Results from a phase 1 study evaluating the pharmacokinetics and safety of a prototype subdermal drug-eluting implant for extended administration of Islatravir, a nucleoside reverse transcriptase translocation inhibitor ( NRTTI ), in healthy volunteers, were presented at the 10th International AIDS Society Conference on HIV Science ( IAS 2019 ) in Mexico City.
The phase 1 randomized, 2-panel, double-blind, placebo-controlled, adaptive design clinical trial evaluated the safety and pharmacokinetics of Islatravir administered using a polymer drug eluting implant, approximately the size of a match ( 2mm by 4cm ), in healthy adult volunteers.
Participants were randomized to receive an implant containing Islatravir at doses of either 62 mg ( n=6 ), 54 mg ( n=6 ) or placebo ( n=4 ) that was inserted sub-dermally in the skin of the upper arm of the non-dominant hand.
After 12 weeks the implant was removed, and participants were evaluated for a further 4 weeks.
Both implant doses resulted in intracellular concentrations of Islatravir, as measured in peripheral blood mononuclear cells, that remained above calculated pharmacokinetic thresholds through 12 weeks.
Based on subsequent modeling, the implant containing Islatravir 62mg was estimated to deliver levels well above the threshold at 12 months ( and even beyond ), providing early evidence for its potential as a once-yearly option for PrEP.
The results of the study have also indicated that control of intracellular concentrations can be managed by varying the Islatravir load in the implant.
In this study, there were no discontinuations due to adverse events and no severe implant-related adverse effects reported.
All participants reported at least one adverse reaction and all drug-associated adverse reaction were assessed to be mild or moderate in severity.
The most common reported side effects occurred at the implant site and included hematoma ( 6/6; 6/6; 4/4 ), pain / tenderness ( 6/6; 3/6; 2/4 ), erythema ( 5/6; 2/6; 0/4 ), induration ( 6/6; 5/6; 0/4 ) and pruritus ( 5/6; 0/6; 1/4 ) for the 62mg; 54mg and placebo groups respectively.
There were no clinically significant differences observed between Islatravir and placebo groups in pooled analysis of vital signs, ECG parameters, and safety laboratory studies. No systemic drug associated effects were noted. ( Xagena )
Source: Merck, 2019