NCT04507321

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

Completed Phase 1 Results posted Last updated 31 January 2022

What this trial tests

Phase 1 trial testing GSK3640254 Oral tablet in HIV Infections in 5 participants. Completed in 23 November 2020.

Timeline

24 September 2020

Primary endpoint
23 November 2020

23 November 2020

Quick facts

Lead sponsor	ViiV Healthcare
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	5
Start date	24 September 2020
Primary completion	23 November 2020
Estimated completion	23 November 2020
Sites	1 location across United Kingdom

Drugs / interventions tested

• GSK3640254 Oral tablet
• [14C]-GSK3640254 intravenous infusion — full drug profile →
• [14C]-GSK3640254 powder — full drug profile →

Conditions studied

• HIV Infections — all drugs for HIV Infections →

Sponsor

ViiV Healthcare — full company profile →

Who can join

Adults 30 to 50, male only, with HIV Infections. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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 Primary · 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

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

Group	Value	95% CI
GSK3640254 Tablet	41234.1841	± 14.5

AUC(0-inf) of Total Radioactivity in Blood Following Administration of Oral Dose of GSK3640254 Primary · Day 1: 2, 4, 6, 8, 10 hours

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

Group	Value	95% CI
GSK3640254 Tablet	NA	± NA

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

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

Group	Value	95% CI
[14C]-GSK3640254 IV	96.5532	± 19.7

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

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

Group	Value	95% CI
[14C]-GSK3640254 IV	105.0882	± 19.1

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

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

Group	Value	95% CI
[14C]-GSK3640254 Oral Suspension	19026.4818	± 21.8

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

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

Group	Value	95% CI
[14C]-GSK3640254 Oral Suspension	23226.8511	± 20.7

AUC(0-inf) of Total Radioactivity in Blood Following Administration of Oral Dose of [14C]-GSK3640254 Primary · Day 1: 2, 4, 6, 8, 10 hours

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.

Group	Value	95% CI
[14C]-GSK3640254 Oral Suspension	NA	± NA

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

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

Group	Value	95% CI
GSK3640254 Tablet	40816.9451	± 14.2

AUC(0-t) of Total Radioactivity in Blood Following Administration of Oral Dose of GSK3640254 Primary · Day 1: 2, 4, 6, 8, 10 hours

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

Group	Value	95% CI
GSK3640254 Tablet	NA	± NA

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

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

Group	Value	95% CI
[14C]-GSK3640254 IV	93.3371	± 20.4

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

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

Group	Value	95% CI
[14C]-GSK3640254 IV	101.8025	± 19.4

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

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

Group	Value	95% CI
[14C]-GSK3640254 Oral Suspension	18828.0326	± 21.7

Adverse events — posted to ClinicalTrials.gov

Time frame: All-cause mortality, SAEs and non-serious AEs were collected from the start of study treatment up to Day 50.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

GSK3640254 Tablet+[14C]-GSK3640254 IV

Serious: 0/5 (0%)

Deaths: 0/5

[14C]-GSK3640254 Oral Suspension

Serious: 0/5 (0%)

Deaths: 0/5

Other adverse events (2 terms — click to expand)

Reaction	System	GSK3640254 Tablet+[14C]-GS…	[14C]-GSK3640254 Oral Susp…
Nausea	Gastrointestinal disorders	—	—
Asthenia	General disorders	—	—

Data from ClinicalTrials.gov NCT04507321 adverse events section.

Sponsor's own description

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.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.