 7.77 | 1.3 ± 5.49 |
| SBP, Day 22, 8 hour, n=6, 6, 6, 6 | -0.3 ± 5.73 | -5.9 ± 2.98 | -5.4 ± 6.27 | 0.6 ± 4.57 |
| SBP, Day 22, 12 hour, n=6, 6, 6, 6 | 4.9 ± 6.14 | 0.1 ± 3.22 | -5.2 ± 8.57 | 5.2 ± 4.07 |
| SBP, Day 23, 24 hour, n=6, 6, 6, 6 | 0.8 ± 8.50 | -5.7 ± 3.77 | -1.2 ± 5.67 | 4.9 ± 6.35 |
| SBP, Day 24, 48 hour, n=6, 6, 6, 6 | 0.3 ± 3.79 | -7.4 ± 4.48 | -0.8 ± 5.02 | 2.8 ± 5.29 |
| SBP, Day 25, 72 hour, n=6, 6, 6, 6 | 1.2 ± 5.37 | -1.0 ± 3.48 | 4.4 ± 5.69 | 5.0 ± 3.87 |
| SBP, Day 29, n=6, 6, 6, 6 | 0.3 ± 6.24 | 6.8 ± 7.69 | -1.0 ± 4.68 | 1.9 ± 5.57 |
| SBP, Day 36, n=6, 6, 6, 5 | -2.8 ± 9.99 | 4.2 ± 7.35 | 0.7 ± 6.11 | 3.2 ± 3.89 |
| SBP, Day 50, n=6, 6, 6, 5 | 8.1 ± 6.28 | 3.9 ± 4.47 | -0.7 ± 7.20 | 2.5 ± 2.32 |
| SBP, Day 71, n=6, 6, 6, 5 | 1.1 ± 7.49 | 4.9 ± 7.81 | 4.1 ± 7.42 | 7.4 ± 5.34 |
| SBP, Follow-up, n=6, 6, 6, 5 | 4.8 ± 8.05 | -2.1 ± 7.16 | 10.0 ± 5.98 | 11.5 ± 5.29 |
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.
| bpm | Part 2: Placebo | Part 2: GSK3389404 30 mg | Part 2: GSK3389404 60 mg | Part 2: GSK3389404 120 mg |
|---|---|---|---|---|
| PR, Day 1, 1 hour, n=6, 6, 6, 6 | -1.5 ± 7.15 | 0.5 ± 3.80 | 0.3 ± 1.54 | -2.4 ± 2.09 |
| PR, Day 1, 2 hour, n=6, 6, 6, 6 | 0.4 ± 4.57 | -1.6 ± 6.79 | 2.9 ± 4.17 | -1.1 ± 3.81 |
| PR, Day 1, 4 hour, n=6, 6, 6, 6 | 4.7 ± 4.13 | 4.6 ± 5.99 | 6.6 ± 3.75 | 2.4 ± 2.79 |
| PR, Day 1, 6 hour, n=6, 6, 6, 6 | 6.4 ± 2.38 | 5.8 ± 7.12 | 7.9 ± 3.27 | 6.6 ± 3.93 |
| PR, Day 1, 8 hour, n=6, 6, 6, 6 | 0.4 ± 1.83 | 3.5 ± 5.39 | 7.8 ± 6.99 | 0.5 ± 3.91 |
| PR, Day 1, 12 hour, n=6, 6, 6, 6 | 4.0 ± 3.29 | 7.2 ± 7.13 | 7.8 ± 6.09 | 3.9 ± 4.59 |
| PR, Day 2, 24 hour, n=6, 6, 6, 6 | 0.6 ± 4.62 | -2.4 ± 4.84 | 2.4 ± 3.33 | -1.1 ± 2.39 |
| PR, Day 3, 48 hour, n=6, 6, 6, 6 | 3.8 ± 4.90 | 4.3 ± 9.58 | 6.2 ± 5.70 | -0.1 ± 2.93 |
| PR, Day 4, 72 hour, n=6, 6, 6, 6 | 10.1 ± 8.83 | 5.7 ± 5.30 | 10.8 ± 8.06 | 4.0 ± 7.05 |
| PR, Day 8, n=6, 6, 6, 6 | 0.5 ± 3.11 | 1.6 ± 8.20 | 7.1 ± 6.86 | -1.6 ± 2.55 |
| PR, Day 15, n=6, 6, 6, 6 | -0.2 ± 10.22 | 4.9 ± 12.25 | 2.4 ± 3.52 | -5.7 ± 6.04 |
| PR, Day 22, pre-dose, n=6, 6, 6, 6 | 2.7 ± 6.80 | 8.0 ± 14.84 | 1.5 ± 1.59 | -2.9 ± 4.51 |
| PR, Day 22, 1 hour, n=6, 6, 6, 6 | 1.4 ± 4.84 | -3.1 ± 4.22 | 2.2 ± 3.35 | -3.2 ± 7.19 |
| PR, Day 22, 4 hour, n=6, 6, 6, 6 | 6.0 ± 4.01 | 4.3 ± 5.87 | 11.5 ± 10.74 | 2.6 ± 6.63 |
| PR, Day 22, 6 hour, n=6, 6, 6, 6 | 7.2 ± 3.75 | 3.8 ± 1.81 | 8.6 ± 3.98 | 2.4 ± 5.99 |
| PR, Day 22, 8 hour, n=6, 6, 6, 6 | 2.2 ± 6.26 | -1.6 ± 5.59 | 5.7 ± 3.61 | -2.1 ± 5.06 |
| PR, Day 22, 12 hour, n=6, 6, 6, 6 | 6.4 ± 4.03 | 5.4 ± 4.64 | 9.3 ± 4.47 | 7.9 ± 7.02 |
| PR, Day 23, 24 hour, n=6, 6, 6, 6 | 3.6 ± 3.46 | 0.0 ± 4.92 | 4.6 ± 6.63 | 0.7 ± 7.64 |
| PR, Day 24, 48 hour, n=6, 6, 6, 6 | 4.1 ± 2.88 | -1.0 ± 4.85 | 3.6 ± 3.79 | 2.9 ± 9.40 |
| PR, Day 25, 72 hour, n=6, 6, 6, 6 | 8.7 ± 10.05 | 7.1 ± 5.05 | 7.0 ± 4.94 | 4.3 ± 7.77 |
| PR, Day 29, n=6, 6, 6, 6 | 8.4 ± 4.76 | 6.9 ± 8.33 | 5.0 ± 1.14 | -0.6 ± 7.41 |
| PR, Day 36, n=6, 6, 6, 5 | 4.1 ± 6.54 | 5.4 ± 7.51 | 3.8 ± 6.10 | -3.2 ± 13.57 |
| PR, Day 50, n=6, 6, 6, 5 | 9.9 ± 4.85 | 1.1 ± 2.09 | 2.2 ± 6.51 | -7.0 ± 6.34 |
| PR, Day 71, n=6, 6, 6, 5 | 6.1 ± 2.74 | 5.1 ± 7.39 | 6.0 ± 2.04 | -1.9 ± 6.93 |
| PR, Follow-up, n=6, 6, 6, 5 | 6.1 ± 6.79 | 2.7 ± 5.08 | 6.0 ± 4.23 | 2.0 ± 5.71 |
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.
| Breaths per minute | Part 2: Placebo | Part 2: GSK3389404 30 mg | Part 2: GSK3389404 60 mg | Part 2: GSK3389404 120 mg |
|---|---|---|---|---|
| RR, Day 1, 1 hour, n=6, 6, 6, 6 | -0.3 ± 1.97 | 0.7 ± 2.73 | 0.0 ± 1.26 | 0.5 ± 1.97 |
| RR, Day 1, 2 hour, n=6, 6, 6, 6 | -0.3 ± 1.97 | -0.3 ± 2.34 | 0.7 ± 1.63 | 0.5 ± 1.22 |
| RR, Day 1, 4 hour, n=6, 6, 6, 6 | 0.0 ± 3.35 | 1.0 ± 3.52 | -0.7 ± 2.42 | -0.5 ± 0.84 |
| RR, Day 1, 6 hour, n=6, 6, 6, 6 | -0.3 ± 2.66 | 1.3 ± 4.13 | 2.0 ± 2.53 | -0.5 ± 0.84 |
| RR, Day 1, 8 hour, n=6, 6, 6, 6 | -0.7 ± 2.73 | 1.3 ± 3.01 | 0.7 ± 2.42 | 0.8 ± 1.83 |
| RR, Day 1, 12 hour, n=6, 6, 6, 6 | 2.0 ± 3.79 | 1.7 ± 2.66 | 3.3 ± 2.42 | 0.5 ± 2.95 |
| RR, Day 2, 24 hour, n=6, 6, 6, 6 | 0.7 ± 2.42 | 1.0 ± 2.10 | -1.7 ± 1.51 | -0.5 ± 0.84 |
| RR, Day 3, 48 hour, n=6, 6, 6, 6 | -1.0 ± 2.10 | -0.3 ± 2.34 | -1.0 ± 2.76 | -0.8 ± 1.60 |
| RR, Day 4, 72 hour, n=6, 6, 6, 6 | 0.8 ± 2.71 | 1.3 ± 3.67 | 0.3 ± 3.44 | -0.2 ± 1.33 |
| RR, Day 8, n=6, 6, 6, 6 | 1.3 ± 1.63 | -0.3 ± 3.88 | 1.3 ± 3.72 | -0.8 ± 3.13 |
| RR, Day 15, n=6, 6, 6, 6 | 0.7 ± 1.63 | 1.5 ± 1.76 | 0.7 ± 2.42 | -0.8 ± 3.13 |
| RR, Day 22, pre-dose, n=6, 6, 6, 6 | 0.0 ± 1.79 | 0.7 ± 2.42 | -1.0 ± 2.45 | -0.5 ± 1.97 |
| RR, Day 22, 1 hour, n=6, 6, 6, 6 | 0.7 ± 3.27 | 0.3 ± 3.88 | -0.3 ± 3.88 | 0.5 ± 1.52 |
| RR, Day 22, 4 hour, n=6, 6, 6, 6 | -0.7 ± 1.63 | 1.8 ± 4.02 | -1.0 ± 3.74 | 0.8 ± 0.98 |
| RR, Day 22, 6 hour, n=6, 6, 6, 6 | 1.0 ± 2.10 | 2.3 ± 3.88 | 3.0 ± 2.76 | 0.2 ± 2.56 |
| RR, Day 22, 8 hour, n=6, 6, 6, 6 | 1.7 ± 1.97 | 2.7 ± 3.50 | -0.7 ± 2.07 | -0.8 ± 1.83 |
| RR, Day 22, 12 hour, n=6, 6, 6, 6 | 2.3 ± 3.20 | 4.3 ± 3.20 | 1.0 ± 2.10 | -1.5 ± 2.35 |
| RR, Day 23, 24 hour, n=6, 6, 6, 6 | 0.7 ± 3.50 | 1.3 ± 2.73 | -0.3 ± 2.94 | -0.5 ± 0.84 |
| RR, Day 24, 48 hour, n=6, 6, 6, 6 | 1.0 ± 3.03 | 1.7 ± 2.94 | -0.3 ± 2.66 | -0.5 ± 2.66 |
| RR, Day 25, 72 hour, n=6, 6, 6, 6 | 1.0 ± 2.76 | 2.7 ± 2.42 | -0.7 ± 3.01 | -1.5 ± 1.22 |
| RR, Day 29, n=6, 6, 6, 6 | 0.7 ± 1.63 | 1.3 ± 2.73 | -1.0 ± 1.67 | -0.2 ± 1.33 |
| RR, Day 36, n=6, 6, 6, 5 | 0.0 ± 3.10 | 0.7 ± 3.27 | 0.0 ± 3.35 | -1.0 ± 1.73 |
| RR, Day 50, n=6, 6, 6, 5 | 0.5 ± 3.56 | 1.0 ± 3.74 | -0.7 ± 3.27 | -0.2 ± 1.48 |
| RR, Day 71, n=6, 6, 6, 5 | 0.2 ± 2.40 | 1.3 ± 1.03 | 0.0 ± 4.00 | 0.6 ± 1.34 |
| RR, Follow-up, n=6, 6, 6, 5 | -1.7 ± 1.51 | -1.0 ± 1.67 | -0.7 ± 3.50 | 0.6 ± 2.61 |
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.
| Degree Celsius | Part 2: Placebo | Part 2: GSK3389404 30 mg | Part 2: GSK3389404 60 mg | Part 2: GSK3389404 120 mg |
|---|---|---|---|---|
| Temperature, Day 1, 1 hour, n=6, 6, 6, 6 | 0.27 ± 0.388 | 0.15 ± 0.288 | -0.05 ± 0.176 | 0.02 ± 0.440 |
| Temperature, Day 1, 2 hour, n=6, 6, 6, 6 | 0.20 ± 0.167 | -0.02 ± 0.256 | 0.05 ± 0.187 | -0.02 ± 0.240 |
| Temperature, Day 1, 4 hour, n=6, 6, 6, 6 | 0.40 ± 0.110 | 0.35 ± 0.308 | 0.02 ± 0.117 | 0.15 ± 0.432 |
| Temperature, Day 1, 6 hour, n=6, 6, 6, 6 | 0.28 ± 0.325 | 0.38 ± 0.454 | 0.10 ± 0.237 | 0.20 ± 0.358 |
| Temperature, Day 1, 8 hour, n=6, 6, 6, 6 | 0.20 ± 0.228 | 0.43 ± 0.408 | -0.13 ± 0.320 | 0.33 ± 0.557 |
| Temperature, Day 1, 12 hour, n=6, 6, 6, 6 | 0.22 ± 0.147 | 0.50 ± 0.369 | -0.15 ± 0.295 | 0.20 ± 0.390 |
| Temperature, Day 2, 24 hour, n=6, 6, 6, 6 | 0.05 ± 0.321 | -0.10 ± 0.379 | -0.18 ± 0.223 | -0.15 ± 0.138 |
| Temperature, Day 3, 48 hour, n=6, 6, 6, 6 | 0.05 ± 0.442 | 0.15 ± 0.489 | -0.22 ± 0.204 | -0.32 ± 0.313 |
| Temperature, Day 4, 72 hour, n=6, 6, 6, 6 | -0.05 ± 0.362 | 0.28 ± 0.595 | 0.30 ± 0.210 | -0.02 ± 0.417 |
| Temperature, Day 8, n=6, 6, 6, 6 | 0.02 ± 0.436 | 0.05 ± 0.235 | 0.10 ± 0.283 | -0.20 ± 0.424 |
| Temperature, Day 15, n=6, 6, 6, 6 | -0.23 ± 0.446 | 0.08 ± 0.376 | -0.05 ± 0.197 | -0.12 ± 0.366 |
| Temperature, Day 22, pre-dose, n=6, 6, 6, 6 | 0.08 ± 0.488 | -0.02 ± 0.331 | -0.22 ± 0.183 | -0.23 ± 0.082 |
| Temperature, Day 22, 1 hour, n=6, 6, 6, 6 | 0.15 ± 0.266 | -0.15 ± 0.315 | -0.07 ± 0.175 | -0.20 ± 0.303 |
| Temperature, Day 22, 4 hour, n=6, 6, 6, 6 | 0.38 ± 0.422 | 0.13 ± 0.513 | 0.07 ± 0.242 | -0.18 ± 0.366 |
| Temperature, Day 22, 6 hour, n=6, 6, 6, 6 | 0.22 ± 0.306 | 0.28 ± 0.248 | 0.17 ± 0.163 | -0.02 ± 0.293 |
| Temperature, Day 22, 8 hour, n=6, 6, 6, 6 | 0.25 ± 0.217 | 0.23 ± 0.367 | -0.05 ± 0.243 | -0.02 ± 0.214 |
| Temperature, Day 22, 12 hour, n=6, 6, 6, 6 | 0.22 ± 0.366 | 0.08 ± 0.299 | 0.27 ± 0.344 | 0.22 ± 0.147 |
| Temperature, Day 23, 24 hour, n=6, 6, 6, 6 | 0.18 ± 0.366 | 0.15 ± 0.536 | -0.13 ± 0.216 | -0.12 ± 0.279 |
| Temperature, Day 24, 48 hour, n=6, 6, 6, 6 | 0.12 ± 0.417 | 0.00 ± 0.352 | -0.08 ± 0.098 | -0.13 ± 0.432 |
| Temperature, Day 25, 72 hour, n=6, 6, 6, 6 | 0.10 ± 0.276 | 0.20 ± 0.562 | 0.12 ± 0.445 | -0.20 ± 0.276 |
| Temperature, Day 29, n=6, 6, 6, 6 | -0.38 ± 0.366 | -0.05 ± 0.187 | -0.15 ± 0.266 | -0.23 ± 0.250 |
| Temperature, Day 36, n=6, 6, 6, 5 | 0.22 ± 0.271 | 0.03 ± 0.350 | -0.20 ± 0.385 | -0.16 ± 0.378 |
| Temperature, Day 50, n=6, 6, 6, 5 | 0.02 ± 0.325 | -0.07 ± 0.480 | -0.37 ± 0.121 | 0.04 ± 0.416 |
| Temperature, Day 71, n=6, 6, 6, 5 | -0.18 ± 0.286 | -0.13 ± 0.378 | -0.53 ± 0.280 | -0.34 ± 0.305 |
| Temperature, Follow-up, n=6, 6, 6, 5 | -0.18 ± 0.479 | 0.08 ± 0.397 | -0.12 ± 0.293 | -0.02 ± 0.259 |
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.
| Participants | Part 1: Placebo | Part 1: GSK3389404 10 mg | Part 1: GSK3389404 30 mg | Part 1: GSK3389404 60 mg | Part 1: GSK3389404 120 mg |
|---|---|---|---|---|---|
| CS | 0 | 0 | 0 | 0 | 0 |
| NCS | 2 | 0 | 1 | 1 | 3 |
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.
| Nanogram*hour per milliliter(ng*hour/mL) | Part 1: GSK3389404 10 mg | Part 1: GSK3389404 30 mg | Part 1: GSK3389404 60 mg | Part 1: GSK3389404 120 mg |
|---|---|---|---|---|
| AUC (0-inf) | 632 ± 171.59 | 2080 ± 801.85 | 4750 ± 1450.8 | 8150 ± 3204.5 |
| AUC (0-t) | 484 ± 80.962 | 1770 ± 961.03 | 3710 ± 1485.6 | 7440 ± 2844.8 |
| AUC (0-24) | 592 ± 105.91 | 1970 ± 855.08 | 4330 ± 1313.5 | 7950 ± 3264.9 |
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.
| ng/mL | Part 1: GSK3389404 10 mg | Part 1: GSK3389404 30 mg | Part 1: GSK3389404 60 mg | Part 1: GSK3389404 120 mg |
|---|---|---|---|---|
| Cmax | 92.5 ± 23.622 | 350 ± 257.48 | 584 ± 366.96 | 889 ± 496.73 |
| C24 | 0.00 ± 0.0000 | 0.00 ± 0.0000 | 3.33 ± 8.1650 | 18.7 ± 17.781 |
| C168 | 0.00 ± 0.0000 | 0.00 ± 0.0000 | 0.00 ± 0.0000 | 0.00 ± 0.0000 |
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.
| Hour | Part 1: GSK3389404 10 mg | Part 1: GSK3389404 30 mg | Part 1: GSK3389404 60 mg | Part 1: GSK3389404 120 mg |
|---|---|---|---|---|
| Tmax | 1.60 ± 1.20 | 1.74 ± 0.48 | 2.67 ± 1.37 | 3.83 ± 0.41 |
| T1/2 | 4.55 ± 3.3937 | 4.67 ± 3.5530 | 6.07 ± 3.9531 | 4.27 ± 1.2281 |
| Tlag | 0.00 ± 0.00 | 0.00 ± 0.00 | 0.00 ± 0.00 | 0.00 ± 0.00 |
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.
| Liter per hour | Part 1: GSK3389404 10 mg | Part 1: GSK3389404 30 mg | Part 1: GSK3389404 60 mg | Part 1: GSK3389404 120 mg |
|---|---|---|---|---|
| Apparent SC Plasma Clearance (CL/F) of GSK3389404 Following Single Dose in Part 1 | 16.8 ± 4.2805 | 15.8 ± 4.6710 | 13.6 ± 3.6934 | 16.2 ± 4.7050 |
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.
| ng*hour/mL | Part 2: GSK3389404 30 mg | Part 2: GSK3389404 60 mg | Part 2: GSK3389404 120 mg |
|---|---|---|---|
| AUC (0-t), n=6, 6, 6 | 1300 ± 286.51 | 4150 ± 1103.1 | 7970 ± 3082.7 |
| AUC (0-24), n=6, 5, 6 | 1410 ± 292.51 | 4940 ± 1131.6 | 8330 ± 3363.3 |
| AUC (0-168), n=6, 5, 6 | 1420 ± 291.72 | 5080 ± 1332.6 | 8480 ± 3249.8 |
| AUC (0-inf), n=6, 5, 6 | 1420 ± 291.72 | 5080 ± 1328.9 | 8480 ± 3249.8 |
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.
| ng/mL | Part 2: GSK3389404 30 mg | Part 2: GSK3389404 60 mg | Part 2: GSK3389404 120 mg |
|---|---|---|---|
| Cmax | 236 ± 64.551 | 723 ± 216.01 | 1280 ± 633.56 |
| C24 | 0.00 ± 0.0000 | 2.58 ± 6.3278 | 16.7 ± 20.848 |
| C168 | 0.00 ± 0.0000 | 0.00 ± 0.0000 | 0.00 ± 0.0000 |
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.
| Hour | Part 2: GSK3389404 30 mg | Part 2: GSK3389404 60 mg | Part 2: GSK3389404 120 mg |
|---|---|---|---|
| Tmax, n=6, 6, 6 | 2.33 ± 1.03 | 2.01 ± 0.02 | 2.42 ± 0.92 |
| T1/2, n=6, 5, 6 | 3.14 ± 1.0621 | 3.47 ± 1.8907 | 4.04 ± 1.7867 |
| Tlag, n=6, 6, 6 | 0.00 ± 0.00 | 0.00 ± 0.00 | 0.00 ± 0.00 |
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.
| Liter per hour | Part 2: GSK3389404 30 mg | Part 2: GSK3389404 60 mg | Part 2: GSK3389404 120 mg |
|---|---|---|---|
| CL/F of GSK3389404 Following Single Dose on Day 1 of Part 2 | 22.1 ± 5.9872 | 12.5 ± 3.4120 | 15.6 ± 4.7861 |
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 ).
| ng*hour/mL | Part 2: GSK3389404 30 mg | Part 2: GSK3389404 60 mg | Part 2: GSK3389404 120 mg |
|---|---|---|---|
| AUC (0-24) | 1486 ± 364.92 | 3973 ± 906.81 | 8918 ± 3447.7 |
| AUC (0-tau) | 1598 ± 565.02 | 4052 ± 873.65 | 9047 ± 3361.3 |
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 ).
| ng/mL | Part 2: GSK3389404 30 mg | Part 2: GSK3389404 60 mg | Part 2: GSK3389404 120 mg |
|---|---|---|---|
| Ctau | 0.000 ± 0.000 | 0.000 ± 0.000 | 0.000 ± 0.000 |
| C24 | 0.000 ± 0.0000 | 4.767 ± 7.4115 | 15.60 ± 18.278 |
| Cmax | 197.7 ± 39.657 | 614.8 ± 211.25 | 1257 ± 799.88 |
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).
| Hour | Part 2: GSK3389404 30 mg | Part 2: GSK3389404 60 mg | Part 2: GSK3389404 120 mg |
|---|---|---|---|
| Tmax | 2.17 ± 0.98 | 2.26 ± 0.88 | 2.67 ± 1.03 |
| T1/2 | 4.768 ± 3.2072 | 3.450 ± 1.6049 | 3.585 ± 1.2332 |
| Tlag | 0.00 ± 0.00 | 0.00 ± 0.00 | 0.00 ± 0.00 |
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).
| Liter per hour | Part 2: GSK3389404 30 mg | Part 2: GSK3389404 60 mg | Part 2: GSK3389404 120 mg |
|---|---|---|---|
| Cl/F of GSK3389404 Following Dosing on Day 22 of Part 2 | 20.50 ± 6.3906 | 15.48 ± 3.6973 | 14.39 ± 3.7029 |
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.
| ratio | GSK3389404 10-120 mg |
|---|---|
| AUC (0-24), n=40 | 1.08 (0.98 to 1.18) |
| AUC (0-inf), n=40 | 1.07 (0.97 to 1.18) |
| Cmax, n=41 | 0.975 (0.83 to 1.12) |
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.
| ratio | GSK3389404 30-120 mg |
|---|---|
| AUC (0-tau) | 1.25 (1.04 to 1.46) |
| Cmax | 1.25 (0.96 to 1.55) |
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.
| Ratio | Part 2: GSK3389404 30 mg | Part 2: GSK3389404 60 mg | Part 2: GSK3389404 120 mg |
|---|---|---|---|
| RAUC, n=6, 5, 6 | 1.115 ± 0.24879 | 0.8596 ± 0.099034 | 1.094 ± 0.24035 |
| RCmax, n=6, 6, 6 | 0.8683 ± 0.16676 | 0.8518 ± 0.18537 | 0.9920 ± 0.32054 |
| RC24, n=0, 1, 3 | — | 0.8580 ± NA | 0.5890 ± 0.51139 |
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.
| Ratio | Part 2: GSK3389404 30 mg | Part 2: GSK3389404 60 mg | Part 2: GSK3389404 120 mg |
|---|---|---|---|
| Time Invariance (LI) of GSK3389404 in Part 2 | 1.115 ± 0.24879 | 0.8598 ± 0.098644 | 1.094 ± 0.24035 |
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.
| Ratio | Part 2: GSK3389404 30 mg | Part 2: GSK3389404 60 mg | Part 2: GSK3389404 120 mg |
|---|---|---|---|
| Day 8 | NA ± NA | NA ± NA | NA ± NA |
| Day 15 | NA ± NA | NA ± NA | NA ± NA |
| Day 22 | NA ± NA | NA ± NA | NA ± NA |
| Day 29 | NA ± NA | NA ± NA | NA ± NA |
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.
No measurements were reported for this outcome.
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.
No measurements were reported for this outcome.
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.
No measurements were reported for this outcome.
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.
No measurements were reported for this outcome.
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.
No measurements were reported for this outcome.
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.
No measurements were reported for this outcome.
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).
No measurements were reported for this outcome.
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).
No measurements were reported for this outcome.
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).
No measurements were reported for this outcome.
Collected over On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment up to 62 days in Part 1 and up to 115 days in Part 2.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Part 1: Placebo | 0/8 (0%) | 0/8 (0%) | 4/8 (50%) |
| Part 1: GSK3389404 10 mg | 0/6 (0%) | 0/6 (0%) | 3/6 (50%) |
| Part 1: GSK3389404 30 mg | 0/6 (0%) | 0/6 (0%) | 2/6 (33.3%) |
| Part 1: GSK3389404 60 mg | 0/6 (0%) | 0/6 (0%) | 3/6 (50%) |
| Part 1: GSK3389404 120 mg | 0/6 (0%) | 0/6 (0%) | 5/6 (83.3%) |
| Part 2: Placebo | 0/6 (0%) | 0/6 (0%) | 3/6 (50%) |
| Part 2: GSK3389404 30 mg | 0/6 (0%) | 0/6 (0%) | 5/6 (83.3%) |
| Part 2: GSK3389404 60 mg | 0/6 (0%) | 0/6 (0%) | 2/6 (33.3%) |
| Part 2: GSK3389404 120 mg | 0/6 (0%) | 0/6 (0%) | 4/6 (66.7%) |
| Event | 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 | Part 2: GSK3389404 120 mg |
|---|---|---|---|---|---|---|---|---|---|
| Viral upper respiratory tract infectionInfections and infestations | 1/8 | 3/6 | 0/6 | 1/6 | 1/6 | 0/6 | 0/6 | 0/6 | 0/6 |
| NasopharyngitisInfections and infestations | 0/8 | 0/6 | 0/6 | 0/6 | 0/6 | 1/6 | 1/6 | 0/6 | 3/6 |
| Injection site bruisingGeneral disorders | 0/8 | 0/6 | 0/6 | 0/6 | 2/6 | 0/6 | 0/6 | 0/6 | 0/6 |
| Injection site erythemaGeneral disorders | 0/8 | 0/6 | 0/6 | 0/6 | 2/6 | 1/6 | 2/6 | 0/6 | 2/6 |
| HeadacheNervous system disorders | 0/8 | 0/6 | 2/6 | 1/6 | 1/6 | 0/6 | 2/6 | 2/6 | 1/6 |
| Eyelid irritationEye disorders | 0/8 | 0/6 | 0/6 | 1/6 | 0/6 | 0/6 | 0/6 | 0/6 | 0/6 |
| Catheter site haematomaGeneral disorders | 0/8 | 0/6 | 0/6 | 1/6 | 0/6 | 0/6 | 0/6 | 0/6 | 0/6 |
| Injection site painGeneral disorders | 1/8 | 0/6 | 0/6 | 0/6 | 0/6 | 0/6 | 0/6 | 0/6 | 1/6 |
| Oral herpesInfections and infestations | 0/8 | 0/6 | 0/6 | 1/6 | 0/6 | 0/6 | 0/6 | 0/6 | 0/6 |
| Alanine aminotransferase increasedInvestigations | 0/8 | 0/6 | 0/6 | 0/6 | 1/6 | 0/6 | 0/6 | 0/6 | 0/6 |
| Age, Continuous(Years) | 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 | Part 2: GSK3389404 120 mg | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Mean | 28.1 ± 8.22 | 27.5 ± 3.78 | 37.5 ± 12.44 | 32.8 ± 7.41 | 37.8 ± 13.41 | — | — | — | — | 32.5 ± 10.03 |
| Age, Continuous(Years) | 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 | Part 2: GSK3389404 120 mg | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Mean | — | — | — | — | — | 38.0 ± 11.78 | 32.2 ± 6.91 | 40.5 ± 11.13 | 38.5 ± 12.23 | 37.3 ± 10.49 |
| Sex: Female, Male(Participants) | 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 | Part 2: GSK3389404 120 mg | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Female | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 2 |
| Male | 8 | 6 | 6 | 6 | 6 | 6 | 6 | 4 | 6 | 54 |
| Race/Ethnicity, Customized(Participants) | 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 | Part 2: GSK3389404 120 mg | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Race/Ethnicity, Customized — Asian-South East Asian heritage | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 2 |
| Race/Ethnicity, Customized — African American/African heritage | 0 | 3 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 4 |
| Race/Ethnicity, Customized — White-White/Caucasian/European heritage | 8 | 3 | 4 | 6 | 6 | 4 | 5 | 3 | 6 | 45 |
| Race/Ethnicity, Customized — Asian-Central/South Asian heritage | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 0 | 3 |
| Race/Ethnicity, Customized — Caribbean | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 |
| Race/Ethnicity, Customized — Caribbean British | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 |
Plan to share: Yes — IPD for this study will be made available via the Clinical Study Data Request site.
Supporting information: Study protocol, Sap, Icf, Csr
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