icon- folder.gif   Conference Reports for NATAP  
 
  4th IAS (Intl AIDS Society) Conference on HIV Pathogenesis, Treatment and Prevention
Sydney, Australia
22-25 July 2007
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The metabolic profile of TMC278, an investigational NNRTI
 
 
  Reported by Jules Levin
4th IAS Conference, 22-25 July, 2007, Sydney, Australia
 
K Ruxrungtham,1 N Bellos,2 J Morales-Ramirez,3
A Timerman,4 J Madruga,5 E Katabira,6 S Vanveggel,7
M Peeters,7 M Stevens,7 P Williams,7 B Woodfall,7 K Boven8
HIVNAT, Thai Red Cross AIDS Research Centre, Chulalongkorn University,
1HIVNAT, Thai Red Cross AIDS Research Centre, Chulalongkorn University, Bangkok,
Thailand,2Southwest Infectious Disease Associates, Dallas, TX, USA, 3Clinical
Research, San Juan, Puerto Rico, 4Hospital Heliopolis, Sao Paulo, Brazil, 5Centro de Referencia e Treinamento DST-AIDS, Sao Paulo, Brasil, 6Makerere University, Kampala, Uganda, 7Tibotec BVBA, Mechelen, Belgium,
8Tibotec Inc., Yardley, PA, USA
 
AUTHOR CONCLUSIONS
TMC278 resulted in minimal changes in lipid profiles at Week 48, and may have a potential benefit versus EFV
 
No TMC278 dose relationship in metabolic parameters
 
Mean changes from baseline in glucose levels and insulin sensitivity were minimal and not clinically relevant for both groups
 
Two 96-week Phase III studies are planned to start Q4 2007
 
BACKGROUND
TMC278, a next-generation NNRTI, has demonstrated in-vitro activity against wild-type and NNRTI-resistant isolates1
 
48-week results from an ongoing Phase IIb dose-finding study (TMC278-C204) demonstrated the potent and sustained efficacy of TMC278 qd in ARV-naive, HIV-1-infected patients2
 
Efavirenz (EFV) is commonly associated with metabolic disturbances, particularly increases in cholesterol and triglyceride levels3
 
48-week primary analysis of TMC278-C204, a Phase IIb study in ARV-naive HIV-1-infected patients
 

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--Ongoing, randomised, active controlled, dose-finding study
--TMC278 blinded for all three dose groups versus open-label EFV
 
Stratification factors
--investigator-selected NRTI backbone: AZT/3TC (75.3%) or TDF/FTC (24.7%) (given as combination or individual components)
--region (Asia and Africa; USA, Europe and Russia; Latin America)
 
Objectives & Methods
To assess the metabolic profile of TMC278 in comparison with EFV in trial TMC278-C204
 
Measured changes from baseline in

--total cholesterol (TC)
--low-density lipoprotein-cholesterol (LDL-C)
--high-density lipoprotein-cholesterol (HDL-C)
--triglycerides (TG)
--glucose
--Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated --Samples were taken at screening, baseline, and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40 and 48
 
Demographic and baseline characteristics
Viral load: 70,000
CD4: 200
33% female
45% caucasian
 

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Baseline Metabolics
*Mean (standard deviation)
HDL: 40 in TMC278 combined arms ; 39 EFV
LDL : 93 combined 278 arms ; 95 in EFV
Total chol : 159 combined 278 arms ; 157 EFV
TG : 135 combined 278 arms ; 117 EFV
Ratio TC :HDL-C : 4.3 combined 278 arms ; 4.2 EFV
Glucose : 90 combined 289 arms ; 93 EFV
 

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Mean changes from baseline in metabolic parameters at 48 weeks

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Mean changes in total cholesterol over time
There was a clear increase from baseline in TC for the EFV group, but a minimal increase for the TMC278 dose groups
 

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Mean changes in LDL-C over time
There was a clear increase from baseline in LDL-C for the EFV group, but not for the TMC278 dose groups
 

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Mean changes in HDL-C over time
HDL-C levels increased over time in all groups, but more so in the EFV group than in the TMC278 dose groups
 

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Mean changes in TC/HDL-C ratio over time
The TC/HDL-C ratio declined from baseline in all groups, the decline was not significantly different among groups
 

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Mean changes in triglycerides over time
There was a small increase from baseline in triglycerides for the EFV group, but not for the TMC278 dose groups

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