Tafalgin is a Russian innovative tetrapeptide pharmaceutical for subcutaneous injection: review of the results of phase I and II clinical trials

Abstract

Introduction. pain syndrome significantly affects quality of life and daily activities of patients with cancer, especially at terminal stages of the disease. Opioid analgesics are considered the “gold standard” of therapy, but their use is associated with bureaucratic difficulties, as well as risk of a number of adverse events and drug dependency. Tafalgin is a Russian innovative tetrapeptide analgesic for subcutaneous injection. phase I and II clinical trials demonstrated its high effectiveness comparable to morphine and favorable safety profile.The study objective is to evaluate the safety, tolerability, and pharmacokinetics of tafalgin after subcutaneous injection in healthy volunteers, as well as effectiveness and safety of varying doses in patients with pain syndrome due to malignant tumors.Materials and methods. Phase I clinical trial included 39 healthy male volunteers. The drug was injected once subcutaneously at doses between 0.05 and 7 mg. plasma samples were obtained in the first 120 hours, and safety profile, tolerability and main pharmacokinetic characteristics of the pharmaceutical were determined. phase II clinical study included 42 patients with severe pain syndrome caused by malignant tumors who previously received morphine. At the 1st stage (10 days), all patients were randomized in groups receiving tafalgin at doses 2, 3, 4, 5, 6 or 7 mg (dosing frequency was determined individually); at the 2nd stage the patients were randomized into tafalgin (with dose determined at the 1st stage) and morphine (with dose determined prior to the clinical trial) groups and received the medications for 7 days. Effectiveness and safety of tafalgin compared to morphine and pharmacokinetic parameters of the studied drug were evaluated.Results. Tafalgin is characterized by fast absorption after subcutaneous administration (less than 30 minutes) which allows for fast clinical effect and absence of accumulation in the body. use of this pharmaceutical in patients with cancer allowed to maintain appropriate pain management achieved earlier through intramuscular morphine administration in 100 % of cases. Dynamics of mean daily pain intensity and necessity of additional analgesics did not differ between the groups. use of tafalgin did not require an increase in the dose or frequency of administration. Comparison of mean daily individual morphine and tafalgin doses showed that equianalgetic potential of the studied pharmaceutical was 1:3. Safety profile of tafalgin was favorable: adverse events during the trial were mild or moderate and not lifethreatening. use of tafalgin was associated with decreased number of opioid-induced adverse effects and improved quality of sleep in patients who previously received morphine parenterally.Conclusion. Data obtained during the first in Russia clinical trial of a new selective pharmaceutical tafalgin with tropism to opioid pl-receptors definitively demonstrates its high effectiveness and safety and shows the necessity of further studies in this field.