Evidence map›Paper›PMID 40287607›Full record

ArticleInfectious diseases and therapy2025

Clinical Pharmacokinetics and Safety of a New HIV-1 Capsid Inhibitor, VH4004280, After Oral Administration in Adults Without HIV.

Nilay Thakkar, Rulan Griesel, Amy Pierce, Veronica Bainbridge, Bronagh Shepherd, Konstantinos Angelis, Andrew Tomlinson, Yash Gandhi, Darin Brimhall, Daijha Anderson and 5 more

Registry-linked trialAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Infectious diseases and therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05163522 (A Randomized, Double-Blind), which is not on this map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT05163522 phase1completednot on this map

A Randomized, Double-Blind (Sponsor Unblinded), Placebo-Controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Orally Administered VH4004280 in Healthy Participants

TypeinterventionalSponsorViiV HealthcareRan2021 to 2023Enrolled73ConditionsHIV InfectionsArmsVH4004280, Placebo, Midazolam
3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Nilay ThakkarGSK, 1250 S Collegeville Road, Collegeville, PA, 19426, USA. nilay.x.thakkar@gsk.com.ORCID http://orcid.org/0000-0002-2846-5796
Rulan GrieselViiV Healthcare, 79 New Oxford Street, London, WC1A 1DG, UK.
Amy PierceViiV Healthcare, 410 Blackwell Street, Durham, NC, 27701, USA.
Veronica BainbridgeGSK, 79 New Oxford Street, London, WC1A 1DG, UK.
Bronagh ShepherdGSK, 79 New Oxford Street, London, WC1A 1DG, UK.
Konstantinos AngelisGSK, 79 New Oxford Street, London, WC1A 1DG, UK.
Andrew TomlinsonGSK, 79 New Oxford Street, London, WC1A 1DG, UK.
Yash GandhiGSK, 1250 S Collegeville Road, Collegeville, PA, 19426, USA.
Darin BrimhallPPD-Thermo Fisher Scientific, 8285 W Arby Avenue, Suite 331, Las Vegas, NV, 89113, USA.
Daijha AndersonViiV Healthcare, 410 Blackwell Street, Durham, NC, 27701, USA.
Susan AndrewsGSK, 1250 S Collegeville Road, Collegeville, PA, 19426, USA.
Carolina AcuipilViiV Healthcare, 410 Blackwell Street, Durham, NC, 27701, USA.
Cynthia McCoigViiV Healthcare, P.T.M., Severo Ochoa 2, 28760, Tres Cantos, Madrid, Spain.
Mark BakerViiV Healthcare, Route de l'Etraz 2, Case Postale 1279, CH-1260, Nyon 1, Switzerland.
Paul BennViiV Healthcare, 79 New Oxford Street, London, WC1A 1DG, UK.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionThe pharmacokinetics, drug-drug interaction potential, and safety of a new HIV-1 capsid inhibitor, VH4004280 (VH-280), are described in this first-time-in-human study.

methodsThis randomized, double-blind, placebo-controlled, phase 1 study assessed oral VH-280 in adults without HIV. In parts 1 and 3, VH-280 was administered as powder-in-bottle (PiB) and tablet formulations, respectively, in single ascending doses. In part 2, VH-280 was administered as a PiB formulation once daily for 14 days in multiple ascending doses. In addition, in part 2, the effect of VH-280 on cytochrome P450 3A (CYP3A) activity was evaluated using midazolam as a probe substrate.

resultsIn total, 73 participants were included (VH-280, n = 57; placebo, n = 16). Plasma exposures for VH-280 were broadly dose-proportional, and median time to maximum observed concentration was 9.0-17.0 h for the PiB and tablet formulations. Geometric mean terminal half-life was 145.8-207.8 h (> 6 days). Compared with PiB, exposures for the tablet formulation were 45-56% lower. Concomitant administration of midazolam after single and multiple doses of VH-280 did not result in clinically significant changes in midazolam or 1-hydroxymidazolam exposures; therefore, VH-280 is not anticipated to inhibit or induce CYP3A4. VH-280 was well-tolerated. Frequency of adverse events (AEs) was comparable between placebo and VH-280 groups. Adverse events related to VH-280 were primarily grade 1. There were no serious AEs, AEs leading to withdrawal from drug or study, or deaths. No trends in vital signs, electrocardiograms, or laboratory hematology parameters were observed, and there were no clinically relevant changes in chemistry parameters.

conclusionsData from this first-time-in-human study further characterize the pharmacokinetics of VH-280 after oral administration, providing support for the development of new capsid inhibitors as part of a complete long-acting regimen for the treatment and prevention of HIV-1. CLINICAL

trial registrationClinicalTrials.gov, NCT05163522.

Indexed as

Capsid inhibitorDrug–drug interactionFirst-time-in-humanHIV-1PharmacokineticsPhase 1Safety

Identifiers

PMID40287607
PMCPMC12151970

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.