New protease inhibitor TMC 114 effective for PI-exhausted patients in early study

Keith Alcorn
Estimated reading time 10 minutes
This article is more than 22 years old.

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.

Glossary

log

Short for logarithm, a scale of measurement often used when describing viral load. A one log change is a ten-fold change, such as from 100 to 10. A two-log change is a one hundred-fold change, such as from 1,000 to 10.

protease inhibitor (PI)

Family of antiretrovirals which target the protease enzyme. Includes amprenavir, indinavir, lopinavir, ritonavir, saquinavir, nelfinavir, and atazanavir.

ribonucleic acid (RNA)

The chemical structure that carries genetic instructions for protein synthesis. Although DNA is the primary genetic material of cells, RNA is the genetic material for some viruses like HIV.

 

hepatotoxicity

Side-effects of drugs of medicines affecting the liver.

control group

A group of participants in a trial who receive standard treatment, or no treatment at all, rather than the experimental treatment which is being tested. Also known as a control arm.

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

114 – drug overview

References

Arasteh K et al.

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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.

style='font-family:Arial'>

Tenth Conference on Retroviruses

and Opportunistic Infections, Boston, abstract 8, 2003.

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