Suitable as eye drops?
The active ingredient was first approved by the FDA (i.e. Food and Drug Administration) in 1994 as an immunosuppressant in humans. Today it is patent-free - which is why it is possible to market it. However, the drug is poorly soluble in water and is not optimal for ocular use in this form. By means of a new formulation, the solubility of the active ingredient can be increased by a factor of more than 200, making it possible to use it as eye drops.
Currently, eye drops containing tacrolimus are only approved in Japan for the treatment of spring conjunctivitis(i.e. allergic conjunctivitis) and are formulated as a suspension containing 1 mg/ml. Work is underway in Europe as a Phase 2 study by Marinomed, a biopharmaceutical company based in Korneuburg, Austria, showed initial dose-dependent efficacy of Tacrosolv eye drops. Tacrosolv is a new aqueous formulation of the active ingredient tacrolimus in low concentration. The company has used plant saponins(i.e. organic plant compounds) to produce poorly soluble active ingredients in micelle form(i.e. molecular complexes stored together). According to the company, the resulting advantages would be:
- Easy application without prior shaking
- A faster effect or bioavailability (i.e., shows how quickly and to what extent a substance is absorbed)
Vienna Study Method:
The clinical, randomized, placebo-controlled, cross-over, phase 2 study was conducted at the Vienna Challenge Chamber in Vienna. The safety and efficacy of two different doses of tacrosolv were investigated. These were 2.5% and 5% of the dose of tacrolimus eye drop products used in Japan, respectively. Study participants received either the higher dosage of 2 drops per day or the lower dosage of one drop per day or placebo (3% propylene glycol in saline) in two treatment cycles. In the first cycle, either tacrosolv or the placebo was administered for 8 days. After a washout period of 13 days, the study continued with placebo or tacrosolv eye drops.
End Objectives of the Study:
The primary end goal of the double-blind study was to evaluate the safety and efficacy of the doses at day 8 of treatment. For this purpose, study participants underwent a provocation test with grass pollen. At 15-minute intervals, study investigators examined symptoms in the eyes. The analysis was determined using average TOS scores (i.e. Total Ocular Symptom Score). These include symptoms such as eye redness, eye itching, watery eye, and foreign body sensation, each graded on a four-point scale (no symptoms, mild, moderate, and severe). Secondary end goal was the onset of efficacy on the first day of treatment and the variances in efficacy of both doses on the last day of administration. Eye redness, so-called Total Nasal Symptom Score (i.e., nasal symptoms, runny nose, itchy nose, and sneezing), nasal airflow, and Total Respiratory Symptom Score (i.e., cough, wheezing, and dyspnea or shortness of breath) were assessed.
Results after Provocation:
Day 8 was able to show a significant reduction in ocular symptoms after the use of tacrosolv compared to day 1. The placebo group did not show any reduction of symptoms. Especially the higher dosage had a good effect, because already 3.5 hours after the provocation test the symptoms decreased significantly. Nasal symptoms also attenuated significantly on the last day within 4 hours after the provocation test.
According to the study, the higher dosage was effective as a treatment for ocular inflammation triggered by allergic reactions in participants in the second phase of the study. Successful completion of the study phases and approval in Europe could mean that eye drops for allergic symptoms in the eye and nose may also be marketed in our latitudes in the near future.
Active ingredients and diseases: