PMID- 25394039
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20160121
LR  - 20181023
IS  - 1758-2652 (Electronic)
IS  - 1758-2652 (Linking)
VI  - 17
IP  - 4 Suppl 3
DP  - 2014
TI  - Safety profile of HIV-1 attachment inhibitor prodrug BMS-663068 in 
      antiretroviral-experienced subjects: week 24 analysis.
PG  - 19530
LID - 10.7448/IAS.17.4.19530 [doi]
LID - 19530 [doi]
AB  - INTRODUCTION: BMS-663068 is a prodrug of BMS-626529, an attachment inhibitor that 
      binds directly to HIV-1 gp120, preventing initial viral attachment and entry into 
      the host CD4+ T-cell. AI438011 is an ongoing, Phase IIb, randomized, 
      active-controlled trial investigating the safety, efficacy and dose-response of 
      BMS-663068 vs. atazanavir/ritonavir (ATV/r) in treatment-experienced (TE), 
      HIV-1-positive subjects. At Week 24, response rates across the BMS-663068 arms 
      were consistent with ATV/r. MATERIALS AND METHODS: Antiretroviral TE subjects 
      (exposure to >/=1 antiretroviral for >/=1 week) with susceptibility to all study 
      drugs (including BMS-626529 IC50 100 nM) were randomized equally to four 
      BMS-663068 arms (400 or 800 mg, BID; 600 or 1200 mg, QD) and a control arm (ATV/r 
      300/100 mg QD), with tenofovir disoproxil fumarate (TDF) + raltegravir (RAL). The 
      complete safety profile through Week 24 is reported. RESULTS: In total, 251 
      subjects were treated (BMS-663068, 200; ATV/r, 51). No BMS-663068-related adverse 
      events (AEs) led to discontinuation. Grade 2-4 drug-related AEs occurred in 
      17/200 (8.5%) subjects across the BMS-633068 arms; however, these events were 
      mostly single instances and no dose-relationship was seen. Similarly, no 
      noticeable trend for Grade 3-4 laboratory abnormalities was seen and Grade 3-4 
      hematologic changes and liver chemistry elevations were uncommon (neutropenia, 
      2.5%; AST/ALT elevations, 1% (n=196)). In the ATV/r arm, Grade 2-4 drug-related 
      AEs occurred in 14/51 (27.5%) subjects and were mostly secondary to 
      gastrointestinal and/or hepatobiliary disorders. Serious adverse events (SAEs) 
      occurred in 13/200 (6.5%) and 5/51 (9.8%) subjects receiving BMS-663068 and 
      ATV/r, respectively; most were secondary to infections and none were related to 
      study drugs. The most common AE reported for BMS-663068 was headache (28/200, 
      14%), occurring in 5/51 (10%) subjects in the ATV/r arm; in the BMS-663068 arms, 
      this was not dose-related. There were no deaths. CONCLUSIONS: BMS-663068 was 
      generally well tolerated across all arms, with no related SAEs or AEs leading to 
      discontinuation and no dose-related safety signals. There were no trends for 
      Grade 2-4 AEs or clinical laboratory abnormalities. These results support 
      continued development of BMS-663068. Note: Previously submitted at IDWeek, 
      Philadelphia, PA, 8 October 2014.
FAU - Lalezari, Jacob
AU  - Lalezari J
AD  - Quest Clinical Research, N/A, San Francisco, CA, USA.
FAU - Latiff, Gulam H
AU  - Latiff GH
AD  - Maxwell Clinic, N/A, Durban, South Africa.
FAU - Brinson, Cynthia
AU  - Brinson C
AD  - Family Medicine, Southwestern Medical School, Austin Branch and Central Texas 
      Clinical Research, Austin, TX, USA.
FAU - Echevarria, Juan
AU  - Echevarria J
AD  - Hospital Nacional Cayetano Heredia, Lima, Peru.
FAU - Trevino-Perez, Sandra
AU  - Trevino-Perez S
AD  - HIV Research Department, Mexico Centre for Clinical Research, Mexico City, 
      Mexico.
FAU - Bogner, Johannes R
AU  - Bogner JR
AD  - Section for Infectious Diseases, Med. IV, Hospital of the University of Munich, 
      Munich, Germany.
FAU - Stock, David
AU  - Stock D
AD  - Research and Development, Bristol-Myers Squibb, Wallingford, CT, USA.
FAU - Joshi, Samit R
AU  - Joshi SR
AD  - Research and Development, Bristol-Myers Squibb, Wallingford, CT, USA.
FAU - Hanna, George J
AU  - Hanna GJ
AD  - Research and Development, Bristol-Myers Squibb, Princeton, NJ, USA.
FAU - Lataillade, Max
AU  - Lataillade M
AD  - Research and Development, Bristol-Myers Squibb, Wallingford, CT, USA.
LA  - eng
PT  - Journal Article
DEP - 20141102
PL  - Switzerland
TA  - J Int AIDS Soc
JT  - Journal of the International AIDS Society
JID - 101478566
PMC - PMC4224850
EDAT- 2014/11/14 06:00
MHDA- 2014/11/14 06:01
PMCR- 2014/11/02
CRDT- 2014/11/14 06:00
PHST- 2014/11/14 06:00 [entrez]
PHST- 2014/11/14 06:00 [pubmed]
PHST- 2014/11/14 06:01 [medline]
PHST- 2014/11/02 00:00 [pmc-release]
AID - 19530 [pii]
AID - 10.7448/IAS.17.4.19530 [doi]
PST - epublish
SO  - J Int AIDS Soc. 2014 Nov 2;17(4 Suppl 3):19530. doi: 10.7448/IAS.17.4.19530. 
      eCollection 2014.