Summary of pharmacokinetic clinical study for Neospastil, film-coated tablets

07 December 2023

Purpose. To prove pharmacokinetic (PK) parameters, tolerability, and safety of the investigational medicinal product (IMP) Neospastil, film-coated tablets, after a single oral administration of the IMP by healthy volunteers.

Objects and methods of the study. Twenty-five volunteers were included in the study; 18 of them met all the inclusion / exclusion criteria and were randomized. Among 18 healthy volunteers randomized, there were 10 males (55.6%) and 8 females (44.4%), aged 18 to 48 years (34,67 ± 10,29 years), with body mass index (BMI) of 18.78 to 29.33 kg/m² (23,46 ± 3,12 kg/m²).

The IMP was administered once as one film-coated tablet dose (10 mg ketorolac tromethamine, 10 mg pitofenone hydrochloride, and 0.1 mg fenpiverinium bromide).

The concentrations of all three analytes (i.e., ketorolac (KRL), pitofenone (PTF), and fenpiverinium (FPV)) in the blood plasma of healthy volunteers were determined using a validated high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method.

Results. The concentrations of each of three analytes in pre-dose blood samples were below the lower limit of quantification (LLOQ) in all volunteers. Area under the plasma concentration curve from administration to last observed concentration at time t (AUC0–t) and maximum plasma concentration (Сmax) for KRL, PTF, and FPV after a single oral administration of a Neospastil, film-coated tablets, are provided in Table 1.

Table 1. Concentrations of KRL, FPV and PTF in plasma blood samples after single oral administration of Neospastil, film-coated tablets (mean ± standard deviation)

Active substance	AUC0–t, ng·h/ml	Сmax, ng/ml
Ketorolac	3490.3 ± 884.0	1102.4 ± 236.6
Fenpiverinium	0.192 ± 0.060	0.017 ± 0.008
Pitofenone	0.633 ± 0.242	0.236 ± 0.084

For KRL and FPV, maximum plasma concentration was reached within 0.50 h (median, n = 18) after a single dose of IMP, while for PTF, it was reached within 4.00 h (median, n = 18). Pharmacokinetic results showed that PK profiles of all three analytes, i.e., KRL, PTF, and FPV, decreased multiexponentially.

During the study, 1 case of adverse reaction (AR) was reported in one healthy volunteer: headache. This case of AR was of mild severity and did not require any therapeutic actions. It resulted in recovery without consequences and was evaluated by the investigator as expected with improbable relation to the IMP.

None of 18 volunteers included in safety and tolerability analysis had any clinically significant changes on physical examination, assessment of vital signs, clinical and laboratory parameters, and electrocardiography.

Conclusions. In this study, pharmacokinetic parameters of Neospastil, film-coated tablets, manufactured by PrJSC “Pharmaceutical Firm “Darnytsia” were evaluated. The IMP tested was safe and well tolerated in healthy volunteers included in this study.

The Sponsor of the study, PrJSC “Pharmaceutical Firm “Darnytsia”, expresses its gratitude to the employees of contract research organization “INNOFAR Clinic – Ukraine Innovative Pharma Research” (Boyany village, Chernivtsi region, Ukraine) and “QUINTA-ANALYTICA s.r.o.” (Prague, Czech Republic) for conducting this study and processing its results.