Trial Outcomes & Findings for A Study to Assess Efficacy and Tolerability of Ketoprofen 40 mg Granules vs Placebo (NCT NCT03836807)
NCT ID: NCT03836807
Last Updated: 2024-04-24
Results Overview
The primary efficacy endpoint is the pain intensity assessment during 6 hours after molar tooth extraction measured as an area under the curve (AUC) of pain intensity assessed with a visual analogue scale (VAS). More precisely, pain is assessed by a horizontal 100 mm scale where 0 mm = no pain and 100 mm = worst pain imaginable, at the timepoints specified here under in the interval from time 0 (baseline value of VAS) to 6 hours after the drug administration. The AUC0-6h is calculated using the trapezoidal rule. Please note that at 0' (just before taking the first medication) VAS should be \>30 mm. The higher the score, the worse the result.
COMPLETED
PHASE3
70 participants
time 0', 5', 10', 15', 30', 60' (1 hour), 90' (1.5 hours), 120' (2 hours), 180' (3 hours), 240' (4 hours), 300' (5 hours), and 360' (6 hours) post-treatment
2024-04-24
Participant Flow
There were 73 screened patients in the study. 70 of them were randomized into the OKITASK® or Placebo groups by 35 patients per each group.
Participant milestones
| Measure |
OKITASK®
Single oral administration of Ketoprofen lysine salt 40 mg granules
Ketoprofen: 40 mg KLS granules (corresponding to 25 mg ketoprofen)
|
Placebo
Single oral administration of placebo granules
Placebo: 0 mg KLS granules
|
|---|---|---|
|
Overall Study
STARTED
|
35
|
35
|
|
Overall Study
Intent To Treat (ITT)
|
35
|
35
|
|
Overall Study
Per Protocol (PP)
|
33
|
35
|
|
Overall Study
Safety Population (SAF)
|
35
|
35
|
|
Overall Study
COMPLETED
|
34
|
35
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
| Measure |
OKITASK®
Single oral administration of Ketoprofen lysine salt 40 mg granules
Ketoprofen: 40 mg KLS granules (corresponding to 25 mg ketoprofen)
|
Placebo
Single oral administration of placebo granules
Placebo: 0 mg KLS granules
|
|---|---|---|
|
Overall Study
Physician Decision
|
1
|
0
|
Baseline Characteristics
A Study to Assess Efficacy and Tolerability of Ketoprofen 40 mg Granules vs Placebo
Baseline characteristics by cohort
| Measure |
Ketoprofen
n=35 Participants
Single oral administration of Ketoprofen lysine salt 40 mg granules
Ketoprofen: 40 mg KLS granules (corresponding to 25 mg ketoprofen)
|
Placebo
n=35 Participants
Single oral administration of placebo granules
Placebo: 0 mg KLS granules
|
Total
n=70 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
35 Participants
n=93 Participants
|
35 Participants
n=4 Participants
|
70 Participants
n=27 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Sex: Female, Male
Female
|
18 Participants
n=93 Participants
|
18 Participants
n=4 Participants
|
36 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
17 Participants
n=93 Participants
|
17 Participants
n=4 Participants
|
34 Participants
n=27 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
White
|
35 Participants
n=93 Participants
|
35 Participants
n=4 Participants
|
70 Participants
n=27 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Region of Enrollment
Russia
|
35 participants
n=93 Participants
|
35 participants
n=4 Participants
|
70 participants
n=27 Participants
|
PRIMARY outcome
Timeframe: time 0', 5', 10', 15', 30', 60' (1 hour), 90' (1.5 hours), 120' (2 hours), 180' (3 hours), 240' (4 hours), 300' (5 hours), and 360' (6 hours) post-treatmentPopulation: The Intent-to-treat (ITT) population included all randomized patients who received at least one dose of study medication and have at least one post-baseline18 efficacy measurement; one patient in the ketoprofen group had missing data of the pain intensity VAS and such data were not replaced according to rules for LOCF; hence no AUC for this patient was calculated.
The primary efficacy endpoint is the pain intensity assessment during 6 hours after molar tooth extraction measured as an area under the curve (AUC) of pain intensity assessed with a visual analogue scale (VAS). More precisely, pain is assessed by a horizontal 100 mm scale where 0 mm = no pain and 100 mm = worst pain imaginable, at the timepoints specified here under in the interval from time 0 (baseline value of VAS) to 6 hours after the drug administration. The AUC0-6h is calculated using the trapezoidal rule. Please note that at 0' (just before taking the first medication) VAS should be \>30 mm. The higher the score, the worse the result.
Outcome measures
| Measure |
OKITASK
n=34 Participants
Single oral administration of Ketoprofen lysine salt 40 mg granules
Ketoprofen: 40 mg KLS granules (corresponding to 25 mg ketoprofen)
|
Placebo
n=35 Participants
Single oral administration of placebo granules
Placebo: 0 mg KLS granules
|
|---|---|---|
|
AUC0-6h of Pain Intensity Between Time 0 (Baseline Value of VAS) and 6 Hours Post-treatment in the ITT Population.
|
5031 mm*min
Standard Deviation 3250
|
7593 mm*min
Standard Deviation 5402
|
PRIMARY outcome
Timeframe: time 0', 5', 10', 15', 30', 60' (1 hour), 90' (1.5 hours), 120' (2 hours), 180' (3 hours), 240' (4 hours), 300' (5 hours), and 360' (6 hours) post-treatmentPopulation: The Per protocol population included those patients who had completed the study treatment period, had all assessments for the primary efficacy analysis and considered compliant. The patients were compliant if they did not have any major protocol violations in the course of the study. For the PP population no data could be missing, hence there were no LOCF or other methods applied.
The primary efficacy endpoint is the pain intensity assessment during 6 hours after molar tooth extraction measured as an area under the curve (AUC) of pain intensity assessed with a visual analogue scale (VAS). More precisely, pain is assessed by a horizontal 100 mm scale where 0 = no pain and 100 = worst pain imaginable, at the timepoints specified here under in the interval from time 0 (baseline value of VAS) to 6 hours after the drug administration. The AUC0-6h is calculated using the trapezoidal rule. Please note that at 0' (just before taking the first medication) VAS should be \>30 mm. The higher the score, the worse the result.
Outcome measures
| Measure |
OKITASK
n=33 Participants
Single oral administration of Ketoprofen lysine salt 40 mg granules
Ketoprofen: 40 mg KLS granules (corresponding to 25 mg ketoprofen)
|
Placebo
n=35 Participants
Single oral administration of placebo granules
Placebo: 0 mg KLS granules
|
|---|---|---|
|
AUC0-6h of Pain Intensity Between Time 0 (Baseline Value of VAS) and 6 Hours Post-treatment in the PP Population.
|
5099 mm*min
Standard Deviation 3275
|
7593 mm*min
Standard Deviation 5402
|
SECONDARY outcome
Timeframe: From time 0 (baseline value of VAS) to 6 hours post-treatment at: 0', 5', 10', 15', 30', 45', 60' (1 hour), 90' (1.5 hours), 120' (2 hours), 180' (3 hours), 240' (4 hours), 300' (5 hours), and 360' (6 hours) after the drug administration.Population: The Intent-to-treat (ITT) population included all randomized patients who received at least one dose of study medication and have at least one post-baseline18 efficacy measurement; one patient in the ketoprofen group had missing data of the pain intensity VAS and such data were not replaced according to rules for LOCF; hence no AUC for this patient was calculated.
This outcome analyzed the evolution and the profile of pain by a horizontal 100 mm Visual Analogue Scale (VAS): 0 no pain - 100 worst pain imaginable at 0' (just before taking the first medication VAS should be \>30 mm) and 5', 10', 15', 30', 60' (1 hour), 90' (1.5 hours), 120' (2 hours), 180' (3 hours), 240'(4 hours), 300' (5 hours), and 360' (6 hours) after the drug administration. The higher the score, the worse the result.
Outcome measures
| Measure |
OKITASK
n=35 Participants
Single oral administration of Ketoprofen lysine salt 40 mg granules
Ketoprofen: 40 mg KLS granules (corresponding to 25 mg ketoprofen)
|
Placebo
n=35 Participants
Single oral administration of placebo granules
Placebo: 0 mg KLS granules
|
|---|---|---|
|
Time Profile of Pain Intensity Using VAS Scale
0 min
|
45.3 mm
Standard Deviation 12.0
|
45.5 mm
Standard Deviation 9.9
|
|
Time Profile of Pain Intensity Using VAS Scale
5min
|
45.2 mm
Standard Deviation 14.2
|
43.9 mm
Standard Deviation 11.5
|
|
Time Profile of Pain Intensity Using VAS Scale
10min
|
40.4 mm
Standard Deviation 16.3
|
40.7 mm
Standard Deviation 13.5
|
|
Time Profile of Pain Intensity Using VAS Scale
15min
|
34.9 mm
Standard Deviation 18.8
|
37.0 mm
Standard Deviation 15.5
|
|
Time Profile of Pain Intensity Using VAS Scale
30min
|
22.4 mm
Standard Deviation 17.9
|
30.9 mm
Standard Deviation 17.8
|
|
Time Profile of Pain Intensity Using VAS Scale
45min
|
16.2 mm
Standard Deviation 16.9
|
24.6 mm
Standard Deviation 17.4
|
|
Time Profile of Pain Intensity Using VAS Scale
1h
|
13.4 mm
Standard Deviation 14.0
|
22.4 mm
Standard Deviation 18.0
|
|
Time Profile of Pain Intensity Using VAS Scale
1,5h
|
12.1 mm
Standard Deviation 12.6
|
22.6 mm
Standard Deviation 19.3
|
|
Time Profile of Pain Intensity Using VAS Scale
2h
|
11.5 mm
Standard Deviation 13.8
|
20.8 mm
Standard Deviation 18.1
|
|
Time Profile of Pain Intensity Using VAS Scale
3h
|
12.7 mm
Standard Deviation 15.6
|
18.2 mm
Standard Deviation 18.3
|
|
Time Profile of Pain Intensity Using VAS Scale
4h
|
13.6 mm
Standard Deviation 13.9
|
18.4 mm
Standard Deviation 19.4
|
|
Time Profile of Pain Intensity Using VAS Scale
5h
|
11.8 mm
Standard Deviation 9.5
|
16.7 mm
Standard Deviation 16.8
|
|
Time Profile of Pain Intensity Using VAS Scale
6h
|
12.6 mm
Standard Deviation 9.9
|
16.5 mm
Standard Deviation 18.2
|
SECONDARY outcome
Timeframe: From time 0 (baseline value of VAS) to 6 hours post-treatment at: 5', 10', 15', 30', 45', 60' (1 hour), 90' (1.5 hours), 120' (2 hours), 180' (3 hours), 240' (4 hours), 300' (5 hours), and 360' (6 hours) after the drug administration.Population: The Intent-to-treat (ITT) population included all randomized patients who received at least one dose of study medication and have at least one post-baseline18 efficacy measurement; one patient in the ketoprofen group had missing data of the pain intensity VAS and such data were not replaced according to rules for LOCF; hence no AUC for this patient was calculated.
This outcome analyzed the evolution of pain relief after administration of OKITASK® and after administration of Placebo, assessed by a horizontal 100 mm Visual Analogue Scale (VAS): 0 no pain relief - 100 maximum relief imaginable at: 0' (just before taking the first medication VAS should be \>30 mm) and 5', 10', 15', 30', 60' (1 hour), 90' (1.5 hours), 120' (2 hours), 180' (3 hours), 240'(4 hours), 300' (5 hours), and 360' (6 hours) after the drug administration. The higher the score, the best the result.
Outcome measures
| Measure |
OKITASK
n=35 Participants
Single oral administration of Ketoprofen lysine salt 40 mg granules
Ketoprofen: 40 mg KLS granules (corresponding to 25 mg ketoprofen)
|
Placebo
n=35 Participants
Single oral administration of placebo granules
Placebo: 0 mg KLS granules
|
|---|---|---|
|
Time Profile of Pain Relief Using VAS Scale
at 5'
|
12.7 mm
Standard Deviation 14.0
|
10.1 mm
Standard Deviation 9.7
|
|
Time Profile of Pain Relief Using VAS Scale
at 10'
|
20.3 mm
Standard Deviation 18.8
|
16.0 mm
Standard Deviation 14.6
|
|
Time Profile of Pain Relief Using VAS Scale
at 15'
|
31.6 mm
Standard Deviation 25.3
|
22.7 mm
Standard Deviation 20.5
|
|
Time Profile of Pain Relief Using VAS Scale
at 30'
|
57.6 mm
Standard Deviation 31.4
|
35.2 mm
Standard Deviation 29.3
|
|
Time Profile of Pain Relief Using VAS Scale
at 45'
|
68.9 mm
Standard Deviation 30.9
|
47.8 mm
Standard Deviation 34.2
|
|
Time Profile of Pain Relief Using VAS Scale
at 1h
|
73.5 mm
Standard Deviation 29.3
|
54.9 mm
Standard Deviation 34.9
|
|
Time Profile of Pain Relief Using VAS Scale
at 1.5h
|
79.7 mm
Standard Deviation 24.7
|
57.4 mm
Standard Deviation 35.6
|
|
Time Profile of Pain Relief Using VAS Scale
at 2h
|
82.1 mm
Standard Deviation 21.3
|
60.1 mm
Standard Deviation 35.9
|
|
Time Profile of Pain Relief Using VAS Scale
at 3h
|
82.8 mm
Standard Deviation 19.7
|
66.1 mm
Standard Deviation 34.2
|
|
Time Profile of Pain Relief Using VAS Scale
at 4h
|
80.5 mm
Standard Deviation 23.5
|
69.7 mm
Standard Deviation 30.8
|
|
Time Profile of Pain Relief Using VAS Scale
at 5h
|
81.4 mm
Standard Deviation 21.8
|
73.9 mm
Standard Deviation 25.0
|
|
Time Profile of Pain Relief Using VAS Scale
at 6h
|
79.8 mm
Standard Deviation 22.7
|
75.8 mm
Standard Deviation 25.4
|
SECONDARY outcome
Timeframe: from 5 min to 6 hours post-dosePopulation: ITT population included all randomized patients who received at least one dose of study medication and have at least one post-baseline 18 efficacy measurement; one patient in the ketoprofen group had missing data of the pain intensity VAS and such data were not replaced according to rules for LOCF; hence no AUC for this patient was calculated. PP population included those patients who had completed the study treatment period, had all assessments for the primary efficacy analysis and compliant.
In addition, area under the curve for pain relief assessment since 5 minutes till 6 hours after the drug administration was evaluated.
Outcome measures
| Measure |
OKITASK
n=34 Participants
Single oral administration of Ketoprofen lysine salt 40 mg granules
Ketoprofen: 40 mg KLS granules (corresponding to 25 mg ketoprofen)
|
Placebo
n=35 Participants
Single oral administration of placebo granules
Placebo: 0 mg KLS granules
|
|---|---|---|
|
AUC5min-6h of Pain Relief Profile in the ITT and in the PP Populations
ITT population
|
27445 mm*min
Standard Deviation 6456
|
22103 mm*min
Standard Deviation 9209
|
|
AUC5min-6h of Pain Relief Profile in the ITT and in the PP Populations
PP population
|
27362 mm*min
Standard Deviation 6538
|
22103 mm*min
Standard Deviation 9209
|
SECONDARY outcome
Timeframe: Day 1Population: The Intent-to-treat (ITT) population included all randomized patients who received at least one dose of study medication and have at least one post-baseline18 efficacy measurement; one patient in the ketoprofen group had missing data of the pain intensity VAS and such data were not replaced according to rules for LOCF; hence no AUC for this patient was calculated.
TFPR was measured by stopwatches, a timepiece designed to measure the amount of time that elapses between its activation and deactivation. Upon study drug administration the patients immediately started a stopwatch, once the patient felt first perceptible pain relief, the stopwatch was stopped. The time between activation and deactivation of a stopwatch defined the outcome measure data. The shortest the time, the better the outcome. Kaplan-Meier estimation of TFPR was expressed by median and 95% CI.
Outcome measures
| Measure |
OKITASK
n=35 Participants
Single oral administration of Ketoprofen lysine salt 40 mg granules
Ketoprofen: 40 mg KLS granules (corresponding to 25 mg ketoprofen)
|
Placebo
n=35 Participants
Single oral administration of placebo granules
Placebo: 0 mg KLS granules
|
|---|---|---|
|
Time to First Perceptible Relief (TFPR)
|
18.5 minutes
Interval 13.6 to 24.1
|
31.4 minutes
Interval 22.0 to 43.0
|
SECONDARY outcome
Timeframe: Day 1Population: The Intent-to-treat (ITT) population included all randomized patients who received at least one dose of study medication and have at least one post-baseline18 efficacy measurement; one patient in the ketoprofen group had missing data of the pain intensity VAS and such data were not replaced according to rules for LOCF; hence no AUC for this patient was calculated.
TMPR will be measured by stopwatches, a timepiece designed to measure the amount of time that elapses between its activation and deactivation. Upon study drug administration the patients will immediately start a stopwatch, once the patient feels meaningful perceptible pain relief, the stopwatch is stopped. The time between activation and deactivation of a stopwatch defines the outcome measure data.
Outcome measures
| Measure |
OKITASK
n=35 Participants
Single oral administration of Ketoprofen lysine salt 40 mg granules
Ketoprofen: 40 mg KLS granules (corresponding to 25 mg ketoprofen)
|
Placebo
n=35 Participants
Single oral administration of placebo granules
Placebo: 0 mg KLS granules
|
|---|---|---|
|
Time to Meaningful Pain Relief (TMPR)
|
36.9 Minutes
Interval 26.9 to 42.4
|
58.4 Minutes
Interval 41.9 to 129.8
|
SECONDARY outcome
Timeframe: Day 1 at 360' or > 60' in case of early discontinuation.Population: The Intent-to-treat (ITT) population included all randomized patients who received at least one dose of study medication and have at least one post-baseline18 efficacy measurement; one patient in the ketoprofen group had missing data of the pain intensity VAS and such data were not replaced according to rules for LOCF; hence no AUC for this patient was calculated.
The patients were asked to provide their current overall assessment answering the question "Considering all the ways that the pain affects you, how well are you doing? The patients marked the answer on the 5-point scale: 1 = very good, 2 = good, 3= satisfactory, 4 = poor, 5 = very poor. If a patient takes rescue medication, the Patient's overall assessment will be performed after the last VAS assessment.
Outcome measures
| Measure |
OKITASK
n=35 Participants
Single oral administration of Ketoprofen lysine salt 40 mg granules
Ketoprofen: 40 mg KLS granules (corresponding to 25 mg ketoprofen)
|
Placebo
n=35 Participants
Single oral administration of placebo granules
Placebo: 0 mg KLS granules
|
|---|---|---|
|
Number of Participants With an Overall Assessment Score of "Very Good", "Satisfactory", "Poor" or "Very Poor" on a (Patient's Overall Assessment) on a 5-point Scale
Very good
|
6 participants
|
2 participants
|
|
Number of Participants With an Overall Assessment Score of "Very Good", "Satisfactory", "Poor" or "Very Poor" on a (Patient's Overall Assessment) on a 5-point Scale
good
|
22 participants
|
24 participants
|
|
Number of Participants With an Overall Assessment Score of "Very Good", "Satisfactory", "Poor" or "Very Poor" on a (Patient's Overall Assessment) on a 5-point Scale
Satisfactory
|
7 participants
|
9 participants
|
|
Number of Participants With an Overall Assessment Score of "Very Good", "Satisfactory", "Poor" or "Very Poor" on a (Patient's Overall Assessment) on a 5-point Scale
poor
|
0 participants
|
0 participants
|
|
Number of Participants With an Overall Assessment Score of "Very Good", "Satisfactory", "Poor" or "Very Poor" on a (Patient's Overall Assessment) on a 5-point Scale
no data
|
0 participants
|
0 participants
|
Adverse Events
OKITASK®
Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
OKITASK®
n=35 participants at risk
Single oral administration of Ketoprofen lysine salt 40 mg granules
Ketoprofen: 40 mg KLS granules (corresponding to 25 mg ketoprofen)
|
Placebo
n=35 participants at risk
Single oral administration of placebo granules
Placebo: 0 mg KLS granules
|
|---|---|---|
|
Nervous system disorders
Headache
|
0.00%
0/35 • From screening day (-4) to follow up ( day 3 +/- 1), up to day 3 post-dose.
More specifically, adverse events are assessed at: * Screening days (day -4 to day 1) * Baseline ( day 1, pre-dose) * following time post-dose: 0.08h; 0.17h; 0.25h; 0.5h; 0.75h; 1h; 1.5h; 2h; 3h; 4h; 5h; 6h. * day one * follow-up ( day 3 +/- 1)
|
2.9%
1/35 • Number of events 1 • From screening day (-4) to follow up ( day 3 +/- 1), up to day 3 post-dose.
More specifically, adverse events are assessed at: * Screening days (day -4 to day 1) * Baseline ( day 1, pre-dose) * following time post-dose: 0.08h; 0.17h; 0.25h; 0.5h; 0.75h; 1h; 1.5h; 2h; 3h; 4h; 5h; 6h. * day one * follow-up ( day 3 +/- 1)
|
Additional Information
Clinical Development & Operations
Dompé farmaceutici S.p.A.
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place