{"id":2683,"date":"2007-04-04T13:03:54","date_gmt":"2007-04-04T12:03:54","guid":{"rendered":"http:\/\/moomango.co.uk\/htb\/?p=2683"},"modified":"2013-09-20T17:17:40","modified_gmt":"2013-09-20T17:17:40","slug":"phase-2-study-comparing-rilpivirine-tmc-278-to-efavirenz-in-treatment-naive-patients-48-week-results","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/2683","title":{"rendered":"Phase 2b study comparing rilpivirine (TMC-278) to efavirenz in treatment-naive patients: 48-week results"},"content":{"rendered":"

Simon Collins, HIV i-Base<\/strong><\/p>\n

48-week results from the primary endpoint of the Phase 2b TMC-278 C204 dose-finding study, of a second generation diarylpyrimidine NNRTI in development from Tibotec were presented in an oral session by Anton Pozniak from Chelsea and Westminster Hospital, London. Rilpivirine (TMC-278) is a once-daily compound that has a similar resistance profile to TMC-125 which is being researched as a second-line treatment after first NNRTI failure.<\/strong><\/p>\n

TMC278-C204 is an ongoing, randomised, active-controlled, partially blinded (efavirenz was unblinded), dose-finding phase 2b trial.<\/p>\n

368 patients (33% women) were randomised 1:1:1:1 to TMC278 25, 75, or 150 mg once daily, or to EFV 600 mg once daily. All arms included investigator-selected background nucleosides: AZT\/3TC (Combivir) was used by 76% of patients and tenofovir\/FTC (Truvada) by 24%. The primary endpoint was the proportion of patients with confirmed viral load <50 copies\/mL (TLOVR definition, non-completer = failure) at 48 weeks.<\/p>\n

Baseline median CD4 and viral load were 203 cells\/mm3 (range 3-970) and 4.85 log copies\/mL (range 2.16-7.13). Median duration of HIV infection was 1 year (range 0-21 years).<\/p>\n

48-week results by intent-to-treat analysis (Time to Loss of Virological Response, TLOVR) showed a similar 80% patients achieving viral suppression <50 copies\/mL across all arms and are detailed in Table 1. All arms showed a mean viral load change of approximately -2.5 logs at week 48 with no differences between arms.<\/p>\n

Table 1: Responses at week-48 in TMC-278 C204<\/strong><\/p>\n\n\n\n\n\n\n\n\n
<\/th>\nTMC-278<\/th>\nefavirenz<\/th>\n<\/tr>\n
25mg<\/th>\n75mg<\/th>\n150mg<\/th>\n<\/tr>\n
N<\/td>\n93<\/td>\n95<\/td>\n91<\/td>\n89<\/td>\n<\/tr>\n
% <50 copies\/mL<\/td>\n81%<\/td>\n80%<\/td>\n77%<\/td>\n81%<\/td>\n<\/tr>\n
Mean change VL<\/td>\n-2.63 log<\/td>\n-2.65 log<\/td>\n-2.63 log<\/td>\n-2.64 log<\/td>\n<\/tr>\n
Change in CD4<\/td>\n+125<\/td>\n+145<\/td>\n+143<\/td>\n+127<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

The tolerability and side effect profile was also similar between groups but there were fewer CNS side effects in the rilpivirine arm and a slightly better lipid profile compared to efavirenz (see Table 2). Mean (SD) changes from baseline of total and LDL cholesterol were 5 mg\/dL (30) and 0 mg\/dL (24) in combined rilpivirine arms versus 31 mg\/dL (30) and 16 mg\/dL (26), respectively with efavirenz. There was one death due to sepsis, not attributed to study drug in the 75mg rilpivirine arm.<\/p>\n

Table 2: Side effects and tolerability in TMC-278 C204 <\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
<\/th>\n25mg<\/th>\n75mg<\/th>\n150mg<\/th>\nEFV<\/th>\n<\/tr>\n
% any side effect<\/td>\n10.8%<\/td>\n10.5%<\/td>\n9.9%<\/td>\n9.0%<\/td>\n<\/tr>\n
% any grade 3\/4*<\/td>\n25.8%<\/td>\n24.3%<\/td>\n24.2%<\/td>\n15.7%<\/td>\n<\/tr>\n
% D\/c adverse event<\/td>\n6%<\/td>\n5%<\/td>\n10%<\/td>\n6%<\/td>\n<\/tr>\n
% D\/c other reasons<\/td>\n4%<\/td>\n8%<\/td>\n7%<\/td>\n8%<\/td>\n<\/tr>\n
Side effects (% pts)<\/th>\n<\/tr>\n
Nausea<\/td>\n15.1<\/td>\n25.3<\/td>\n20.9<\/td>\n18.0<\/td>\n<\/tr>\n
CNS disorders<\/td>\n34.4<\/td>\n34.7<\/td>\n30.8<\/td>\n52.8<\/td>\n<\/tr>\n
Headache<\/td>\n6.5<\/td>\n11.6<\/td>\n5.5<\/td>\n7.9<\/td>\n<\/tr>\n
Dissyness<\/td>\n5.4<\/td>\n5.3<\/td>\n5.5<\/td>\n27.0<\/td>\n<\/tr>\n
Somnolence<\/td>\n2.2<\/td>\n3.2<\/td>\n4.4<\/td>\n10.1<\/td>\n<\/tr>\n
Psychiatric disorders<\/td>\n14.0<\/td>\n12.6<\/td>\n13.2<\/td>\n15.7<\/td>\n<\/tr>\n
Vertigo<\/td>\n1.1<\/td>\n2.1<\/td>\n0<\/td>\n10.1<\/td>\n<\/tr>\n
Abnormal dreams<\/td>\n1.1<\/td>\n6.3<\/td>\n0<\/td>\n10.1<\/td>\n<\/tr>\n
Skin, cutaneous reactions<\/td>\n22.6<\/td>\n25.5<\/td>\n25.7<\/td>\n33.7<\/td>\n<\/tr>\n
All rash**<\/td>\n5.4<\/td>\n6.3<\/td>\n12.1<\/td>\n15.1<\/td>\n<\/tr>\n
Vomiting<\/td>\n3.2<\/td>\n7.4<\/td>\n3.3<\/td>\n9.0<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

* Reported as higher investigator reporting as there were no differences in lab reporting between the TMC and EFV arms.<\/p>\n

**All grade 1\/2 except one pt in 75mg arm probably related to dapsone.<\/p>\n

Resistance data was not presented for patients failing to achieve or maintain viral suppression.<\/p>\n

Tibotec have selected the 75mg dose to take forward in Phase 3 studies.<\/p>\n

Reference:<\/p>\n

    \n
  1. Pozniak A, Morales-Ramirez J, Mohap L et al. 48-Week Primary Analysis of Trial TMC278-C204: TMC278 Demonstrates Potent and Sustained Efficacy in ART-naive Patients. Oral abstract 144LB.
    \nhttp:\/\/www.retroconference.org\/2007\/Abstracts\/30659.htm<\/a>
    \nThe oral presentation can be viewed online from the CROI website (see Wednesday, 10.00-12.00am Clinical Trials).<\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

    Simon Collins, HIV i-Base 48-week results from the primary endpoint of the Phase 2b TMC-278 C204 dose-finding study, of a second generation diarylpyrimidine NNRTI in development from Tibotec were presented in an oral session by Anton Pozniak from Chelsea and …<\/p>\n","protected":false},"author":4,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,3],"tags":[61],"class_list":["post-2683","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-antiretrovirals","tag-croi-2007"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/2683","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/users\/4"}],"replies":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/comments?post=2683"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/2683\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=2683"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=2683"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=2683"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}