Phase 1 N=16 Randomized Double-blind Treatment

GSK3640254 First Time in Human (FTIH) Study in Healthy Volunteers

Infection, Human Immunodeficiency Virus · HIV Infections

Bottom Line

View on ClinicalTrials.gov: NCT03231943 ↗

Enrolled (actual)

Serious AEs

0.0%

Results posted

Oct 2019

Primary outcome: Primary: Part 1:Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) — 3; 2; 4; 3 Participants

Study Design & Population

Study type: Interventional
Phase: Phase 1
Interventions: GSK3640254 (Drug); Placebo (Drug)
Age: Adult · 18+ yrs
Sex: All
Sponsor: ViiV Healthcare
Primary completion: Sep 2018

Outcome Measures

Outcome	Result	p-value
PRIMARY Part 1:Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs)	3; 2; 4; 3; 3; 4	—
PRIMARY Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets.	-0.002; -0.002; 0.005; -0.002; -0.007; 0.002	—
PRIMARY Part 1: Change From Baseline in Hematology Parameters: Erythrocytes.	0.118; 0.338; -0.005; 0.147; 0.212; 0.198	—
PRIMARY Part 1: Change From Baseline in Hematology Parameters: Erythrocytes Mean Corpuscular Volume (Erythrocyte MCV).	-0.50; -0.03; 0.17; 0.70; -1.07; -0.28	—
PRIMARY Part 1: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin (Erythrocyte MCH)	0.12; 0.18; 0.00; -0.15; 0.25; 0.15	—
PRIMARY Part 1: Change From Baseline in Hematology Parameter: Hematocrit	0.0080; 0.0288; 0.0003; 0.0163; 0.0128; 0.0155	—
PRIMARY Part 1: Change From Baseline in Hematology Parameter: Percentage of Reticulocytes	0.00050; 0.00055; 0.00118; -0.00023; 0.00022; -0.00015	—
PRIMARY Part 1: Change From Baseline in Hematology Parameter: Hemoglobin (Hb)	4.2; 10.8; 0.0; 3.5; 7.7; 6.8	—
PRIMARY Part 1: Change From Baseline in Clinical Chemistry Parameter: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP)	-1.7; 0.3; 0.8; -3.8; -0.5; -3.8	—
PRIMARY Part 1: Change From Baseline in Clinical Chemistry Parameters : Bicarbonate, Calcium, Chloride, Magnesium, Phosphate, Potassium, Sodium, Urea	0.7; 3.0; -3.2; 2.2; -0.2; 0.5	—
PRIMARY Part 1: Change From Baseline in Cholesterol, Glucose, High Density Lipoprotein (HDL) Cholesterol, Low Density Cholesterol (LDL) Cholesterol, Triglycerides	0.40; 0.32; -0.05; 0.02; -0.06; 0.13	—
PRIMARY Part 1: Change From Baseline in Chemistry Parameter: Glucose	-0.16; -0.30; -0.25; -0.28; -0.17; -0.08	—
PRIMARY Part 1: Change From Baseline in Clinical Chemistry Parameter: Bilirubin, Creatinine, Direct Bilirubin	-2.5; -0.2; -5.3; -1.5; 0.2; -1.7	—
PRIMARY Part 1: Change From Baseline in Clinical Chemistry Parameter: Protein	-0.3; 2.5; -5.2; -1.0; -1.2; 0.7	—
PRIMARY Part 1: Number of Participants With Abnormal Urinalysis	0; 0; 0; 0; 0; 0	—
PRIMARY Part 1: Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)	2.5; 3.2; 6.3; 4.7; 6.2; 2.2	—
PRIMARY Part 1: Change From Baseline in Vital Signs: Pulse Rate	13.3; 5.2; 14.5; 13.7; 11.3; 7.5	—
PRIMARY Part 1: Change From Baseline in Vital Signs: Temperature	0.33; 0.15; 0.03; 0.18; 0.10; 0.00	—
PRIMARY Part 1: Change From Baseline in Vital Sign: Respiratory Rate	1.5; 0.8; -0.3; 1.0; -1.0; 0.3	—
PRIMARY Part 1: Number of Participants With Abnormal Electrocardiogram (ECG) Findings	0; 0; 0; 0; 0; 0	—
PRIMARY Part 2: Number of Participants AEs and SAEs	4; 5; 19; 6; 10; 0	—
PRIMARY Part 2: Change From Baseline in Abnormal Hematology Findings: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets.	0.003; 0.000; -0.004; 0.001; -0.004; -0.002	—
PRIMARY Part 2: Change From Baseline in Hematology Parameter: Erythrocytes	0.135; 0.200; 0.128; 0.440; 0.131; 0.193	—
PRIMARY Part 2: Change From Baseline in Hematology Parameter: Erythrocytes MCV	-0.20; -0.63; -0.27; -1.13; -0.16; -0.50	—
PRIMARY Part 2: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin (Erythrocyte MCH)	-0.10; -0.35; -0.08; -0.46; -0.14; -0.32	—
PRIMARY Part 2: Change From Baseline in Hematology Parameter: Hematocrit	0.0102; 0.0140; 0.0096; 0.0314; 0.0108; 0.0133	—
PRIMARY Part 2: Change From Baseline in Hematology Parameter: Percentage of Reticulocytes	0.00093; -0.00103; 0.00088; -0.00037; 0.00117; 0.00215	—
PRIMARY Part 2: Change From Baseline in Hematology Parameter: Hb	3.3; 4.3; 3.4; 10.6; 3.4; 3.8	—
PRIMARY Part 2: Change From Baseline in Chemistry Parameter: ALT, AST,ALP	-1.2; 1.0; 0.5; 1.7; -0.4; 0.0	—
PRIMARY Part 1: Change From Baseline in Bicarbonate, Calcium, Chloride, Cholesterol, Magnesium, Phosphate, Potassium, Sodium, Urea	0.7; -1.3; 0.2; 1.1; 0.4; 1.8	—
PRIMARY Part 2: Change From Baseline in Cholesterol, HDL Cholesterol, LDL Cholesterol, Triglycerides	0.08; 0.07; 0.16; 0.36; 0.38; -0.05	—
PRIMARY Part 2: Change From Baseline in Chemistry Parameter: Glucose	0.02; 0.20; -0.10; -0.09; -0.12; 0.15	—
PRIMARY Part 2: Change From Baseline in Chemistry Parameter: Bilirubin, Creatinine, Direct Bilirubin	-1.3; -0.8; -0.7; -2.6; -0.9; -1.5	—
PRIMARY Part 2: Change From Baseline in Chemistry Parameter: Protein	-0.5; -1.0; 0.2; 1.7; -0.9; 1.5	—
PRIMARY Part 2: Number of Participants With Abnormal Urinalysis	0; 0; 0; 0; 0	—
PRIMARY Part 2: Change From Baseline in Vital Signs: SBP and DBP	0.5; 1.2; -0.5; 2.9; -1.1; 0.5	—
PRIMARY Part 2: Change From Baseline in Vital Sign: Pulse Rate	-0.3; 0.6; 1.6; -3.4; 5.3; 0.3	—
PRIMARY Part 2: Change From Baseline in Vital Sign: Temperature	0.38; 0.08; 0.11; 0.11; 0.09; 0.25	—
PRIMARY Part 2: Change From Baseline in Vital Sign: Respiratory Rate	-1.0; 2.2; 0.2; 0.1; 0.8; -0.5	—
PRIMARY Part 2: Number of Participants With Abnormal ECG Findings	0; 0; 0; 0; 0; 0	—
SECONDARY Part 1: Area Under the Plasma Concentration Time Curve (AUC) From Zero to 24 Hour (AUC[0-24]) of GSK3640254	0.056; 0.171; 0.576; 1.546; 4.177; 7.334	—
SECONDARY Part 1: AUC From Zero to Time of Last Sample Taken (AUC[0-Tlast]) of GSK3640254	0.020; 0.184; 1.082; 2.816; 8.060; 14.068	—
SECONDARY Part 1: AUC From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of GSK3640254	0.057; 0.329; 1.227; 2.992; 8.539; 14.952	—
SECONDARY Part 1: Apparent Terminal Phase Half-life (T1/2) of GSK3640254	7.886; 20.486; 25.332; 21.221; 22.838; 22.620	—
SECONDARY Part 1: Apparent Oral Clearance (CL/F) of GSK3640254	17.685; 9.119; 8.152; 10.027; 11.711; 13.376	—
SECONDARY Part 1: Maximum Observed Concentration (Cmax), Concentration of GSK3640254 at 24 Hours (C24) and Last Quantifiable Concentration (Clast) of GSK3640254	0.005; 0.014; 0.047; 0.130; 0.372; 0.579	—
SECONDARY Part 1: Time of Occurrence of Cmax (Tmax), Lag Time (Tlag), and Time to Reach Clast (Tlast) of GSK3640254	3.500; 4.500; 3.500; 4.000; 3.750; 3.000	—
SECONDARY Part 2: AUC(0-24) of GSK3640254: Day 1	2.855; 6.801; 8.257; 13.456	—
SECONDARY Part 2: Cmax, C24 of GSK3640254 on Day 1	0.215; 0.536; 0.614; 1.044; 0.082; 0.207	—
SECONDARY Part 2: Tmax, Tlag of GSK3640254 on Day 1	3.750; 4.250; 4.000; 4.000; 0.508; 0.500	—
SECONDARY Part 2: Tmax GSK3640254 on Day 14	3.775; 4.000; 3.750; 4.250	—
SECONDARY Part 2: Cmax of GSK3640254 on Day 14	0.414; 1.182; 1.402; 2.156	—
SECONDARY Part 2: AUC From Pre-dose to the End of the Dosing Interval at Steady State (AUC[0-tau]): Day 14	6.282; 17.506; 21.501; 31.954	—
SECONDARY Part 2: Plasma Trough Concentration (Ctau) of GSK3640254: Day 14	0.186; 0.558; 0.630; 0.980	—
SECONDARY Part 2: T1/2 of GSK3640254: Day 14	24.847; 28.358; 22.125; 22.350	—
SECONDARY Part 2: CL/F of GSK3640254: Day 14	7.959; 5.712; 9.302; 10.014	—
SECONDARY Part 1: Dose Proportionality (AUC[0-inf]) Following Single Dose of GSK3640254 on Day 1	0.057; 0.329; 1.1227; 2.992; 8.539; 14.952	—
SECONDARY Part 1: Dose Proportionality (AUC0-24) Following Single Dose of GSK3640254 on Day 1	0.056; 0.171; 0.576; 1.546; 4.177; 7.334	—
SECONDARY Part 1: Dose Proportionality for Cmax Following Single Dose of GSK3640254 on Day 1	0.005; 0.014; 0.047; 0.130; 0.372; 0.579	—
SECONDARY Part 2: Dose Proportionality (AUC0-tau) Following Repeated Dose of GSK3640254 on Day 14	6.282; 17.506; 21.501; 31.954	—
SECONDARY Part 2: Dose Proportionality (Ctrough) Following Repeated Dose of GSK3640254 on Day 14	0.205; 0.593; 0.615; 1.255	—
SECONDARY Part 2: Dose Proportionality (Cmax) Following Repeated Dose of GSK3640254 on Day 14	0.414; 1.182; 1.402; 2.156	—
SECONDARY Part 2: Accumulation Ratio of AUC(0-tau) (R [AUC{0-TAU}]) From Day 1 to Day 14	2.2005; 2.5739; 2.6167; 2.3634	—
SECONDARY Part 2: Accumulation Ratio of Cmax (R [CMAX]) From Day 1 to Day 14	1.9276; 2.2069; 2.2994; 2.0650	—
SECONDARY Part 2: Accumulation Ratio of C(Tau) (R[CTAU]) From Day 2 to Day 15	2.1408; 2.5847; 2.5335; 2.1666	—
SECONDARY Part 2: Pre-dose Concentration of GSK3640254 on Day 2 to Day 14	90.20; 221.55; 283.37; 476.58; 155.93; 449.82	—
SECONDARY Part 2: Dose Proportionality (Cmax) Following Repeated Dose of GSK3640254 at Day 1	0.215; 0.536; 0.614; 1.044	—
SECONDARY Part 2: Dose Proportionality (AUC0-24) Following Repeated Dose of GSK3640254 at Day 1	2.855; 6.801; 8.257; 13.456	—

Summary

Human immuno deficiency virus 1 (HIV-1) infections continues to be a serious health threat throughout the world and development of medicines with new mechanism of action have an important role to play. GSK3640254 is a maturation inhibitor (MI) and can be effective in HIV-1 treatment. This randomized, 2-part, single and repeat increasing dose study will collect information on safety, tolerability and drug levels in the body of in healthy subjects for GSK3640254. The information collected in this study will help in further clinical development of GSK3640254, including a Phase IIA Proof of Concept (PoC) study in HIV-infected subjects. Approximately 16 healthy subjects will be randomized to receive single oral dose of GSK3640254 and placebo in Part 1 and approximately 56 healthy subjects will be randomized to receive repeat oral dose of GSK3640254 or placebo in Part 2. All doses will be given immediately after a moderate fat meal. Maximum duration of study participation will be approximately 12 weeks.

Eligibility Criteria

Inclusion Criteria

Subjects must be 18 to 55 years of age inclusive, at the time of signing the informed consent.
Subjects who are overtly healthy as determined by medical evaluation including medical history and psychiatric history, physical examination, laboratory tests, and 24 hour Holter monitoring.
Body weight >=50.0 kilogram (kg) (110 pounds) for men and 45.0kg (99 pounds) for women and body mass index (BMI) within the range 18.5-32.0 kg per meter square (kg/m^2) (inclusive).
Male or female subjects. A male subject must agree to use contraception during the treatment period and for at least 14 weeks following the last dose, corresponding to the time needed to eliminate study treatment for potential genotoxic and teratogenic study treatments plus an additional 90 days (spermatogenesis cycle). In addition, male subjects must refrain from donating sperm during this period. A female subject is eligible to participate if she is not a woman of childbearing potential (WOCBP).
Capable of giving signed informed consent.

Exclusion Criteria

Alanine transaminase (ALT) >1.5 into upper limit of normal (ULN).
Bilirubin >1.5 into ULN (isolated bilirubin >1.5 into ULN is acceptable if bilirubin is fractionated and direct bilirubin 100 beats per minute (bpm) for males and 100 bpm for females; PR interval 220 millisecond (msec); QRS duration 120 msec; the Fridericia's QT correction formula (QTcF) interval >450 msec.
Evidence of previous myocardial infarction (does not include ST segment changes associated with re-polarization).
Any conduction abnormality (including but not specific to left or right complete bundle branch block, Atrioventricular block [2nd degree or higher], Wolff-Parkinson-White [WPW] syndrome).
Sinus Pauses >3 seconds.
Any significant arrhythmia which, in the opinion of the Investigator or GlaxoSmithKline/ViiV medical monitor, will interfere with the safety for the individual subject.
Non-sustained or sustained ventricular tachycardia (3 consecutive ventricular ectopic beats).
History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of >14 units. One unit is equivalent to 8 gram of alcohol: a half-pint approximately 240 mL of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
Regular use of tobacco- or nicotine-containing products within 3 months prior to screening.
History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the Investigator or medical monitor, contraindicates their participation.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03231943). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.