Neospastil (ketorolac tromethamine / pitofenone hydrochloride / fenpiverinium bromide fixed-dose combination) in a form of solution for injections and film-coated tablets has been studied as a treatment for pain after surgical abdominal and pelvic operations. The aim of the study was to test the hypothesis that Neospastil was non-inferior (phase II) and superior (phase III) than ketorolac tromethamine monotherapy due to the additional relaxing effect of pitofenone and fenpiverinium on the smooth muscles of internal organs. The study also aimed to show that Neospastil is safe and well-tolerated in people who have pain after surgical abdominal and pelvic operations. Study treatment was initiated with parenteral form of study drug (first 24 hours) and then switched to oral formulation. This trial was conducted in accordance with the ethical principles of Good Clinical Practice and International Council for Harmonization (ICH) Harmonized Tripartite Guidelines.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
424
These medicines were used for patients of Group 1 (phase II) and Group 4 (phase III). Stage 1 (1st day of study treatment) - Ketorolac tromethamine, solution for injection, 1 ml every 8 hours. Stage 2 (2nd day of study treatment) - Neospastil, film-coated tablets, 1 tablet every 6 hours. Stage 3 (3rd-5th days of study treatment) - Neospastil, film-coated tablets, 1 tablet on demand with an interval of at least 6 hours, not more than 4 tablets per day.
These medicines were used for patients of Group 2 (phase II) and Group 5 (phase III). Stage 1 (1st day of study treatment) - Ketorolac tromethamine, solution for injection, 1 ml every 8 hours. Stage 2 (2nd day of study treatment) - Ketorolac tromethamine, coated tablets, 1 tablet every 6 hours. Stage 3 (3rd-5th days of study treatment) - Ketorolac tromethamine, coated tablets, 1 tablet on demand with an interval of at least 6 hours, not more than 4 tablets per day.
These medicines were used for patients of Group 3 (phase II) and Group 6 (phase III). Stage 1 (1st day of study treatment) - Neospastil, solution for injection, 2 ml every 8 hours. Stage 2 (2nd day of study treatment) - Neospastil, film-coated tablets, 1 tablet every 6 hours. Stage 3 (3rd-5th days of study treatment) - Neospastil, film-coated tablets, on demand 1 tablet with an interval of at least 6 hours, not more than 4 tablets per day.
Regional municipal nonprofitable institution "Chernivtsi regional clinical hospital", urological department
Chernivtsi, Ukraine
Communal enterprise "Dnipropetrovsk Regional Clinical Hospital named after І.І. Mechnikov" Dnipropetrovsk Regional Council", urology department №1
Dnipro, Ukraine
Communal enterprise "Dnipropetrovsk Regional Clinical Hospital named after І.І. Mechnikov" Dnipropetrovsk Regional Council", urology department №2
Dnipro, Ukraine
Communal noncomercial enterprise of the Kharkiv Regional Council "Regional Medical Clinical Center of Urology and Nephrology named after V.I. Shapovala", urology department №5
Kharkiv, Ukraine
Communal noncomercial enterprise "Kyiv City Clinical Hospital #3" Kyiv City Council (Kyiv City State Administration), urological department
Kyiv, Ukraine
Medical Center of the LLC "Harmony of Beauty"
Kyiv, Ukraine
State Institution "Institute of Urology of the National Academy of Medical Sciences of Ukraine", I Urological Department
Kyiv, Ukraine
Communal noncomercial enterprise of the Lviv Regional Council "Lviv Regional Clinical Hospital", department of urology
Lviv, Ukraine
Municipal Non-profit Enterprise "Lviv Clinical Hospital for Emergency Medical Care"
Lviv, Ukraine
Communal noncomercial enterprise "City Clinical Hospital #10" Odesa City Council, urological department #2
Odesa, Ukraine
...and 4 more locations
Proportion of study subjects who achieved a response to treatment within the first 24 hours of using IMP in the form of solution for injections.
This primary endpoint was evaluated using the following combined primary (main) efficacy variable. The patient who met all of the following criteria (1.1-1.3) was considered as a "responder". The patient who didn't meet at least one of the following criteria was classified as a "non-responder". 1.1. Reduction in pain intensity at rest compared to the initial level by ≥ 50 % within the first 90 min. after the first dose of IMP in the form of a solution for injections (i.e., at least at one of the following time points 30 \[±5\] min., 60 \[±10\] min. and/or 90 \[±15\] min.). 1.2. During the study treatment, the intensity of pain at rest is \< 4 points on the 11-point NRS at time points between 2 and 24 hours (i.e. 120 \[±20\] min., 4 \[±0.5\] h., 6 \[±1\] h., 8 \[±1\] h., 16 \[±2\] h. and 24 \[±2\] h.) after starting the use of IMP in the form of solution for injections. 1.3. The study subject didn't receive other analgesics during the first 24 hours of the study treatment.
Time frame: Stage 1 (1st day of treatment).
Proportion of study subjects who achieved a response to treatment within the first 24 hours of using IMP in the form of tablets.
This primary endpoint was evaluated using the following combined primary (main) efficacy variable. The patient who met all of the following criteria (2.1-2.3) was considered as a "responder". The patient who didn't meet at least one of the following criteria was classified as a "non-responder". 2.1. Reduction in pain intensity at movements compared to the initial level by ≥ 50 % within the first 120 min. after the first dose of IMP in the form of tablets (i.e., at least at one of the following time points 60 \[±10 min., 90 \[±15\] min. and/or 120 \[±20\] min.). 2.2. During the study treatment, the intensity of pain during movement is \< 4 points on the 11-point NRS at time points between 3 and 24 hours (i.e. 3 \[±0.5\] h, 4 \[±0.5\] h, 6 \[±1\] h, 12 \[±2\] h, 18 \[±2\] h and 24 \[±2\] h) after starting to use IMP in the form of tablets. 2.3. The study subject didn't receive other analgesics within 24 hours since beginning of the IMP usage in the form of tablets.
Time frame: Stage 2 (2nd day of treatment).
Time to a noticeable and distinct decrease in the intensity of pain at rest from the first dose of IMP in the form of a solution for injections.
Time frame: Stage 1 (1st day of treatment)
Pain intensity at rest and during movements according to the 11-point NRS at time points during the study treatment.
Time frame: Stage 1 (1st day of treatment), Stage 2 (2nd day of treatment) and Stage 3 (3rd-5th days of treatment)
Area under the curve of pain intensity at rest and during movements according to the 11-point NRS at time points within 24 hours after the first dose of IMP in the form of solution for injections and IMP in the form of tablets.
Time frame: Stage 1 (1st day of treatment) and Stage 2 (2nd day of treatment)
Sum of pain intensity differences (SPID) at rest and during movements within 6 hours after the first dose of IMP in the form of solution for injections or IMP in the form of tablets.
Time frame: First 6 hours of Stage 1 (1st day of treatment) and Stage 2 (2nd day of treatment)
The proportion of patients who achieved a response to treatment.
A response to treatment based on the patient's overall assessment of pain control within 24 hours using of IMP in the form of a solution for injections and IMP in the form of tablets, as well as at the end of the study treatment.
Time frame: Stage 1 (1st day of treatment), Stage 2 (2nd day of treatment) and Stage 3 (3rd-5th days of treatment)
The number of IMP doses administered during 3-5 days of the study treatment (per patient).
Time frame: Stage 3 (3rd-5th day of treatment)
Proportion of patients who used another analgesic since the first dose of IMP.
Time frame: Stage 1 (1st day of treatment), Stage 2 (2nd day of treatment) and Stage 3 (3rd-5th days of treatment)
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