A randomized, double-blind placebo controlled trial of balapiravir, a polymerase inhibitor, in adult dengue patients.

Abstract

BACKGROUND:

Dengue is the most common arboviral infection of humans. There are currently no specific treatments for dengue. Balapiravir is a prodrug of a nucleoside analogue (called R1479) and an inhibitor of hepatitis C virus replication in vivo.

METHODS:

We conducted in vitro experiments to determine the potency of balapiravir against dengue viruses and then an exploratory, dose-escalating, randomized placebo-controlled trial in adult male patients with dengue with <48 hours of fever.

RESULTS:

The clinical and laboratory adverse event profile in patients receiving balapiravir at doses of 1500 mg (n = 10) or 3000 mg (n = 22) orally for 5 days was similar to that of patients receiving placebo (n = 32), indicating balapiravir was well tolerated. However, twice daily assessment of viremia and daily assessment of NS1 antigenemia indicated balapiravir did not measurably alter the kinetics of these virological markers, nor did it reduce the fever clearance time. The kinetics of plasma cytokine concentrations and the whole blood transcriptional profile were also not attenuated by balapiravir treatment.

CONCLUSIONS:

Although this trial, the first of its kind in dengue, does not support balapiravir as a candidate drug, it does establish a framework for antiviral treatment trials in dengue and provides the field with a clinically evaluated benchmark molecule.

CLINICAL TRIALS REGISTRATION:

NCT01096576.

• Authors: Nguyet Minh Nguyen, Chau Nguyen Bich Tran, Lam Khanh Phung, Kien Thi Hue Duong, Huy le Anh Huynh, Jeremy Farrar, Quyen Than Ha Nguyen, Hien Tinh Tran, Chau Van Vinh Nguyen, Laura Merson, Long Truong Hoang, Martin L Hibberd, Pauline P K Aw, Andreas Wilm, Niranjan Nagarajan, Dung Thi Nguyen, Mai Phuong Pham, Truong Thanh Nguyen, Hassan Javanbakht, Klaus Klumpp, Janet Hammond, Rosemary Petric, Marcel Wolbers, Chinh Tran Nguyen, Cameron P Simmons
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 207 Issue 9 Pg. 1442-50 (May 01 2013) ISSN: 1537-6613 [Electronic] United States
• PMID: 22807519 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Viral
• Antiviral Agents
• Nucleosides
• Placebos
• balapiravir

Topics

• Administration, Oral
• Adult
• Antigens, Viral (blood)
• Antiviral Agents (administration & dosage, adverse effects)
• Dengue (drug therapy, pathology, virology)
• Dengue Virus (isolation & purification)
• Double-Blind Method
• Fever (drug therapy)
• Humans
• Male
• Nucleosides (administration & dosage, adverse effects)
• Placebos (administration & dosage)
• Treatment Outcome
• Viral Load
• Viremia (drug therapy)
• Young Adult