TAR-0520, a new candidate in oncodermatology: Results of a phase 1 program in healthy volunteers

Abstract

Purpose

TAR-0520 gel is a new topical formulation of brimonidine tartrate designed to prevent chemotherapy-induced skin toxicities. We report here the main outcomes of the phase 1 program which included two double-blind, randomized trials in healthy volunteers (TAR006 and TAR012) and were performed to evaluate the safety, local tolerability, pharmacokinetics, and pharmacodynamics (PD) of TAR-0520 gel.

Method

In TAR006, participants received four concentrations of TAR-0520 gel (0.5%, 0.75%, 1% and 1.5% of Brimonidine tartrate), placebo, or active comparator (Mirvaso® Galderma International, France) applied daily to the chest for 21 days, while TAR012 evaluated TAR-0520 gel 1% and 1.5% on the chest and face over the same duration. Local tolerance was assessed daily in both studies using mean cumulative irritation index and maximum irritation score as key endpoints. Skin blanching was assessed via chromameter-measured reductions in skin redness as a marker of vasoconstriction and product potency. In TAR006, systemic exposure to brimonidine tartrate was assessed from blood samples collected in a separate cohort treated with TAR-0520 gel 1%.

Results

Overall, 28 participants were randomized in TAR006 and 26 were randomized in TAR012. Both studies showed excellent local tolerance with 50 healthy volunteers reporting no evidence of irritation with any treatment and four patients reporting barely perceptible minimal erythema. No adverse events related to TAR-0520 gel were reported. Minimal systemic absorption was observed that was not considered to be clinically relevant. PD studies indicated dose-dependent vasoconstriction with once-daily use lasting over 24 h.

Conclusion

Under the conditions of these studies, TAR-0520 gel presents a very favorable safety profile with little to no local irritation and insignificant systemic exposure. Allowing a superficial skin vasoconstriction over a period of 24 h, it offers a safe, patient-friendly, and adaptable topical solution. The 1.5% concentration was selected for further development and phase II trials for managing chemotherapy-related skin toxicities are in progress.

Registration details

- TARIAN 006, 2023–504178-39–00 approved 24/08/203.

- TARIAN 012, 2324CMCL096 approved 28/05/2024.

Introduction

Chemotherapy-induced skin toxicities are common and can significantly affect patients’ quality of life [1–6]. These adverse events vary depending on the chemotherapy agents used, ranging from mild dryness and irritation to severe dermatological reactions. Among the most distressing are alopecia, a well-known side effect of agents such as docetaxel, paclitaxel, and cyclophosphamide; Hand-Foot Syndrome, characterized by redness, swelling, and pain on the palms and soles; and the acneiform papulopustular eruption frequently observed with epidermal growth factor receptor (EGFR) inhibitors.

Management of these skin toxicities requires early recognition and prompt intervention using topical treatments, such as emollients or medicated creams, or systemic therapies [7, 8]. In recent years, cooling devices have been increasingly employed to prevent or mitigate these side effects. These devices reduce blood flow by cooling the skin, particularly the scalp, before, during, and after chemotherapy, thereby limiting chemotherapy exposure to the skin with the intent of limiting local concentrations below toxicity thresholds.

While cooling systems have shown efficacy in controlled clinical trials, they suffer from significant limitations [9–12]. The first is poor local tolerability: patients frequently report discomfort from the cold, chills, scalp or extremity pain, and a sense of heaviness, leading to treatment discontinuation in up to 30% of cases. The second limitation is logistical: high-end cooling systems are technically complex, expensive, and cumbersome, while simpler alternatives, like socks or gloves kept in freezers, quickly lose their cooling effect. The most critical limitation, however, is duration: the cooling effect is confined to a short window, typically a few hours, when the patient is physically present at the clinic. This timing does not align with the prolonged circulation of chemotherapeutic agents, especially those with long plasma half-lives.

To address these limitations, we explored the concept of pharmacologically induced vasoconstriction as an alternative to vasoconstriction induced by physical cooling. Topically applied α-adrenergic agonists, originally developed to treat elevated intraocular pressure and nasal congestion, were later approved for managing persistent facial erythema in rosacea. Two such agents are brimonidine (Mirvaso® Galderma International, France), a selective α2-adrenergic agonist, and oxymetazoline (Rhofade®), an α1A-adrenergic agonist. Pharmacological profiling reveals that brimonidine is highly selective for α2 receptors—particularly α2A, which are prevalent in small cutaneous vessels such as capillaries [13]. In contrast, oxymetazoline exhibits lower selectivity and notable off-target activity, including binding to the 5-HT2B serotonin receptor, which has been associated with drug-induced valvulopathy [14].

When applied to the skin, brimonidine induces localized and reversible vasoconstriction limited to superficial cutaneous vessels, while maintaining systemic exposure within proven safety thresholds [15]. However, the currently marketed formulation has two main drawbacks: a short duration of action (less than 12 h) and insufficient potency when used outside of its approved indication of facial rosacea.

To overcome these limitations, a novel formulation of topical brimonidine tartrate (TAR-0520, Tarian Gel) was developed with two key objectives: (1) to achieve extended vasoconstriction lasting up to 24 h, and (2) to deliver enhanced potency without compromising safety through increased systemic exposure. By inducing, a localized (at application site) and sustained, pharmacologically driven vasoconstriction over a 24-h period, TAR-0520 aims to prevent, or at least markedly reduce, the severity of chemotherapy-induced cutaneous toxicities by maintaining decreased skin perfusion throughout the period of systemic drug exposure. To account for differences in pharmacokinetics, particularly the elimination half-life of each chemotherapeutic agent, the duration of TAR-0520 administration will be tailored to the specific chemotherapy regimen. For example, cetuximab has an elimination half-life of 112 h, and TAR-0520 will therefore be applied daily for 7 days; for paclitaxel, whose elimination half-life is 28.7 h, TAR-0520 will be applied daily for 3 days.

In this study, we investigated the systemic safety, local skin tolerance, pharmacokinetic (PK) profile and pharmacodynamics (PD) of TAR-0520 gel in two phase I studies (TAR006 and TAR012).

Methods

Study design and participants

TAR006 and TAR012 were monocentric, double-blind, randomized phase I trials in healthy volunteers. Both studies received approval from local health authorities and ethics committees (TARIAN 006, 2023–504178-39–00 approved 24/08/203; TARIAN 012, 2324CMCL096 approved 28/05/2024) and were conducted in compliance with applicable Good Clinical Practice (GCP) guidelines.

TAR006 was conducted in two parts. Part 1 consisted of an intra-individual 21-day local tolerance study with a PD evaluation. Part 2 was initiated following satisfactory completion of part 1 and consisted of a preliminary PK study to explore systemic exposure to brimonidine and local and systemic safety following the topical application of TAR-0520 gel for 5 days under maximized conditions of use. TAR012 was conducted after satisfactory completion of TAR006 and consisted of a dose ranging PD study of TAR-0520 gel when applied to the face or the chest for 21 days.

For both studies, key eligibility criteria were (1) age ≥ 18 and < 60 years at the time of signing the informed consent form, (2) considered healthy with no intercurrent disease after medical examination, and (3) no clinically significant allergies or history of significant adverse reactions to brimonidine or related compounds. In TAR012, participants were also required to have a Fitzpatrick phototype of II (fair skin, blue eyes) to IV (light brown skin). Female participants of childbearing potential were required to be non-pregnant, non-lactating and willing to use effect contraceptive methods throughout the study. All patients provided informed consent prior to participation in the study.

Treatment

In TAR006 part 1, all participants received six test products: four escalating concentrations of TAR-0520 gel (0.5%, 0.75%, 1% and 1.5% brimonidine tartrate), placebo (vehicle gel without active ingredient) and an active comparator approved for treatment of rosacea (Mirvaso® 3 mg/g gel, equivalent to 0.5% brimonidine tartrate, Laboratoire Galderma International). Using a standard 21-day local tolerance model, trained technicians applied 16 mg of each test product on six predefined mini-zones (4 cm² each) on the chest of each participant on 6 days per week (Fig. 1). All participants were randomized, with each randomization number corresponding to a specific application sequence of each product to the six application sites on the chest.

Fig. 1.

Product application schemes in study TAR006 and TAR012

In TAR012, participants received applications of TAR-0520 gel to four predefined treatment areas: two 49 cm² area of the chest and two 12.25 cm² area on the face (cheeks) (Fig. 1). Four TAR-0520 gel treatment regimens were evaluated: (1) 1.5% at 2 mg/cm² (equivalent to 100 mg of drug product applied to each chest site and 25 mg applied to each cheek); (2) 1.5% at 4 mg/cm² (200 mg applied to each chest site and 50 mg applied to each cheek); (3) 1% at 2 mg/cm² (100 mg applied to each chest site and 25 mg applied to each cheek); and (4) 1% at 4 mg/cm² (200 mg applied to each chest site and 50 mg applied to each cheek). Participants were randomized to receive two of the four treatment regimens, with one regimen applied to the chest and cheek on the left side of the body and the other applied to the chest and cheek on the right side. Participants received the treatment every weekday (Monday to Friday) for three consecutive weeks. After the final treatment, participants were randomly allocated to a treatment-free period of 4 or 7 days before a last visit (Day 23 or Day 26) in which a last application of test product was applied using the same regimen as before.

For both studies, the investigator and participants were blinded, with the products dispensed by a designated person other than the investigator.

Safety and tolerability

In both studies, local tolerance was evaluated daily prior to application using either an 8-point irritation scale (TAR006) or a 6-point irritation scale (TAR012). In TAR006, local tolerance was evaluated daily through to Day 22, and in TAR012, it was evaluated daily from Day 2 to Day 19. In both studies, key endpoints included the mean cumulative irritancy index (MCII) and the maximum irritation score observed during the study. The MCII is a quantitative measure used in local tolerance studies to assess the degree of skin irritation from repeated product applications over time. It is calculated as the sum of all subjects’ total irritation scores for the product divided by the number of evaluations and the number of subjects. MCII is typically interpreted using ranges that classify a product’s irritancy potential: CII ≈ 0.0–0.5 → non-irritant (excellent skin tolerance); CII ≈ 0.5–2.0 → very slightly/mildly irritant; CII ≈ 2.0–5.0 → moderately irritant; and CII > 5.0 → strongly/severely irritant. A mean CII score of 0 to 1 and a worst irritation score < 3 were considered as non- or weakly irritant.

All participants underwent physical examinations, vital sign monitoring, and standard laboratory safety assessments (hematology and biochemistry) at screening and at the final study visit in both studies. Adverse events (AEs) were reported individually on an ongoing basis.

Pharmacodynamic evaluation

Chromametry – Instrumental evaluation of skin blanching/vasoconstriction

In both studies, the effect of TAR-0520 gel on skin blanching/vasoconstriction was assessed objectively using a chromameter (CR 400 Chromameter, Konica Minolta). In the CIELAB color space, the a* parameter represents the color axis ranging from green (negative values) to red (positive values). For skin, higher redness corresponds to higher a* values, meaning that the more red the skin appears, the higher the a* value. A decrease in the red color component, reflecting superficial capillary vasoconstriction, served as a PD marker, with both intensity and duration providing insight into product potency. This validated skin blanching/vasoconstriction model is commonly used for evaluating the potency of topically applied corticosteroids based on their vasoconstrictive properties [16].

In TAR006 part 1, chromametry assessments were performed in a subgroup of participants on the six test sites and one control untreated area on Days 1, 8, and 15. The subgroup was divided into two cohorts for logistical reasons: one cohort were assessed every 2 h over the 12 h following product application, and the second cohort were assessed every 2 h from 14–24 h after application of the product. PD endpoints were absolute mean a* values at each timepoint and area under the curve from 0 to 24 h (AUC_0–24 h) for parameter Δa* (a* adjusted to baseline value measured at Day 1). AUC_0–24 h for Δa*was calculated using the trapezoidal method for control untreated skin and for each of the six treated areas. For each area, the mean AUC_0–24 h was calculated across individuals and the percentage difference was determined for each treatment compared with control.

In TAR012, chromametry assessments were performed on the chest and face before product application and 2 and 4 h after application on Days 1, 3, 5, 19 and 23 or 26. Additional assessments were performed before and 4 h after application on Days 8, 12 and 15. Median change in a* values from baseline were calculated across concentrations, doses and treatment breaks.

Clinical scores – Visual evaluation of skin blanching/vasoconstriction

In TAR012, visual assessments were performed on the chest and face test areas 4 h after product application on Days 1, 3, and 5. The investigator scored the blanching effect using a skin blanching visual scale that ranged from 0 (normal skin color) to 4 (maximal blanching). Visual assessments were not performed in TAR006.

Pharmacokinetic evaluation

In TAR006 part 2, a separate cohort of 8 participants received 2 g of TAR-0520 gel 1% applied over a 1000 cm² area (upper chest, upper back, and face) for five consecutive days. Blood samples were collected pre-dose and at multiple time points (40 min, 75 min, 2.5 h, 4 h, 6 h, 12 h, and 24 h) post-application on Days 1 and 5. PK parameters evaluated included maximum plasma concentration (C_max), time to reach C_max (T_max), AUC_0–24 h, and terminal half-life. A validated liquid chromatography-mass spectrometry (LC–MS/MS) analytical method with a lower limit of quantification of 11.68 pg/mL was used for quantification of brimonidine in plasma.

Results

Demographics

In TAR006, participants were treated between November 2023 and March 2024. Part 1 (safety and PD evaluations) randomized 20 participants, eleven women and nine men with a mean age of 45.5 years (range: 27–58), and part 2 (PK evaluations) enrolled 8 participants, three women and five men with a mean age of 39.0 years (range: 22–50). A subgroup of 12 participants completed the PD assessment in TAR006. In TAR012, participants were treated between June 2024 and August 2024. This study randomized 26 female subjects, with a mean age of 37 years (range: 18–58). All participants in both TAR006 and TAR012 completed the study and treatment compliance was 100%. Patient demographics are summarized in Table 1.

Table 1.

Study populations

	TAR006		TAR012
	Local tolerance (part 1)	PK (part 2)
Enrolled, n	20	8	26
Completed, n (%)	20 (100)	8 (100)	26 (100)
Sex, n (%)
Male	9 (45)	5 (63)	0
Female	11 (55)	3 (37)	26 (100)
Age, years, mean (range)	45.5 (27–58)	39.0 (22–50)	37 (18–58)
Fitzpatrick phototype, n (%)
Type II	3 (15.0)	2 (25.0)	1 (4%)
Type III	14 (70.0)	6 (75.0)	12 (46%)
Type IV	3 (15.0)	0	13 (50%)

Safety and local tolerability

No serious AEs, no changes in clinical examination or vital signs and no clinically relevant changes in blood parameters were reported in the two studies. In TAR006 part 1, seven AEs were reported by five participants. None of the AEs were cutaneous and most were headaches. All AEs were rated as mild, were resolved and were not considered to be related to the treatment. No AEs were reported in TAR006 part 2 or in TAR012.

In TAR006, the worst score observed in the 21-day local tolerance study was 1, defined as “barely perceptible minimal erythema” (Table 2). This score was reported on Day 8 for TAR-0520 gel 0.5% in one participant, on Days 4 and 13 for TAR-0520 gel 1% for a second participant, and on Day 13 for vehicle for a third participant. A score of 1 was also observed for Mirvaso® on Days 12 and 13 for a single participant. A score of 0 was reported at all other evaluations for these four participants. In TAR006 part 2, the tolerance score was 0 for all eight participants for all applications zones and visits (data not shown). In TAR012, all scores were 0 at each evaluation and for each treatment regimen (Table 2).

Table 2.

Local tolerance of TAR-052 versus placebo and comparator product in TAR006 and TAR012

	TAR006 (part 1, N = 20)						TAR012 (N = 26)
	TAR-0520 gel				Mirvaso®	Vehicle	TAR-0520 gel
	0.5%	0.75%	1%	1.5%	0.5%		1% at 2 mg/cm2	1% at 4 mg/cm2	1.5% at 2 mg/cm2	1.5% at 4 mg/cm2
CII	0.05	0	0.1	0	0.1	0.05	0	0	0	0
Worst score, n (%)	20 (100)	20 (100)	20 (100%)	20 (100)	20 (100)	20 (100)	13 (100)	13 (100)	13 (100)	13 (100)
No irritation (0)	19 (95)	20 (100)	19 (95)	20 (100)	19 (95)	19 (95)	13 (100)	13 (100)	13 (100)	13 (100)
Minimal barely perceptible erythema (1)	1 (5)	0	1 (5)	0	1 (5)	1 (5)	0	0	0	0
Mild irritation or worse (≥ 2)	0	0	0	0	0	0	0	0	0	0

CII, cumulative irritation index.

Pharmacodynamics

Chromametry – Instrumental evaluation of skin blanching/vasoconstriction

In TAR006, the chromametric measure of a* showed a decrease in skin redness for all active treatments (TAR-0520 gel and Mirvaso®) compared to the vehicle or to the control area. Mirvaso® exhibited substantially less intense and shorter effects compared to all four TAR-0520 gel concentrations, with a peak at 6 h and a return to pre-treatment values at 12 h. While some variability was observed, a trend for larger and prolonged changes could be seen with higher concentrations of TAR-0520 gel, TAR-0520 gel at 1.5% showing the greatest effects with a peak at 4 h and a slow return to normal over 24 h. The AUC for Δa* between 0 and 24 h (control adjusted) showed a dose–response trend for TAR-0520 gel and higher potency than Mirvaso® (Fig. 2).

Fig. 2.

Percentage difference in Δa*AUC_0–24 h for vehicle, Mirvaso® or TAR-0520 gel treatments compared with untreated skin (TAR006). Area under the curve from 0 to 24 h was calculated for Δa* (a* adjusted to the baseline value measured at Day 1) for control skin (AUC_0–24 h control) and for each of the six treated areas (AUC_0–24 h treatment). For each area, the mean AUC_0–24 h was calculated across individuals. The percentage difference was then calculated for each treatment by subtracting the mean AUC_0–24 h control from the mean AUC_0–24 h treatment, dividing this value by the mean AUC_0–24 h control and multiplying by 100. AUC, area under the concentration time curve

In the TAR0012 study, a single application of each tested regimen resulted in a rapid reduction in redness (as assessed by the chromametric a* parameter), with more intense effects seen on the face than on the chest. Regimen 1 (1.5% gel, 2 mg/cm²) demonstrated the highest impact on redness (25% reduction in a* on the face), whereas regimen 4 (1% gel at 4 mg/cm²) showed the least impact (16% reduction in a* on the face) (Fig. 3). Repeated applications over the study period resulted in a diminished redness-reduction effect, although a 4-day break from treatment partially or completely restored treatment effectiveness (Fig. 3).

Fig. 3.

Median percent change in a* from baseline to 4 h on the (a) face and (b) chest (TAR012). Median % change from baseline in a* parameter was calculated 4 h after the application of TAR-0520 gel on the first day of treatment (D1) and after 3 weeks of treatment followed by a 4-day treatment break (D23)

Clinical scores – Visual evaluation of skin blanching/vasoconstriction

In TAR012, the mean visual blanching score as assessed by the investigator ranged from 2.1 to 2.5 on the face and from 1.2 to 1.4 on the chest across all treatment regimens and treatment days at four hours post-application.

Pharmacokinetics

Using an assay with a lower limit of quantification of 11.68 µg/mL, brimonidine exposure could be quantified for only 16/72 samples (22%) on Day 1 and for 45/72 samples (62.5%) on Day 5. For three participants, all samples collected on Day 1 were below the limit of quantification (BLQ), whereas on Day 5, one subject had all samples BLQ. On Day 1, quantifiable brimonidine concentrations ranged from 12.37 pg/mL to 53.35 pg/mL, while on Day 5, concentrations ranged from 11.99 pg/mL to 100.93 pg/mL. The PK profile on Days 1 and 5 is shown in Table 3. The mean AUC_0–24 h was 401.2 pg*h/mL (range 195.9–795.1) on Day 1 compared to 554.9 pg*h/mL (range 185.1–1806.3) on Day 5. There was no evidence of accumulation of brimonidine following repeated application over 5 days, with the ratio of AUC_0–24 h on Day 5 to Day 1 being 1.74.

Table 3.

Pharmacokinetic profile of TAR-052 1% gel in TAR006

	Day 1 (N = 8)				Day 5 (N = 8)
Subject	Tmax (h)	Cmax (μg/mL)	AUC0–24 h (pg*h/mL) MIN*	AUC0–24 h (pg*h/mL) MAX*	Tmax (h)	Cmax (μg/mL)	AUC0–24 h (pg*h/mL) MIN*	AUC0–24 h (pg*h/mL) MAX*
1	BLQ	BLQ	0	276.4	BLQ	BLQ	0	280.3
2	12	22.51	307.5	389.25	12	38.34	766.54	766.54
3	BLQ	BLQ	0	280.32	12	17.94	236.66	340.78
4	12	32.76	458.01	539.77	8	43.25	881.21	881.21
5	12	53.35	736.7	795.08	12	100.93	1806.27	1806.27
6	12	19.04	274.9	356.66	2.5	74.27	545.71	567.61
7	BLQ	BLQ	0	280.32	12	14.12	185.14	301.94
8	12	15.73	195.9	324.4	12	19.69	347.88	398.51

Blood concentrations of brimonidine were measured using a validated analytical method.

*Two methods were used to calculate AUC_0–24 h for participants where not all samples could be quantified: (1) the MIN method replaced all BLQ results by the value 0; (2) the MAX method replaced all BLQ values by the value 11.68 pg/mL.

BLQ, below the limit of quantification (11.68 pg/mL); C_max, maximum plasma concentration; T_max, time to reach C_max, AUC_0–24 h, area under the concentration–time curve from 0 to 24 h.

Discussion

Brimonidine tartrate is a well-established alpha-2A adrenergic agonist that has been approved for decades as a topical treatment for glaucoma and rosacea [15]. While systemic adrenergic receptor agonists may pose risks such as hypotension and sedation, topical application of brimonidine is generally considered safe. Its safety profile is largely benign and characterized by local adverse effects similar to those seen with other topical medications. Despite the relatively high concentrations used, the newly developed brimonidine tartrate formulation demonstrated a favorable safety profile in the two phase I studies reported here, with no systemic safety concerns and only occasional reports of very mild local intolerance, supporting its classification as a non-irritant product.

In addition, systemic exposure to brimonidine tartrate remained very low when TAR-0520 gel 1% was applied once daily under maximized conditions, using a 2 g dose over the upper chest, upper back and face. Due to its 24-h extended-release profile, brimonidine tartrate permeates the skin gradually, resulting in clinically insignificant plasma concentrations. Despite using a highly sensitive method for brimonidine quantification in plasma, many samples remained below the limit of quantification. Notably, these systemic levels are comparable to those observed with currently marketed brimonidine formulations [15], despite TAR-0520 gel containing a substantially higher concentration of brimonidine tartrate. Mean AUC_0–24 h values were 568 pg*h/mL [range: 124–1490] on Day 1 for ophthalmically delivered Alphagan® 0.2% (Allergan, USA), 262 pg*h/mL [10–733] on Day 4 for dermally delivered Mirvaso® 0.5%, and 554 pg*h/mL [185–1806] on Day 5 for dermally delivered TAR-0520 gel 1%. In addition, no accumulation occurred following multiple daily applications of TAR-0520. This suggests that the favorable safety profile of marketed products may be extrapolated to the newly developed TAR-0520 gel, even at its higher concentration.

While the safety profile of TAR-0520 gel appears comparable to that of the currently marketed topical brimonidine formulations, PD data suggest that its vasoconstrictive potential may be enhanced in both potency and duration. As assessed via skin color measurement using a chromameter and the a* parameter for redness, TAR-0520 gel 1.5% provided sustained activity over 24 h versus a 12-h effect observed with Mirvaso® 0.3% gel (containing 0.5% brimonidine tartrate). The AUC_0–24 h adjusted for control was 18.17 for TAR-0520 gel 1.5% compared to 2.49 for Mirvaso®, indicating a sevenfold greater overall 24-h PD effect. In TAR012, regimen 1 (1.5% gel, 2 mg/cm²) demonstrated the highest initial impact on redness whereas regimen 4 (1% gel at 4 mg/cm²) showed least impact. This may suggest that a higher concentration and lower volume may achieve optimal vasoconstriction. Although multiple applications over 3 weeks in TAR012 resulted in a diminished redness-reduction effect, a 4-day treatment break restored treatment effectiveness. An intermittent treatment regimen with breaks may therefore be required for optimal PD effect.

Several limitations should be considered when interpreting these findings. The number of participants was small, as is inherent to a phase 1 design, and only female participants were enrolled in TAR012, which occurred by chance rather than by design. The statistical analysis was descriptive, with no formal comparisons performed. In addition, there are an absence of data in darker skin phototypes, long-term tolerability data, and comparative percutaneous absorption data across facial, scalp, palmar, and plantar regions; however, these limitations should be considered in the context of the well-established safety profile of the active ingredient, which has been in marketed use for several decades without new safety signal. Finally, as this was a phase 1 study, no clinical efficacy data were generated, and no conclusions can be drawn regarding the therapeutic benefit of TAR-0520 in the intended patient population.

Based on the promising findings reported here, TAR-0520 has received approval for evaluation in subsequent phase II studies, including clinical trials targeting EGFR inhibitor-induced skin toxicities, taxane-induced peripheral neuropathy, capecitabine-induced hand-foot syndrome, and chemotherapy-induced alopecia. Currently, three phase II trials evaluating the safety and efficacy of TAR-0520 gel are underway. The first is a multicentric, randomized, double-blind, placebo-controlled study to evaluate the effect of TAR-0520 1.5% gel on EGFR inhibitor-induced folliculitis in metastatic colorectal cancer (NCT06818058). In this study, patients will receive TAR-0520 gel once daily for 7 consecutive days in each cancer treatment cycle, followed by a 7-day treatment-free period. The second is an open-label, intra-individual study to evaluate the effect of TAR-0520 1.5% gel on taxane-induced peripheral neuropathy (TARIAN 014, NCT07082764). In this study, participants will receive TAR-0520 gel twice daily for 3 days within each treatment cycle. The third is an open-label, intra-individual study to evaluate the effect of TAR-0520 1.5% gel on capecitabine-induced HFS (TARIAN 008).

Conclusion

The phase 1 program conducted with TAR-0520 gel, a novel sustained-release formulation of brimonidine tartrate, confirmed its vasoconstrictive potency in a convenient once-daily regimen. The safety profile is expected to be comparable to that of already marketed products, supported by similarly low systemic exposure and absence of drug accumulation. These findings support a highly favorable benefit–risk profile and justify the selection of TAR-0520 gel 1.5% as the lead candidate for further development in oncodermatology.

Author contributions

All authors contributed to the study conception, design, and oversight. Material preparation, data collection and analysis were performed by Philippe Andres, Janusz Czernielewski and Alexandra Lamquin. Study product development and manufacturing of GMP batches were under the responsibility of Gareth Winckle. The first draft of the manuscript was written by Philippe Andres and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Editorial support was provided by Steph Carter (Lyrical Medical Writing Services Ltd, UK) funded by Tarian Pharma.

Funding

Tarian Pharma, the sponsor of the two reported studies, is a privately owned pharmaceutical company. The two studies were funded by contributions from the founders and shareholders, with additional support from the French Bank of Investment.

Data availability

The full data set will be made available upon request to academic researchers.

Declarations

Competing interests

The authors of this publication are the founders of Tarian Pharma, the company developing the test product used in the two clinical trials in this publication.

Ethics approval

The two reported studies were performed in line with the principles of the Declaration of Helsinki. Approval of the first study was granted by the Ethics Committee “CPP Sud-Méditerranéen 4” from Montpellier. Approval of the second study was granted by the Ethics Committee “Clinical Research Regulatory Council (CRRC)” from the Republic of Mauritius.

Consent to participate

Informed consent was obtained from all individual participants included in the two studies.

Consent to publish

No individual details, images or videos are included in this manuscript.