Dataset Information

Phase Ib Trial To Evaluate the Safety and Pharmacokinetics of Multiple Ascending Doses of Filociclovir (MBX-400, Cyclopropavir) in Healthy Volunteers.

ABSTRACT: Filociclovir (MBX-400, cyclopropavir) is an antiviral agent with activity against cytomegalovirus (CMV). A phase 1, double-blind, randomized, placebo-controlled (3:1 ratio), single-center, multiple-ascending-dose trial was conducted to assess the safety, tolerability, and pharmacokinetics of filociclovir. Filociclovir (n?=?18) or placebo (n?=?6) was administered as a daily oral dose (100?mg, 350?mg, or 750?mg) for 7?days to normal healthy adults (ages, 25 to 65?years) who were monitored for 22?days. Safety assessments included clinical, laboratory, and electrocardiogram monitoring. Plasma and urine samplings were used to determine pharmacokinetic parameters. All study product-related adverse events were mild, most commonly gastrointestinal (17%), nervous system (11%), and skin and subcutaneous tissue (11%) disorders. One subject had reversible grade 3 elevation in serum creatinine and bilirubin, which was associated with an ?1-log increase in plasma filociclovir exposure compared to levels for other subjects in the same (750-mg) cohort. No other serious adverse events were observed. Plasma exposures (area under the concentration-time curve from 0 to 24 h [AUC0-24]) on days 1 and 7 were similar, suggesting negligible dose accumulation. There was a sublinear increase in plasma exposure with dose, which plateaued at the daily dose of 350?mg. The amount of filociclovir recovered in the urine remained proportional to plasma exposure (AUC). Doses as low as 100?mg achieved plasma concentrations sufficient to inhibit CMV in vitro (This study has been registered at ClinicalTrials.gov under identifier NCT02454699.).

SUBMITTER: Rouphael NG

PROVIDER: S-EPMC6709474 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Phase Ib Trial To Evaluate the Safety and Pharmacokinetics of Multiple Ascending Doses of Filociclovir (MBX-400, Cyclopropavir) in Healthy Volunteers.

Rouphael Nadine G NG Hurwitz Selwyn J SJ Hart Mari M Beck Allison A Anderson Evan J EJ Deye Gregory G Osborn Blaire B Cai Shu Yi SY Focht Chris C Amegashie Cyrille C Bowlin Terry L TL Brooks Jennifer J Mulligan Mark J MJ

Antimicrobial agents and chemotherapy 20190823 9

Filociclovir (MBX-400, cyclopropavir) is an antiviral agent with activity against cytomegalovirus (CMV). A phase 1, double-blind, randomized, placebo-controlled (3:1 ratio), single-center, multiple-ascending-dose trial was conducted to assess the safety, tolerability, and pharmacokinetics of filociclovir. Filociclovir (<i>n</i> = 18) or placebo (<i>n</i> = 6) was administered as a daily oral dose (100 mg, 350 mg, or 750 mg) for 7 days to normal healthy adults (ages, 25 to 65 years) who were moni ...[more]

PMID: 31285228

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Dataset Information

Phase Ib Trial To Evaluate the Safety and Pharmacokinetics of Multiple Ascending Doses of Filociclovir (MBX-400, Cyclopropavir) in Healthy Volunteers.

Publications

Phase Ib Trial To Evaluate the Safety and Pharmacokinetics of Multiple Ascending Doses of Filociclovir (MBX-400, Cyclopropavir) in Healthy Volunteers.

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