Abstract | UNLABELLED: The anti-hepatitis C virus (HCV) effect and safety of three different oral doses of the cyclophilin inhibitor Debio 025 in combination with pegylated interferon-alpha2a (PEG IFN-alpha2a) were investigated in a multicenter, randomized, double-blind, placebo-controlled escalating dose-ranging phase II study in treatment-naïve patients with chronic hepatitis C. Doses of 200, 600, and 1,000 mg/day Debio 025 in combination with PEG IFN-alpha2a 180 microg/week for 4 weeks were compared with monotherapy with either 1,000 mg/day Debio 025 or 180 microg/week PEG IFN-alpha2a. In patients with genotypes 1 and 4, the 600- and 1,000-mg combination treatments induced a continuous decay in viral load that reached -4.61 +/- 1.88 and -4.75 +/- 2.19 log(10) IU/mL at week 4, respectively. In patients with genotypes 2 and 3, HCV RNA levels at week 4 were reduced by -5.91 +/- 1.11 and -5.89 +/- 0.43 log(10) IU/mL, respectively, with the same treatment regimens. Adverse events were comparable between treatment groups apart from a higher incidence of neutropenia associated with PEG IFN-alpha2a and an increased incidence of isolated hyperbilirubinemia at the highest dose of Debio 025 (1,000 mg/day). CONCLUSION: These results confirm that Debio 025 has a potent activity and an additive effect on HCV RNA reduction in genotype 1 and 4 patients at 600 and 1,000 mg/day when combined with PEG IFN-alpha2a.
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Authors | Robert Flisiak, Saya V Feinman, Maciej Jablkowski, Andrzej Horban, Wieslaw Kryczka, Małgorzata Pawlowska, Jenny E Heathcote, Giuseppe Mazzella, Carmen Vandelli, Valérie Nicolas-Métral, Pierre Grosgurin, Jorge S Liz, Pietro Scalfaro, Hervé Porchet, Raf Crabbé |
Journal | Hepatology (Baltimore, Md.)
(Hepatology)
Vol. 49
Issue 5
Pg. 1460-8
(May 2009)
ISSN: 1527-3350 [Electronic] United States |
PMID | 19353740
(Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antiviral Agents
- Interferon alpha-2
- Interferon-alpha
- Recombinant Proteins
- Polyethylene Glycols
- Cyclosporine
- peginterferon alfa-2a
- alisporivir
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Topics |
- Adult
- Aged
- Antiviral Agents
(therapeutic use)
- Cyclosporine
(administration & dosage, adverse effects)
- Double-Blind Method
- Drug Therapy, Combination
- Female
- Hepatitis C, Chronic
(drug therapy)
- Humans
- Interferon alpha-2
- Interferon-alpha
(therapeutic use)
- Male
- Middle Aged
- Polyethylene Glycols
(therapeutic use)
- Recombinant Proteins
- Viral Load
- Young Adult
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