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Clinical Trial Results:
A Randomized, Double-Blind (Sponsor-unblinded), Placebo-Controlled, Adaptive Trial to Investigate the Antiviral Effect, Safety, Tolerability and Pharmacokinetics of GSK3640254 in HIV-1 Infected Treatment-Naïve Adults

Summary
EudraCT number	2018-002208-15
Trial protocol	FR ES IT
Global end of trial date	06 Feb 2020

Results information
Results version number	v1(current)
This version publication date	12 Feb 2021
First version publication date	12 Feb 2021
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

208132

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

ViiV Healthcare

Sponsor organisation address

980 Great West Road, Brentford, Middlesex, United Kingdom, TW8 9GS

Public contact

GSK Response Center, ViiV Healthcare, 1 8664357343, GSKClinicalSupportHD@gsk.com

Scientific contact

GSK Response Center, ViiV Healthcare, 1 8664357343, GSKClinicalSupportHD@gsk.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

28 May 2020

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

06 Feb 2020

Was the trial ended prematurely?

Main objective of the trial

To evaluate the antiviral activity of GSK3640254 in HIV-1-infected participants during 10 days of monotherapy

Protection of trial subjects

Not applicable

Background therapy

Evidence for comparator

Actual start date of recruitment

31 Jan 2019

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

France: 4

Country: Number of subjects enrolled

Germany: 1

Country: Number of subjects enrolled

Italy: 5

Country: Number of subjects enrolled

South Africa: 3

Country: Number of subjects enrolled

Spain: 21

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

This was a randomized, double-blind, placebo-controlled, adaptive clinical trial to evaluate the antiviral effect, safety, tolerability and pharmacokinetic (PK)/pharmacodynamics (PD) of GSK3640254 over 10 days in study Part 1 and over 7 days in study Part 2.

Screening details

A total of 34 participants (14 participants in Part 1 and 20 participants in Part 2) were enrolled in this study. This study was conducted in France, Germany, Italy, South Africa and Spain.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Part 1: GSK3640254 10 mg

Arm description

Participants received GSK3640254 10 milligram (mg), capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Arm type

Experimental

Investigational medicinal product name

GSK3640254

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

GSK3640254 was available as capsules at unit dose strength of 5, 20 and 100 milligrams (mg) to be administered orally with 240 milliliters of water following ingestion of a moderate calorie and fat meal

Part 1: GSK3640254 200 mg

Arm description

Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Arm type

Experimental

Investigational medicinal product name

GSK3640254

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Part 1: Placebo

Arm description

Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Placebo was available as capsules to be administered orally with 240 milliliters of water following ingestion of a moderate calorie and fat meal.

Part 2: GSK3640254 40 mg

Arm description

Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Arm type

Experimental

Investigational medicinal product name

GSK3640254

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Part 2: GSK3640254 80 mg

Arm description

Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Arm type

Experimental

Investigational medicinal product name

GSK3640254

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Part 2: GSK3640254 140 mg

Arm description

Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Arm type

Experimental

Investigational medicinal product name

GSK3640254

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Part 2: Placebo

Arm description

Participants received placebo capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Placebo was available as capsules to be administered orally with 240 milliliters of water following ingestion of a moderate calorie and fat meal.

Number of subjects in period 1	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Started	6	6	2	6	6	6	2
Completed	6	6	2	6	6	6	2

Baseline characteristics

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Reporting group title

Part 1: GSK3640254 10 mg

Reporting group description

Participants received GSK3640254 10 milligram (mg), capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Reporting group title

Part 1: GSK3640254 200 mg

Reporting group description

Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Reporting group title

Part 1: Placebo

Reporting group description

Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Reporting group title

Part 2: GSK3640254 40 mg

Reporting group description

Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Reporting group title

Part 2: GSK3640254 80 mg

Reporting group description

Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Reporting group title

Part 2: GSK3640254 140 mg

Reporting group description

Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Reporting group title

Part 2: Placebo

Reporting group description

Participants received placebo capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Reporting group values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo	Total
Number of subjects	6	6	2	6	6	6	2	34
Age Categorical
Units: Participants
<=18 years	0	0	0	0	0	0	0	0
19-64 years	6	6	2	6	6	6	2	34
>=65 years	0	0	0	0	0	0	0	0
Sex: Female, Male
Units: Participants
Female	0	0	0	1	0	1	0	2
Male	6	6	2	5	6	5	2	32
Race/Ethnicity, Customized
Units: Subjects
American Indian or Alaska Native	2	0	0	0	0	0	1	3
Asian: South East Asian Heritage	1	0	0	0	0	0	0	1
Black or African American	0	0	0	1	2	1	0	4
White: White/Caucasian/European Heritage	2	5	2	5	4	5	1	24
Multiple: American Indian or Alaska Native & White	1	1	0	0	0	0	0	2

End points

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Reporting group title

Part 1: GSK3640254 10 mg

Reporting group description

Participants received GSK3640254 10 milligram (mg), capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Reporting group title

Part 1: GSK3640254 200 mg

Reporting group description

Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Reporting group title

Part 1: Placebo

Reporting group description

Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Reporting group title

Part 2: GSK3640254 40 mg

Reporting group description

Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Reporting group title

Part 2: GSK3640254 80 mg

Reporting group description

Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Reporting group title

Part 2: GSK3640254 140 mg

Reporting group description

Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Reporting group title

Part 2: Placebo

Reporting group description

Participants received placebo capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Subject analysis set title

GSK3640254 10 mg to 200 mg

Subject analysis set type

Sub-group analysis

Subject analysis set description

In Part 1, participants received GSK3640254 10 mg, 200 mg, capsules, orally for 10 days and in Part 2, participants received GSK3640254 40 mg, 80 mg, 140 mg, capsules, orally for 7 days.

Primary: Part 1: Maximum Change from Baseline in plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) at Day 11

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End point title

Part 1: Maximum Change from Baseline in plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) at Day 11 ^[1] ^[2]

End point description

Plasma samples were collected for quantitative analysis of plasma HIV-1 RNA. A HIV-1 RNA polymerase chain reaction (PCR) assay with a lower limit of detection (LLOD) of 50 copies per milliliter was used. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Intent-To-Treat Exposed Population consisted of all participants who met study criteria and were enrolled into the study with documented evidence of having received at least 1 dose of treatment and at least one post-Baseline HIV-1 RNA measurement.

End point type

Primary

End point timeframe

Baseline (Day 1) and Day 11

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical data to report.
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Number of subjects analysed	6 ^[3]	6 ^[4]	2 ^[5]
Units: Copies per milliliter
arithmetic mean (standard deviation)	-8605.8 ± 4604.40	-100719.8 ± 89182.99	-3406.5 ± 2591.55

Notes
[3] - Intent-To-Treat Exposed Population.
[4] - Intent-To-Treat Exposed Population.
[5] - Intent-To-Treat Exposed Population.

No statistical analyses for this end point

Primary: Part 2: Maximum Change from Baseline in plasma HIV-1 RNA at Day 8

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End point title

Part 2: Maximum Change from Baseline in plasma HIV-1 RNA at Day 8 ^[6] ^[7]

End point description

Plasma samples were collected for quantitative analysis of plasma HIV-1 RNA. An HIV-1 RNA PCR assay with an LLOD of 50 copies per milliliter was used. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

End point type

Primary

End point timeframe

Baseline (Day 1) and Day 8

Notes
[6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical data to report.
[7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Number of subjects analysed	6 ^[8]	6 ^[9]	6 ^[10]	2 ^[11]
Units: Copies per milliliter
arithmetic mean (standard deviation)	-48655.0 ± 26269.41	-37904.3 ± 38814.54	-64904.2 ± 83798.67	-123478.5 ± 175276.92

Notes
[8] - Intent-To-Treat Exposed Population.
[9] - Intent-To-Treat Exposed Population.
[10] - Intent-To-Treat Exposed Population.
[11] - Intent-To-Treat Exposed Population.

No statistical analyses for this end point

Secondary: Part 1: Number of Participants with Non-Serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs)

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End point title

Part 1: Number of Participants with Non-Serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs) ^[12]

End point description

An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or other situations as per Medical or scientific judgment. Safety Population consisted of all participants who were enrolled into the study with documented evidence of having received at least 1 dose of randomized treatment.

End point type

Secondary

End point timeframe

Up to Day 24

Notes
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Number of subjects analysed	6 ^[13]	6 ^[14]	2 ^[15]
Units: Participants
Non-SAEs	3	5	0
SAEs	1	0	0

Notes
[13] - Safety Population.
[14] - Safety Population.
[15] - Safety Population.

No statistical analyses for this end point

Secondary: Part 2: Number of participants with Non-SAEs and SAEs

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End point title

Part 2: Number of participants with Non-SAEs and SAEs ^[16]

End point description

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or other situations as per Medical or scientific judgment.

End point type

Secondary

End point timeframe

Up to Day 12

Notes
[16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Number of subjects analysed	6 ^[17]	6 ^[18]	6 ^[19]	2 ^[20]
Units: Participants
Non-SAEs	5	4	4	0
SAEs	0	0	1	0

Notes
[17] - Safety Population.
[18] - Safety Population.
[19] - Safety Population.
[20] - Safety Population.

No statistical analyses for this end point

Secondary: Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes, Platelet Count

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End point title

Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes, Platelet Count ^[21]

End point description

Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils, leukocytes and platelet count. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Days 8 to 10)

Notes
[21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Number of subjects analysed	6 ^[22]	6 ^[23]	2 ^[24]
Units: 10^9 cells per liter
arithmetic mean (standard deviation)
Basophils	0.005 ± 0.0266	-0.017 ± 0.0234	0.015 ± 0.0212
Eosinophils	-0.023 ± 0.1296	0.058 ± 0.1134	-0.025 ± 0.0212
Lymphocytes	-0.027 ± 0.5267	0.458 ± 0.4412	0.070 ± 0.0566
Monocytes	0.100 ± 0.1124	-0.000 ± 0.0980	0.055 ± 0.0212
Neutrophils	-0.045 ± 0.4624	-0.525 ± 0.8169	0.345 ± 0.1485
Leukocytes	0.02 ± 0.679	-0.02 ± 1.057	0.45 ± 0.212
Platelet count	25.0 ± 46.35	11.8 ± 12.04	13.0 ± 2.83

Notes
[22] - Safety Population.
[23] - Safety Population.
[24] - Safety Population.

No statistical analyses for this end point

Secondary: Part 1: Change From Baseline in Hematology Parameter: Hemoglobin

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End point title

Part 1: Change From Baseline in Hematology Parameter: Hemoglobin ^[25]

End point description

Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the hematology parameter: hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Days 8 to 10)

Notes
[25] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Number of subjects analysed	6 ^[26]	6 ^[27]	2 ^[28]
Units: Grams per liter
arithmetic mean (standard deviation)	-4.2 ± 4.96	-1.8 ± 5.98	-1.0 ± 5.66

Notes
[26] - Safety Population.
[27] - Safety Population.
[28] - Safety Population.

No statistical analyses for this end point

Secondary: Part 1: Change From Baseline in Hematology Parameter: Hematocrit

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End point title

Part 1: Change From Baseline in Hematology Parameter: Hematocrit ^[29]

End point description

Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the hematology parameter: hematocrit. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Days 8 to 10)

Notes
[29] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Number of subjects analysed	6 ^[30]	6 ^[31]	2 ^[32]
Units: Proportion of red blood cells in blood
arithmetic mean (standard deviation)	-0.0117 ± 0.01684	-0.0073 ± 0.01919	-0.0010 ± 0.01838

Notes
[30] - Safety Population.
[31] - Safety Population.
[32] - Safety Population.

No statistical analyses for this end point

Secondary: Part 1: Change From Baseline in Hematology Parameter: Erythrocytes

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End point title

Part 1: Change From Baseline in Hematology Parameter: Erythrocytes ^[33]

End point description

Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the hematology parameter: erythrocytes. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Days 8 to 10)

Notes
[33] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Number of subjects analysed	6 ^[34]	6 ^[35]	2 ^[36]
Units: 10^12 cells per liter
arithmetic mean (standard deviation)	-0.10 ± 0.190	-0.07 ± 0.197	0.00 ± 0.141

Notes
[34] - Safety Population.
[35] - Safety Population.
[36] - Safety Population.

No statistical analyses for this end point

Secondary: Part 1: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume

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End point title

Part 1: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume ^[37]

End point description

Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the hematology parameter: erythrocytes mean corpuscular volume. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Days 8 to 10)

Notes
[37] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Number of subjects analysed	6 ^[38]	6 ^[39]	2 ^[40]
Units: Femtoliter
arithmetic mean (standard deviation)	0.0 ± 0.89	-0.3 ± 1.03	0.0 ± 0.00

Notes
[38] - Safety Population.
[39] - Safety Population.
[40] - Safety Population.

No statistical analyses for this end point

Secondary: Part 1: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin

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End point title

Part 1: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin ^[41]

End point description

Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the hematology parameter: erythrocytes mean corpuscular hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Days 8 to 10)

Notes
[41] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Number of subjects analysed	6 ^[42]	6 ^[43]	2 ^[44]
Units: Picograms
arithmetic mean (standard deviation)	-0.08 ± 0.286	0.03 ± 0.266	-0.15 ± 0.071

Notes
[42] - Safety Population.
[43] - Safety Population.
[44] - Safety Population.

No statistical analyses for this end point

Secondary: Part 1: Change From Baseline in Hematology Parameter: Reticulocytes/Erythrocyte

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End point title

Part 1: Change From Baseline in Hematology Parameter: Reticulocytes/Erythrocyte ^[45]

End point description

Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the hematology parameter: reticulocytes/erythrocyte (erythro). Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Days 8 to 10)

Notes
[45] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Number of subjects analysed	6 ^[46]	6 ^[47]	2 ^[48]
Units: Percentage of reticulocytes in erythro
arithmetic mean (standard deviation)	0.0042 ± 0.00449	0.0012 ± 0.00172	0.0020 ± 0.00000

Notes
[46] - Safety Population.
[47] - Safety Population.
[48] - Safety Population.

No statistical analyses for this end point

Secondary: Part 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes, Platelet Count

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End point title

Part 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes, Platelet Count ^[49]

End point description

Blood samples were collected to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils, leukocytes and platelet count. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Day 7)

Notes
[49] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Number of subjects analysed	5 ^[50]	6 ^[51]	6 ^[52]	2 ^[53]
Units: 10^9 cells per liter
arithmetic mean (standard deviation)
Basophils, n=5,6,5,2	0.010 ± 0.0141	0.020 ± 0.0237	0.022 ± 0.0084	-0.005 ± 0.0354
Eosinophils, n=5,6,5,2	-0.066 ± 0.2145	-0.047 ± 0.1775	0.034 ± 0.0404	0.020 ± 0.0000
Lymphocytes, n=5,6,5,2	0.006 ± 0.4458	-0.062 ± 0.4731	0.536 ± 0.4766	-0.110 ± 0.2687
Monocytes, n=5,6,5,2	-0.020 ± 0.0869	0.022 ± 0.1705	-0.084 ± 0.1436	-0.130 ± 0.1131
Neutrophils, n=5,6,5,2	0.424 ± 0.6401	1.678 ± 2.1754	0.432 ± 0.7007	-0.215 ± 0.3182
Leukocytes, n=5,6,6,2	0.34 ± 0.385	1.62 ± 2.244	0.52 ± 1.211	-0.45 ± 0.071
Platelet count, n=4,6,6,2	1.5 ± 45.82	17.5 ± 30.26	16.0 ± 21.57	4.5 ± 0.71

Notes
[50] - Safety Population.
[51] - Safety Population.
[52] - Safety Population.
[53] - Safety Population.

No statistical analyses for this end point

Secondary: Part 2: Change From Baseline in Hematology Parameter: Hemoglobin

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End point title

Part 2: Change From Baseline in Hematology Parameter: Hemoglobin ^[54]

End point description

Blood samples were collected to analyze the hematology parameter: hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Only those participants with data available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Day 7)

Notes
[54] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Number of subjects analysed	5 ^[55]	6 ^[56]	6 ^[57]	2 ^[58]
Units: Grams per liter
arithmetic mean (standard deviation)	-8.0 ± 5.10	-4.7 ± 6.59	-1.7 ± 7.31	-8.0 ± 1.41

Notes
[55] - Safety Population.
[56] - Safety Population.
[57] - Safety Population.
[58] - Safety Population.

No statistical analyses for this end point

Secondary: Part 2: Change From Baseline in Hematology Parameter: Hematocrit

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End point title

Part 2: Change From Baseline in Hematology Parameter: Hematocrit ^[59]

End point description

Blood samples were collected to analyze the hematology parameter: hematocrit. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Only those participants with data available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Day 7)

Notes
[59] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Number of subjects analysed	5 ^[60]	6 ^[61]	6 ^[62]	2 ^[63]
Units: Proportion of red blood cells in blood
arithmetic mean (standard deviation)	-0.0230 ± 0.01762	-0.0123 ± 0.02096	-0.0058 ± 0.02094	-0.0315 ± 0.01485

Notes
[60] - Safety Population.
[61] - Safety Population.
[62] - Safety Population.
[63] - Safety Population.

No statistical analyses for this end point

Secondary: Part 2: Change From Baseline in Hematology Parameter: Erythrocytes

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End point title

Part 2: Change From Baseline in Hematology Parameter: Erythrocytes ^[64]

End point description

Blood samples were collected to analyze the hematology parameter: erythrocytes. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Only those participants with data available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Day 7)

Notes
[64] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Number of subjects analysed	5 ^[65]	6 ^[66]	6 ^[67]	2 ^[68]
Units: 10^12 cells per liter
arithmetic mean (standard deviation)	-0.24 ± 0.207	-0.17 ± 0.216	-0.08 ± 0.223	-0.30 ± 0.000

Notes
[65] - Safety Population.
[66] - Safety Population.
[67] - Safety Population.
[68] - Safety Population.

No statistical analyses for this end point

Secondary: Part 2: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume

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End point title

Part 2: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume ^[69]

End point description

Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular volume. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Only those participants with data available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Day 7)

Notes
[69] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Number of subjects analysed	5 ^[70]	6 ^[71]	6 ^[72]	2 ^[73]
Units: Femtoliter
arithmetic mean (standard deviation)	-0.2 ± 0.45	0.2 ± 0.98	0.2 ± 0.98	-2.0 ± 2.83

Notes
[70] - Safety Population.
[71] - Safety Population.
[72] - Safety Population.
[73] - Safety Population.

No statistical analyses for this end point

Secondary: Part 2: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin

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End point title

Part 2: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin ^[74]

End point description

Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Only those participants with data available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Day 7)

Notes
[74] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Number of subjects analysed	5 ^[75]	6 ^[76]	6 ^[77]	2 ^[78]
Units: Picograms
arithmetic mean (standard deviation)	-0.28 ± 0.850	-0.05 ± 0.187	-0.02 ± 0.337	-0.05 ± 0.354

Notes
[75] - Safety Population.
[76] - Safety Population.
[77] - Safety Population.
[78] - Safety Population.

No statistical analyses for this end point

Secondary: Part 2: Change From Baseline in Hematology Parameter: Reticulocytes/Erythro

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End point title

Part 2: Change From Baseline in Hematology Parameter: Reticulocytes/Erythro ^[79]

End point description

Blood samples were collected to analyze the hematology parameter: reticulocytes/erythro. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Only those participants with data available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Day 7)

Notes
[79] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Number of subjects analysed	5 ^[80]	6 ^[81]	6 ^[82]	2 ^[83]
Units: Percentage of reticulocytes in erythro
arithmetic mean (standard deviation)	0.0030 ± 0.00235	0.0017 ± 0.00258	0.0007 ± 0.00350	0.0020 ± 0.00283

Notes
[80] - Safety Population.
[81] - Safety Population.
[82] - Safety Population.
[83] - Safety Population.

No statistical analyses for this end point

Secondary: Part 1: Change From Baseline in Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Calcium, Chloride, Phosphate, Potassium, Magnesium, Sodium, Urea, high density lipoprotein (HDL) Cholesterol, low density lipoprotein (LDL) Cholesterol

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End point title

Part 1: Change From Baseline in Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Calcium, Chloride, Phosphate, Potassium, Magnesium, Sodium, Urea, high density lipoprotein (HDL) Cholesterol, low density lipoprotein (LDL) Cholesterol ^[84]

End point description

Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the chemistry parameters: glucose, cholesterol, triglycerides, calcium, chloride, phosphate, potassium, magnesium, sodium, urea, HDL cholesterol and LDL cholesterol. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. 99999 indicates data is not available. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Days 8 to 10)

Notes
[84] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Number of subjects analysed	6 ^[85]	6 ^[86]	2 ^[87]
Units: Millimoles per liter
arithmetic mean (standard deviation)
Glucose, n=6,6,2	-0.20 ± 0.253	0.28 ± 0.595	0.00 ± 0.424
Cholesterol, n=0,0,0	99999 ± 99999	99999 ± 99999	99999 ± 99999
Triglycerides, n=0,0,0	99999 ± 99999	99999 ± 99999	99999 ± 99999
Calcium, n=6,6,2	-0.007 ± 0.1343	-0.027 ± 0.0468	0.020 ± 0.0283
Chloride, n=6,6,2	0.0 ± 2.10	0.8 ± 3.06	-0.5 ± 3.54
Phosphate, n=6,6,2	0.042 ± 0.1594	0.058 ± 0.1772	-0.075 ± 0.1061
Potassium, n=6,6,2	0.02 ± 0.240	-0.03 ± 0.242	-0.10 ± 0.000
Magnesium, n=6,6,2	0.000 ± 0.0551	-0.007 ± 0.0561	-0.020 ± 0.0283
Sodium, n=6,6,2	0.2 ± 2.40	-0.8 ± 1.60	-1.0 ± 1.41
Urea, n=6,6,2	-0.08 ± 1.021	-0.08 ± 0.801	1.00 ± 0.000
HDL cholesterol, n=0,0,0	99999 ± 99999	99999 ± 99999	99999 ± 99999
LDL cholesterol, n=0,0,0	99999 ± 99999	99999 ± 99999	99999 ± 99999

Notes
[85] - Safety Population.
[86] - Safety Population.
[87] - Safety Population.

No statistical analyses for this end point

Secondary: Part 1: Change From Baseline in Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST)

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End point title

Part 1: Change From Baseline in Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) ^[88]

End point description

Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the chemistry parameters: ALT, ALP and AST. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Days 8 to 10)

Notes
[88] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Number of subjects analysed	6 ^[89]	6 ^[90]	2 ^[91]
Units: International units per liter
arithmetic mean (standard deviation)
ALT	2.7 ± 7.79	-1.7 ± 4.46	9.5 ± 6.36
ALP	10.5 ± 23.36	-3.5 ± 4.64	-4.0 ± 1.41
AST	-0.5 ± 3.94	-2.0 ± 8.60	4.5 ± 2.12

Notes
[89] - Safety Population.
[90] - Safety Population.
[91] - Safety Population.

No statistical analyses for this end point

Secondary: Part 1: Change From Baseline in Chemistry Parameters: Creatinine, Bilirubin

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End point title

Part 1: Change From Baseline in Chemistry Parameters: Creatinine, Bilirubin ^[92]

End point description

Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the chemistry parameters: creatinine and bilirubin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Days 8 to 10)

Notes
[92] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Number of subjects analysed	6 ^[93]	6 ^[94]	2 ^[95]
Units: Micromoles per liter
arithmetic mean (standard deviation)
Creatinine	1.77 ± 5.565	-1.33 ± 4.291	0.00 ± 0.000
Bilirubin	-0.3 ± 3.20	-2.0 ± 2.53	3.0 ± 9.90

Notes
[93] - Safety Population.
[94] - Safety Population.
[95] - Safety Population.

No statistical analyses for this end point

Secondary: Part 1: Change From Baseline in Chemistry Parameters: Protein

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End point title

Part 1: Change From Baseline in Chemistry Parameters: Protein ^[96]

End point description

Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the chemistry parameter: protein. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Days 8 to 10)

Notes
[96] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Number of subjects analysed	6 ^[97]	6 ^[98]	2 ^[99]
Units: Grams per liter
arithmetic mean (standard deviation)	-1.3 ± 4.93	-1.0 ± 2.97	1.0 ± 2.83

Notes
[97] - Safety Population.
[98] - Safety Population.
[99] - Safety Population.

No statistical analyses for this end point

Secondary: Part 1: Change From Baseline in Chemistry Parameters: Amylase, Lipase

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End point title

Part 1: Change From Baseline in Chemistry Parameters: Amylase, Lipase ^[100]

End point description

Blood samples were collected to analyze the chemistry parameters: amylase and lipase. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Only those participants with data available at the specified time points were analyzed. Amylase and lipase results were collected for two participants in GSK3640254 10 mg arm during Part 1 of the study. No data were collected for Placebo and GSK3640254 200 mg arms at Visit 6 (Day 11) due to delays in approval of Protocol Amendment 02 into which testing for amylase and lipase was added.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 6 (Day 11)

Notes
[100] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Number of subjects analysed	2 ^[101]	0 ^[102]	0 ^[103]
Units: Units per liter
arithmetic mean (standard deviation)
Amylase	0.0 ± 11.31	±	±
Lipase	-2.0 ± 2.83	±	±

Notes
[101] - Safety Population.
[102] - Safety Population.
[103] - Safety Population.

No statistical analyses for this end point

Secondary: Part 2: Change From Baseline in Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Calcium, Chloride, Phosphate, Potassium, Magnesium, Sodium, Urea, HDL Cholesterol, LDL Cholesterol

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End point title

Part 2: Change From Baseline in Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Calcium, Chloride, Phosphate, Potassium, Magnesium, Sodium, Urea, HDL Cholesterol, LDL Cholesterol ^[104]

End point description

Blood samples were collected to analyze the chemistry parameters: glucose, cholesterol, triglycerides, calcium, chloride, phosphate, potassium, magnesium, sodium, urea, HDL cholesterol and LDL cholesterol. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles). 99999 indicates that, standard deviation could not be calculated for single participant. 88888 indicates, data is not available.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Day 7)

Notes
[104] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Number of subjects analysed	6 ^[105]	6 ^[106]	6 ^[107]	1 ^[108]
Units: Millimoles per liter
arithmetic mean (standard deviation)
Glucose, n=6,6,6,1	-0.05 ± 0.327	0.18 ± 1.085	-0.03 ± 0.446	0.50 ± 99999
Cholesterol, n=0,0,0,0	88888 ± 88888	88888 ± 88888	88888 ± 88888	88888 ± 88888
Triglycerides, n=0,0,0,0	88888 ± 88888	88888 ± 88888	88888 ± 88888	88888 ± 88888
Calcium, n=6,6,6,1	-0.057 ± 0.0638	-0.027 ± 0.0628	0.030 ± 0.1002	0.000 ± 99999
Chloride, n=6,6,6,1	-0.7 ± 2.25	-0.2 ± 1.47	-0.7 ± 2.34	-2.0 ± 99999
Phosphate, n=6,6,6,1	-0.117 ± 0.2160	0.067 ± 0.1211	0.083 ± 0.1329	0.000 ± 99999
Potassium, n=6,6,6,1	-0.20 ± 0.261	0.05 ± 0.383	0.20 ± 0.210	-0.10 ± 99999
Magnesium, n=6,6,6,1	0.007 ± 0.0484	0.007 ± 0.0413	0.027 ± 0.0501	0.000 ± 99999
Sodium, n=6,6,6,1	-0.8 ± 2.23	-0.3 ± 1.37	-0.2 ± 1.72	-4.0 ± 99999
Urea, n=6,6,6,1	-0.42 ± 0.861	-0.25 ± 1.037	-0.33 ± 0.931	-0.50 ± 99999
HDL cholesterol, n=0,0,0,0	88888 ± 88888	88888 ± 88888	88888 ± 88888	88888 ± 88888
LDL cholesterol, n=0,0,0,0	88888 ± 88888	88888 ± 88888	88888 ± 88888	88888 ± 88888

Notes
[105] - Safety Population.
[106] - Safety Population.
[107] - Safety Population.
[108] - Safety Population.

No statistical analyses for this end point

Secondary: Part 2: Change From Baseline in Chemistry Parameters: ALT, ALP, AST

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End point title

Part 2: Change From Baseline in Chemistry Parameters: ALT, ALP, AST ^[109]

End point description

Blood samples were collected to analyze the chemistry parameters: ALT, ALP and AST. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Only those participants with data available at the specified time points were analyzed. 99999 indicates that, standard deviation could not be calculated for single participant.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Day 7)

Notes
[109] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Number of subjects analysed	6 ^[110]	6 ^[111]	6 ^[112]	1 ^[113]
Units: International units per liter
arithmetic mean (standard deviation)
ALT	-3.8 ± 6.62	-1.2 ± 3.76	-6.2 ± 8.33	-1.0 ± 99999
ALP	-3.2 ± 3.19	-0.7 ± 5.35	-1.8 ± 8.61	-1.0 ± 99999
AST	-5.2 ± 9.37	0.3 ± 5.79	-4.7 ± 7.37	4.0 ± 99999

Notes
[110] - Safety Population.
[111] - Safety Population.
[112] - Safety Population.
[113] - Safety Population.

No statistical analyses for this end point

Secondary: Part 2: Change From Baseline in Chemistry Parameters: Creatinine, Bilirubin

Top of page

End point title

Part 2: Change From Baseline in Chemistry Parameters: Creatinine, Bilirubin ^[114]

End point description

Blood samples were collected to analyze the chemistry parameters: creatinine and bilirubin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Only those participants with data available at the specified time points were analyzed. 99999 indicates that, standard deviation could not be calculated for single participant.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Day 7)

Notes
[114] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Number of subjects analysed	6 ^[115]	6 ^[116]	6 ^[117]	1 ^[118]
Units: Micromoles per liter
arithmetic mean (standard deviation)
Creatinine	1.35 ± 3.230	-3.38 ± 2.230	-0.17 ± 8.362	-0.90 ± 99999
Bilirubin	-0.3 ± 2.34	1.3 ± 6.02	0.3 ± 1.51	0.0 ± 99999

Notes
[115] - Safety Population.
[116] - Safety Population.
[117] - Safety Population.
[118] - Safety Population.

No statistical analyses for this end point

Secondary: Part 2: Change From Baseline in Chemistry Parameters: Protein

Top of page

End point title

Part 2: Change From Baseline in Chemistry Parameters: Protein ^[119]

End point description

Blood samples were collected to analyze the chemistry parameter: protein. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Only those participants with data available at the specified time points were analyzed. 99999 indicates that, standard deviation could not be calculated for single participant.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Day 7)

Notes
[119] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Number of subjects analysed	6 ^[120]	6 ^[121]	6 ^[122]	1 ^[123]
Units: Grams per liter
arithmetic mean (standard deviation)	-2.2 ± 3.25	-0.8 ± 4.07	1.5 ± 4.64	-2.0 ± 99999

Notes
[120] - Safety Population.
[121] - Safety Population.
[122] - Safety Population.
[123] - Safety Population.

No statistical analyses for this end point

Secondary: Part 2: Change From Baseline in Chemistry Parameters: Amylase, Lipase

Top of page

End point title

Part 2: Change From Baseline in Chemistry Parameters: Amylase, Lipase ^[124]

End point description

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Day 7)

Notes
[124] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Number of subjects analysed	6 ^[125]	6 ^[126]	6 ^[127]	1 ^[128]
Units: Units per liter
arithmetic mean (standard deviation)
Amylase	-2.3 ± 8.62	0.8 ± 9.87	6.7 ± 7.84	-10.0 ± 99999
Lipase	-1.0 ± 8.27	-2.2 ± 6.37	4.5 ± 8.29	8.0 ± 99999

Notes
[125] - Safety Population.
[126] - Safety Population.
[127] - Safety Population.
[128] - Safety Population.

No statistical analyses for this end point

Secondary: Part 1: Change From Baseline in Urinalysis Parameter: Specific Gravity

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End point title

Part 1: Change From Baseline in Urinalysis Parameter: Specific Gravity ^[129]

End point description

Urine samples were collected at Baseline and one sample between Days 8 to 10 to analyze the urinalysis parameter: specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Days 8 to 10)

Notes
[129] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Number of subjects analysed	6 ^[130]	6 ^[131]	2 ^[132]
Units: Ratio
arithmetic mean (standard deviation)	0.0002 ± 0.00615	0.0008 ± 0.00232	0.0000 ± 0.00283

Notes
[130] - Safety Population.
[131] - Safety Population.
[132] - Safety Population.

No statistical analyses for this end point

Secondary: Part 1: Change From Baseline in Urinalysis Parameter: Urobilinogen

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End point title

Part 1: Change From Baseline in Urinalysis Parameter: Urobilinogen ^[133]

End point description

Urine samples were collected at Baseline and one sample between Days 8 to 10 to analyze the urinalysis parameter: urobilinogen. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Days 8 to 10)

Notes
[133] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Number of subjects analysed	6 ^[134]	6 ^[135]	2 ^[136]
Units: Micromoles per liter
arithmetic mean (standard deviation)	4.50 ± 6.971	0.00 ± 0.000	0.00 ± 0.000

Notes
[134] - Safety Population.
[135] - Safety Population.
[136] - Safety Population.

No statistical analyses for this end point

Secondary: Part 1: Change From Baseline in Urinalysis Parameter: Potential of Hydrogen (pH)

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End point title

Part 1: Change From Baseline in Urinalysis Parameter: Potential of Hydrogen (pH) ^[137]

End point description

Urine samples were collected at Baseline and one sample between Days 8 to 10 to analyze the urinalysis parameter: pH. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acidic pH (5.0 - 6.0). Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Days 8 to 10)

Notes
[137] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Number of subjects analysed	6 ^[138]	6 ^[139]	2 ^[140]
Units: pH
arithmetic mean (standard deviation)	0.17 ± 1.033	-0.33 ± 0.683	-0.50 ± 0.000

Notes
[138] - Safety Population.
[139] - Safety Population.
[140] - Safety Population.

No statistical analyses for this end point

Secondary: Part 2: Change From Baseline in Urinalysis Parameter: Specific Gravity

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End point title

Part 2: Change From Baseline in Urinalysis Parameter: Specific Gravity ^[141]

End point description

Urine samples were collected to analyze the urinalysis parameter: specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Day 7)

Notes
[141] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Number of subjects analysed	6 ^[142]	6 ^[143]	6 ^[144]	2 ^[145]
Units: Ratio
arithmetic mean (standard deviation)	0.0010 ± 0.00746	-0.0022 ± 0.00794	0.0018 ± 0.00744	-0.0110 ± 0.00424

Notes
[142] - Safety Population.
[143] - Safety Population.
[144] - Safety Population.
[145] - Safety Population.

No statistical analyses for this end point

Secondary: Part 2: Change From Baseline in Urinalysis Parameter: Urobilinogen

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End point title

Part 2: Change From Baseline in Urinalysis Parameter: Urobilinogen ^[146]

End point description

Urine samples were collected to analyze the urinalysis parameter: urobilinogen. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Day 7)

Notes
[146] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Number of subjects analysed	6 ^[147]	6 ^[148]	6 ^[149]	2 ^[150]
Units: Micromoles per liter
arithmetic mean (standard deviation)	0.00 ± 0.000	4.50 ± 6.971	0.00 ± 0.000	0.00 ± 0.000

Notes
[147] - Safety Population.
[148] - Safety Population.
[149] - Safety Population.
[150] - Safety Population.

No statistical analyses for this end point

Secondary: Part 2: Change From Baseline in Urinalysis Parameter: pH

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End point title

Part 2: Change From Baseline in Urinalysis Parameter: pH ^[151]

End point description

Urine samples were collected to analyze the urinalysis parameter: pH. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acidic pH (5.0 - 6.0). Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Day 7)

Notes
[151] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Number of subjects analysed	6 ^[152]	6 ^[153]	6 ^[154]	2 ^[155]
Units: pH
arithmetic mean (standard deviation)	0.17 ± 0.683	-0.17 ± 0.683	0.08 ± 0.492	0.25 ± 0.354

Notes
[152] - Safety Population.
[153] - Safety Population.
[154] - Safety Population.
[155] - Safety Population.

No statistical analyses for this end point

Secondary: Part 1: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

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End point title

Part 1: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) ^[156]

End point description

SBP and DBP were measured in the semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Days 8 to 10)

Notes
[156] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Number of subjects analysed	6 ^[157]	6 ^[158]	2 ^[159]
Units: Millimeters of mercury
arithmetic mean (standard deviation)
SBP	-2.5 ± 8.41	0.5 ± 9.65	-1.5 ± 3.54
DBP	-0.3 ± 14.50	0.8 ± 4.67	0.5 ± 0.71

Notes
[157] - Safety Population.
[158] - Safety Population.
[159] - Safety Population.

No statistical analyses for this end point

Secondary: Part 1: Change From Baseline in Respiratory Rate

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End point title

Part 1: Change From Baseline in Respiratory Rate ^[160]

End point description

Respiratory rate was measured in the semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Days 8 to 10)

Notes
[160] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Number of subjects analysed	6 ^[161]	6 ^[162]	2 ^[163]
Units: Breaths per minute
arithmetic mean (standard deviation)	-1.0 ± 1.79	0.2 ± 2.32	-1.0 ± 1.41

Notes
[161] - Safety Population.
[162] - Safety Population.
[163] - Safety Population.

No statistical analyses for this end point

Secondary: Part 1: Change From Baseline in Pulse Rate

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End point title

Part 1: Change From Baseline in Pulse Rate ^[164]

End point description

Pulse rate was measured in the semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Days 8 to 10)

Notes
[164] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Number of subjects analysed	6 ^[165]	6 ^[166]	2 ^[167]
Units: Beats per minute
arithmetic mean (standard deviation)	-5.2 ± 4.36	5.5 ± 10.99	6.0 ± 2.83

Notes
[165] - Safety Population.
[166] - Safety Population.
[167] - Safety Population.

No statistical analyses for this end point

Secondary: Part 2: Change From Baseline in SBP and DBP

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End point title

Part 2: Change From Baseline in SBP and DBP ^[168]

End point description

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Day 7)

Notes
[168] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Number of subjects analysed	6 ^[169]	6 ^[170]	6 ^[171]	2 ^[172]
Units: Millimeters of mercury
arithmetic mean (standard deviation)
SBP	1.0 ± 8.27	-2.2 ± 4.45	7.3 ± 11.55	1.0 ± 2.83
DBP	-1.8 ± 2.40	-1.0 ± 6.36	2.3 ± 15.72	-0.5 ± 7.78

Notes
[169] - Safety Population.
[170] - Safety Population.
[171] - Safety Population.
[172] - Safety Population.

No statistical analyses for this end point

Secondary: Part 2: Change From Baseline in Respiratory Rate

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End point title

Part 2: Change From Baseline in Respiratory Rate ^[173]

End point description

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Day 7)

Notes
[173] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Number of subjects analysed	6 ^[174]	6 ^[175]	6 ^[176]	2 ^[177]
Units: Breaths per minute
arithmetic mean (standard deviation)	-0.2 ± 1.83	0.2 ± 1.47	-1.0 ± 4.47	0.5 ± 2.12

Notes
[174] - Safety Population.
[175] - Safety Population.
[176] - Safety Population.
[177] - Safety Population.

No statistical analyses for this end point

Secondary: Part 2: Change From Baseline in Pulse Rate

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End point title

Part 2: Change From Baseline in Pulse Rate ^[178]

End point description

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Day 7)

Notes
[178] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Number of subjects analysed	6 ^[179]	6 ^[180]	6 ^[181]	2 ^[182]
Units: Beats per minute
arithmetic mean (standard deviation)	4.2 ± 17.36	2.0 ± 11.14	2.8 ± 6.40	10.5 ± 7.78

Notes
[179] - Safety Population.
[180] - Safety Population.
[181] - Safety Population.
[182] - Safety Population.

No statistical analyses for this end point

Secondary: Part 1: Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval, Corrected QT Interval Using Bazett's Formula (QTcB), Corrected QT Interval Using Fridericia's Formula (QTcF)

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End point title

Part 1: Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval, Corrected QT Interval Using Bazett's Formula (QTcB), Corrected QT Interval Using Fridericia's Formula (QTcF) ^[183]

End point description

Twelve lead ECGs were obtained to measure PR Interval, QRS Duration, QT Interval, QTcB Interval and QTcF Interval. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

End point type

Secondary

End point timeframe

Baseline (Day 1), Visit 5 (Days 8 to 10: Pre-dose, 2, 4 and 6 hours)

Notes
[183] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Number of subjects analysed	6 ^[184]	6 ^[185]	2 ^[186]
Units: Milliseconds
arithmetic mean (standard deviation)
PR Interval- Days 8 to 10: Pre-dose	-0.4 ± 5.32	-7.6 ± 5.69	-2.5 ± 2.12
PR Interval- Days 8 to 10: 2 hours	1.4 ± 5.47	-6.3 ± 9.71	-11.5 ± 0.71
PR Interval- Days 8 to 10: 4 hours	-0.1 ± 10.00	0.2 ± 9.81	-3.5 ± 0.71
PR Interval- Days 8 to 10: 6 hours	1.4 ± 13.22	-5.9 ± 3.93	-25.0 ± 4.24
QRS Duration- Days 8 to 10: Pre-dose	-3.1 ± 6.65	-3.4 ± 9.90	-5.3 ± 3.30
QRS Duration- Days 8 to 10: 2 hours	-2.1 ± 6.60	0.4 ± 6.27	0.2 ± 4.01
QRS Duration- Days 8 to 10: 4 hours	-3.3 ± 3.50	-1.7 ± 6.75	-1.3 ± 3.77
QRS Duration- Days 8 to 10: 6 hours	-3.6 ± 5.56	-2.9 ± 4.55	-2.3 ± 13.20
QT Interval- Days 8 to 10: Pre-dose	0.7 ± 8.15	-2.7 ± 19.60	-19.7 ± 21.21
QT Interval- Days 8 to 10: 2 hours	-2.4 ± 17.61	4.4 ± 20.33	-28.7 ± 4.24
QT Interval- Days 8 to 10: 4 hours	8.7 ± 18.43	8.9 ± 13.72	-25.2 ± 19.09
QT Interval- Days 8 to 10: 6 hours	5.7 ± 16.48	5.8 ± 14.19	-24.2 ± 21.92
QTcB Interval- Days 8 to 10: Pre-dose	1.65 ± 15.813	3.60 ± 18.218	-1.38 ± 6.435
QTcB Interval- Days 8 to 10: 2 hours	-10.45 ± 22.433	-4.60 ± 14.266	-27.38 ± 32.315
QTcB Interval- Days 8 to 10: 4 hours	0.77 ± 15.517	-10.37 ± 20.176	-30.23 ± 51.760
QTcB Interval- Days 8 to 10: 6 hours	2.65 ± 13.391	-9.15 ± 15.513	-4.88 ± 11.102
QTcF Interval- Days 8 to 10: Pre-dose	1.2 ± 10.75	1.2 ± 9.56	-7.7 ± 11.31
QTcF Interval- Days 8 to 10: 2 hours	-7.5 ± 19.44	-1.3 ± 14.06	-27.7 ± 22.63
QTcF Interval- Days 8 to 10: 4 hours	3.7 ± 15.18	-3.7 ± 10.84	-28.7 ± 41.01
QTcF Interval- Days 8 to 10: 6 hours	4.0 ± 12.82	-3.8 ± 13.06	-12.2 ± 14.85

Notes
[184] - Safety Population.
[185] - Safety Population.
[186] - Safety Population.

No statistical analyses for this end point

Secondary: Part 2: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcB, QTcF

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End point title

Part 2: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcB, QTcF ^[187]

End point description

End point type

Secondary

End point timeframe

Baseline (Day 1), Visit 5 (Day 7: Pre-dose, 2, 4 and 6 hours)

Notes
[187] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Number of subjects analysed	6 ^[188]	6 ^[189]	6 ^[190]	2 ^[191]
Units: Milliseconds
arithmetic mean (standard deviation)
PR Interval- Day 7: Pre-dose	9.7 ± 13.92	-1.1 ± 6.89	-7.3 ± 9.20	-7.3 ± 0.47
PR Interval- Day 7: 2 hours	6.1 ± 14.20	-2.4 ± 7.90	-3.1 ± 8.61	6.2 ± 2.59
PR Interval- Day 7: 4 hours	5.2 ± 22.87	1.1 ± 8.56	-8.3 ± 6.81	4.7 ± 5.19
PR Interval- Day 7: 6 hours	3.9 ± 16.80	-2.3 ± 6.24	-2.1 ± 5.82	-7.8 ± 9.66
QRS Duration- Day 7: Pre-dose	3.9 ± 5.11	3.2 ± 7.81	-0.4 ± 6.87	2.3 ± 7.07
QRS Duration- Day 7: 2 hours	2.4 ± 4.18	0.7 ± 4.89	-0.1 ± 8.45	4.3 ± 1.41
QRS Duration- Day 7: 4 hours	1.7 ± 4.06	0.1 ± 4.41	-3.1 ± 6.25	3.8 ± 3.54
QRS Duration- Day 7: 6 hours	0.5 ± 11.78	-0.1 ± 3.04	-0.8 ± 3.70	2.8 ± 6.36
QT Interval- Day 7: Pre-dose	-7.4 ± 33.78	-1.6 ± 13.03	5.0 ± 20.49	3.2 ± 2.59
QT Interval- Day 7: 2 hours	-24.4 ± 33.17	-4.4 ± 8.90	1.8 ± 12.60	-0.3 ± 6.13
QT Interval- Day 7: 4 hours	-12.8 ± 25.96	4.2 ± 12.84	-1.7 ± 13.65	11.2 ± 19.56
QT Interval- Day 7: 6 hours	-21.4 ± 36.18	5.9 ± 12.19	0.7 ± 12.92	2.7 ± 7.54
QTcB Interval- Day 7: Pre-dose	-4.16 ± 14.780	0.34 ± 11.468	3.45 ± 6.785	-7.08 ± 2.569
QTcB Interval- Day 7: 2 hours	2.90 ± 19.936	0.09 ± 14.494	-4.88 ± 17.444	-18.23 ± 2.923
QTcB Interval- Day 7: 4 hours	-6.96 ± 23.150	-0.56 ± 13.559	1.30 ± 14.341	-23.83 ± 2.781
QTcB Interval- Day 7: 6 hours	-3.26 ± 16.691	4.17 ± 12.302	-1.68 ± 10.181	-9.83 ± 17.489
QTcF Interval- Day 7: Pre-dose	-5.9 ± 18.89	-0.5 ± 4.12	4.1 ± 9.23	-3.3 ± 0.94
QTcF Interval- Day 7: 2 hours	-7.2 ± 22.91	-1.3 ± 8.73	-2.3 ± 12.87	-12.3 ± 0.47
QTcF Interval- Day 7: 4 hours	-9.4 ± 21.24	1.2 ± 8.15	0.6 ± 9.00	-12.3 ± 4.71
QTcF Interval- Day 7: 6 hours	-9.5 ± 19.08	4.5 ± 5.69	-0.8 ± 7.79	-5.8 ± 8.72

Notes
[188] - Safety Population.
[189] - Safety Population.
[190] - Safety Population.
[191] - Safety Population.

No statistical analyses for this end point

Secondary: Part 1: Absolute Values for Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes, Platelet Count

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End point title

Part 1: Absolute Values for Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes, Platelet Count ^[192]

End point description

Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils, leukocytes and platelet count. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Days 8 to 10)

Notes
[192] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Number of subjects analysed	6 ^[193]	6 ^[194]	2 ^[195]
Units: 10^9 cells per liter
arithmetic mean (standard deviation)
Baseline (Day 1): Basophils, n=6,5,2	0.052 ± 0.0279	0.056 ± 0.0321	0.030 ± 0.0000
Days 8 to 10: Basophils, n=6,6,2	0.057 ± 0.0266	0.037 ± 0.0186	0.045 ± 0.0212
Baseline (Day 1): Eosinophils, n=6,5,2	0.212 ± 0.1783	0.150 ± 0.0616	0.105 ± 0.0212
Days 8 to 10: Eosinophils, n=6,6,2	0.188 ± 0.0873	0.202 ± 0.1003	0.080 ± 0.0424
Baseline (Day 1): Lymphocytes, n=6,5,2	2.303 ± 0.5431	1.810 ± 0.4341	2.010 ± 0.0707
Days 8 to 10: Lymphocytes, n=6,6,2	2.277 ± 0.4484	2.217 ± 0.6693	2.080 ± 0.1273
Baseline (Day 1): Monocytes, n=6,5,2	0.552 ± 0.2033	0.530 ± 0.1814	0.460 ± 0.0000
Days 8 to 10: Monocytes, n=6,6,2	0.652 ± 0.1907	0.508 ± 0.2088	0.515 ± 0.0212
Baseline (Day 1): Neutrophils, n=6,5,2	2.935 ± 0.4803	3.094 ± 0.7279	1.840 ± 0.4101
Days 8 to 10: Neutrophils, n=6,6,2	2.890 ± 0.6049	2.635 ± 0.4068	2.185 ± 0.2616
Baseline (Day 1): Leukocytes, n=6,5,2	6.05 ± 1.071	5.64 ± 1.172	4.45 ± 0.495
Days 8 to 10: Leukocytes, n=6,6,2	6.07 ± 0.929	5.60 ± 1.158	4.90 ± 0.283
Baseline (Day 1): Platelet count, n=6,5,2	208.8 ± 38.48	202.0 ± 39.26	195.5 ± 12.02
Days 8 to 10: Platelet count, n=6,6,2	233.8 ± 70.34	205.0 ± 43.38	208.5 ± 14.85

Notes
[193] - Safety Population.
[194] - Safety Population.
[195] - Safety Population.

No statistical analyses for this end point

Secondary: Part 1: Absolute Values for Hematology Parameter: Hemoglobin

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End point title

Part 1: Absolute Values for Hematology Parameter: Hemoglobin ^[196]

End point description

Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the hematology parameter: hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Days 8 to 10)

Notes
[196] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Number of subjects analysed	6 ^[197]	6 ^[198]	2 ^[199]
Units: Grams per liter
arithmetic mean (standard deviation)
Baseline (Day 1): n=6,5,2	144.2 ± 11.55	135.4 ± 9.42	148.0 ± 4.24
Days 8 to 10: n=6,6,2	140.0 ± 12.18	138.7 ± 12.72	147.0 ± 9.90

Notes
[197] - Safety Population.
[198] - Safety Population.
[199] - Safety Population.

No statistical analyses for this end point

Secondary: Part 1: Absolute Values for Hematology Parameter: Hematocrit

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End point title

Part 1: Absolute Values for Hematology Parameter: Hematocrit ^[200]

End point description

Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the hematology parameter: hematocrit. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Days 8 to 10)

Notes
[200] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Number of subjects analysed	6 ^[201]	6 ^[202]	2 ^[203]
Units: Proportion of red blood cells in blood
arithmetic mean (standard deviation)
Baseline (Day 1): n=6,5,2	0.4338 ± 0.02709	0.4112 ± 0.02523	0.4395 ± 0.01344
Days 8 to 10: n=6,6,2	0.4222 ± 0.03456	0.4158 ± 0.02827	0.4385 ± 0.03182

Notes
[201] - Safety Population.
[202] - Safety Population.
[203] - Safety Population.

No statistical analyses for this end point

Secondary: Part 1: Absolute Values for Hematology Parameter: Erythrocytes

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End point title

Part 1: Absolute Values for Hematology Parameter: Erythrocytes ^[204]

End point description

Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the hematology parameter: erythrocytes. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Days 8 to 10)

Notes
[204] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Number of subjects analysed	6 ^[205]	6 ^[206]	2 ^[207]
Units: 10^12 cells per liter
arithmetic mean (standard deviation)
Baseline (Day 1): n=6,5,2	4.90 ± 0.228	4.58 ± 0.259	4.90 ± 0.283
Days 8 to 10: n=6,6,2	4.80 ± 0.290	4.63 ± 0.327	4.90 ± 0.424

Notes
[205] - Safety Population.
[206] - Safety Population.
[207] - Safety Population.

No statistical analyses for this end point

Secondary: Part 1: Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Volume

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End point title

Part 1: Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Volume ^[208]

End point description

Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the hematology parameter: erythrocytes mean corpuscular volume. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Days 8 to 10)

Notes
[208] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Number of subjects analysed	6 ^[209]	6 ^[210]	2 ^[211]
Units: Femtoliter
arithmetic mean (standard deviation)
Baseline (Day 1): n=6,5,2	88.5 ± 3.67	90.2 ± 3.49	90.0 ± 1.41
Days 8 to 10: n=6,6,2	88.5 ± 4.09	90.0 ± 2.28	90.0 ± 1.41

Notes
[209] - Safety Population.
[210] - Safety Population.
[211] - Safety Population.

No statistical analyses for this end point

Secondary: Part 1: Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin

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End point title

Part 1: Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin ^[212]

End point description

Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the hematology parameter: erythrocytes mean corpuscular hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Days 8 to 10)

Notes
[212] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Number of subjects analysed	6 ^[213]	6 ^[214]	2 ^[215]
Units: Picograms
arithmetic mean (standard deviation)
Baseline (Day 1): n=6,5,2	29.38 ± 1.780	29.64 ± 0.879	30.25 ± 0.636
Days 8 to 10: n=6,6,2	29.30 ± 1.747	29.97 ± 0.942	30.10 ± 0.707

Notes
[213] - Safety Population.
[214] - Safety Population.
[215] - Safety Population.

No statistical analyses for this end point

Secondary: Part 1: Absolute Values for Hematology Parameter: Reticulocytes/Erythro

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End point title

Part 1: Absolute Values for Hematology Parameter: Reticulocytes/Erythro ^[216]

End point description

Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the hematology parameter: reticulocytes/erythro. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Days 8 to 10)

Notes
[216] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Number of subjects analysed	6 ^[217]	6 ^[218]	2 ^[219]
Units: Percentage of reticulocytes in erythro
arithmetic mean (standard deviation)
Baseline (Day 1): n=6,5,2	0.0137 ± 0.00726	0.0078 ± 0.00349	0.0110 ± 0.00424
Days 8 to 10: n=6,6,2	0.0178 ± 0.01139	0.0088 ± 0.00264	0.0130 ± 0.00424

Notes
[217] - Safety Population.
[218] - Safety Population.
[219] - Safety Population.

No statistical analyses for this end point

Secondary: Part 2: Absolute Values for Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes, Platelet Count

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End point title

Part 2: Absolute Values for Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes, Platelet Count ^[220]

End point description

Blood samples were collected to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils, leukocytes and platelet count. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Day 7)

Notes
[220] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Number of subjects analysed	6 ^[221]	6 ^[222]	6 ^[223]	2 ^[224]
Units: 10^9 cells per liter
arithmetic mean (standard deviation)
Baseline (Day 1): Basophils, n=6,6,5,2	0.042 ± 0.0232	0.042 ± 0.0117	0.030 ± 0.0200	0.040 ± 0.0283
Day 7: Basophils, n=5,6,5,2	0.050 ± 0.0274	0.062 ± 0.0223	0.054 ± 0.0251	0.035 ± 0.0071
Baseline (Day 1): Eosinophils, n=6,6,5,2	0.402 ± 0.3307	0.290 ± 0.2628	0.320 ± 0.2542	0.055 ± 0.0354
Day 7: Eosinophils, n=5,6,5,2	0.316 ± 0.1780	0.243 ± 0.1546	0.210 ± 0.1239	0.075 ± 0.0354
Baseline (Day 1): Lymphocytes, n=6,6,5,2	1.990 ± 0.3013	2.047 ± 0.6167	2.236 ± 0.3010	1.865 ± 0.3606
Day 7: Lymphocytes, n=5,6,5,2	1.960 ± 0.3450	1.985 ± 0.2983	2.694 ± 0.7060	1.755 ± 0.0919
Baseline (Day 1): Monocytes, n=6,6,5,2	0.560 ± 0.2082	0.477 ± 0.1442	0.534 ± 0.1459	0.435 ± 0.1061
Day 7: Monocytes, n=5,6,5,2	0.530 ± 0.2210	0.498 ± 0.2647	0.414 ± 0.1467	0.305 ± 0.0071
Baseline (Day 1): Neutrophils, n=6,6,5,2	2.512 ± 1.2631	2.442 ± 1.1951	3.060 ± 0.5711	2.280 ± 1.0465
Day 7: Neutrophils, n=5,6,5,2	2.826 ± 1.1821	4.120 ± 2.9025	3.344 ± 0.6322	2.065 ± 1.3647
Baseline (Day 1): Leukocytes, n=6,6,5,2	5.50 ± 1.633	5.28 ± 1.947	6.20 ± 0.938	4.65 ± 1.485
Day 7: Leukocytes, n=5,6,6,2	5.66 ± 1.527	6.90 ± 3.310	6.55 ± 0.973	4.20 ± 1.414
Baseline (Day 1): Platelet count, n=5,6,5,2	276.6 ± 54.29	236.7 ± 41.87	232.2 ± 40.12	197.0 ± 59.40
Day 7: Platelet count, n=4,6,6,2	292.0 ± 77.06	254.2 ± 37.39	249.0 ± 38.72	201.5 ± 60.10

Notes
[221] - Safety Population.
[222] - Safety Population.
[223] - Safety Population.
[224] - Safety Population.

No statistical analyses for this end point

Secondary: Part 2: Absolute Values for Hematology Parameter: Hemoglobin

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End point title

Part 2: Absolute Values for Hematology Parameter: Hemoglobin ^[225]

End point description

Blood samples were collected to analyze the hematology parameter: hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Day 7)

Notes
[225] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Number of subjects analysed	6 ^[226]	6 ^[227]	6 ^[228]	2 ^[229]
Units: Grams per liter
arithmetic mean (standard deviation)
Baseline (Day 1): n=6,6,5,2	136.3 ± 16.34	149.2 ± 13.44	141.2 ± 7.98	147.0 ± 7.07
Day 7: n=5,6,6,2	129.4 ± 19.55	144.5 ± 7.87	135.8 ± 11.02	139.0 ± 8.49

Notes
[226] - Safety Population.
[227] - Safety Population.
[228] - Safety Population.
[229] - Safety Population.

No statistical analyses for this end point

Secondary: Part 2: Absolute Values for Hematology Parameter: Hematocrit

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End point title

Part 2: Absolute Values for Hematology Parameter: Hematocrit ^[230]

End point description

Blood samples were collected to analyze the hematology parameter: hematocrit. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Day 7)

Notes
[230] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Number of subjects analysed	6 ^[231]	6 ^[232]	6 ^[233]	2 ^[234]
Units: Proportion of red blood cells in blood
arithmetic mean (standard deviation)
Baseline (Day 1): n=6,6,5,2	0.4037 ± 0.04646	0.4505 ± 0.02992	0.4222 ± 0.01879	0.4330 ± 0.01838
Day 7: n=5,6,6,2	0.3826 ± 0.05125	0.4382 ± 0.01579	0.4062 ± 0.03107	0.4015 ± 0.03323

Notes
[231] - Safety Population.
[232] - Safety Population.
[233] - Safety Population.
[234] - Safety Population.

No statistical analyses for this end point

Secondary: Part 2: Absolute Values for Hematology Parameter: Erythrocytes

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End point title

Part 2: Absolute Values for Hematology Parameter: Erythrocytes ^[235]

End point description

Blood samples were collected to analyze the hematology parameter: erythrocytes. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Day 7)

Notes
[235] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Number of subjects analysed	6 ^[236]	6 ^[237]	6 ^[238]	2 ^[239]
Units: 10^12 cells per liter
arithmetic mean (standard deviation)
Baseline (Day 1): n=6,6,5,2	4.53 ± 0.476	5.17 ± 0.450	4.74 ± 0.230	4.80 ± 0.000
Day 7: n=5,6,6,2	4.26 ± 0.503	5.00 ± 0.518	4.52 ± 0.431	4.50 ± 0.000

Notes
[236] - Safety Population.
[237] - Safety Population.
[238] - Safety Population.
[239] - Safety Population.

No statistical analyses for this end point

Secondary: Part 2: Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Volume

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End point title

Part 2: Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Volume ^[240]

End point description

Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular volume. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Day 7)

Notes
[240] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Number of subjects analysed	6 ^[241]	6 ^[242]	6 ^[243]	2 ^[244]
Units: Femtoliter
arithmetic mean (standard deviation)
Baseline (Day 1): n=6,6,5,2	88.8 ± 3.76	87.8 ± 8.59	89.2 ± 1.64	91.0 ± 4.24
Day 7: n=5,6,6,2	89.6 ± 3.44	88.0 ± 8.53	90.0 ± 2.97	89.0 ± 7.07

Notes
[241] - Safety Population.
[242] - Safety Population.
[243] - Safety Population.
[244] - Safety Population.

No statistical analyses for this end point

Secondary: Part 2: Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin

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End point title

Part 2: Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin ^[245]

End point description

Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Day 7)

Notes
[245] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Number of subjects analysed	6 ^[246]	6 ^[247]	6 ^[248]	2 ^[249]
Units: Picograms
arithmetic mean (standard deviation)
Baseline (Day 1): n=6,6,5,2	30.07 ± 1.870	29.15 ± 3.531	29.80 ± 0.925	30.95 ± 1.485
Day 7: n=5,6,6,2	30.22 ± 2.017	29.10 ± 3.553	29.97 ± 0.898	30.90 ± 1.838

Notes
[246] - Safety Population.
[247] - Safety Population.
[248] - Safety Population.
[249] - Safety Population.

No statistical analyses for this end point

Secondary: Part 2: Absolute Values for Hematology Parameter: Reticulocytes/Erythro

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End point title

Part 2: Absolute Values for Hematology Parameter: Reticulocytes/Erythro ^[250]

End point description

Blood samples were collected to analyze the hematology parameter: reticulocytes/erythro. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Day 7)

Notes
[250] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Number of subjects analysed	6 ^[251]	6 ^[252]	6 ^[253]	2 ^[254]
Units: Percentage of reticulocytes in erythro
arithmetic mean (standard deviation)
Baseline (Day 1): n=6,6,5,2	0.0102 ± 0.00223	0.0082 ± 0.00147	0.0108 ± 0.00492	0.0070 ± 0.00141
Day 7: n=5,6,6,2	0.0124 ± 0.00297	0.0098 ± 0.00160	0.0107 ± 0.00344	0.0090 ± 0.00141

Notes
[251] - Safety Population.
[252] - Safety Population.
[253] - Safety Population.
[254] - Safety Population.

No statistical analyses for this end point

Secondary: Part 1: Absolute Values for Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Calcium, Chloride, Phosphate, Potassium, Magnesium, Sodium, Urea, HDL Cholesterol, LDL Cholesterol

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End point title

Part 1: Absolute Values for Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Calcium, Chloride, Phosphate, Potassium, Magnesium, Sodium, Urea, HDL Cholesterol, LDL Cholesterol ^[255]

End point description

Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the chemistry parameters: glucose, cholesterol, triglycerides, calcium, chloride, phosphate, potassium, magnesium, sodium, urea, HDL cholesterol and LDL cholesterol. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles). 99999 indicates data is not available.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Days 8 to 10)

Notes
[255] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Number of subjects analysed	6 ^[256]	6 ^[257]	2 ^[258]
Units: Millimoles per liter
arithmetic mean (standard deviation)
Baseline (Day 1): Glucose, n=6,6,2	5.28 ± 0.556	4.88 ± 0.546	5.40 ± 0.141
Days 8 to 10: Glucose, n=6,6,2	5.08 ± 0.618	5.17 ± 0.528	5.40 ± 0.283
Baseline (Day 1): Cholesterol, n=6,6,2	4.700 ± 1.2345	4.058 ± 0.9641	4.350 ± 0.6364
Days 8 to 10: Cholesterol, n=0,0,0	99999 ± 99999	99999 ± 99999	99999 ± 99999
Baseline (Day 1): Triglycerides, n=6,6,2	1.070 ± 0.4527	1.150 ± 0.5114	0.950 ± 0.4101
Days 8 to 10: Triglycerides, n=0,0,0	99999 ± 99999	99999 ± 99999	99999 ± 99999
Baseline (Day 1): Calcium, n=6,6,2	2.300 ± 0.1073	2.313 ± 0.0961	2.330 ± 0.0141
Days 8 to 10: Calcium, n=6,6,2	2.293 ± 0.0816	2.287 ± 0.0561	2.350 ± 0.0424
Baseline (Day 1): Chloride, n=6,6,2	104.2 ± 0.41	105.8 ± 2.48	105.0 ± 2.83
Days 8 to 10: Chloride, n=6,6,2	104.2 ± 1.72	106.7 ± 1.21	104.5 ± 0.71
Baseline (Day 1): Phosphate, n=6,6,2	1.117 ± 0.1835	1.083 ± 0.1889	1.200 ± 0.0707
Days 8 to 10: Phosphate, n=6,6,2	1.158 ± 0.1882	1.142 ± 0.2245	1.125 ± 0.1768
Baseline (Day 1): Potassium, n=6,6,2	4.10 ± 0.210	4.30 ± 0.276	4.15 ± 0.212
Days 8 to 10: Potassium, n=6,6,2	4.12 ± 0.349	4.27 ± 0.216	4.05 ± 0.212
Baseline (Day 1): Magnesium, n=6,6,2	0.847 ± 0.0393	0.853 ± 0.0450	0.880 ± 0.0283
Days 8 to 10: Magnesium, n=6,6,2	0.847 ± 0.0561	0.847 ± 0.0393	0.860 ± 0.0000
Baseline (Day 1): Sodium, n=6,6,2	138.3 ± 2.25	139.8 ± 0.75	139.0 ± 0.00
Days 8 to 10: Sodium, n=6,6,2	138.5 ± 2.17	139.0 ± 0.89	138.0 ± 1.41
Baseline (Day 1): Urea, n=6,6,2	5.33 ± 0.516	5.83 ± 1.169	5.00 ± 0.707
Days 8 to 10: Urea, n=6,6,2	5.25 ± 1.037	5.75 ± 0.524	6.00 ± 0.707
Baseline (Day 1): HDL cholesterol, n=6,6,2	1.192 ± 0.1960	1.025 ± 0.0612	1.075 ± 0.0354
Days 8 to 10: HDL cholesterol, n=0,0,0	99999 ± 99999	99999 ± 99999	99999 ± 99999
Baseline (Day 1): LDL cholesterol, n=6,6,2	3.017 ± 1.0452	2.507 ± 0.7842	2.840 ± 0.4808
Days 8 to 10: LDL cholesterol, n=0,0,0	99999 ± 99999	99999 ± 99999	99999 ± 99999

Notes
[256] - Safety Population.
[257] - Safety Population.
[258] - Safety Population.

No statistical analyses for this end point

Secondary: Part 1: Absolute Values for Chemistry Parameters: ALT, ALP, AST

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End point title

Part 1: Absolute Values for Chemistry Parameters: ALT, ALP, AST ^[259]

End point description

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Days 8 to 10)

Notes
[259] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Number of subjects analysed	6 ^[260]	6 ^[261]	2 ^[262]
Units: International units per liter
arithmetic mean (standard deviation)
Baseline (Day 1): ALT	31.3 ± 15.67	19.7 ± 15.82	20.0 ± 8.49
Days 8 to 10: ALT	34.0 ± 21.58	18.0 ± 11.85	29.5 ± 14.85
Baseline (Day 1): ALP	62.0 ± 10.55	62.3 ± 19.13	63.0 ± 2.83
Days 8 to 10: ALP	72.5 ± 27.68	58.8 ± 16.46	59.0 ± 1.41
Baseline (Day 1): AST	26.7 ± 9.42	23.3 ± 10.76	20.0 ± 8.49
Days 8 to 10: AST	26.2 ± 11.27	21.3 ± 4.63	24.5 ± 10.61

Notes
[260] - Safety Population.
[261] - Safety Population.
[262] - Safety Population.

No statistical analyses for this end point

Secondary: Part 1: Absolute Values for Chemistry Parameters: Creatinine, Bilirubin

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End point title

Part 1: Absolute Values for Chemistry Parameters: Creatinine, Bilirubin ^[263]

End point description

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Days 8 to 10)

Notes
[263] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Number of subjects analysed	6 ^[264]	6 ^[265]	2 ^[266]
Units: Micromoles per liter
arithmetic mean (standard deviation)
Baseline (Day 1): Creatinine	82.05 ± 11.319	81.35 ± 3.861	88.40 ± 3.818
Days 8 to 10: Creatinine	83.82 ± 13.674	80.02 ± 6.239	88.40 ± 3.818
Baseline (Day 1): Bilirubin	11.7 ± 6.38	8.0 ± 2.83	15.0 ± 1.41
Days 8 to 10: Bilirubin	11.3 ± 3.50	6.0 ± 1.79	18.0 ± 8.49

Notes
[264] - Safety Population.
[265] - Safety Population.
[266] - Safety Population.

No statistical analyses for this end point

Secondary: Part 1: Absolute Values for Chemistry Parameters: Protein

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End point title

Part 1: Absolute Values for Chemistry Parameters: Protein ^[267]

End point description

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Days 8 to 10)

Notes
[267] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Number of subjects analysed	6 ^[268]	6 ^[269]	2 ^[270]
Units: Grams per liter
arithmetic mean (standard deviation)
Baseline (Day 1)	72.2 ± 3.06	70.3 ± 2.34	69.0 ± 1.41
Days 8 to 10	70.8 ± 3.60	69.3 ± 5.05	70.0 ± 1.41

Notes
[268] - Safety Population.
[269] - Safety Population.
[270] - Safety Population.

No statistical analyses for this end point

Secondary: Part 1: Absolute Values for Chemistry Parameters: Amylase, Lipase

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End point title

Part 1: Absolute Values for Chemistry Parameters: Amylase, Lipase ^[271]

End point description

Blood samples were collected to analyze the chemistry parameters: amylase and lipase. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Only those participants with data available at the specified time points were analyzed. Amylase and lipase results were collected for two participants in GSK3640254 10 mg arm during Part 1 of the study. No data were collected for Placebo and GSK3640254 200 mg arms at Visit 6 (Day 11) due to delays in approval of Protocol Amendment 02 into which testing for amylase and lipase was added.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 6 (Day 11)

Notes
[271] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Number of subjects analysed	2 ^[272]	0 ^[273]	0 ^[274]
Units: Units per liter
arithmetic mean (standard deviation)
Baseline (Day 1): Amylase	57.0 ± 11.31	±	±
Day 11: Amylase	57.0 ± 0.00	±	±
Baseline (Day 1): Lipase	28.5 ± 4.95	±	±
Day 11: Lipase	26.5 ± 7.78	±	±

Notes
[272] - Safety Population.
[273] - Safety Population.
[274] - Safety Population.

No statistical analyses for this end point

Secondary: Part 2: Absolute Values for Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Calcium, Chloride, Phosphate, Potassium, Magnesium, Sodium, Urea, HDL Cholesterol, LDL Cholesterol

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End point title

Part 2: Absolute Values for Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Calcium, Chloride, Phosphate, Potassium, Magnesium, Sodium, Urea, HDL Cholesterol, LDL Cholesterol ^[275]

End point description

Blood samples were collected to analyze the chemistry parameters: glucose, cholesterol, triglycerides, calcium, chloride, phosphate, potassium, magnesium, sodium, urea, HDL cholesterol and LDL cholesterol. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles). 99999 indicates that, standard deviation could not be calculated for single participant. 88888 indicates data is not available.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Day 7)

Notes
[275] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Number of subjects analysed	6 ^[276]	6 ^[277]	6 ^[278]	2 ^[279]
Units: Millimoles per liter
arithmetic mean (standard deviation)
Baseline (Day 1): Glucose, n=6,6,6,2	4.68 ± 0.306	4.72 ± 0.928	4.80 ± 0.456	4.90 ± 0.849
Day 7: Glucose, n=6,6,6,1	4.63 ± 0.408	4.90 ± 0.190	4.77 ± 0.320	4.80 ± 99999
Baseline (Day 1): Cholesterol, n=6,6,6,2	4.233 ± 0.6758	4.375 ± 1.1626	4.150 ± 0.8573	3.400 ± 0.3536
Day 7: Cholesterol, n=0,0,0,0	88888 ± 88888	88888 ± 88888	88888 ± 88888	88888 ± 88888
Baseline (Day 1): Triglycerides, n=6,6,6,2	1.183 ± 0.1924	1.447 ± 0.6008	1.120 ± 0.4879	0.540 ± 0.1980
Day 7: Triglycerides, n=0,0,0,0	88888 ± 88888	88888 ± 88888	88888 ± 88888	88888 ± 88888
Baseline (Day 1): Calcium, n=6,6,6,2	2.330 ± 0.0629	2.320 ± 0.0980	2.290 ± 0.0701	2.280 ± 0.0849
Day 7: Calcium, n=6,6,6,1	2.273 ± 0.0628	2.293 ± 0.0766	2.320 ± 0.0780	2.220 ± 99999
Baseline (Day 1): Chloride, n=6,6,6,2	103.0 ± 1.67	102.2 ± 2.64	103.7 ± 2.34	105.5 ± 0.71
Day 7: Chloride, n=6,6,6,1	102.3 ± 1.51	102.0 ± 1.79	103.0 ± 1.10	104.0 ± 99999
Baseline (Day 1): Phosphate, n=6,6,6,2	1.317 ± 0.1693	1.108 ± 0.1281	1.083 ± 0.1211	0.950 ± 0.2828
Day 7: Phosphate, n=6,6,6,1	1.200 ± 0.1265	1.175 ± 0.1969	1.167 ± 0.1329	0.750 ± 99999
Baseline (Day 1): Potassium, n=6,6,6,2	4.07 ± 0.476	3.98 ± 0.325	3.95 ± 0.164	4.10 ± 0.424
Day 7: Potassium, n=6,6,6,1	3.87 ± 0.273	4.03 ± 0.242	4.15 ± 0.122	3.70 ± 99999
Baseline (Day 1): Magnesium, n=6,6,6,2	0.790 ± 0.0395	0.830 ± 0.0518	0.803 ± 0.0320	0.810 ± 0.0707
Day 7: Magnesium, n=6,6,6,1	0.797 ± 0.0731	0.837 ± 0.0427	0.830 ± 0.0654	0.760 ± 99999
Baseline (Day 1): Sodium, n=6,6,6,2	137.7 ± 1.63	138.5 ± 2.43	137.8 ± 3.06	140.5 ± 2.12
Day 7: Sodium, n=6,6,6,1	136.8 ± 3.54	138.2 ± 1.94	137.7 ± 1.97	138.0 ± 99999
Baseline (Day 1): Urea, n=6,6,6,2	4.50 ± 1.517	4.25 ± 1.508	5.92 ± 1.068	6.25 ± 2.475
Day 7: Urea, n=6,6,6,1	4.08 ± 0.970	4.00 ± 0.632	5.58 ± 0.492	4.00 ± 99999
Baseline (Day 1): HDL cholesterol, n=6,6,6,2	1.242 ± 0.3277	1.133 ± 0.3312	1.200 ± 0.3194	1.250 ± 0.0707
Day 7: HDL cholesterol, n=0,0,0,0	88888 ± 88888	88888 ± 88888	88888 ± 88888	88888 ± 88888
Baseline (Day 1): LDL cholesterol, n=6,6,6,2	2.448 ± 0.6649	2.578 ± 0.8267	2.437 ± 0.6955	1.905 ± 0.3748
Day 7: LDL cholesterol, n=0,0,0,0	88888 ± 88888	88888 ± 88888	88888 ± 88888	88888 ± 88888

Notes
[276] - Safety Population.
[277] - Safety Population.
[278] - Safety Population.
[279] - Safety Population.

No statistical analyses for this end point

Secondary: Part 2: Absolute Values for Chemistry Parameters: ALT, ALP, AST

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End point title

Part 2: Absolute Values for Chemistry Parameters: ALT, ALP, AST ^[280]

End point description

Blood samples were collected to analyze the chemistry parameters: ALT, ALP and AST. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles). 99999 indicates that, standard deviation could not be calculated for single participant.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Day 7)

Notes
[280] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Number of subjects analysed	6 ^[281]	6 ^[282]	6 ^[283]	2 ^[284]
Units: International units per liter
arithmetic mean (standard deviation)
Baseline (Day 1): ALT, n=6,6,6,2	18.3 ± 14.07	17.8 ± 7.63	33.2 ± 23.07	34.5 ± 6.36
Day 7: ALT, n=6,6,6,1	14.5 ± 7.66	16.7 ± 5.24	27.0 ± 18.00	29.0 ± 99999
Baseline (Day 1): ALP, n=6,6,6,2	63.3 ± 15.08	63.7 ± 4.68	60.8 ± 9.00	43.0 ± 18.38
Day 7: ALP, n=6,6,6,1	60.2 ± 16.53	63.0 ± 5.25	59.0 ± 5.18	55.0 ± 99999
Baseline (Day 1): AST, n=6,6,6,2	26.8 ± 15.39	18.5 ± 6.60	26.7 ± 8.14	50.0 ± 39.60
Day 7: AST, n=6,6,6,1	21.7 ± 6.74	18.8 ± 3.31	22.0 ± 3.74	26.0 ± 99999

Notes
[281] - Safety Population.
[282] - Safety Population.
[283] - Safety Population.
[284] - Safety Population.

No statistical analyses for this end point

Secondary: Part 2: Absolute Values for Chemistry Parameters: Creatinine, Bilirubin

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End point title

Part 2: Absolute Values for Chemistry Parameters: Creatinine, Bilirubin ^[285]

End point description

Blood samples were collected to analyze the chemistry parameters: creatinine and bilirubin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles). 99999 indicates that, standard deviation could not be calculated for single participant.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Day 7)

Notes
[285] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Number of subjects analysed	6 ^[286]	6 ^[287]	6 ^[288]	2 ^[289]
Units: Micromoles per liter
arithmetic mean (standard deviation)
Baseline (Day 1): Creatinine, n=6,6,6,2	71.30 ± 12.207	73.67 ± 7.120	73.52 ± 12.761	86.65 ± 13.789
Day 7: Creatinine, n=6,6,6,1	72.65 ± 14.109	70.28 ± 8.269	73.35 ± 8.195	76.00 ± 99999
Baseline (Day 1): Bilirubin, n=6,6,6,2	10.0 ± 5.66	9.3 ± 1.03	7.7 ± 3.44	11.0 ± 7.07
Day 7: Bilirubin, n=6,6,6,1	9.7 ± 4.97	10.7 ± 5.47	8.0 ± 2.83	6.0 ± 99999

Notes
[286] - Safety Population.
[287] - Safety Population.
[288] - Safety Population.
[289] - Safety Population.

No statistical analyses for this end point

Secondary: Part 2: Absolute Values for Chemistry Parameters: Protein

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End point title

Part 2: Absolute Values for Chemistry Parameters: Protein ^[290]

End point description

Blood samples were collected to analyze the chemistry parameter: protein. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles). 99999 indicates that, standard deviation could not be calculated for single participant.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Day 7)

Notes
[290] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Number of subjects analysed	6 ^[291]	6 ^[292]	6 ^[293]	2 ^[294]
Units: Grams per liter
arithmetic mean (standard deviation)
Baseline (Day 1): n=6,6,6,2	78.8 ± 12.78	73.3 ± 5.50	76.7 ± 10.03	73.5 ± 0.71
Day 7: n=6,6,6,1	76.7 ± 12.01	72.5 ± 5.13	78.2 ± 8.93	72.0 ± 99999

Notes
[291] - Safety Population.
[292] - Safety Population.
[293] - Safety Population.
[294] - Safety Population.

No statistical analyses for this end point

Secondary: Part 2: Absolute Values for Chemistry Parameters: Amylase, Lipase

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End point title

Part 2: Absolute Values for Chemistry Parameters: Amylase, Lipase ^[295]

End point description

Blood samples were collected to analyze the chemistry parameters: amylase and lipase. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles). 99999 indicates that, standard deviation could not be calculated for single participant.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Day 7)

Notes
[295] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Number of subjects analysed	6 ^[296]	6 ^[297]	6 ^[298]	2 ^[299]
Units: Units per liter
arithmetic mean (standard deviation)
Baseline (Day 1): Amylase, n=6,6,6,2	47.2 ± 18.15	51.0 ± 21.65	55.2 ± 18.61	56.0 ± 25.46
Day 7: Amylase, n=6,6,6,1	44.8 ± 17.81	51.8 ± 22.71	61.8 ± 25.86	64.0 ± 99999
Baseline (Day 1): Lipase, n=6,6,6,2	26.5 ± 14.08	29.7 ± 10.95	43.2 ± 32.32	26.0 ± 14.14
Day 7: Lipase, n=6,6,6,1	25.5 ± 11.64	27.5 ± 13.40	47.7 ± 34.70	44.0 ± 99999

Notes
[296] - Safety Population.
[297] - Safety Population.
[298] - Safety Population.
[299] - Safety Population.

No statistical analyses for this end point

Secondary: Part 1: Absolute Values for Urinalysis Parameter: Specific Gravity

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End point title

Part 1: Absolute Values for Urinalysis Parameter: Specific Gravity ^[300]

End point description

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Days 8 to 10)

Notes
[300] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Number of subjects analysed	6 ^[301]	6 ^[302]	2 ^[303]
Units: Ratio
arithmetic mean (standard deviation)
Baseline (Day 1)	1.0238 ± 0.00677	1.0233 ± 0.00320	1.0240 ± 0.00283
Days 8 to 10	1.0240 ± 0.00533	1.0242 ± 0.00279	1.0240 ± 0.00000

Notes
[301] - Safety Population.
[302] - Safety Population.
[303] - Safety Population.

No statistical analyses for this end point

Secondary: Part 1: Absolute Values for Urinalysis Parameter: Urobilinogen

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End point title

Part 1: Absolute Values for Urinalysis Parameter: Urobilinogen ^[304]

End point description

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Days 8 to 10)

Notes
[304] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Number of subjects analysed	6 ^[305]	6 ^[306]	2 ^[307]
Units: Micromoles per liter
arithmetic mean (standard deviation)
Baseline (Day 1)	3.40 ± 0.000	3.40 ± 0.000	3.40 ± 0.000
Days 8 to 10	7.90 ± 6.971	3.40 ± 0.000	3.40 ± 0.000

Notes
[305] - Safety Population.
[306] - Safety Population.
[307] - Safety Population.

No statistical analyses for this end point

Secondary: Part 1: Absolute Values for Urinalysis Parameter: pH

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End point title

Part 1: Absolute Values for Urinalysis Parameter: pH ^[308]

End point description

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Days 8 to 10)

Notes
[308] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Number of subjects analysed	6 ^[309]	6 ^[310]	2 ^[311]
Units: pH
arithmetic mean (standard deviation)
Baseline (Day 1)	5.67 ± 0.931	5.75 ± 0.689	5.75 ± 0.354
Days 8 to 10	5.83 ± 0.753	5.42 ± 0.585	5.25 ± 0.354

Notes
[309] - Safety Population.
[310] - Safety Population.
[311] - Safety Population.

No statistical analyses for this end point

Secondary: Part 2: Absolute Values for Urinalysis Parameter: Specific Gravity

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End point title

Part 2: Absolute Values for Urinalysis Parameter: Specific Gravity ^[312]

End point description

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Day 7)

Notes
[312] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Number of subjects analysed	6 ^[313]	6 ^[314]	6 ^[315]	2 ^[316]
Units: Ratio
arithmetic mean (standard deviation)
Baseline (Day 1)	1.0223 ± 0.00866	1.0272 ± 0.00360	1.0255 ± 0.00918	1.0375 ± 0.00495
Day 7	1.0233 ± 0.00686	1.0250 ± 0.00522	1.0273 ± 0.00327	1.0265 ± 0.00919

Notes
[313] - Safety Population.
[314] - Safety Population.
[315] - Safety Population.
[316] - Safety Population.

No statistical analyses for this end point

Secondary: Part 2: Absolute Values for Urinalysis Parameter: Urobilinogen

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End point title

Part 2: Absolute Values for Urinalysis Parameter: Urobilinogen ^[317]

End point description

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Day 7)

Notes
[317] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Number of subjects analysed	6 ^[318]	6 ^[319]	6 ^[320]	2 ^[321]
Units: Micromoles per liter
arithmetic mean (standard deviation)
Baseline (Day 1)	3.40 ± 0.000	3.40 ± 0.000	3.40 ± 0.000	3.40 ± 0.000
Day 7	3.40 ± 0.000	7.90 ± 6.971	3.40 ± 0.000	3.40 ± 0.000

Notes
[318] - Safety Population.
[319] - Safety Population.
[320] - Safety Population.
[321] - Safety Population.

No statistical analyses for this end point

Secondary: Part 2: Absolute Values for Urinalysis Parameter: pH

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End point title

Part 2: Absolute Values for Urinalysis Parameter: pH ^[322]

End point description

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Day 7)

Notes
[322] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Number of subjects analysed	6 ^[323]	6 ^[324]	6 ^[325]	2 ^[326]
Units: pH
arithmetic mean (standard deviation)
Baseline (Day 1)	5.33 ± 0.258	5.83 ± 0.753	5.25 ± 0.418	5.50 ± 0.000
Day 7	5.50 ± 0.775	5.67 ± 0.258	5.33 ± 0.258	5.75 ± 0.354

Notes
[323] - Safety Population.
[324] - Safety Population.
[325] - Safety Population.
[326] - Safety Population.

No statistical analyses for this end point

Secondary: Part 1: Absolute Values for SBP and DBP

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End point title

Part 1: Absolute Values for SBP and DBP ^[327]

End point description

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Days 8 to 10)

Notes
[327] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Number of subjects analysed	6 ^[328]	6 ^[329]	2 ^[330]
Units: Millimeters of mercury
arithmetic mean (standard deviation)
Baseline (Day 1): SBP	120.2 ± 13.36	121.8 ± 12.25	106.0 ± 11.31
Days 8 to 10: SBP	117.7 ± 8.87	122.3 ± 7.94	104.5 ± 7.78
Baseline (Day 1): DBP	70.3 ± 17.32	66.7 ± 10.80	64.0 ± 5.66
Days 8 to 10: DBP	70.0 ± 6.81	67.5 ± 9.91	64.5 ± 4.95

Notes
[328] - Safety Population.
[329] - Safety Population.
[330] - Safety Population.

No statistical analyses for this end point

Secondary: Part 1: Absolute Values for Respiratory Rate

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End point title

Part 1: Absolute Values for Respiratory Rate ^[331]

End point description

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Days 8 to 10)

Notes
[331] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Number of subjects analysed	6 ^[332]	6 ^[333]	2 ^[334]
Units: Breaths per minute
arithmetic mean (standard deviation)
Baseline (Day 1)	16.0 ± 2.61	16.2 ± 3.31	15.0 ± 4.24
Days 8 to 10	15.0 ± 1.26	16.3 ± 2.73	14.0 ± 2.83

Notes
[332] - Safety Population.
[333] - Safety Population.
[334] - Safety Population.

No statistical analyses for this end point

Secondary: Part 1: Absolute Values for Pulse Rate

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End point title

Part 1: Absolute Values for Pulse Rate ^[335]

End point description

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Days 8 to 10)

Notes
[335] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Number of subjects analysed	6 ^[336]	6 ^[337]	2 ^[338]
Units: Beats per minute
arithmetic mean (standard deviation)
Baseline (Day 1)	81.8 ± 18.25	65.8 ± 14.22	60.0 ± 2.83
Days 8 to 10	76.7 ± 21.13	71.3 ± 11.93	66.0 ± 5.66

Notes
[336] - Safety Population.
[337] - Safety Population.
[338] - Safety Population.

No statistical analyses for this end point

Secondary: Part 2: Absolute Values for SBP and DBP

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End point title

Part 2: Absolute Values for SBP and DBP ^[339]

End point description

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Day 7)

Notes
[339] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Number of subjects analysed	6 ^[340]	6 ^[341]	6 ^[342]	2 ^[343]
Units: Millimeters of mercury
arithmetic mean (standard deviation)
Baseline (Day 1): SBP	117.0 ± 7.95	116.5 ± 11.04	112.2 ± 9.93	105.5 ± 2.12
Day 7: SBP	118.0 ± 12.07	114.3 ± 8.36	119.5 ± 8.87	106.5 ± 4.95
Baseline (Day 1): DBP	71.5 ± 4.51	74.0 ± 4.69	71.8 ± 12.89	71.0 ± 12.73
Day 7: DBP	69.7 ± 4.50	73.0 ± 5.06	74.2 ± 5.27	70.5 ± 4.95

Notes
[340] - Safety Population.
[341] - Safety Population.
[342] - Safety Population.
[343] - Safety Population.

No statistical analyses for this end point

Secondary: Part 2: Absolute Values for Respiratory Rate

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End point title

Part 2: Absolute Values for Respiratory Rate ^[344]

End point description

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Day 7)

Notes
[344] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Number of subjects analysed	6 ^[345]	6 ^[346]	6 ^[347]	2 ^[348]
Units: Breaths per minute
arithmetic mean (standard deviation)
Baseline (Day 1)	17.3 ± 2.66	17.2 ± 1.17	17.2 ± 2.40	16.0 ± 0.00
Day 7	17.2 ± 2.56	17.3 ± 2.07	16.2 ± 2.23	16.5 ± 2.12

Notes
[345] - Safety Population.
[346] - Safety Population.
[347] - Safety Population.
[348] - Safety Population.

No statistical analyses for this end point

Secondary: Part 2: Absolute Values for Pulse Rate

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End point title

Part 2: Absolute Values for Pulse Rate ^[349]

End point description

End point type

Secondary

End point timeframe

Baseline (Day 1) and Visit 5 (Day 7)

Notes
[349] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Number of subjects analysed	6 ^[350]	6 ^[351]	6 ^[352]	2 ^[353]
Units: Beats per minute
arithmetic mean (standard deviation)
Baseline (Day 1)	68.3 ± 9.91	74.5 ± 8.36	77.0 ± 10.16	64.5 ± 13.44
Day 7	72.5 ± 16.34	76.5 ± 7.87	79.8 ± 12.45	75.0 ± 5.66

Notes
[350] - Safety Population.
[351] - Safety Population.
[352] - Safety Population.
[353] - Safety Population.

No statistical analyses for this end point

Secondary: Part 1: Absolute Values for ECG Parameters: PR, QRS, QT, QTcB and QTcF intervals

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End point title

Part 1: Absolute Values for ECG Parameters: PR, QRS, QT, QTcB and QTcF intervals ^[354]

End point description

Twelve lead ECGs were obtained to measure PR interval, QRS duration, QT interval, QTcF interval and QTcB interval. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

End point type

Secondary

End point timeframe

Baseline (Day 1), Visit 5 (Days 8 to 10: Pre-dose, 2, 4 and 6 hours)

Notes
[354] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Number of subjects analysed	6 ^[355]	6 ^[356]	2 ^[357]
Units: Milliseconds
arithmetic mean (standard deviation)
PR Interval- Baseline (Day 1)	136.6 ± 14.49	168.4 ± 15.48	176.5 ± 27.58
PR Interval- Days 8 to 10: Pre-dose	136.2 ± 15.26	160.8 ± 19.60	174.0 ± 29.70
PR Interval- Days 8 to 10: 2 hours	138.0 ± 14.46	162.2 ± 11.53	165.0 ± 28.28
PR Interval- Days 8 to 10: 4 hours	136.5 ± 12.10	168.7 ± 13.81	173.0 ± 28.28
PR Interval- Days 8 to 10: 6 hours	138.0 ± 9.10	162.5 ± 15.06	151.5 ± 23.33
QRS Duration- Baseline (Day 1)	93.1 ± 4.54	95.7 ± 6.85	85.8 ± 11.08
QRS Duration- Days 8 to 10: Pre-dose	90.0 ± 7.46	92.3 ± 7.74	80.5 ± 7.78
QRS Duration- Days 8 to 10: 2 hours	91.0 ± 6.36	96.2 ± 7.17	86.0 ± 7.07
QRS Duration- Days 8 to 10: 4 hours	89.8 ± 5.91	94.0 ± 6.42	84.5 ± 14.85
QRS Duration- Days 8 to 10: 6 hours	89.5 ± 7.04	92.8 ± 10.11	83.5 ± 2.12
QT Interval- Baseline (Day 1)	367.6 ± 26.04	378.7 ± 26.75	372.7 ± 29.70
QT Interval- Days 8 to 10: Pre-dose	368.3 ± 23.35	376.0 ± 31.46	353.0 ± 8.49
QT Interval- Days 8 to 10: 2 hours	365.2 ± 25.39	383.2 ± 26.84	344.0 ± 25.46
QT Interval- Days 8 to 10: 4 hours	376.3 ± 22.70	387.7 ± 29.34	347.5 ± 10.61
QT Interval- Days 8 to 10: 6 hours	373.3 ± 26.48	384.5 ± 25.37	348.5 ± 7.78
QTcB Interval- Baseline (Day 1)	412.15 ± 31.539	397.75 ± 22.914	388.43 ± 39.598
QTcB Interval- Days 8 to 10: Pre-dose	413.80 ± 42.176	401.35 ± 22.923	387.05 ± 33.163
QTcB Interval- Days 8 to 10: 2 hours	401.70 ± 37.316	393.15 ± 26.290	361.05 ± 7.283
QTcB Interval- Days 8 to 10: 4 hours	412.92 ± 42.143	387.38 ± 24.454	358.20 ± 12.162
QTcB Interval- Days 8 to 10: 6 hours	414.80 ± 34.569	388.60 ± 23.893	383.55 ± 28.496
QTcF Interval- Baseline (Day 1)	396.2 ± 17.67	391.2 ± 19.11	383.2 ± 36.06
QTcF Interval- Days 8 to 10: Pre-dose	397.3 ± 25.34	392.3 ± 20.64	375.5 ± 24.75
QTcF Interval- Days 8 to 10: 2 hours	388.7 ± 22.72	389.8 ± 22.89	355.5 ± 13.44
QTcF Interval- Days 8 to 10: 4 hours	399.8 ± 25.87	387.5 ± 21.27	354.5 ± 4.95
QTcF Interval- Days 8 to 10: 6 hours	400.2 ± 19.22	387.3 ± 22.03	371.0 ± 21.21

Notes
[355] - Safety Population.
[356] - Safety Population.
[357] - Safety Population.

No statistical analyses for this end point

Secondary: Part 2: Absolute Values for ECG Parameters: PR, QRS, QT, QTcB and QTcF intervals

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End point title

Part 2: Absolute Values for ECG Parameters: PR, QRS, QT, QTcB and QTcF intervals ^[358]

End point description

End point type

Secondary

End point timeframe

Baseline (Day 1), Visit 5 (Day 7: Pre-dose, 2, 4 and 6 hours)

Notes
[358] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Number of subjects analysed	6 ^[359]	6 ^[360]	6 ^[361]	2 ^[362]
Units: Milliseconds
arithmetic mean (standard deviation)
PR Interval- Baseline (Day 1)	156.8 ± 33.02	162.9 ± 29.73	162.8 ± 20.83	144.3 ± 6.13
PR Interval- Day 7: Pre-dose	166.5 ± 25.62	161.8 ± 31.06	155.5 ± 26.10	137.0 ± 5.66
PR Interval- Day 7: 2 hours	162.8 ± 28.34	160.5 ± 28.73	159.7 ± 26.04	150.5 ± 3.54
PR Interval- Day 7: 4 hours	162.0 ± 24.85	164.0 ± 31.51	154.5 ± 20.51	149.0 ± 11.31
PR Interval- Day 7: 6 hours	160.7 ± 24.81	160.7 ± 27.25	160.7 ± 25.90	136.5 ± 3.54
QRS Duration- Baseline (Day 1)	92.6 ± 10.22	95.1 ± 21.97	88.9 ± 7.40	85.7 ± 11.31
QRS Duration- Day 7: Pre-dose	96.5 ± 8.14	98.3 ± 28.86	88.5 ± 3.99	88.0 ± 4.24
QRS Duration- Day 7: 2 hours	95.0 ± 9.78	95.8 ± 19.29	88.8 ± 4.49	90.0 ± 12.73
QRS Duration- Day 7: 4 hours	94.3 ± 8.89	95.2 ± 18.94	85.8 ± 4.88	89.5 ± 7.78
QRS Duration- Day 7: 6 hours	93.2 ± 10.61	95.0 ± 21.29	88.2 ± 8.11	88.5 ± 17.68
QT Interval- Baseline (Day 1)	386.6 ± 28.86	355.9 ± 25.37	362.5 ± 19.45	378.8 ± 1.18
QT Interval- Day 7: Pre-dose	379.2 ± 33.30	354.3 ± 31.94	367.5 ± 26.93	382.0 ± 1.41
QT Interval- Day 7: 2 hours	362.2 ± 31.24	351.5 ± 25.05	364.3 ± 17.32	378.5 ± 4.95
QT Interval- Day 7: 4 hours	373.8 ± 24.25	360.2 ± 23.07	360.8 ± 18.64	390.0 ± 18.38
QT Interval- Day 7: 6 hours	365.2 ± 34.53	361.8 ± 25.88	363.2 ± 19.50	381.5 ± 6.36
QTcB Interval- Baseline (Day 1)	402.88 ± 26.814	398.24 ± 25.587	411.18 ± 15.858	406.73 ± 20.742
QTcB Interval- Day 7: Pre-dose	398.72 ± 26.663	398.58 ± 21.075	414.63 ± 17.816	399.65 ± 18.173
QTcB Interval- Day 7: 2 hours	405.78 ± 10.923	398.33 ± 33.672	406.30 ± 27.565	388.50 ± 17.819
QTcB Interval- Day 7: 4 hours	395.92 ± 22.851	397.68 ± 20.635	412.48 ± 27.377	382.90 ± 17.961
QTcB Interval- Day 7: 6 hours	399.62 ± 19.074	402.42 ± 22.916	409.50 ± 19.009	396.90 ± 3.253
QTcF Interval- Baseline (Day 1)	397.4 ± 24.60	383.5 ± 23.72	394.1 ± 12.71	397.3 ± 13.67
QTcF Interval- Day 7: Pre-dose	391.5 ± 24.01	383.0 ± 24.90	398.2 ± 18.58	394.0 ± 12.73
QTcF Interval- Day 7: 2 hours	390.2 ± 12.16	382.2 ± 30.20	391.8 ± 22.44	385.0 ± 14.14
QTcF Interval- Day 7: 4 hours	388.0 ± 18.21	384.7 ± 20.42	394.7 ± 18.91	385.0 ± 18.38
QTcF Interval- Day 7: 6 hours	387.8 ± 11.29	388.0 ± 21.76	393.3 ± 17.20	391.5 ± 4.95

Notes
[359] - Safety Population.
[360] - Safety Population.
[361] - Safety Population.
[362] - Safety Population.

No statistical analyses for this end point

Secondary: Part 1: Area under the plasma concentration time curve from zero to 24 (AUC[0-24]) following administration of GSK3640254 on Day 1

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End point title

Part 1: Area under the plasma concentration time curve from zero to 24 (AUC[0-24]) following administration of GSK3640254 on Day 1 ^[363]

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. Pharmacokinetic (PK) Population consisted of all participants who received GSK3640254 and underwent plasma PK sampling during the study. Only those participants with data available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Notes
[363] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg
Number of subjects analysed	5 ^[364]	6 ^[365]
Units: Hours*microgram per milliliter
geometric mean (geometric coefficient of variation)	0.6946 ± 13.5	12.3929 ± 91.3

Notes
[364] - PK Population.
[365] - PK Population.

No statistical analyses for this end point

Secondary: Part 1: Maximum observed concentration (Cmax) following administration of GSK3640254 on Day 1

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End point title

Part 1: Maximum observed concentration (Cmax) following administration of GSK3640254 on Day 1 ^[366]

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

End point type

Secondary

End point timeframe

Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Notes
[366] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg
Number of subjects analysed	6 ^[367]	6 ^[368]
Units: Microgram per milliliter
geometric mean (geometric coefficient of variation)	0.0591 ± 177.4	0.9381 ± 82.3

Notes
[367] - PK Population.
[368] - PK Population.

No statistical analyses for this end point

Secondary: Part 1: Time to maximum observed concentration (Tmax) following administration of GSK3640254 on Day 1

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End point title

Part 1: Time to maximum observed concentration (Tmax) following administration of GSK3640254 on Day 1 ^[369]

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

End point type

Secondary

End point timeframe

Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Notes
[369] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg
Number of subjects analysed	6 ^[370]	6 ^[371]
Units: Hours
median (full range (min-max))	2.9250 (0.000 to 5.000)	5.5250 (3.917 to 8.050)

Notes
[370] - PK Population.
[371] - PK Population.

No statistical analyses for this end point

Secondary: Part 1: Concentration at 24 hours post-dose (C24) following administration of GSK3640254 on Day 1

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End point title

Part 1: Concentration at 24 hours post-dose (C24) following administration of GSK3640254 on Day 1 ^[372]

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

End point type

Secondary

End point timeframe

Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Notes
[372] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg
Number of subjects analysed	6 ^[373]	6 ^[374]
Units: Microgram per milliliter
geometric mean (geometric coefficient of variation)	0.0180 ± 27.5	0.3553 ± 92.7

Notes
[373] - PK Population.
[374] - PK Population.

No statistical analyses for this end point

Secondary: Part 1: Absorption lag time (Tlag) following administration of GSK3640254 on Day 1

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End point title

Part 1: Absorption lag time (Tlag) following administration of GSK3640254 on Day 1 ^[375]

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

End point type

Secondary

End point timeframe

Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Notes
[375] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg
Number of subjects analysed	6 ^[376]	6 ^[377]
Units: Hours
median (full range (min-max))	0.500 (0.00 to 1.00)	0.000 (0.00 to 1.00)

Notes
[376] - PK Population.
[377] - PK Population.

No statistical analyses for this end point

Secondary: Part 2: AUC(0-24) following administration of GSK3640254 on Day 1

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End point title

Part 2: AUC(0-24) following administration of GSK3640254 on Day 1 ^[378]

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

End point type

Secondary

End point timeframe

Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Notes
[378] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg
Number of subjects analysed	6 ^[379]	6 ^[380]	6 ^[381]
Units: Hours*microgram per milliliter
geometric mean (geometric coefficient of variation)	3.2527 ± 31.7	6.1228 ± 38.8	14.0335 ± 36.6

Notes
[379] - PK Population.
[380] - PK Population.
[381] - PK Population.

No statistical analyses for this end point

Secondary: Part 2: Cmax following administration of GSK3640254 on Day 1

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End point title

Part 2: Cmax following administration of GSK3640254 on Day 1 ^[382]

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

End point type

Secondary

End point timeframe

Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Notes
[382] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg
Number of subjects analysed	6 ^[383]	6 ^[384]	6 ^[385]
Units: Microgram per milliliter
geometric mean (geometric coefficient of variation)	0.2316 ± 30.5	0.4329 ± 33.6	0.9178 ± 41.5

Notes
[383] - PK Population.
[384] - PK Population.
[385] - PK Population.

No statistical analyses for this end point

Secondary: Part 2: Tmax following administration of GSK3640254 on Day 1

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End point title

Part 2: Tmax following administration of GSK3640254 on Day 1 ^[386]

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

End point type

Secondary

End point timeframe

Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Notes
[386] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg
Number of subjects analysed	6 ^[387]	6 ^[388]	6 ^[389]
Units: Hours
median (full range (min-max))	4.4167 (3.967 to 8.000)	4.0750 (2.950 to 6.167)	5.5083 (3.000 to 6.250)

Notes
[387] - PK Population.
[388] - PK Population.
[389] - PK Population.

No statistical analyses for this end point

Secondary: Part 2: C24 following administration of GSK3640254 on Day 1

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End point title

Part 2: C24 following administration of GSK3640254 on Day 1 ^[390]

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

End point type

Secondary

End point timeframe

Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Notes
[390] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg
Number of subjects analysed	6 ^[391]	6 ^[392]	6 ^[393]
Units: Microgram per milliliter
geometric mean (geometric coefficient of variation)	0.0951 ± 33.7	0.1856 ± 36.2	0.4207 ± 33.8

Notes
[391] - PK Population.
[392] - PK Population.
[393] - PK Population.

No statistical analyses for this end point

Secondary: Part 2: Tlag following administration of GSK3640254 on Day 1

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End point title

Part 2: Tlag following administration of GSK3640254 on Day 1 ^[394]

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

End point type

Secondary

End point timeframe

Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Notes
[394] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg
Number of subjects analysed	6 ^[395]	6 ^[396]	6 ^[397]
Units: Hours
median (full range (min-max))	0.483 (0.00 to 2.00)	0.000 (0.00 to 1.00)	0.000 (0.00 to 1.00)

Notes
[395] - PK Population.
[396] - PK Population.
[397] - PK Population.

No statistical analyses for this end point

Secondary: Part 1: Area under the plasma drug concentration-time curve from pre-dose to the end of the dosing interval at steady state (AUC[0-tau]) following repeat dose administration of GSK3640254 on Days 8 to 10

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End point title

Part 1: Area under the plasma drug concentration-time curve from pre-dose to the end of the dosing interval at steady state (AUC[0-tau]) following repeat dose administration of GSK3640254 on Days 8 to 10 ^[398]

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

End point type

Secondary

End point timeframe

Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Notes
[398] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg
Number of subjects analysed	6 ^[399]	6 ^[400]
Units: Hours*microgram per milliliter
geometric mean (geometric coefficient of variation)	0.9082 ± 44.7	27.9363 ± 18.4

Notes
[399] - PK Population.
[400] - PK Population.

No statistical analyses for this end point

Secondary: Part 1: Cmax following repeat dose administration of GSK3640254 on Days 8 to 10

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End point title

Part 1: Cmax following repeat dose administration of GSK3640254 on Days 8 to 10 ^[401]

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

End point type

Secondary

End point timeframe

Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Notes
[401] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg
Number of subjects analysed	6 ^[402]	6 ^[403]
Units: Microgram per milliliter
geometric mean (geometric coefficient of variation)	0.0549 ± 41.3	1.8559 ± 19.5

Notes
[402] - PK Population.
[403] - PK Population.

No statistical analyses for this end point

Secondary: Part 1: Tmax following repeat dose administration of GSK3640254 on Days 8 to 10

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End point title

Part 1: Tmax following repeat dose administration of GSK3640254 on Days 8 to 10 ^[404]

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

End point type

Secondary

End point timeframe

Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Notes
[404] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg
Number of subjects analysed	6 ^[405]	6 ^[406]
Units: Hours
median (full range (min-max))	4.0167 (1.867 to 5.000)	5.4833 (3.000 to 6.200)

Notes
[405] - PK Population.
[406] - PK Population.

No statistical analyses for this end point

Secondary: Part 1: Pre-dose concentration (C0) following repeat dose administration of GSK3640254 on Days 8 to 10

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End point title

Part 1: Pre-dose concentration (C0) following repeat dose administration of GSK3640254 on Days 8 to 10 ^[407]

End point description

Blood sample was collected at indicated time point for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. Only those participants with data available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

Days 8 to 10: Pre-dose

Notes
[407] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg
Number of subjects analysed	6 ^[408]	5 ^[409]
Units: Microgram per milliliter
geometric mean (geometric coefficient of variation)	0.0268 ± 41.6	0.6928 ± 33.6

Notes
[408] - PK Population.
[409] - PK Population.

No statistical analyses for this end point

Secondary: Part 1: Concentration at end of dosing interval (Ctau) following repeat dose administration of GSK3640254 on Days 8 to 10

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End point title

Part 1: Concentration at end of dosing interval (Ctau) following repeat dose administration of GSK3640254 on Days 8 to 10 ^[410]

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

End point type

Secondary

End point timeframe

Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Notes
[410] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg
Number of subjects analysed	6 ^[411]	6 ^[412]
Units: Microgram per milliliter
geometric mean (geometric coefficient of variation)	0.0267 ± 47.0	0.7033 ± 29.6

Notes
[411] - PK Population.
[412] - PK Population.

No statistical analyses for this end point

Secondary: Part 1: Apparent terminal phase half-life (t1/2) following repeat dose administration of GSK3640254 on Days 8 to 10

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End point title

Part 1: Apparent terminal phase half-life (t1/2) following repeat dose administration of GSK3640254 on Days 8 to 10 ^[413]

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. 99999 indicates that, t1/2 could not be calculated as the criteria of a span ratio [ratio of half-life to time used for half-life calculation] for at least 2 participants could not be fulfilled due to lack of available data.

End point type

Secondary

End point timeframe

Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Notes
[413] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg
Number of subjects analysed	6 ^[414]	6 ^[415]
Units: Hours
median (full range (min-max))	99999 (-99999 to 99999)	99999 (-99999 to 99999)

Notes
[414] - PK Population.
[415] - PK Population.

No statistical analyses for this end point

Secondary: Part 1: Apparent oral clearance (CL/F) following repeat dose administration of GSK3640254 on Days 8 to 10

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End point title

Part 1: Apparent oral clearance (CL/F) following repeat dose administration of GSK3640254 on Days 8 to 10 ^[416]

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

End point type

Secondary

End point timeframe

Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Notes
[416] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg
Number of subjects analysed	6 ^[417]	6 ^[418]
Units: Milliliter per hour
geometric mean (geometric coefficient of variation)	11010.5393 ± 44.7	7159.1443 ± 18.4

Notes
[417] - PK Population.
[418] - PK Population.

No statistical analyses for this end point

Secondary: Part 2: AUC(0-tau) following repeat dose administration of GSK3640254 on Day 7

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End point title

Part 2: AUC(0-tau) following repeat dose administration of GSK3640254 on Day 7 ^[419]

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

End point type

Secondary

End point timeframe

Day 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Notes
[419] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg
Number of subjects analysed	6 ^[420]	6 ^[421]	6 ^[422]
Units: Hours*microgram per milliliter
geometric mean (geometric coefficient of variation)	7.4626 ± 26.8	11.8256 ± 26.7	29.2952 ± 27.9

Notes
[420] - PK Population.
[421] - PK Population.
[422] - PK Population.

No statistical analyses for this end point

Secondary: Part 2: Cmax following repeat dose administration of GSK3640254 on Day 7

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End point title

Part 2: Cmax following repeat dose administration of GSK3640254 on Day 7 ^[423]

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

End point type

Secondary

End point timeframe

Day 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Notes
[423] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg
Number of subjects analysed	6 ^[424]	6 ^[425]	6 ^[426]
Units: Microgram per milliliter
geometric mean (geometric coefficient of variation)	0.4692 ± 20.6	0.7470 ± 23.7	1.8574 ± 26.0

Notes
[424] - PK Population.
[425] - PK Population.
[426] - PK Population.

No statistical analyses for this end point

Secondary: Part 2: Tmax following repeat dose administration of GSK3640254 on Day 7

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End point title

Part 2: Tmax following repeat dose administration of GSK3640254 on Day 7 ^[427]

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

End point type

Secondary

End point timeframe

Day 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Notes
[427] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg
Number of subjects analysed	6 ^[428]	6 ^[429]	6 ^[430]
Units: Hours
median (full range (min-max))	4.0583 (2.000 to 8.000)	4.5750 (4.000 to 5.183)	4.0750 (2.917 to 5.200)

Notes
[428] - PK Population.
[429] - PK Population.
[430] - PK Population.

No statistical analyses for this end point

Secondary: Part 2: C0 following repeat dose administration of GSK3640254 on Day 7

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End point title

Part 2: C0 following repeat dose administration of GSK3640254 on Day 7 ^[431]

End point description

Blood sample was collected at indicated time point for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

End point type

Secondary

End point timeframe

Day 7: Pre-dose

Notes
[431] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg
Number of subjects analysed	6 ^[432]	6 ^[433]	6 ^[434]
Units: Microgram per milliliter
geometric mean (geometric coefficient of variation)	0.2155 ± 24.2	0.3575 ± 38.0	0.7520 ± 38.8

Notes
[432] - PK Population.
[433] - PK Population.
[434] - PK Population.

No statistical analyses for this end point

Secondary: Part 2: Ctau following repeat dose administration of GSK3640254 on Day 7

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End point title

Part 2: Ctau following repeat dose administration of GSK3640254 on Day 7 ^[435]

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

End point type

Secondary

End point timeframe

Day 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Notes
[435] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg
Number of subjects analysed	6 ^[436]	6 ^[437]	6 ^[438]
Units: Microgram per milliliter
geometric mean (geometric coefficient of variation)	0.2187 ± 30.1	0.3599 ± 31.1	0.7979 ± 34.1

Notes
[436] - PK Population.
[437] - PK Population.
[438] - PK Population.

No statistical analyses for this end point

Secondary: Part 2: t1/2 following repeat dose administration of GSK3640254 on Day 7

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End point title

Part 2: t1/2 following repeat dose administration of GSK3640254 on Day 7 ^[439]

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. 99999 indicates that, t1/2 could not be calculated as the criteria of a span ratio [ratio of half-life to time used for half-life calculation] for at least 2 participants could not be fulfilled due to lack of available data.

End point type

Secondary

End point timeframe

Day 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Notes
[439] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg
Number of subjects analysed	6 ^[440]	6 ^[441]	6 ^[442]
Units: Hours
median (full range (min-max))	99999 (-99999 to 99999)	99999 (-99999 to 99999)	99999 (-99999 to 99999)

Notes
[440] - PK Population.
[441] - PK Population.
[442] - PK Population.

No statistical analyses for this end point

Secondary: Part 2: CL/F following repeat dose administration of GSK3640254 on Day 7

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End point title

Part 2: CL/F following repeat dose administration of GSK3640254 on Day 7 ^[443]

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

End point type

Secondary

End point timeframe

Day 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Notes
[443] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg
Number of subjects analysed	6 ^[444]	6 ^[445]	6 ^[446]
Units: Milliliter per hour
geometric mean (geometric coefficient of variation)	5360.0526 ± 26.8	6764.9862 ± 26.7	4778.9430 ± 27.9

Notes
[444] - PK Population.
[445] - PK Population.
[446] - PK Population.

No statistical analyses for this end point

Secondary: Part 1 and Part 2: Change From Baseline in Plasma HIV-1 RNA Relative to Day 8 AUC(0-tau)

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End point title

Part 1 and Part 2: Change From Baseline in Plasma HIV-1 RNA Relative to Day 8 AUC(0-tau) ^[447]

End point description

Plasma samples were collected for quantitative analysis of HIV-1 RNA. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Statistical analysis for relationship between PK parameters (AUC) and PD measures (Change from Baseline in plasma HIV-1 RNA) were explored using a frequentist three parameter Emax non-linear model. The model parameters estimated included: maximum response (Emax), PK parameter value that attains 50 percent (%) of the maximal effect (EC50) and residual variability (s2e). PK/PD Population consisted of participants who met criteria for Per-Protocol and Pharmacokinetic Population analysis sets and who underwent PD sampling during the study.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Day 8

Notes
[447] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg
Number of subjects analysed	6 ^[448]	6 ^[449]	6 ^[450]	6 ^[451]	6 ^[452]
Units: Copies per milliliter
arithmetic mean (standard deviation)	12071.4 ± 42117.29	-113331.4 ± 89475.00	-48655.0 ± 26269.41	-37904.3 ± 38814.54	-64861.5 ± 83728.15

Notes
[448] - PK/PD Population.
[449] - PK/PD Population.
[450] - PK/PD Population.
[451] - PK/PD Population.
[452] - PK/PD Population.

Statistical Analysis of Emax

Comparison groups

Part 1: GSK3640254 10 mg v Part 1: GSK3640254 200 mg v Part 2: GSK3640254 40 mg v Part 2: GSK3640254 80 mg v Part 2: GSK3640254 140 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Emax

Point estimate

-1.937

Confidence interval

level

95%

sides

2-sided

lower limit

-2.484

upper limit

-1.389

Statistical Analysis of EC50

Comparison groups

Part 1: GSK3640254 10 mg v Part 1: GSK3640254 200 mg v Part 2: GSK3640254 40 mg v Part 2: GSK3640254 80 mg v Part 2: GSK3640254 140 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

EC50

Point estimate

7.094

Confidence interval

level

95%

sides

2-sided

lower limit

0.585

upper limit

13.602

Statistical Analysis of s2e

Comparison groups

Part 1: GSK3640254 10 mg v Part 1: GSK3640254 200 mg v Part 2: GSK3640254 40 mg v Part 2: GSK3640254 80 mg v Part 2: GSK3640254 140 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

s2e

Point estimate

0.137

Confidence interval

level

95%

sides

2-sided

lower limit

0.062

upper limit

0.212

Secondary: Part 1 and Part 2: Change From Baseline in Plasma HIV-1 RNA Relative to Day 8 Cmax

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End point title

Part 1 and Part 2: Change From Baseline in Plasma HIV-1 RNA Relative to Day 8 Cmax ^[453]

End point description

End point type

Secondary

End point timeframe

Baseline (Day 1) and Day 8

Notes
[453] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg
Number of subjects analysed	6 ^[454]	6 ^[455]	6 ^[456]	6 ^[457]	6 ^[458]
Units: Copies per milliliter
arithmetic mean (standard deviation)	12071.4 ± 42117.29	-113331.4 ± 89475.00	-48655.0 ± 26269.41	-37904.3 ± 38814.54	-64861.5 ± 83728.15

Notes
[454] - PK/PD Population.
[455] - PK/PD Population.
[456] - PK/PD Population.
[457] - PK/PD Population.
[458] - PK/PD Population.

Statistical Analysis of Emax

Comparison groups

Part 1: GSK3640254 10 mg v Part 1: GSK3640254 200 mg v Part 2: GSK3640254 40 mg v Part 2: GSK3640254 80 mg v Part 2: GSK3640254 140 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Emax

Point estimate

-1.929

Confidence interval

level

95%

sides

2-sided

lower limit

-2.479

upper limit

-1.379

Statistical Analysis of EC50

Comparison groups

Part 1: GSK3640254 10 mg v Part 1: GSK3640254 200 mg v Part 2: GSK3640254 40 mg v Part 2: GSK3640254 80 mg v Part 2: GSK3640254 140 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

EC50

Point estimate

0.446

Confidence interval

level

95%

sides

2-sided

lower limit

0.03

upper limit

0.861

Statistical Analysis of s2e

Comparison groups

Part 1: GSK3640254 10 mg v Part 1: GSK3640254 200 mg v Part 2: GSK3640254 40 mg v Part 2: GSK3640254 80 mg v Part 2: GSK3640254 140 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

s2e

Point estimate

0.139

Confidence interval

level

95%

sides

2-sided

lower limit

0.063

upper limit

0.216

Secondary: Part 1 and Part 2: Change From Baseline in Plasma HIV-1 RNA Relative to Day 8 Ctau

Top of page

End point title

Part 1 and Part 2: Change From Baseline in Plasma HIV-1 RNA Relative to Day 8 Ctau ^[459]

End point description

End point type

Secondary

End point timeframe

Baseline (Day 1) and Day 8

Notes
[459] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg
Number of subjects analysed	6 ^[460]	6 ^[461]	6 ^[462]	6 ^[463]	6 ^[464]
Units: Copies per milliliter
arithmetic mean (standard deviation)	12071.4 ± 42117.29	-113331.4 ± 89475.00	-48655.0 ± 26269.41	-37904.3 ± 38814.54	-64861.5 ± 83728.15

Notes
[460] - PK/PD Population.
[461] - PK/PD Population.
[462] - PK/PD Population.
[463] - PK/PD Population.
[464] - PK/PD Population.

Statistical Analysis of Emax

Comparison groups

Part 1: GSK3640254 10 mg v Part 1: GSK3640254 200 mg v Part 2: GSK3640254 40 mg v Part 2: GSK3640254 80 mg v Part 2: GSK3640254 140 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Emax

Point estimate

-1.926

Confidence interval

level

95%

sides

2-sided

lower limit

-2.498

upper limit

-1.354

Statistical Analysis of EC50

Comparison groups

Part 1: GSK3640254 10 mg v Part 1: GSK3640254 200 mg v Part 2: GSK3640254 40 mg v Part 2: GSK3640254 80 mg v Part 2: GSK3640254 140 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

EC50

Point estimate

0.197

Confidence interval

level

95%

sides

2-sided

lower limit

0.007

upper limit

0.386

Statistical Analysis of s2e

Comparison groups

Part 1: GSK3640254 10 mg v Part 1: GSK3640254 200 mg v Part 2: GSK3640254 40 mg v Part 2: GSK3640254 80 mg v Part 2: GSK3640254 140 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

s2e

Point estimate

0.144

Confidence interval

level

95%

sides

2-sided

lower limit

0.065

upper limit

0.222

Secondary: Part 1: Accumulation ratio following repeat dose administration of GSK3640254

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End point title

Part 1: Accumulation ratio following repeat dose administration of GSK3640254 ^[465]

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The accumulation ratios (Ro) were calculated as Ro_AUC equal to (=) AUC(0-tau) Days 8 to 10 divided by (/) AUC(0-24) Day 1; Ro_Cmax=Cmax Days 8 to 10/Cmax Day 1; and Ro_Ctau=Ctau Days 8 to 10/C24 Day 1. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

End point type

Secondary

End point timeframe

Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose; Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Notes
[465] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg
Number of subjects analysed	6 ^[466]	6 ^[467]
Units: Ratio
geometric mean (geometric coefficient of variation)
Ro_AUC(0-tau), n=5,6	1.5352 ± 24.5	2.2542 ± 72.1
Ro_Cmax, n=6,6	0.9287 ± 171.7	1.9785 ± 69.4
Ro_Ctau, n=6,6	1.4790 ± 22.2	1.9796 ± 61.2

Notes
[466] - PK Population.
[467] - PK Population.

No statistical analyses for this end point

Secondary: Part 2: Accumulation ratio following repeat dose administration of GSK3640254

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End point title

Part 2: Accumulation ratio following repeat dose administration of GSK3640254 ^[468]

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The accumulation ratios (Ro) were calculated as Ro_AUC=AUC(0-tau) Day 7/AUC(0-24) Day 1; Ro_Cmax=Cmax Day 7/Cmax Day 1; and Ro_Ctau=Ctau Day 7/C24 Day 1.

End point type

Secondary

End point timeframe

Days 1 and 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Notes
[468] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg
Number of subjects analysed	6 ^[469]	6 ^[470]	6 ^[471]
Units: Ratio
geometric mean (geometric coefficient of variation)
Ro_AUC(0-tau)	2.2943 ± 11.2	1.9314 ± 18.6	2.0875 ± 29.2
Ro_Cmax	2.0258 ± 24.4	1.7258 ± 17.6	2.0236 ± 37.5
Ro_Ctau	2.2985 ± 6.4	1.9389 ± 20.8	1.8967 ± 16.0

Notes
[469] - PK Population.
[470] - PK Population.
[471] - PK Population.

No statistical analyses for this end point

Secondary: Part 1 and Part 2: Dose proportionality of GSK3640254 administered on Day 1 based on AUC(0-24)

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End point title

Part 1 and Part 2: Dose proportionality of GSK3640254 administered on Day 1 based on AUC(0-24)

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. Dose proportionality was assessed using Power model with logarithm of dose as fixed effect. Slope and 90% confidence interval for the slope are presented.

End point type

Secondary

End point timeframe

Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

End point values	GSK3640254 10 mg to 200 mg
Number of subjects analysed	30
Units: Slope of log dose
number (confidence interval 90%)	1.018 (0.876 to 1.160)

No statistical analyses for this end point

Secondary: Part 1 and Part 2: Dose proportionality of GSK3640254 administered on Day 1 based on Cmax

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End point title

Part 1 and Part 2: Dose proportionality of GSK3640254 administered on Day 1 based on Cmax

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. Dose proportionality was assessed using Power model with logarithm of dose as fixed effect. Slope and 90% confidence interval for the slope are presented.

End point type

Secondary

End point timeframe

Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

End point values	GSK3640254 10 mg to 200 mg
Number of subjects analysed	30
Units: Slope of log dose
number (confidence interval 90%)	0.964 (0.774 to 1.154)

No statistical analyses for this end point

Secondary: Part 1 and Part 2: Dose proportionality of GSK3640254 administered on Day 1 based on C24

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End point title

Part 1 and Part 2: Dose proportionality of GSK3640254 administered on Day 1 based on C24

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. Dose proportionality was assessed using Power model with logarithm of dose as fixed effect. Slope and 90% confidence interval for the slope are presented.

End point type

Secondary

End point timeframe

Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

End point values	GSK3640254 10 mg to 200 mg
Number of subjects analysed	30
Units: Slope of log dose
number (confidence interval 90%)	1.061 (0.924 to 1.199)

No statistical analyses for this end point

Secondary: Part 1 and Part 2: Dose proportionality of GSK3640254 following repeat dose administration based on AUC(0-tau)

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End point title

Part 1 and Part 2: Dose proportionality of GSK3640254 following repeat dose administration based on AUC(0-tau)

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. Dose proportionality was assessed using Power model with logarithm of dose as fixed effect. Slope and 90% confidence interval for the slope are presented.

End point type

Secondary

End point timeframe

Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose; Day 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

End point values	GSK3640254 10 mg to 200 mg
Number of subjects analysed	30
Units: Slope of log dose
number (confidence interval 90%)	1.179 (1.074 to 1.283)

No statistical analyses for this end point

Secondary: Part 1 and Part 2: Dose proportionality of GSK3640254 following repeat dose administration based on Cmax

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End point title

Part 1 and Part 2: Dose proportionality of GSK3640254 following repeat dose administration based on Cmax

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. Dose proportionality was assessed using Power model with logarithm of dose as fixed effect. Slope and 90% confidence interval for the slope are presented.

End point type

Secondary

End point timeframe

Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose; Day 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

End point values	GSK3640254 10 mg to 200 mg
Number of subjects analysed	30
Units: Slope of log dose
number (confidence interval 90%)	1.204 (1.107 to 1.302)

No statistical analyses for this end point

Secondary: Part 1 and Part 2: Dose proportionality of GSK3640254 following repeat dose administration based on Ctau

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End point title

Part 1 and Part 2: Dose proportionality of GSK3640254 following repeat dose administration based on Ctau

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. Dose proportionality was assessed using Power model with logarithm of dose as fixed effect. Slope and 90% confidence interval for the slope are presented.

End point type

Secondary

End point timeframe

Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose; Day 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

End point values	GSK3640254 10 mg to 200 mg
Number of subjects analysed	30
Units: Slope of log dose
number (confidence interval 90%)	1.137 (1.018 to 1.257)

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Part 1: up to Day 24; Part 2: up to Day 12

Adverse event reporting additional description

Safety Population consisted of all participants who were enrolled into the study with documented evidence of having received at least 1 dose of randomized treatment.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

22.1

Reporting group title

Part 1: GSK3640254 200 mg

Reporting group description

Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Reporting group title

Part 1: GSK3640254 10 mg

Reporting group description

Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Reporting group title

Part 1: Placebo

Reporting group description

Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Reporting group title

Part 2: GSK3640254 40 mg

Reporting group description

Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Reporting group title

Part 2: Placebo

Reporting group description

Participants received placebo capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Reporting group title

Part 2: GSK3640254 80 mg

Reporting group description

Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Reporting group title

Part 2: GSK3640254 140 mg

Reporting group description

Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Serious adverse events	Part 1: GSK3640254 200 mg	Part 1: GSK3640254 10 mg	Part 1: Placebo	Part 2: GSK3640254 40 mg	Part 2: Placebo	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)
number of deaths (all causes)	0	0	0	0	0	0	0
number of deaths resulting from adverse events
Cardiac disorders
Congestive cardiomyopathy
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Anal abscess
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Part 1: GSK3640254 200 mg	Part 1: GSK3640254 10 mg	Part 1: Placebo	Part 2: GSK3640254 40 mg	Part 2: Placebo	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg
Total subjects affected by non serious adverse events
subjects affected / exposed	5 / 6 (83.33%)	3 / 6 (50.00%)	0 / 2 (0.00%)	5 / 6 (83.33%)	0 / 2 (0.00%)	4 / 6 (66.67%)	4 / 6 (66.67%)
Investigations
Alanine aminotransferase increased
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0	0	0
Aspartate aminotransferase increased
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0	0	0
Cardiac disorders
Myocarditis
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0	0	0
Nervous system disorders
Headache
subjects affected / exposed	2 / 6 (33.33%)	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)
occurrences all number	2	0	0	1	0	0	1
Migraine
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0
Presyncope
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0
Blood and lymphatic system disorders
Lymphadenopathy
subjects affected / exposed	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	1	0	0	0	0	0
Neutropenia
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0
General disorders and administration site conditions
Asthenia
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0
Fatigue
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	2	0	0	0
Nodule
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0
Pyrexia
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 2 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	1	0	1	0	0	0
Abdominal pain
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	2 / 6 (33.33%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	3	0
Vomiting
subjects affected / exposed	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	1	0	0	0	0	0
Constipation
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	0	0	1
Nausea
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0	0	0
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
subjects affected / exposed	2 / 6 (33.33%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)
occurrences all number	2	0	0	0	0	0	1
Catarrh
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0
Epistaxis
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0
Skin and subcutaneous tissue disorders
Dermatitis atopic
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0
Pruritus
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	0	0	1
Rash maculo-papular
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	0	0	1
Renal and urinary disorders
Chromaturia
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0	0	0
Musculoskeletal and connective tissue disorders
Pain in extremity
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0
Spinal pain
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0	0	0
Infections and infestations
Nasopharyngitis
subjects affected / exposed	2 / 6 (33.33%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)
occurrences all number	2	0	0	0	0	0	0
Meningococcal infection
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0	0	0
Pharyngitis
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0
Upper respiratory tract infection
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0
Urinary tract infection
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	0	0	1
Viral infection
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0
Metabolism and nutrition disorders
Hyperglycaemia
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0	0	0
Insulin resistance
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0	0	0
Vitamin D deficiency
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0	0	0

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

28 Sep 2018

Amendment 1: The original version of the protocol was not submitted to any health authority (HA) worldwide. Key elements of the original protocol design were discussed with the United States Food and Drug Administration (US FDA) in the context of pre-Investigational New Drug (IND) feedback (i.e. scientific advice). To this end, the overall design, duration, and sample population remain the same. However, minor changes were made to exclusion criteria, participant monitoring, and reasons for discontinuation to enhance the safety of trial participants. Finally, other administrative changes and updates were made (e.g. succinct results from two Phase 1 clinical trials in healthy volunteers).

10 Jan 2019

Amendment 2: Feedback from a Health Authority has provided greater specificity and clarification to existing exclusion criteria on psychiatric disease. Additionally, we have clarified that participants who are recently infected with HIV-1 should be excluded. Next, the human PK data available from Study 207187 Single ascending dose/Multiple ascending dose (SAD/MAD) resulted in the removal of contraceptive requirements of male participants and any pregnancy monitoring requirements of female partners (of male participants). Further clarification on prohibited concomitant medications was provided. Finally, minor changes/clarifications were made to participant monitoring and reasons for discontinuation.

26 Aug 2019

Amendment 3: Data from Part 1 showed a decline in Human immunodeficiency virus-1 (HIV-1) Ribonucleic Acid (RNA) and reasonable pharmacokinetic (PK) profile. There were no clinically significant trends in adverse events (AEs), vital signs, electrocardiogram (ECG) findings, or chemistry/haematology laboratory abnormalities across dosing arms. However, some participants receiving GSK3640254 had treatment emergent resistance mutations associated with maturation inhibitors observed on or after Day 11 (after 10 days of receiving GSK3640254 monotherapy). Additionally, no resistance to existing and commercially available classes of antiretroviral medications (e.g., reverse transcriptase, protease, integrase) was observed at Day 11 as there is no known cross-resistance between maturation inhibitors and other classes of anti-retrovirals (ARVs). Genotypic analysis of samples at Clinic Visit 5 (Study Day 8 or 9) revealed no treatment emergent resistance. As a result, Sponsor made two substantial changes to decrease the risk of treatment emergent resistance to participants in Part 2: 1) decrease the duration of monotherapy from 10 days to 7 days based on the interim genotypic analysis, and 2) start Investigator selected combination anti-retroviral therapy (cART) immediately after completion of monotherapy and the Part 2 primary endpoint (i.e., after the collection of HIV-1 RNA on Day 8).

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A Randomized, Double-Blind (Sponsor-unblinded), Placebo-Controlled, Adaptive Trial to Investigate the Antiviral Effect, Safety, Tolerability and Pharmacokinetics of GSK3640254 in HIV-1 Infected Treatment-Naïve Adults

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Part 1: Maximum Change from Baseline in plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) at Day 11

Primary: Part 1: Maximum Change from Baseline in plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) at Day 11

Primary: Part 2: Maximum Change from Baseline in plasma HIV-1 RNA at Day 8

Primary: Part 2: Maximum Change from Baseline in plasma HIV-1 RNA at Day 8

Secondary: Part 1: Number of Participants with Non-Serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs)

Secondary: Part 1: Number of Participants with Non-Serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs)

Secondary: Part 2: Number of participants with Non-SAEs and SAEs

Secondary: Part 2: Number of participants with Non-SAEs and SAEs

Secondary: Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes, Platelet Count

Secondary: Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes, Platelet Count

Secondary: Part 1: Change From Baseline in Hematology Parameter: Hemoglobin

Secondary: Part 1: Change From Baseline in Hematology Parameter: Hemoglobin

Secondary: Part 1: Change From Baseline in Hematology Parameter: Hematocrit

Secondary: Part 1: Change From Baseline in Hematology Parameter: Hematocrit

Secondary: Part 1: Change From Baseline in Hematology Parameter: Erythrocytes

Secondary: Part 1: Change From Baseline in Hematology Parameter: Erythrocytes

Secondary: Part 1: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume

Secondary: Part 1: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume

Secondary: Part 1: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin

Secondary: Part 1: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin

Secondary: Part 1: Change From Baseline in Hematology Parameter: Reticulocytes/Erythrocyte

Secondary: Part 1: Change From Baseline in Hematology Parameter: Reticulocytes/Erythrocyte

Secondary: Part 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes, Platelet Count

Secondary: Part 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes, Platelet Count

Secondary: Part 2: Change From Baseline in Hematology Parameter: Hemoglobin

Secondary: Part 2: Change From Baseline in Hematology Parameter: Hemoglobin

Secondary: Part 2: Change From Baseline in Hematology Parameter: Hematocrit

Secondary: Part 2: Change From Baseline in Hematology Parameter: Hematocrit

Secondary: Part 2: Change From Baseline in Hematology Parameter: Erythrocytes

Secondary: Part 2: Change From Baseline in Hematology Parameter: Erythrocytes

Secondary: Part 2: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume

Secondary: Part 2: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume

Secondary: Part 2: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin

Secondary: Part 2: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin

Secondary: Part 2: Change From Baseline in Hematology Parameter: Reticulocytes/Erythro

Secondary: Part 2: Change From Baseline in Hematology Parameter: Reticulocytes/Erythro

Secondary: Part 1: Change From Baseline in Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Calcium, Chloride, Phosphate, Potassium, Magnesium, Sodium, Urea, high density lipoprotein (HDL) Cholesterol, low density lipoprotein (LDL) Cholesterol

Secondary: Part 1: Change From Baseline in Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Calcium, Chloride, Phosphate, Potassium, Magnesium, Sodium, Urea, high density lipoprotein (HDL) Cholesterol, low density lipoprotein (LDL) Cholesterol

Secondary: Part 1: Change From Baseline in Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST)

Secondary: Part 1: Change From Baseline in Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST)

Secondary: Part 1: Change From Baseline in Chemistry Parameters: Creatinine, Bilirubin

Secondary: Part 1: Change From Baseline in Chemistry Parameters: Creatinine, Bilirubin

Secondary: Part 1: Change From Baseline in Chemistry Parameters: Protein

Secondary: Part 1: Change From Baseline in Chemistry Parameters: Protein

Secondary: Part 1: Change From Baseline in Chemistry Parameters: Amylase, Lipase

Secondary: Part 1: Change From Baseline in Chemistry Parameters: Amylase, Lipase

Secondary: Part 2: Change From Baseline in Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Calcium, Chloride, Phosphate, Potassium, Magnesium, Sodium, Urea, HDL Cholesterol, LDL Cholesterol

Secondary: Part 2: Change From Baseline in Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Calcium, Chloride, Phosphate, Potassium, Magnesium, Sodium, Urea, HDL Cholesterol, LDL Cholesterol

Secondary: Part 2: Change From Baseline in Chemistry Parameters: ALT, ALP, AST

Secondary: Part 2: Change From Baseline in Chemistry Parameters: ALT, ALP, AST

Secondary: Part 2: Change From Baseline in Chemistry Parameters: Creatinine, Bilirubin

Secondary: Part 2: Change From Baseline in Chemistry Parameters: Creatinine, Bilirubin

Secondary: Part 2: Change From Baseline in Chemistry Parameters: Protein

Secondary: Part 2: Change From Baseline in Chemistry Parameters: Protein

Secondary: Part 2: Change From Baseline in Chemistry Parameters: Amylase, Lipase

Secondary: Part 2: Change From Baseline in Chemistry Parameters: Amylase, Lipase

Secondary: Part 1: Change From Baseline in Urinalysis Parameter: Specific Gravity

Secondary: Part 1: Change From Baseline in Urinalysis Parameter: Specific Gravity

Secondary: Part 1: Change From Baseline in Urinalysis Parameter: Urobilinogen

Secondary: Part 1: Change From Baseline in Urinalysis Parameter: Urobilinogen

Secondary: Part 1: Change From Baseline in Urinalysis Parameter: Potential of Hydrogen (pH)

Secondary: Part 1: Change From Baseline in Urinalysis Parameter: Potential of Hydrogen (pH)

Secondary: Part 2: Change From Baseline in Urinalysis Parameter: Specific Gravity

Secondary: Part 2: Change From Baseline in Urinalysis Parameter: Specific Gravity

Secondary: Part 2: Change From Baseline in Urinalysis Parameter: Urobilinogen

Secondary: Part 2: Change From Baseline in Urinalysis Parameter: Urobilinogen

Secondary: Part 2: Change From Baseline in Urinalysis Parameter: pH

Secondary: Part 2: Change From Baseline in Urinalysis Parameter: pH

Secondary: Part 1: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

Secondary: Part 1: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

Clinical Trial Results:
A Randomized, Double-Blind (Sponsor-unblinded), Placebo-Controlled, Adaptive Trial to Investigate the Antiviral Effect, Safety, Tolerability and Pharmacokinetics of GSK3640254 in HIV-1 Infected Treatment-Naïve Adults