The Belgian company Tibotec today unveiled the first
clinical data on their new protease inhibitor TMC114 at the Tenth Conference on
Retroviruses and Opportunistic Infections in Boston.
TMC114 is a second generation protease inhibitor active
against protease inhibitor-resistant viruses.
The drug was administered with a 100mg dose of ritonavir
acting as a pharmacokinetic booster in 50 patients who had experienced
virologic failure of multiple PIs. It was administered as a liquid PEG
formulation.
Participants were randomised to receive TMC114/ritonavir at
doses of 300/100mg (group A) and 600/100mg (group B) twice daily, or 900/100mg
once daily (group C). A control group continued the failing regimen (group D).
No other antiretrovirals in the failing regimen were changed.
Median baseline viral load was 4.3 log (approximately 20,000
copies/ml), and median prior PI exposure was three PIs in each group except
group C. 46% were resistant to all currently available protease inhibitors, but
the median reduction in susceptibility to TMC-114 at baseline was 1.4-fold
compared to wild type.
A – 300/100mg
B
600/100mg
C
900/100mg
D - Continue failing PI
Median prior no. of PIs
3
3
4
3
Median no. of PIs susceptible to
1
1
0
1
Median no of primary PI mutations
7
6
7
8
Median HIV RNA reduction to day 14
-1.24 log
- 1.50
- 1.13
+0.02
% with > 1 log HIV RNA reduction
69%
92%
69%
17%
Median Cmin
1.2ug/ml
1.4ug/ml
1.6ug/ml
N/a
Median AUC
53.3ug/ml
60.4ug/ml
67.9ug/ml
N/a
Two discontinuations occurred due to adverse events – severe
rash and hepatotoxicity, and five grade 3 or 4 adverse events were reported,
all gastrointestinal or headache.
Forty per cent of patients had viral load below 400
copies/ml at day 14.
Further information on this website
href="http://www.aidsmap.com/treatments/ixdata/english/b33b0d82-9e51-435a-a2dd-94a9a470e624.htm">TMC
References
Arasteh K et al.
style='font-size:10.0pt;mso-bidi-font-size:12.0pt;mso-ascii-font-family:"Times New Roman";
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font-weight:normal'>First Clinical Results on Antiretroviral Activity,
Pharmacokinetics, and Safety of TMC114, an HIV-1 Protease Inhibitor, in
Multiple PI-experienced Patients.
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Tenth Conference on Retrovirusesand Opportunistic Infections, Boston, abstract 8, 2003.