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.
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A – 300/100mg
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B 600/100mg
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C 900/100mg
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D - Continue failing PI
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Median prior no. of PIs
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3
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3
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4
|
3
|
|
Median no. of PIs susceptible to
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1
|
1
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0
|
1
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|
Median no of primary PI mutations
|
7
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6
|
7
|
8
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Median HIV RNA reduction to day 14
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-1.24 log
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- 1.50
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- 1.13
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+0.02
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% with > 1 log HIV RNA reduction
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69%
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92%
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69%
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17%
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Median Cmin
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1.2ug/ml
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1.4ug/ml
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1.6ug/ml
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N/a
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|
Median AUC
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53.3ug/ml
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60.4ug/ml
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67.9ug/ml
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N/a
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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
Arasteh K et al. style='font-size:10.0pt;mso-bidi-font-size:12.0pt;mso-ascii-font-family:"Times New Roman";
mso-hansi-font-family:"Times New Roman";mso-bidi-font-family:"Times New Roman";
font-weight:normal'>First Clinical Results on Antiretroviral Activity,
Pharmacokinetics, and Safety of TMC114, an HIV-1 Protease Inhibitor, in
Multiple PI-experienced Patients. style='font-family:Arial'>
and Opportunistic Infections, Boston, abstract 8, 2003.