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| ID | Type | Description | Link |
|---|---|---|---|
| 2015-003781-84 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1: GSK3389404 10 mg | Experimental | Subjects will receive a single dose of GSK3389404 10 mg by subcutaneous injection on Day 1 of Part 1. |
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| Part 1: Placebo | Placebo Comparator | 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. |
|
| Part 1: GSK3389404 30 mg | Experimental | Subjects will receive a single dose of GSK3389404 30 mg by subcutaneous injection on Day 1 of Part 1. |
|
| Part 1: GSK3389404 60 mg | Experimental | Subjects will receive a single dose of GSK3389404 60 mg by subcutaneous injection on Day 1 of Part 1. |
|
| Part 1: GSK3389404 120 mg | Experimental | Subjects will receive a single dose of GSK3389404 120 mg by subcutaneous injection on Day 1 of Part 1. |
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| Part 2: GSK3389404 30 mg |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GSK3389404 | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. |
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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:
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:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | London | NW10 7EW | United Kingdom | |||
| GSK Investigational Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30861337 | Background | Han K, Cremer J, Elston R, Oliver S, Baptiste-Brown S, Chen S, Gardiner D, Davies M, Saunders J, Hamatake R, Losos J, Leivers M, Hood S, van der Berg F, Paff M, Ritter JM, Theodore D. A Randomized, Double-Blind, Placebo-Controlled, First-Time-in-Human Study to Assess the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses of GSK3389404 in Healthy Subjects. Clin Pharmacol Drug Dev. 2019 Aug;8(6):790-801. doi: 10.1002/cpdd.670. Epub 2019 Mar 12. |
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IPD for this study will be made available via the Clinical Study Data Request site.
IPD is available via the Clinical Study Data Request site (click on the link provided below)
Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
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.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | Part 1: GSK3389404 10 mg | Participants received a single dose of GSK3389404 10 mg by subcutaneous injection on Day 1 of Part 1. |
| FG002 | Part 1: GSK3389404 30 mg | Participants received a single dose of GSK3389404 30 mg by subcutaneous injection on Day 1 of Part 1. |
| FG003 | Part 1: GSK3389404 60 mg | Participants received a single dose of GSK3389404 60 mg by subcutaneous injection on Day 1 of Part 1. |
| FG004 | Part 1: GSK3389404 120 mg | Participants received a single dose of GSK3389404 120 mg by subcutaneous injection on Day 1 of Part 1. |
| FG005 | 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. |
| FG006 | Part 2: GSK3389404 30 mg | Participants received a single dose of GSK3389404 30 mg by subcutaneous injection QW for 4 weeks in Part 2. |
| FG007 | Part 2: GSK3389404 60 mg | Participants received a single dose of GSK3389404 60 mg by subcutaneous injection QW for 4 weeks in Part 2. |
| FG008 | Part 2: GSK3389404 120 mg | Participants received a single dose of GSK3389404 120 mg by subcutaneous injection QW for 4 weeks in Part 2. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Single-Ascending Dose(Part 1-62 Days) |
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| Multiple-Ascending Dose(Part 2-115 Days) |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | Part 1: GSK3389404 10 mg |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Data for Part 1 is presented. |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Safety Population | Posted | Count of Participants | Participants | Up to 62 days |
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.
On treatment SAEs and non-serious AEs were reported for the Safety Population.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Eyelid irritation | Eye disorders | MedDRA 18.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 |
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| ID | Term |
|---|---|
| D006509 | Hepatitis B |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D018347 | Hepadnaviridae Infections |
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| Experimental |
Subjects will receive a single dose of GSK3389404 30 mg by subcutaneous injection QW for 4 weeks in Part 2. |
|
| Part 2: Placebo | Placebo Comparator | 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. |
|
| Part 2: GSK3389404 60 mg | Experimental | Subjects will receive a single dose of GSK3389404 60 mg by subcutaneous injection QW for 4 weeks in Part 2. |
|
| Part 2: GSK3389404 120 mg | Experimental | Subjects will receive a single dose of GSK3389404 120 mg by subcutaneous injection QW for 4 weeks in Part 2. |
|
| Matching Placebo | Drug | Placebo is supplied as solution for injection vial. It's physical appearance is clear colourless solution. |
|
| 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. | 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. | 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. | 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 | 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 | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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 ). | 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 ). | 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). | 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). | 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 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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). | 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). | 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). | 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) |
| London |
| SE1 1YR |
| United Kingdom |
| COMPLETED |
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| NOT COMPLETED |
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Participants received a single dose of GSK3389404 10 mg by subcutaneous injection on Day 1 of Part 1.
| BG002 | Part 1: GSK3389404 30 mg | Participants received a single dose of GSK3389404 30 mg by subcutaneous injection on Day 1 of Part 1. |
| BG003 | Part 1: GSK3389404 60 mg | Participants received a single dose of GSK3389404 60 mg by subcutaneous injection on Day 1 of Part 1. |
| BG004 | Part 1: GSK3389404 120 mg | Participants received a single dose of GSK3389404 120 mg by subcutaneous injection on Day 1 of Part 1. |
| BG005 | 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. |
| BG006 | Part 2: GSK3389404 30 mg | Participants received a single dose of GSK3389404 30 mg by subcutaneous injection QW for 4 weeks in Part 2. |
| BG007 | Part 2: GSK3389404 60 mg | Participants received a single dose of GSK3389404 60 mg by subcutaneous injection QW for 4 weeks in Part 2. |
| BG008 | Part 2: GSK3389404 120 mg | Participants received a single dose of GSK3389404 120 mg by subcutaneous injection QW for 4 weeks in Part 2. |
| BG009 | Total | Total of all reporting groups |
N=32 for Part 1
| Mean |
| Standard Deviation |
| Years |
|
| Age, Continuous | Data for Part 2 is presented. | N=24 for Part 2 | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| ID |
|---|
| Title |
|---|
| Description |
|---|
| OG000 | 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. |
| OG001 | Part 1: GSK3389404 10 mg | Participants received a single dose of GSK3389404 10 mg by subcutaneous injection on Day 1 of Part 1. |
| OG002 | Part 1: GSK3389404 30 mg | Participants received a single dose of GSK3389404 30 mg by subcutaneous injection on Day 1 of Part 1. |
| OG003 | Part 1: GSK3389404 60 mg | Participants received a single dose of GSK3389404 60 mg by subcutaneous injection on Day 1 of Part 1. |
| OG004 | Part 1: GSK3389404 120 mg | Participants received a single dose of GSK3389404 120 mg by subcutaneous injection on Day 1 of Part 1. |
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| 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. | Safety Population | Posted | Count of Participants | Participants | Up to 115 days |
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| 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. | Safety Population | Posted | Count of Participants | Participants | Up to 62 days |
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| 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. | Safety Population | Posted | Count of Participants | Participants | Up to 115 days |
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| 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. | Safety Population | Posted | Mean | Standard Deviation | Gram per liter (g/L) | Day 1 (pre-dose) and up to 31 days |
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| 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. | Safety Population | Posted | Mean | Standard Deviation | Microgram per liter (ug/L) | Day 1 (pre-dose) and up to 31 days |
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| 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 | Safety Population | Posted | Mean | Standard Deviation | mg per liter (mg/L) | Day 1 (pre-dose) and up to 31 days |
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| 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 | Safety Population | Posted | Mean | Standard Deviation | G/L | Day 1 (pre-dose) and Day 22 |
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| 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. | Safety Population | Posted | Mean | Standard Deviation | ug/L | Day 1 (pre-dose) and Day 22 |
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| 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. | Safety Population | Posted | Mean | Standard Deviation | mg/L | Day 1 (pre-dose) and Day 22 |
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| 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. | Safety Population | Posted | Mean | Standard Deviation | Millimeter of mercury (mmHg) | Day 1 (pre-dose) and up to 30 days |
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| 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. | Safety Population | Posted | Mean | Standard Deviation | Beats per minute (bpm) | Day 1 (pre-dose) and up to 30 days |
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| 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. | Safety Population. Only data available at the specified time points was analyzed. (represented by n=X in the category titles). | Posted | Mean | Standard Deviation | Breaths per minute | Day 1 (pre-dose) and up to 30 days |
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| 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. | Safety Population | Posted | Mean | Standard Deviation | Degree Celsius | Day 1 (pre-dose) and up to 30 days |
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| 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. | Safety Population. Only data available at the specified time points was analyzed. (represented by n=X in the category titles). | Posted | Mean | Standard Deviation | mmHg | Day 1 (pre-dose) and up to 115 days |
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| 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. | Safety Population. Only data available at the specified time points was analyzed. (represented by n=X in the category titles). | Posted | Mean | Standard Deviation | bpm | Day 1 (pre-dose) and up to 115 days |
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| 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. | Safety Population. Only data available at the specified time points was analyzed. (represented by n=X in the category titles). | Posted | Mean | Standard Deviation | Breaths per minute | Day 1 (pre-dose) and up to 115 days |
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| 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. | Safety Population. Only data available at the specified time points was analyzed. (represented by n=X in the category titles). | Posted | Mean | Standard Deviation | Degree Celsius | Day 1 (pre-dose) and up to 115 days |
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| 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. | Safety Population | Posted | Count of Participants | Participants | Day 1 (pre-dose) and up to 31 days |
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| 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. | Pharmacokinetic Concentration Population | Posted | Mean | Standard Deviation | Nanogram*hour per milliliter(ng*hour/mL) | 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 |
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| 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. | Pharmacokinetic Concentration Population | Posted | Mean | Standard Deviation | ng/mL | 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 |
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| 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. | Pharmacokinetic Concentration Population | Posted | Mean | Standard Deviation | Hour | 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 |
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| 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. | Pharmacokinetic Concentration Population | Posted | Mean | Standard Deviation | Liter per hour | 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 |
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| 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. | Pharmacokinetic Concentration Population. Only data available at the specified time points was analyzed. (represented by n=X in the category titles). | Posted | Mean | Standard Deviation | ng*hour/mL | 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 |
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| 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. | Pharmacokinetic Concentration Population | Posted | Mean | Standard Deviation | ng/mL | 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 |
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| 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. | Pharmacokinetic Concentration Population. Only data available at the specified time points was analyzed. (represented by n=X in the category titles). | Posted | Mean | Standard Deviation | Hour | 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 |
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| 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. | Pharmacokinetic Concentration Population | Posted | Mean | Standard Deviation | Liter per hour | 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 |
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| 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 ). | Pharmacokinetic Concentration Population | Posted | Mean | Standard Deviation | ng*hour/mL | 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) |
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| 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 ). | Pharmacokinetic Concentration Population | Posted | Mean | Standard Deviation | ng/mL | 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) |
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| 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). | Pharmacokinetic Concentration Population | Posted | Mean | Standard Deviation | Hour | 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) |
|
|
|
| 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). | Pharmacokinetic Concentration Population | Posted | Mean | Standard Deviation | Liter per hour | 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) |
|
|
|
| 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. | 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). | Posted | Number | 90% Confidence Interval | ratio | 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. |
|
|
|
| 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. | Pharmacokinetic Concentration Population | Posted | Number | 90% Confidence Interval | ratio | 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 |
|
|
|
| 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. | Pharmacokinetic Concentration Population. Only data available at the specified time points was analyzed. (represented by n=X in the category titles). | Posted | Mean | Standard Deviation | Ratio | 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) |
|
|
|
| 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. | Pharmacokinetic Concentration Population | Posted | Mean | Standard Deviation | Ratio | 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) |
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|
|
| 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. | Pharmacokinetic Concentration Population | Posted | Mean | Standard Deviation | Ratio | Pre-dose on Days 8, 15, 22 and 29 |
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|
| 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. | 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. | Posted | 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 |
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|
| 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. | 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. | Posted | 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 |
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| 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. | 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. | Posted | 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 |
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|
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| 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. | 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. | Posted | 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 |
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|
| 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. | 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. | Posted | 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 |
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|
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| 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. | 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. | Posted | 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 |
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|
| 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). | 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. | Posted | 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) |
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|
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| 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). | 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. | Posted | 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) |
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| 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). | 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. | Posted | 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) |
|
|
|
| 0 |
| 8 |
| 0 |
| 8 |
| 4 |
| 8 |
| EG001 | Part 1: GSK3389404 10 mg | Participants received a single dose of GSK3389404 10 mg by subcutaneous injection on Day 1 of Part 1. | 0 | 6 | 0 | 6 | 3 | 6 |
| EG002 | Part 1: GSK3389404 30 mg | Participants received a single dose of GSK3389404 30 mg by subcutaneous injection on Day 1 of Part 1. | 0 | 6 | 0 | 6 | 2 | 6 |
| EG003 | Part 1: GSK3389404 60 mg | Participants received a single dose of GSK3389404 60 mg by subcutaneous injection on Day 1 of Part 1. | 0 | 6 | 0 | 6 | 3 | 6 |
| EG004 | Part 1: GSK3389404 120 mg | Participants received a single dose of GSK3389404 120 mg by subcutaneous injection on Day 1 of Part 1. | 0 | 6 | 0 | 6 | 5 | 6 |
| EG005 | 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. | 0 | 6 | 0 | 6 | 3 | 6 |
| EG006 | Part 2: GSK3389404 30 mg | Participants received a single dose of GSK3389404 30 mg by subcutaneous injection QW for 4 weeks in Part 2. | 0 | 6 | 0 | 6 | 5 | 6 |
| EG007 | Part 2: GSK3389404 60 mg | Participants received a single dose of GSK3389404 60 mg by subcutaneous injection QW for 4 weeks in Part 2. | 0 | 6 | 0 | 6 | 2 | 6 |
| EG008 | Part 2: GSK3389404 120 mg | Participants received a single dose of GSK3389404 120 mg by subcutaneous injection QW for 4 weeks in Part 2. | 0 | 6 | 0 | 6 | 4 | 6 |
| Catheter site haematoma | General disorders | MedDRA 18.1 | Systematic Assessment |
|
| Injection site bruising | General disorders | MedDRA 18.1 | Systematic Assessment |
|
| Injection site erythema | General disorders | MedDRA 18.1 | Systematic Assessment |
|
| Injection site pain | General disorders | MedDRA 18.1 | Systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA 18.1 | Systematic Assessment |
|
| Oral herpes | Infections and infestations | MedDRA 18.1 | Systematic Assessment |
|
| Viral upper respiratory tract infection | Infections and infestations | MedDRA 18.1 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA 18.1 | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA 18.1 | Systematic Assessment |
|
| Blood creatine phosphokinase increased | Investigations | MedDRA 18.1 | Systematic Assessment |
|
| Hepatic enzyme increased | Investigations | MedDRA 18.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 18.1 | Systematic Assessment |
|
| Presyncope | Nervous system disorders | MedDRA 18.1 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA 18.1 | Systematic Assessment |
|
| Abdominal tenderness | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Food poisoning | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Injection site discomfort | General disorders | MedDRA 18.1 | Systematic Assessment |
|
| Injection site pruritus | General disorders | MedDRA 18.1 | Systematic Assessment |
|
| Injection site swelling | General disorders | MedDRA 18.1 | Systematic Assessment |
|
| Herpes virus infection | Infections and infestations | MedDRA 18.1 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 18.1 | Systematic Assessment |
|
| Foot fracture | Injury, poisoning and procedural complications | MedDRA 18.1 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 18.1 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 18.1 | Systematic Assessment |
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| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 18.1 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 18.1 | Systematic Assessment |
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| Somnolence | Nervous system disorders | MedDRA 18.1 | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 18.1 | Systematic Assessment |
|
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
| D004266 |
| DNA Virus Infections |
| D014777 | Virus Diseases |
| D006525 | Hepatitis, Viral, Human |
| D006505 | Hepatitis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| Male |
|
| African American/African heritage |
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| White-White/Caucasian/European heritage |
|
| Asian-Central/South Asian heritage |
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| Caribbean |
|
| Caribbean British |
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| Any SAE |
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| AELD |
|
| C4 |
|
| C3, Day 22 |
|
| C4, Day 1 |
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| C4, Day 22 |
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| C5a, Day 22 |
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| Bb, Day 22 |
|
| DBP, 2 hour |
|
| DBP, 4 hour |
|
| DBP, 8 hour |
|
| DBP, 12 hour |
|
| DBP, 24 hour |
|
| DBP, 48 hour |
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| DBP, 72 hour |
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| DBP, Day 8 |
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| DBP, Day 30 |
|
| SBP, 1 hour |
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| SBP, 2 hour |
|
| SBP, 4 hour |
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| SBP, 8 hour |
|
| SBP, 12 hour |
|
| SBP, 24 hour |
|
| SBP, 48 hour |
|
| SBP, 72 hour |
|
| SBP, Day 8 |
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| SBP, Day 30 |
|
| PR, 2 hour |
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| PR, 4 hour |
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| PR, 8 hour |
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| PR, 12 hour |
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| PR, 24 hour |
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| PR, 48 hour |
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| PR, 72 hour |
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| PR, Day 8 |
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| PR, Day 30 |
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|
| RR, 2 hour, n=8, 6, 6, 6, 6 |
|
|
| RR, 4 hour, n=8, 6, 6, 5, 6 |
|
|
| RR, 8 hour, n=8, 6, 6, 6, 6 |
|
|
| RR, 12 hour, n=8, 6, 6, 6, 6 |
|
|
| RR, 24 hour, n=8, 6, 6, 6, 6 |
|
|
| RR, 48 hour, n=8, 6, 6, 6, 6 |
|
|
| RR, 72 hour, n=8, 6, 6, 6, 6 |
|
|
| RR, Day 8, n=8, 6, 6, 6, 6 |
|
|
| RR, Day 30, n=8, 6, 6, 6, 6 |
|
|
| Temperature, 2 hour |
|
| Temperature, 4 hour |
|
| Temperature, 8 hour |
|
| Temperature, 12 hour |
|
| Temperature, 24 hour |
|
| Temperature, 48 hour |
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| Temperature, 72 hour |
|
| Temperature, Day 8 |
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| Temperature, Day 30 |
|
|
| DBP, Day 1, 2 hour, n=6, 6, 6, 6 |
|
|
| DBP, Day 1, 4 hour, n=6, 6, 6, 6 |
|
|
| DBP, Day 1, 6 hour, n=6, 6, 6, 6 |
|
|
| DBP, Day 1, 8 hour, n=6, 6, 6, 6 |
|
|
| DBP, Day 1, 12 hour, n=6, 6, 6, 6 |
|
|
| DBP, Day 2, 24 hour, n=6, 6, 6, 6 |
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|
| DBP, Day 3, 48 hour, n=6, 6, 6, 6 |
|
|
| DBP, Day 4, 72 hour, n=6, 6, 6, 6 |
|
|
| DBP, Day 8, n=6, 6, 6, 6 |
|
|
| DBP, Day 15, n=6, 6, 6, 6 |
|
|
| DBP, Day 22, pre-dose, n=6, 6, 6, 6 |
|
|
| DBP, Day 22, 1 hour, n=6, 6, 6, 6 |
|
|
| DBP, Day 22, 4 hour, n=6, 6, 6, 6 |
|
|
| DBP, Day 22, 6 hour, n=6, 6, 6, 6 |
|
|
| DBP, Day 22, 8 hour, n=6, 6, 6, 6 |
|
|
| DBP, Day 22, 12 hour, n=6, 6, 6, 6 |
|
|
| DBP, Day 23, 24 hour, n=6, 6, 6, 6 |
|
|
| DBP, Day 24, 48 hour, n=6, 6, 6, 6 |
|
|
| DBP, Day 25, 72 hour, n=6, 6, 6, 6 |
|
|
| DBP, Day 29, n=6, 6, 6, 6 |
|
|
| DBP, Day 36, n=6, 6, 6, 5 |
|
|
| DBP, Day 50, n=6, 6, 6, 5 |
|
|
| DBP, Day 71, n=6, 6, 6, 5 |
|
|
| DBP, Follow-up, n=6, 6, 6, 5 |
|
|
| SBP, Day 1, 1 hour, n=6, 6, 6, 6 |
|
|
| SBP, Day 1, 2 hour, n=6, 6, 6, 6 |
|
|
| SBP, Day 1, 4 hour, n=6, 6, 6, 6 |
|
|
| SBP, Day 1, 6 hour, n=6, 6, 6, 6 |
|
|
| SBP, Day 1, 8 hour, n=6, 6, 6, 6 |
|
|
| SBP, Day 1, 12 hour, n=6, 6, 6, 6 |
|
|
| SBP, Day 2, 24 hour, n=6, 6, 6, 6 |
|
|
| SBP, Day 3, 48 hour, n=6, 6, 6, 6 |
|
|
| SBP, Day 4, 72 hour, n=6, 6, 6, 6 |
|
|
| SBP, Day 8, n=6, 6, 6, 6 |
|
|
| SBP, Day 15, n=6, 6, 6, 6 |
|
|
| SBP, Day 22, pre-dose, n=6, 6, 6, 6 |
|
|
| SBP, Day 22, 1 hour, n=6, 6, 6, 6 |
|
|
| SBP, Day 22, 4 hour, n=6, 6, 6, 6 |
|
|
| SBP, Day 22, 6 hour, n=6, 6, 6, 6 |
|
|
| SBP, Day 22, 8 hour, n=6, 6, 6, 6 |
|
|
| SBP, Day 22, 12 hour, n=6, 6, 6, 6 |
|
|
| SBP, Day 23, 24 hour, n=6, 6, 6, 6 |
|
|
| SBP, Day 24, 48 hour, n=6, 6, 6, 6 |
|
|
| SBP, Day 25, 72 hour, n=6, 6, 6, 6 |
|
|
| SBP, Day 29, n=6, 6, 6, 6 |
|
|
| SBP, Day 36, n=6, 6, 6, 5 |
|
|
| SBP, Day 50, n=6, 6, 6, 5 |
|
|
| SBP, Day 71, n=6, 6, 6, 5 |
|
|
| SBP, Follow-up, n=6, 6, 6, 5 |
|
|
|
| PR, Day 1, 2 hour, n=6, 6, 6, 6 |
|
|
| PR, Day 1, 4 hour, n=6, 6, 6, 6 |
|
|
| PR, Day 1, 6 hour, n=6, 6, 6, 6 |
|
|
| PR, Day 1, 8 hour, n=6, 6, 6, 6 |
|
|
| PR, Day 1, 12 hour, n=6, 6, 6, 6 |
|
|
| PR, Day 2, 24 hour, n=6, 6, 6, 6 |
|
|
| PR, Day 3, 48 hour, n=6, 6, 6, 6 |
|
|
| PR, Day 4, 72 hour, n=6, 6, 6, 6 |
|
|
| PR, Day 8, n=6, 6, 6, 6 |
|
|
| PR, Day 15, n=6, 6, 6, 6 |
|
|
| PR, Day 22, pre-dose, n=6, 6, 6, 6 |
|
|
| PR, Day 22, 1 hour, n=6, 6, 6, 6 |
|
|
| PR, Day 22, 4 hour, n=6, 6, 6, 6 |
|
|
| PR, Day 22, 6 hour, n=6, 6, 6, 6 |
|
|
| PR, Day 22, 8 hour, n=6, 6, 6, 6 |
|
|
| PR, Day 22, 12 hour, n=6, 6, 6, 6 |
|
|
| PR, Day 23, 24 hour, n=6, 6, 6, 6 |
|
|
| PR, Day 24, 48 hour, n=6, 6, 6, 6 |
|
|
| PR, Day 25, 72 hour, n=6, 6, 6, 6 |
|
|
| PR, Day 29, n=6, 6, 6, 6 |
|
|
| PR, Day 36, n=6, 6, 6, 5 |
|
|
| PR, Day 50, n=6, 6, 6, 5 |
|
|
| PR, Day 71, n=6, 6, 6, 5 |
|
|
| PR, Follow-up, n=6, 6, 6, 5 |
|
|
|
| RR, Day 1, 2 hour, n=6, 6, 6, 6 |
|
|
| RR, Day 1, 4 hour, n=6, 6, 6, 6 |
|
|
| RR, Day 1, 6 hour, n=6, 6, 6, 6 |
|
|
| RR, Day 1, 8 hour, n=6, 6, 6, 6 |
|
|
| RR, Day 1, 12 hour, n=6, 6, 6, 6 |
|
|
| RR, Day 2, 24 hour, n=6, 6, 6, 6 |
|
|
| RR, Day 3, 48 hour, n=6, 6, 6, 6 |
|
|
| RR, Day 4, 72 hour, n=6, 6, 6, 6 |
|
|
| RR, Day 8, n=6, 6, 6, 6 |
|
|
| RR, Day 15, n=6, 6, 6, 6 |
|
|
| RR, Day 22, pre-dose, n=6, 6, 6, 6 |
|
|
| RR, Day 22, 1 hour, n=6, 6, 6, 6 |
|
|
| RR, Day 22, 4 hour, n=6, 6, 6, 6 |
|
|
| RR, Day 22, 6 hour, n=6, 6, 6, 6 |
|
|
| RR, Day 22, 8 hour, n=6, 6, 6, 6 |
|
|
| RR, Day 22, 12 hour, n=6, 6, 6, 6 |
|
|
| RR, Day 23, 24 hour, n=6, 6, 6, 6 |
|
|
| RR, Day 24, 48 hour, n=6, 6, 6, 6 |
|
|
| RR, Day 25, 72 hour, n=6, 6, 6, 6 |
|
|
| RR, Day 29, n=6, 6, 6, 6 |
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|
| RR, Day 36, n=6, 6, 6, 5 |
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|
| RR, Day 50, n=6, 6, 6, 5 |
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|
| RR, Day 71, n=6, 6, 6, 5 |
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|
| RR, Follow-up, n=6, 6, 6, 5 |
|
|
|
| Temperature, Day 1, 2 hour, n=6, 6, 6, 6 |
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|
| Temperature, Day 1, 4 hour, n=6, 6, 6, 6 |
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|
| Temperature, Day 1, 6 hour, n=6, 6, 6, 6 |
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|
| Temperature, Day 1, 8 hour, n=6, 6, 6, 6 |
|
|
| Temperature, Day 1, 12 hour, n=6, 6, 6, 6 |
|
|
| Temperature, Day 2, 24 hour, n=6, 6, 6, 6 |
|
|
| Temperature, Day 3, 48 hour, n=6, 6, 6, 6 |
|
|
| Temperature, Day 4, 72 hour, n=6, 6, 6, 6 |
|
|
| Temperature, Day 8, n=6, 6, 6, 6 |
|
|
| Temperature, Day 15, n=6, 6, 6, 6 |
|
|
| Temperature, Day 22, pre-dose, n=6, 6, 6, 6 |
|
|
| Temperature, Day 22, 1 hour, n=6, 6, 6, 6 |
|
|
| Temperature, Day 22, 4 hour, n=6, 6, 6, 6 |
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|
| Temperature, Day 22, 6 hour, n=6, 6, 6, 6 |
|
|
| Temperature, Day 22, 8 hour, n=6, 6, 6, 6 |
|
|
| Temperature, Day 22, 12 hour, n=6, 6, 6, 6 |
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|
| Temperature, Day 23, 24 hour, n=6, 6, 6, 6 |
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|
| Temperature, Day 24, 48 hour, n=6, 6, 6, 6 |
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|
| Temperature, Day 25, 72 hour, n=6, 6, 6, 6 |
|
|
| Temperature, Day 29, n=6, 6, 6, 6 |
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|
| Temperature, Day 36, n=6, 6, 6, 5 |
|
|
| Temperature, Day 50, n=6, 6, 6, 5 |
|
|
| Temperature, Day 71, n=6, 6, 6, 5 |
|
|
| Temperature, Follow-up, n=6, 6, 6, 5 |
|
|
| NCS |
|
| AUC (0-t) |
|
| AUC (0-24) |
|
| C24 |
|
| C168 |
|
| T1/2 |
|
| Tlag |
|
| AUC (0-24), n=6, 5, 6 |
|
|
| AUC (0-168), n=6, 5, 6 |
|
|
| AUC (0-inf), n=6, 5, 6 |
|
|
|
| C168 |
|
| T1/2, n=6, 5, 6 |
|
|
| Tlag, n=6, 6, 6 |
|
|
|
|
| Cmax |
|
|
| Tlag |
|
|
| Cmax, n=41 |
|
|
| RCmax, n=6, 6, 6 |
|
|
| RC24, n=0, 1, 3 |
|
|
| RCtau, n=0, 0, 0 |
|
| Day 15 |
|
| Day 22 |
|
| Day 29 |
|