Safety, tolerability, and preliminary efficacy of 48 weeks of etravirine therapy in a phase IIb dose-ranging study involving treatment-experienced patients with HIV-1 infection

Julio Montaner, Patrick Yeni, Nathan N. Clumeck, Gerd Fätkenheuer, Jose Gatell, Phillip Hay, Elena Seminari, Monika P. Peeters, Monika Schöller-Gyüre, Myriam Simonts, Brian Woodfall

Research output: Contribution to journalArticle

Abstract

Background. Etravirine (ETR; also known as TMC125) is a new nonnucleoside reverse-transcriptase inhibitor with activity against wild-type and nonnucleoside reverse-transcriptase inhibitor-resistant human immunodeficiency virus type 1 (HIV-1). Methods. This randomized, phase IIb, placebo-controlled, 2-stage, dose-escalating trial evaluated the safety, tolerability, and preliminary efficacy of 3 twice-daily doses of ETR (experimental formulation TF035; compared with placebo), administered with an individually optimized background regimen, in treatment-experienced HIV-1-infected patients. In stage 1 of the trial, 166 patients received ETR (400 mg or 800 mg twice daily) or placebo. In stage 2 of the trial, 74 patients received ETR (800 mg or 1200 mg twice daily) or placebo. The primary objective was to assess the safety and tolerability of the regimens over 48 weeks. Results. Neuropsychiatric adverse events (AEs) of interest occurred in 46.6% of patients in the combined ETR group and in 45.5% of patients in the combined placebo group (P = .89). Clinically relevant hepatic AEs occurred in 3.4% of patients who received ETR and in 6.1% of patients who received placebo (P = .47), and rash occurred in 19.5% and 12.1%, respectively (P = .25). In general, there was no evidence of a relationship between ETR dose and specific AEs. Most AEs were severity grade 1 or 2; the incidence of grade 3 or 4 AEs was comparable between groups (27.0% in the combined ETR group vs. 27.3% in the placebo group). Plasma preparation tubes were used for viral load measurement. In stage 1, there was no statistically significant difference in efficacy between ETR and placebo. In stage 2, the decrease in log10 plasma viral load between baseline and week 24 was statistically significantly greater in patients who received ETR, compared with patients who received placebo; a trend in favor of ETR persisted until week 48. Conclusions. ETR was generally safe and well tolerated during long-term administration in treatment-experienced, HIV-1-infected patients, and it had a safety profile comparable to that of placebo.

Original languageEnglish
Pages (from-to)969-978
Number of pages10
JournalClinical Infectious Diseases
Volume47
Issue number7
DOIs
Publication statusPublished - Oct 1 2008

Fingerprint

etravirine
Virus Diseases
HIV-1
Placebos
Safety
Therapeutics
Reverse Transcriptase Inhibitors
Viral Load

ASJC Scopus subject areas

  • Infectious Diseases
  • Microbiology (medical)

Cite this

Safety, tolerability, and preliminary efficacy of 48 weeks of etravirine therapy in a phase IIb dose-ranging study involving treatment-experienced patients with HIV-1 infection. / Montaner, Julio; Yeni, Patrick; Clumeck, Nathan N.; Fätkenheuer, Gerd; Gatell, Jose; Hay, Phillip; Seminari, Elena; Peeters, Monika P.; Schöller-Gyüre, Monika; Simonts, Myriam; Woodfall, Brian.

In: Clinical Infectious Diseases, Vol. 47, No. 7, 01.10.2008, p. 969-978.

Research output: Contribution to journalArticle

Montaner, J, Yeni, P, Clumeck, NN, Fätkenheuer, G, Gatell, J, Hay, P, Seminari, E, Peeters, MP, Schöller-Gyüre, M, Simonts, M & Woodfall, B 2008, 'Safety, tolerability, and preliminary efficacy of 48 weeks of etravirine therapy in a phase IIb dose-ranging study involving treatment-experienced patients with HIV-1 infection', Clinical Infectious Diseases, vol. 47, no. 7, pp. 969-978. https://doi.org/10.1086/591705
Montaner, Julio ; Yeni, Patrick ; Clumeck, Nathan N. ; Fätkenheuer, Gerd ; Gatell, Jose ; Hay, Phillip ; Seminari, Elena ; Peeters, Monika P. ; Schöller-Gyüre, Monika ; Simonts, Myriam ; Woodfall, Brian. / Safety, tolerability, and preliminary efficacy of 48 weeks of etravirine therapy in a phase IIb dose-ranging study involving treatment-experienced patients with HIV-1 infection. In: Clinical Infectious Diseases. 2008 ; Vol. 47, No. 7. pp. 969-978.
@article{31315b0f16474e0e93085e5b574276fb,
title = "Safety, tolerability, and preliminary efficacy of 48 weeks of etravirine therapy in a phase IIb dose-ranging study involving treatment-experienced patients with HIV-1 infection",
abstract = "Background. Etravirine (ETR; also known as TMC125) is a new nonnucleoside reverse-transcriptase inhibitor with activity against wild-type and nonnucleoside reverse-transcriptase inhibitor-resistant human immunodeficiency virus type 1 (HIV-1). Methods. This randomized, phase IIb, placebo-controlled, 2-stage, dose-escalating trial evaluated the safety, tolerability, and preliminary efficacy of 3 twice-daily doses of ETR (experimental formulation TF035; compared with placebo), administered with an individually optimized background regimen, in treatment-experienced HIV-1-infected patients. In stage 1 of the trial, 166 patients received ETR (400 mg or 800 mg twice daily) or placebo. In stage 2 of the trial, 74 patients received ETR (800 mg or 1200 mg twice daily) or placebo. The primary objective was to assess the safety and tolerability of the regimens over 48 weeks. Results. Neuropsychiatric adverse events (AEs) of interest occurred in 46.6{\%} of patients in the combined ETR group and in 45.5{\%} of patients in the combined placebo group (P = .89). Clinically relevant hepatic AEs occurred in 3.4{\%} of patients who received ETR and in 6.1{\%} of patients who received placebo (P = .47), and rash occurred in 19.5{\%} and 12.1{\%}, respectively (P = .25). In general, there was no evidence of a relationship between ETR dose and specific AEs. Most AEs were severity grade 1 or 2; the incidence of grade 3 or 4 AEs was comparable between groups (27.0{\%} in the combined ETR group vs. 27.3{\%} in the placebo group). Plasma preparation tubes were used for viral load measurement. In stage 1, there was no statistically significant difference in efficacy between ETR and placebo. In stage 2, the decrease in log10 plasma viral load between baseline and week 24 was statistically significantly greater in patients who received ETR, compared with patients who received placebo; a trend in favor of ETR persisted until week 48. Conclusions. ETR was generally safe and well tolerated during long-term administration in treatment-experienced, HIV-1-infected patients, and it had a safety profile comparable to that of placebo.",
author = "Julio Montaner and Patrick Yeni and Clumeck, {Nathan N.} and Gerd F{\"a}tkenheuer and Jose Gatell and Phillip Hay and Elena Seminari and Peeters, {Monika P.} and Monika Sch{\"o}ller-Gy{\"u}re and Myriam Simonts and Brian Woodfall",
year = "2008",
month = "10",
day = "1",
doi = "10.1086/591705",
language = "English",
volume = "47",
pages = "969--978",
journal = "Clinical Infectious Diseases",
issn = "1058-4838",
publisher = "NLM (Medline)",
number = "7",

}

TY - JOUR

T1 - Safety, tolerability, and preliminary efficacy of 48 weeks of etravirine therapy in a phase IIb dose-ranging study involving treatment-experienced patients with HIV-1 infection

AU - Montaner, Julio

AU - Yeni, Patrick

AU - Clumeck, Nathan N.

AU - Fätkenheuer, Gerd

AU - Gatell, Jose

AU - Hay, Phillip

AU - Seminari, Elena

AU - Peeters, Monika P.

AU - Schöller-Gyüre, Monika

AU - Simonts, Myriam

AU - Woodfall, Brian

PY - 2008/10/1

Y1 - 2008/10/1

N2 - Background. Etravirine (ETR; also known as TMC125) is a new nonnucleoside reverse-transcriptase inhibitor with activity against wild-type and nonnucleoside reverse-transcriptase inhibitor-resistant human immunodeficiency virus type 1 (HIV-1). Methods. This randomized, phase IIb, placebo-controlled, 2-stage, dose-escalating trial evaluated the safety, tolerability, and preliminary efficacy of 3 twice-daily doses of ETR (experimental formulation TF035; compared with placebo), administered with an individually optimized background regimen, in treatment-experienced HIV-1-infected patients. In stage 1 of the trial, 166 patients received ETR (400 mg or 800 mg twice daily) or placebo. In stage 2 of the trial, 74 patients received ETR (800 mg or 1200 mg twice daily) or placebo. The primary objective was to assess the safety and tolerability of the regimens over 48 weeks. Results. Neuropsychiatric adverse events (AEs) of interest occurred in 46.6% of patients in the combined ETR group and in 45.5% of patients in the combined placebo group (P = .89). Clinically relevant hepatic AEs occurred in 3.4% of patients who received ETR and in 6.1% of patients who received placebo (P = .47), and rash occurred in 19.5% and 12.1%, respectively (P = .25). In general, there was no evidence of a relationship between ETR dose and specific AEs. Most AEs were severity grade 1 or 2; the incidence of grade 3 or 4 AEs was comparable between groups (27.0% in the combined ETR group vs. 27.3% in the placebo group). Plasma preparation tubes were used for viral load measurement. In stage 1, there was no statistically significant difference in efficacy between ETR and placebo. In stage 2, the decrease in log10 plasma viral load between baseline and week 24 was statistically significantly greater in patients who received ETR, compared with patients who received placebo; a trend in favor of ETR persisted until week 48. Conclusions. ETR was generally safe and well tolerated during long-term administration in treatment-experienced, HIV-1-infected patients, and it had a safety profile comparable to that of placebo.

AB - Background. Etravirine (ETR; also known as TMC125) is a new nonnucleoside reverse-transcriptase inhibitor with activity against wild-type and nonnucleoside reverse-transcriptase inhibitor-resistant human immunodeficiency virus type 1 (HIV-1). Methods. This randomized, phase IIb, placebo-controlled, 2-stage, dose-escalating trial evaluated the safety, tolerability, and preliminary efficacy of 3 twice-daily doses of ETR (experimental formulation TF035; compared with placebo), administered with an individually optimized background regimen, in treatment-experienced HIV-1-infected patients. In stage 1 of the trial, 166 patients received ETR (400 mg or 800 mg twice daily) or placebo. In stage 2 of the trial, 74 patients received ETR (800 mg or 1200 mg twice daily) or placebo. The primary objective was to assess the safety and tolerability of the regimens over 48 weeks. Results. Neuropsychiatric adverse events (AEs) of interest occurred in 46.6% of patients in the combined ETR group and in 45.5% of patients in the combined placebo group (P = .89). Clinically relevant hepatic AEs occurred in 3.4% of patients who received ETR and in 6.1% of patients who received placebo (P = .47), and rash occurred in 19.5% and 12.1%, respectively (P = .25). In general, there was no evidence of a relationship between ETR dose and specific AEs. Most AEs were severity grade 1 or 2; the incidence of grade 3 or 4 AEs was comparable between groups (27.0% in the combined ETR group vs. 27.3% in the placebo group). Plasma preparation tubes were used for viral load measurement. In stage 1, there was no statistically significant difference in efficacy between ETR and placebo. In stage 2, the decrease in log10 plasma viral load between baseline and week 24 was statistically significantly greater in patients who received ETR, compared with patients who received placebo; a trend in favor of ETR persisted until week 48. Conclusions. ETR was generally safe and well tolerated during long-term administration in treatment-experienced, HIV-1-infected patients, and it had a safety profile comparable to that of placebo.

UR - http://www.scopus.com/inward/record.url?scp=52449097524&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=52449097524&partnerID=8YFLogxK

U2 - 10.1086/591705

DO - 10.1086/591705

M3 - Article

C2 - 18764771

AN - SCOPUS:52449097524

VL - 47

SP - 969

EP - 978

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

SN - 1058-4838

IS - 7

ER -