Single subcutaneous TOP-N53 doses increased skin perfusion in healthy male volunteersEarly study shows a new drug increases blood flow to skin in healthy men

medRxiv Published April 19, 2026 Study authors: Seitz, F.; Gerth, H. U.; Tenor, H.; Ludin, C.; Bhide, Y.; Schaefer, M.; Cracowski, J.-L.; Naef, R. DOI ↗ Editorial oversight: Dr. Julia Lee, PhD · Oncology, Genomics & Drug Development

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Key Takeaway

Consider that single subcutaneous TOP-N53 doses increased skin perfusion in a small Phase I trial, supporting cautious further study.

This was a randomized, double-blind, vehicle-controlled Phase I trial in 29 healthy male volunteers. The study assessed the safety, tolerability, pharmacokinetics, and pharmacodynamics of a single subcutaneous TOP-N53 dose, compared to a vehicle comparator, with follow-up up to 24 h post injection.

The primary outcomes were safety and tolerability, with secondary outcomes including local and systemic parameters, plasma concentrations of TOP-N53 and TOP-52, and skin perfusion measured by Laser Speckle Contrast Imaging (LSCI). The main result was sustained dose-dependent increases in local skin perfusion at doses of 4.84 ug and 9.075 ug TOP-N53 SC.

Safety findings showed no local or systemic adverse reactions and no serious adverse events. The intervention was reported as safe and well tolerated. Discontinuations were not reported.

Key limitations include the small sample size of 29 participants and the short follow-up period of up to 24 h. The study population was limited to healthy male volunteers, which may not generalize to other groups.

The practice relevance noted is encouraging its further clinical development as a topical treatment for chronic wounds with microvascular dysfunction. This is an early-phase finding and does not establish efficacy for clinical use.

This early research tested a new medication named TOP-N53 in a small group of 29 healthy men. The team gave each participant a single dose under the skin and watched them for up to 24 hours. They measured safety, how the drug moved through the body, and changes in skin blood flow using a special imaging tool called Laser Speckle Contrast Imaging.

The main finding was that the drug caused a sustained increase in local skin blood flow. This effect grew stronger with higher doses, specifically at 4.84 micrograms and 9.075 micrograms. No serious side effects occurred, and the drug was considered safe and well tolerated by the volunteers during this short observation period.

While these results are encouraging for future development of a topical treatment for chronic wounds, readers should be careful not to assume this drug is ready for use. This was a Phase I trial focused on safety in healthy people, not patients with wounds. More research is needed to confirm if it helps heal wounds in sick patients.

What this means for you:

Early study in healthy men shows new drug safely increases skin blood flow; more research needed.

Study Details

Study typeRct

EvidenceLevel 2

PublishedApr 2026

View Original Abstract ↓

Chronic wounds, such as diabetic and ischemic ulcers, involve impaired perfusion and delayed healing. TOP-N53 is a novel bifunctional molecule combining nitric oxide (NO) release with phosphodiesterase-5 (PDE5) inhibition to enhance local NO-cGMP signalling, resulting in vasodilation and angiogenesis. This first-in-human, randomized, double-blind, vehicle-controlled Phase I trial assessed the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single subcutaneous TOP-N53 doses in 29 healthy male volunteers. Each participant received injections of TOP-N53 and vehicle in the same forearm, but either at the proximal or at the distal site in an intra-individually blinded manner. Safety assessments included local and systemic parameters. PK and PD responses were evaluated by analysis of TOPN53 and its bioactivation metabolite TOP-52 in plasma, and by Laser Speckle Contrast Imaging (LSCI), a non-invasive method to measure skin perfusion, respectively. TOP-N53 was safe and well tolerated, with no serious adverse events or local or systemic adverse reactions. Plasma concentrations remained below the quantification limit and LSCI showed sustained dose-dependent increases in local skin perfusion at doses of 4.84 ug and 9.075 ug TOP-N53 SC for up to 24 h post injection when compared to vehicle. These findings support the favourable safety and tolerability profile of TOP-N53 associated with locally improved skin perfusion, encouraging its further clinical development as a topical treatment for chronic wounds with microvascular dysfunction.

Single subcutaneous TOP-N53 doses increased skin perfusion in healthy male volunteersEarly study shows a new drug increases blood flow to skin in healthy men

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Single subcutaneous TOP-N53 doses increased skin perfusion in healthy male volunteersEarly study shows a new drug increases blood flow to skin in healthy men

Study Details

Mazdutide monotherapy reduces HbA1c and promotes weight loss in Chinese adults with type 2 diabetes over 48 weeks

New Drug Lowers Sugar and Shrinks Weight in Diabetes

Clinical research that matters. Delivered to your inbox.

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