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document
Safety , pharmacokinetics and pharmacodynamics of GS-9620 , an oral Toll-like receptor 7 agonist . BACKGROUND GS-9620 is a novel oral agonist of Toll-like receptor 7 ( TLR7 ) in development for the treatment of chronic viral hepatitis . TLR7 is a highly conserved innate immune receptor expressed primarily on plasmacytoid dendritic cells and B lymphocytes . The aim of this double-blind , placebo-controlled , single ascending-dose study was to investigate the safety , tolerability , pharmacokinetics and pharmacodynamics of GS-9620 in healthy volunteers . METHODS In total , 75 healthy volunteers ( 8 subjects in each of the 10 cohorts ; 5 subjects participated in two cohorts ) were randomized ( 6:2 ) to receive a single dose of GS-9620 ( 0.3 , 1 , 2 , 4 , 6 , 8 or 12 mg ) or placebo . RESULTS GS-9620 was well-absorbed and well-tolerated in oral doses up to 12 mg . Minimal treatment-related adverse events were seen at doses up to 8 mg. Serum interferon ( IFN ) -α was only detected in subjects who received 8 or 12 mg doses , and the adverse event profile at 8 and 12 mg doses was generally consistent with that associated with IFN-α exposure ( flu-like symptoms ) , consistent with the mechanism of TLR7 agonism . All adverse events resolved within 72 h. Induction of chemokines/cytokines and IFN-stimulated genes were seen at GS-9620 doses ≥ 2 mg , well below doses that induced serum IFN-α or led to clinical adverse events . CONCLUSIONS GS-9620 demonstrates safety and pharmacodynamic activity at doses up to 12 mg. Pharmacodynamic activity is seen before adverse events , suggesting the potential for induction of an antiviral response without systemic adverse events in subjects with chronic viral hepatitis .
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Intervention_Pharmacological
GS-9620
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Intervention_Pharmacological
GS-9620
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Intervention_Control
placebo-controlled
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Intervention_Pharmacological
GS-9620
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Intervention_Pharmacological
single dose of GS-9620 ( 0.3 , 1 , 2 , 4 , 6 , 8 or 12 mg )
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Intervention_Pharmacological
GS-9620
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Outcome_Other
safety
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Outcome_Other
tolerability
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Outcome_Physical
pharmacokinetics
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Outcome_Physical
pharmacodynamics
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Outcome_Other
well-absorbed
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Outcome_Physical
well-tolerated
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Outcome_Adverse-effects
Minimal treatment-related adverse events
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Participant_Condition
healthy volunteers .