Phase 2a randomized controlled trial of short-term activity, safety, and pharmacokinetics of a novel nonnucleoside reverse transcriptase inhibitor, RDEA806, in HIV-1-positive, antiretroviral-naïve subjects

Antimicrobial Agents and Chemotherapy

Volumn 54, Issue 8, 2010, Pages 3170-3178

  Moyle, Graeme ^a   Boffito, Marta ^a   Stoehr, Albrecht ^b   Rieger, Armin ^c   Shen, Zancong ^d   Manhard, Kimberly ^d   Sheedy, Beth ^d   Hingorani, Vijay ^d   Raney, Anneke ^d   Nguyen, Mai ^d   Nguyen, Tranh ^d   Ong, Voon ^d   Yeh, Li Tain ^d   Quart, Barry ^d  

^a CHELSEA AND WESTMINSTER HOSPITAL   (United Kingdom)

^b Allgemeines Krankenhaus Eilbek   (Germany)

^c Universitatsklinik fur Dermatologie   (Austria)

^d Ardea Biosciences Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

PLACEBO; RDEA 806; RNA DIRECTED DNA POLYMERASE INHIBITOR; UNCLASSIFIED DRUG; VIRUS RNA;

ABDOMINAL DISCOMFORT; ABDOMINAL PAIN; ADULT; ANTIVIRAL ACTIVITY; AREA UNDER THE CURVE; ARTICLE; BACKACHE; CLINICAL ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DIARRHEA; DOSAGE SCHEDULE COMPARISON; DRUG ACTIVITY; DRUG DOSE COMPARISON; DRUG DOSE ESCALATION; DRUG HALF LIFE; DRUG HYPERSENSITIVITY; DRUG POTENCY; DRUG SAFETY; DRUG STRUCTURE; DRUG TOLERABILITY; ERYTHEMA; FATIGUE; HEADACHE; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; IMMUNE RESPONSE; INSOMNIA; MALE; MULTICENTER STUDY; MYALGIA; PHARMACODYNAMICS; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; PRURITUS; RANDOMIZED CONTROLLED TRIAL; SIDE EFFECT; TIME TO MAXIMUM PLASMA CONCENTRATION; URIC ACID BLOOD LEVEL; VIRUS LOAD;

ADULT; ANTI-HIV AGENTS; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; HIV INFECTIONS; HIV-1; HUMANS; MALE; MIDDLE AGED; REVERSE TRANSCRIPTASE INHIBITORS; RNA, VIRAL; TREATMENT OUTCOME; VIRAL LOAD; YOUNG ADULT;

EID: 77955386895     PISSN: 00664804     EISSN: 10986596     Source Type: Journal    
DOI: 10.1128/AAC.00268-10     Document Type: Article

References (17)

1. Domingo, P., I. Suárez-Lozano, F. Torres, R. Teira, J. Lopez-Aldeguer, F. Vidal, A. Muñoz, P. Viciana, F. Lozano, A. Vergara, B. Roca, M. L. García Alcalde, J. Cosín, A. Terrón, M. J. Galindo, P. Geijo, E. Ribera, J. Gonzalez, T. Sanchez, J. R. Lacalle, and M. Garrido. 2008. First-line antiretroviral therapy with efavirenz or lopinavir/ritonavir plus two nucleoside analogues: the SUSKA study, a non-randomized comparison from the VACH cohort. J. Antimicrob. Chemother. 61:1348-1358.
2. European AIDS Clinical Society. Guidelines for the clinical management and treatment of HIV infected adults in Europe. http://www. europeanaidsclinicalsociety.org. Accessed 10 September 2009.
3. Hamatake, R., Z. Zhang, W. Xu, D. Bellows, A. Raney, J.-L. Girardet, and B. Quart. 2007. RDEA806 a potent NNRTI with a high genetic barrier to resistance, poster H-1041, abstr. 1662. Abstr. 47th Intersci. Conf. Antimicrob. Agents Chemother. American Society for Microbiology, Washington, DC.
4. Johnson, V., F. Brun-Vézinet, B. Clotet, H. Günthard, D. Kuritzkes, D. Pillay, J. Schapiro, and D. Richman. 2007. Update of the drug resistance mutations in HIV-1: 2007. International AIDS Society - USA. Top. HIV Med. 15:119-125.
5. Little, S. J., S. Holte, J. P. Routy, E. S. Daar, M. Markowitz, and A. C. Collier. 2002. Antiretroviral drug resistance among patients recently infected with HIV. N. Engl. J. Med. 347:385-394.
6. Maesaka, J. K., A. J. Cusano, H. L. Thies, F. P. Siegal, and A. W. Dreisbach. 1990. Hypouricemia in acquired immunodeficiency syndrome. Am. J. Kidney Dis. 15:252-257.
7. Moyle, G., M. Boffito, Z. Shen, K. Manhard, B. Sheedy, V. Hingorani, M. Nguyen, T. Nguyen, B. Quart, L. Yeh, and V. Ong. 2008. RDEA806, a novel HIV non-nucleoside reverse transcriptase inhibitor, shows positive outcome in treatment of naïve HIV patients, abstr. H-893. Abstr. 48th Annu. Intersci. Conf. Antimicrob. Agents Chemother. (ICAAC)-Infect. Dis. Soc. Am. (IDSA) 46th Annu. Meet. American Society for Microbiology and Infectious Diseases Society of America, Washington, DC.
8. Rousseau, M. N., L. Vergne, B. Montes, M. Peeters, J. Reynes, E. Delaporte, and M. Segondy. 2001. Patterns of resistance mutations to antiretroviral drugs in extensively treated HIV-1-infected patients with failure of highly active antiretroviral therapy. J. Acquir. Immune Defic. Syndr. 26:36-43.
9. Reference deleted.
10. Tibotec Therapeutics, L. P. Division of Centocor Ortho Biotech Products. 2008. Intelence® (etravirine) U.S. package insert. Tibotec Therapeutics, Raritan, NJ.
11. U.S. Department of Health and Human Services, Panel on Antiretroviral Guidelines for Adults and Adolescents. 2008. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents, p. 1-139. http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf. Accessed 10 September 2009.
12. U.S. Food and Drug Administration. 2005. ICH E14 guidance for industry. Clinical evaluation of QT/QTc interval prolongation and proarrhythmic potential for non-antiarrhythmic drugs. Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Rockville, MD.
13. Xu, W., B. Groschel, R. Straney, Z. Zhang, D. Bellows, R. Hamatake, J.-L. Girardet, B. Quart, and A. Raney. 2008. Resistance to RDEA806 requires multiple mutations which have limited cross-resistance to other NNRTIs, poster H-1222. Abstr. 48th Annu. Intersci. Conf. Antimicrob. Agents Chemother. (ICAAC)-Infect. Dis. Soc. Am. (IDSA) 46th Annu. Meet. American Society for Microbiology and Infectious Diseases Society of America, Washington, DC.
14. Yeh, L., R. Hamatake, H. Kim, S. Gunawan, R. Daswani, K. Tieu, C. Dadson, and B. Quart. 2007. RDEA806, a potent non-nucleoside reverse transcriptase inhibitor with less potential for drug-drug interactions, abstr. 3390. Abstr. 47th. Intersci. Conf. Antimicrob. Agents Chemother. American Society for Microbiology, Washington, DC.
15. Yeh, L., S. Ramael, S. Comhaire, V. Hingorani, K. Manhard, M. Nguyes, K. Tieu, and B. Quart. 2007. Safety and pharmacokinetics of ascending single oral doses of RDEA806, a novel HIV non-nucleoside reverse transcriptase inhibitor, in healthy volunteers, poster A-1429, abstr. 1609. Abstr. 47th Intersci. Conf. Antimicrob. Agents Chemother. American Society for Microbiology, Washington, DC.
16. Yeh, L., V. Hingorani, K. Manhard, V. Borges, M. Nguyen, K. Tieu, and B. Quart. 2008. Safety and uric acid lowering effect in humans following multiple doses of RDEA806, a novel prodrug for the potential treatment of hyperuricemia, poster THU0356. Annual EULAR 2008 Eur. Congr. Rheumatol.
17. Yeh, L., Z. Shen, B. Kerr, I. Tamai, V. Hingorani, V. Ong, T. Nguyen, M. Nguyen, B. Sheedy, K. Manhard, and B. Quart. 2009. RDEA594: a potent URAT1 inhibitor without affecting other important renal transporters, OAT1 and OAT3, abstr. THU0452. Abstr. Eur. Congr. Rheumatol.