Evidence map›Paper›PMID 25870057›Full record

Trial reportAntimicrobial agents and chemotherapy2015

Pharmacokinetic interactions between BMS-626529, the active moiety of the HIV-1 attachment inhibitor prodrug BMS-663068, and ritonavir or ritonavir-boosted atazanavir in healthy subjects.

Li Zhu, Matthew Hruska, Carey Hwang, Vaishali Shah, Michael Furlong, George J Hanna, Richard Bertz, Ishani Savant Landry

Open access · bronzeAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.0field-weighted citation impact, top 26% of its field
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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 26 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Trial
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Targeting HIV-1 reservoirs in T cell subsets.Frontiers in immunology · 2023
    Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Investigational protease inhibitors as antiretroviral therapies.Expert opinion on investigational drugs · 2016
    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

8 authors at 1 institution in 1 country.

Li ZhuBristol-Myers Squibb, Research and Development, Princeton, New Jersey, USA li.zhu@bms.com.
Matthew HruskaBristol-Myers Squibb, Research and Development, Princeton, New Jersey, USA.
Carey HwangBristol-Myers Squibb, Research and Development, Princeton, New Jersey, USA.
Vaishali ShahBristol-Myers Squibb, Research and Development, Princeton, New Jersey, USA.
Michael FurlongBristol-Myers Squibb, Research and Development, Princeton, New Jersey, USA.
George J HannaBristol-Myers Squibb, Research and Development, Princeton, New Jersey, USA.
Richard BertzBristol-Myers Squibb, Research and Development, Princeton, New Jersey, USA.
Ishani Savant LandryBristol-Myers Squibb, Research and Development, Princeton, New Jersey, USA.
Bristol-Myers Squibb (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BMS-663068 is a prodrug of BMS-626529, a first-in-class attachment inhibitor that binds directly to HIV-1 gp120, preventing initial viral attachment and entry into host CD4(+) T cells. This open-label, multiple-dose, four-sequence, crossover study addressed potential two-way drug-drug interactions following coadministration of BMS-663068 (BMS-626529 is a CYP3A4 substrate), atazanavir (ATV), and ritonavir (RTV) (ATV and RTV are CYP3A4 inhibitors). Thirty-six healthy subjects were randomized 1:1:1:1 to receive one of four treatment sequences with three consecutive treatments: BMS-663068 at 600 mg twice daily (BID), BMS-663068 at 600 mg BID plus RTV at 100 mg once daily (QD), ATV at 300 mg QD plus RTV at 100 mg QD (RTV-boosted ATV [ATV/r]), or BMS-663068 at 600 mg BID plus ATV at 300 mg QD plus RTV at 100 mg QD. Compared with the results obtained by administration of BMS-663068 alone, coadministration of BMS-663068 with ATV/r increased the BMS-626529 maximum concentration in plasma (Cmax) and the area under the concentration-time curve in one dosing interval (AUCtau) by 68% and 54%, respectively. Similarly, coadministration of BMS-663068 with RTV increased the BMS-626529 Cmax and AUCtau by 53% and 45%, respectively. Compared with the results obtained by administration of ATV/r alone, ATV and RTV systemic exposures remained similar following coadministration of BMS-663068 with ATV/r. BMS-663068 was generally well tolerated, and there were no adverse events (AEs) leading to discontinuation, serious AEs, or deaths. Moderate increases in BMS-626529 systemic exposure were observed following coadministration of BMS-663068 with ATV/r or RTV. However, the addition of ATV to BMS-663068 plus RTV did not further increase BMS-626529 systemic exposure. ATV and RTV exposures remained similar following coadministration of BMS-663068 with either ATV/r or RTV. BMS-663068 was generally well tolerated alone or in combination with either RTV or ATV/r.

Indexed as

AdolescentAdultAnti-HIV AgentsAtazanavir SulfateCross-Over StudiesDrug InteractionsDrug Therapy, CombinationFemaleHIV-1HIV Envelope Protein gp120HIV Fusion InhibitorsHumansMaleMiddle AgedOrganophosphatesPiperazinesAnti-HIV AgentsAtazanavir SulfateBMS-626529fostemsavirgp120 protein, Human immunodeficiency virus 1HIV Envelope Protein gp120HIV Fusion InhibitorsOrganophosphatesPiperazinesRitonavirTriazoles

Identifiers

PMID25870057
PMCPMC4468697
OpenAlexW2069644313

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.