Pharmacokinetics and Metabolism of 14 Carbon [14C]-GSK3640254

NCT04507321 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 2130512019-004444-30
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, single-center, single group, non-randomized, two-period, single sequence, mass balance study which will enroll 6 healthy male participants. This study will assess the pharmacokinetics, balance/excretion, and metabolism of GSK3640254 in humans using \[14C\]-radiolabeled drug substance administered as an intravenous (IV) infusion and via the oral route. The study will also provide an assessment of GSK3640254 absorption, metabolism and excretion following administration of a \[14C\]-radiolabeled oral suspension. Each participant will be involved in the study for up to 10 weeks which will include a screening period, two treatment periods (treatment Periods 1 and 2) separated by a washout of at least 13 days between oral doses, and a follow-up visit 7-14 days after the last assessment in treatment Period 2.

Conditions

HIV Infections

Keywords

Human Immunodeficiency Virus (HIV); GSK3640254; Pharmacokinetics; Radiolabeled; Mass balance

Outcome Measures

Primary Outcomes (51)

• Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) in Plasma Following Administration of Oral Dose of GSK3640254

  Blood samples were collected at the indicated time points for Pharmacokinetic (PK) analysis. PK parameters were calculated by standard non-compartmental analysis.

  Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

• AUC(0-inf) of Total Radioactivity in Blood Following Administration of Oral Dose of GSK3640254

  Blood samples were collected at indicated time points. Data was not collected because a discrepancy has been identified in the Objectives and Endpoints section of the Protocol, which incorrectly states one of the Primary Endpoints. The Objectives and Endpoints section incorrectly states that the PK parameters of both the parent and total drug-related material (radioactivity) in plasma and blood would be presented. Neither the Schedule of Activities nor the Study Assessments and Procedures sections of the Protocol address the sampling and measurement of concentrations of parent drug in blood or calculation of derived PK parameters. Consequently, no parent analyte measurements were performed for blood samples. Thus, the reference to parent analyte specifically for blood, in the Objectives and Endpoints section was an error. Only samples and measurements for total drug-related material (radioactivity) in blood and plasma, and parent drug in plasma were collected to derive PK parameters.

  Day 1: 2, 4, 6, 8, 10 hours

• AUC(0-inf) in Plasma Following Administration of IV Dose of [14C]-GSK3640254

  Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.

  Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

• AUC(0-inf) of Total Radioactivity in Plasma Following Administration of IV Dose of [14C]-GSK3640254

  Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.

  Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

• AUC(0-inf) in Plasma Following Administration of Oral Dose of [14C]-GSK3640254

  Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.

  Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

• AUC(0-inf) of Total Radioactivity in Plasma Following Administration of Oral Dose of [14C]-GSK3640254

  Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.

  Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

• AUC(0-inf) of Total Radioactivity in Blood Following Administration of Oral Dose of [14C]-GSK3640254

  Blood samples were collected at indicated time points for PK analysis. Data was not collected for this Outcome measure as AUC(0-inf) is not calculable for total radioactivity in blood due to insufficient sampling in the terminal phase.

  Day 1: 2, 4, 6, 8, 10 hours

• AUC From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC[0-t]) in Plasma Following Administration of Oral Dose of GSK3640254

  Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.

  Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

• AUC(0-t) of Total Radioactivity in Blood Following Administration of Oral Dose of GSK3640254

  Blood samples were collected at indicated time points. Data was not collected because a discrepancy has been identified in the Objectives and Endpoints section of the Protocol, which incorrectly states one of the Primary Endpoints. The Objectives and Endpoints section incorrectly states that the PK parameters of both the parent and total drug-related material (radioactivity) in plasma and blood would be presented. Neither the Schedule of Activities nor the Study Assessments and Procedures sections of the Protocol address the sampling and measurement of concentrations of parent drug in blood or calculation of derived PK parameters. Consequently, no parent analyte measurements were performed for blood samples. Thus, the reference to parent analyte specifically for blood, in the Objectives and Endpoints section was an error. Only samples and measurements for total drug-related material (radioactivity) in blood and plasma, and parent drug in plasma were collected to derive PK parameters.

  Day 1: 2, 4, 6, 8, 10 hours

• AUC(0-t) in Plasma Following Administration of IV Dose of [14C]-GSK3640254

  Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.

  Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

• AUC(0-t) of Total Radioactivity in Plasma Following Administration of IV Dose of [14C]-GSK3640254

  Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.

  Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

• AUC (0-t) in Plasma Following Administration of Oral Dose of [14C]-GSK3640254

  Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.

  Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

• AUC(0-t) of Total Radioactivity in Plasma Following Administration of Oral Dose of [14C]-GSK3640254

  Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.

  Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

• AUC(0-t) of Total Radioactivity in Blood Following Administration of Oral Dose of [14C]-GSK3640254

  Blood samples were collected at indicated time points for PK analysis.

  Day 1: 2, 4, 6, 8, 10 hours

• Maximum Observed Concentration (Cmax) in Plasma Following Administration of Oral Dose of GSK3640254

  Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.

  Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

• Cmax of Total Radioactivity in Blood Following Administration of Oral Dose of GSK3640254

  Blood samples were collected at indicated time points. Data was not collected because a discrepancy has been identified in the Objectives and Endpoints section of the Protocol, which incorrectly states one of the Primary Endpoints. The Objectives and Endpoints section incorrectly states that the PK parameters of both the parent and total drug-related material (radioactivity) in plasma and blood would be presented. Neither the Schedule of Activities nor the Study Assessments and Procedures sections of the Protocol address the sampling and measurement of concentrations of parent drug in blood or calculation of derived PK parameters. Consequently, no parent analyte measurements were performed for blood samples. Thus, the reference to parent analyte specifically for blood, in the Objectives and Endpoints section was an error. Only samples and measurements for total drug-related material (radioactivity) in blood and plasma, and parent drug in plasma were collected to derive PK parameters.

  Day 1: 2, 4, 6, 8, 10 hours

• Cmax in Plasma Following Administration of IV Dose of [14C]-GSK3640254

  Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.

  Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

• Cmax of Total Radioactivity in Plasma Following Administration of IV Dose of [14C]-GSK3640254

  Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.

  Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

• Cmax in Plasma Following Administration of Oral Dose of [14C]-GSK3640254

  Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.

  Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

• Cmax of Total Radioactivity in Plasma Following Administration of Oral Dose of [14C]-GSK3640254

  Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.

  Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

• Cmax of Total Radioactivity in Blood Following Administration of Oral Dose of [14C]-GSK3640254

  Blood samples were collected at indicated time points for PK analysis.

  Day 1: 2, 4, 6, 8, 10 hours

• Time of Occurrence of Cmax (Tmax) in Plasma Following Administration of Oral Dose of GSK3640254

  Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.

  Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

• Tmax of Total Radioactivity in Blood Following Administration of Oral Dose of GSK3640254

  Blood samples were collected at indicated time points. Data was not collected because a discrepancy has been identified in the Objectives and Endpoints section of the Protocol, which incorrectly states one of the Primary Endpoints. The Objectives and Endpoints section incorrectly states that the PK parameters of both the parent and total drug-related material (radioactivity) in plasma and blood would be presented. Neither the Schedule of Activities nor the Study Assessments and Procedures sections of the Protocol address the sampling and measurement of concentrations of parent drug in blood or calculation of derived PK parameters. Consequently, no parent analyte measurements were performed for blood samples. Thus, the reference to parent analyte specifically for blood, in the Objectives and Endpoints section was an error. Only samples and measurements for total drug-related material (radioactivity) in blood and plasma, and parent drug in plasma were collected to derive PK parameters.

  Day 1: 2, 4, 6, 8, 10 hours

• Tmax in Plasma Following Administration of IV Dose of [14C]-GSK3640254

  Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.

  Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

• Tmax of Total Radioactivity in Plasma Following Administration of IV Dose of [14C]-GSK3640254

  Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.

  Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

• Tmax in Plasma Following Administration of Oral Dose of [14C]-GSK3640254

  Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.

  Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

• Tmax of Total Radioactivity in Plasma Following Administration of Oral Dose of [14C]-GSK3640254

  Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.

  Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

• Tmax of Total Radioactivity in Blood Following Administration of Oral Dose of [14C]-GSK3640254

  Blood samples were collected at indicated time points for PK analysis.

  Day 1: 2, 4, 6, 8, 10 hours

• Terminal Phase Half-life (T1/2) in Plasma Following Administration of Oral Dose of GSK3640254

  Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.

  Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

• T1/2 of Total Radioactivity in Blood Following Administration of Oral Dose of GSK3640254

  Blood samples were collected at indicated time points. Data was not collected because a discrepancy has been identified in the Objectives and Endpoints section of the Protocol, which incorrectly states one of the Primary Endpoints. The Objectives and Endpoints section incorrectly states that the PK parameters of both the parent and total drug-related material (radioactivity) in plasma and blood would be presented. Neither the Schedule of Activities nor the Study Assessments and Procedures sections of the Protocol address the sampling and measurement of concentrations of parent drug in blood or calculation of derived PK parameters. Consequently, no parent analyte measurements were performed for blood samples. Thus, the reference to parent analyte specifically for blood, in the Objectives and Endpoints section was an error. Only samples and measurements for total drug-related material (radioactivity) in blood and plasma, and parent drug in plasma were collected to derive PK parameters.

  Day 1: 2, 4, 6, 8, 10 hours

• T1/2 in Plasma Following Administration of IV Dose of [14C]-GSK3640254

  Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.

  Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

• T1/2 of Total Radioactivity in Plasma Following Administration of IV Dose of [14C]-GSK3640254

  Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.

  Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

• T1/2 in Plasma Following Administration of Oral Dose of [14C]-GSK3640254

  Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.

  Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

• T1/2 of Total Radioactivity in Plasma Following Administration of Oral Dose of [14C]-GSK3640254

  Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.

  Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

• T1/2 of Total Radioactivity in Blood Following Administration of Oral Dose of [14C]-GSK3640254

  Blood samples were collected at indicated time points for PK analysis. Data was not collected for this Outcome measure as T1/2 is not calculable for total radioactivity in blood due to insufficient sampling in the terminal phase.

  Day 1: 2, 4, 6, 8, 10 hours

• Volume of Distribution at Steady State (Vss) in Plasma Following Administration of IV Dose of [14C]-GSK3640254

  Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.

  Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

• Clearance (CL) in Plasma Following Administration of IV Dose of [14C]-GSK3640254

  Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.

  Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

• Renal Clearance (CLr) Following Administration of IV Dose of [14C]-GSK3640254

  Blood samples were collected at the indicated time points for PK analysis. Renal clearance was calculated as (Cumulative amount \[Ae\]\[Urine\] for Period 1)/(Plasma AUC\[0-inf\]).

  Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

• CLr Following Administration of Oral Dose of [14C]-GSK3640254

  Blood samples were collected at the indicated time points for PK analysis. Renal clearance was calculated as (Cumulative Ae\[Urine\] for Period 2)/(Plasma AUC\[0-inf\]).

  Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

• Oral Clearance (CL/F) in Plasma Following Administration of Oral Dose of GSK3640254

  Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.

  Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

• CL/F in Plasma Following Administration Oral Dose of [14C]-GSK3640254

  Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.

  Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

• Apparent Volume of Distribution (Vz/F) Following Administration of Oral Dose of GSK3640254

  Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.

  Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

• Vz/F Following Administration of Oral Dose of [14C]-GSK3640254

  Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis.

  Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

• Absolute Oral Bioavailability of GSK3640254

  Absolute bioavailability is the amount of drug from a formulation that reaches the systemic circulation relative to an IV dose, computed as ratio of AUC(Oral Tablet)/Dose(Oral Tablet) with AUC(IV)/Dose(IV). Plasma samples were collected from participants at indicated time points. Absolute bioavailability from the oral tablet and IV doses were analyzed using AUC(0-inf) and AUC(0-t) pharmacokinetic parameters.

  Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

• Percentage of Drug Escaping First Pass Hepatic Clearance (Fh) Following Administration of [14C]-GSK3640254 IV

  Blood samples were collected at the indicated time points for PK analysis. Fh was expressed as percentage and was calculated as: 1 minus hepatic extraction ratio multiplied by 100. Hepatic extraction ratio=hepatic blood clearance (milliliters per minute)/hepatic blood flow (milliliters per minute).

  Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.25, 5.5, 6, 7, 8, 9, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

• Percentage of Drug Absorbed (Fa) Following Administration of [14C]-GSK3640254 Oral Suspension

  Blood samples were collected at the indicated time points for PK analysis. Fa was expressed as percentage which was calculated as ratio of oral bioavailability and Fh multiplied by 100.

  Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

• Percentage of Drug Escaping Gut Metabolism (Fg) Following Administration of [14C]-GSK3640254 Oral Suspension

  Blood samples were collected at the indicated time points for PK analysis. Fg is defined as the fraction metabolized by gut wall as a fraction of the oral dose and was expressed as 1 minus Metabolite load following intravenous and oral administration multiplied by 100.

  Day 1 (Pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

• Percentage of Total Radioactive Dose Excreted in Urine Following Administration of IV Dose of [14C]-GSK3640254

  Urine samples were collected at indicated timepoints to measure percentage of the total radioactive drug-related material excreted in urine. Percentage of radioactive dose excreted in urine was calculated as (amount excreted in urine divided by administered radioactivity dose) multiplied by 100. Not applicable (NA) indicates that No concentration values detected for pre-dose.

  Day 1 (Pre-dose), 5, 24, 48, 72, 96, 120, 144 and 163 hours post-dose

• Percentage of Total Radioactive Dose Excreted in Urine Following Administration of Oral Dose of [14C]-GSK3640254

  Urine samples were collected at indicated timepoints to measure percentage of the total radioactive drug-related material excreted in urine. Percentage of radioactive dose excreted in urine was calculated as (amount excreted in urine divided by administered radioactivity dose) multiplied by 100.

  Day 1 (Pre-dose), 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264 and 288 hours post-dose

• Percentage of Total Radioactive Dose Excreted in Feces Following Administration of IV Dose of [14C]-GSK3640254

  Fecal samples were collected at indicated timepoints to measure percentage of the total radioactive drug-related material excreted in feces. Percentage of radioactive dose excreted was calculated as (amount excreted in feces homogenate divided by administered radioactivity dose) multiplied by 100. NA indicates that No concentration values detected for pre-dose.

  Day 1 (Pre-dose), 24, 48, 72, 96, 120, 144 and 163 hours post-dose

• Percentage of Total Radioactive Dose Excreted in Feces Following Administration of Oral Dose of [14C]-GSK3640254

  Fecal samples were collected at indicated timepoints to measure percentage of the total radioactive drug-related material excreted in feces. Percentage of radioactive dose excreted was calculated as (amount excreted in feces homogenate divided by administered radioactivity dose) multiplied by 100.

  Day 1 (Pre-dose), 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264 and 288 hours post-dose

Secondary Outcomes (11)

• Number of Participants With Non-serious Adverse Events (AEs) and Serious AEs (SAEs)

  Up to 50 days

• Number of Participants With Worst Case Hematology Results Relative to Normal Range Post Baseline Relative to Baseline

  Baseline (Day 1: pre-dose) and Up to 50 Days

• Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post Baseline Relative to Baseline

  Baseline (Day 1: pre-dose) and Up to 50 Days

• Number of Participants With Clinically Significant Urinalysis Findings

  Up to 50 days

• Number of Participants With Worst Case Post Baseline Abnormal 12-Lead Electrocardiogram (ECG) Findings

  Baseline (Day 1: pre-dose) and Up to 50 days

Study Arms (1)

GSK3640254 tablet + [14C]-GSK3640254 IV/[14C] oral suspension

EXPERIMENTAL

Participants will receive a single oral dose of GSK3640254 200 milligram (mg) (2×100 mg) tablets with a moderate fat meal. Participants will then be administered a 100 microgram (mcg) dose (approximately 3.7 kilobecquerel; 100 nano Curie) of \[14C\]-GSK3640254 as an IV infusion for 1 hour on Day 1 in treatment Period 1, On Day 1 in treatment Period 2, participants will receive a single oral dose of 85 mg (approximately 3.15 megabecquerel; 85 micro Curie) \[14C\]-GSK3640254 administered as an oral suspension with a moderate fat meal. A wash out period of at least 13 days will be maintained between oral doses of treatment periods.

Drug: GSK3640254 Oral tablet; Drug: [14C]-GSK3640254 intravenous infusion; Drug: [14C]-GSK3640254 powder

Interventions

GSK3640254 Oral tablet DRUG

GSK3640254 will be available as white film-coated round tablets to be administered via oral route with meal in the morning with 240 milliliter (mL) of water at room temperature.

GSK3640254 tablet + [14C]-GSK3640254 IV/[14C] oral suspension

[14C]-GSK3640254 intravenous infusion DRUG

\[14C\]-GSK3640254 will be available as clear, colorless solution free from visible particulates to be administered via the IV route.

GSK3640254 tablet + [14C]-GSK3640254 IV/[14C] oral suspension

[14C]-GSK3640254 powder DRUG

\[14C\]-GSK3640254 will be available as white powder to be reconstituted into a suspension with 25 mL of vehicle before dosing so as to administer 85 mg dose with meal in the morning.

GSK3640254 tablet + [14C]-GSK3640254 IV/[14C] oral suspension

Eligibility Criteria

• Age: 30 Years - 50 Years
• Gender Eligibility Details: Male participants will be part of this study.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Participant must be 30 to 50 years of age inclusive, at the time of signing the informed consent.
• Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, vital signs and ECG. A participant with a clinical abnormality or laboratory parameter (i.e. outside the reference range for the population being studied), which is not specifically listed in the eligibility criteria, may be included only if the investigator agrees and documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
• History of regular bowel movements (averaging one or more bowel movements per day).
• Non-smoker, or ex-smoker who hasn't regularly smoked for the 6 months before Screening.
• Body weight of 50 kilograms (kg) and above, and body mass index (BMI) within the range 19.0 to 31.0 kg/square meter (m\^2) (inclusive).
• Male participants are eligible to participate if they agree to the following during the study, including washout periods: Refrain from donating sperm and either a) be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent or b) Agree to use a male condom when having penile-vaginal intercourse with a woman of childbearing potential unless vasectomized.
• Capable of giving signed informed consent.

You may not qualify if:

• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). Participants with a history of cholecystectomy must be excluded.
• Significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention; or interfering with the interpretation of data.
• Any clinically relevant abnormality identified at the Screening medical assessment (physical examination/medical history) clinical laboratory tests, or 12-lead ECG.
• Current episode, recent history, or chronic history of diarrhea.
• Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
• Any history of significant underlying psychiatric disorder, including, but not limited to, schizophrenia, bipolar disorder with or without psychotic symptoms, other psychotic disorders, or schizotypal (personality) disorder.
• Any history of major depressive disorder with or without suicidal features, or anxiety disorders that required medical intervention (pharmacologic or not) such as hospitalization or other inpatient treatment and/or chronic (\>6 months) outpatient treatment. Participants with other conditions such as adjustment disorder or dysthymia that have required shorter term medical therapy (\<6 months) without inpatient treatment and are currently well-controlled clinically or resolved may be considered for entry after discussion and agreement with the ViiV Healthcare (VH)/GlaxoSmithKline (GSK) Medical Monitor.
• Any pre-existing physical or other psychiatric condition (including alcohol or drug abuse), which, in the opinion of the investigator (with or without psychiatric evaluation), could interfere with the participant's ability to comply with the dosing schedule and protocol.
• Regular use of known drugs of abuse or history of drug abuse or dependence within 6 months of the study.
• Regular alcohol consumption within 6 months prior to the study defined as an average weekly intake of \>21 units. One unit is equivalent to 8 grams of alcohol: a glass (equivalent to \[\~\]240 mL) of beer, 1 small glass (\~100 mL) of wine or 1 (\~25 mL) measure of spirits.
• History of or regular use of tobacco- or nicotine-containing products in the 3 months prior to Screening.
• Medical history of cardiac arrhythmias, prior myocardial infarction in the past 3 months, or cardiac disease or a family or personal history of long QT syndrome.
• QT duration corrected for heart rate by Fridericia's formula (QTcF) \>450 milliseconds (msec).
• At Screening or prior to the first dose, a supine blood pressure (BP) that is persistently higher than 140/90 millimeters of mercury (mmHg).
• At Screening or prior to the first dose, a supine mean heart rate (HR) outside the range of 50 to 100 beats per minute (bpm). A heart rate from 100 to 110 bpm can be rechecked by ECG or vital signs within 30 minutes to verify eligibility.

Sponsors & Collaborators

• ViiV Healthcare: lead

Study Sites (1)

GSK Investigational Site

London, NW10 7EW, United Kingdom

Location

MeSH Terms

Conditions

HIV Infections; Acquired Immunodeficiency Syndrome

Interventions

GSK3640254

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: ViiV Healthcare

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  ViiV Healthcare

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: This will be an open-label study.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants will receive non-radiolabeled GSK3640254 oral tablets concomitantly with radiolabeled \[14C\]-GSK3640254 administered as an IV infusion in treatment Period 1 and radiolabeled \[14C\]-GSK3640254 as an oral suspension in treatment Period 2.

Study Record Dates

• First Submitted: August 6, 2020
• First Posted: August 11, 2020
• Study Start: September 24, 2020
• Primary Completion: November 23, 2020
• Study Completion: November 23, 2020
• Last Updated: January 31, 2022
• Results First Posted: January 31, 2022

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

GB (1)