Trial Outcomes & Findings for Crossover, Single Dose Randomized, Bioequivalence of Ketoprofen Lysine Salt Immediate Release vs Oral Solution (NCT NCT02350296)
NCT ID: NCT02350296
Last Updated: 2024-04-19
Results Overview
Cmax = maximum plasma concentration. Cmax a of ketoprofen was calculated from plasma concentrations after single oral dose of test and reference products. Plasma concentrations of ketoprofen were measured in each study period at the timepoints hereunder reported. Arithmetic means + standard deviation are reported hereunder.
COMPLETED
PHASE1
30 participants
0, 1, 2, 3, 4, 5, 6, 7 and 8 hours post-dose
2024-04-19
Participant Flow
30 healthy volunteers were randomized, receiving a single dose of Test and Reference treatment. Based on the cross-over design, a single dose of product was given orally in one of the two possible sequences: in the "test-reference" arm, subjects received Ketoprofen lysine salt (KLS) firstly and then the reference product OKI. In the "Reference-Test" arm, subjects received reference product OKi first, then Ketoprofen lysine salt (KLS)"). A wash-out interval separated the 2 treatment periods.
Participant milestones
| Measure |
Sequence "Test - Reference"
Participants first received a single dose of Ketoprofen lysine salt (KLS, Test product)), 40 mg immediate release tablets (corresponding to 25 mg ketoprofen) under fasting conditions (day 1). After a washout interval of at least 4 days, the participants then received a single dose of the reference product OKi®, KLS 40 mg granules for oral solution, always under fasting conditions (day 1). This according to the study randomised cross-over design.
There were no premature discontinuations during the study
|
Sequence "Reference - Test"
Participants first received a single dose of the reference product OKi®, KLS 40 mg granules for oral solution, under fasting conditions (day 1). After a washout interval of at least 4 days, the participants then received a single dose of Ketoprofen lysine salt (KLS, Test product)), 40 mg immediate release tablets (corresponding to 25 mg ketoprofen) always under fasting conditions (day 1).This according to the study randomized cross-over design.
|
|---|---|---|
|
First Treatment Period
STARTED
|
15
|
15
|
|
First Treatment Period
COMPLETED
|
15
|
15
|
|
First Treatment Period
NOT COMPLETED
|
0
|
0
|
|
Washout Period (at Least 4 Days)
STARTED
|
15
|
15
|
|
Washout Period (at Least 4 Days)
COMPLETED
|
15
|
15
|
|
Washout Period (at Least 4 Days)
NOT COMPLETED
|
0
|
0
|
|
Second Treatment Period
STARTED
|
15
|
15
|
|
Second Treatment Period
COMPLETED
|
15
|
15
|
|
Second Treatment Period
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Crossover, Single Dose Randomized, Bioequivalence of Ketoprofen Lysine Salt Immediate Release vs Oral Solution
Baseline characteristics by cohort
| Measure |
All Study Participants
n=30 Participants
Enrolled Set: all enrolled subjects. This analysis set was used for the analysis of demographic, baseline and background characteristics.
Safety Set: all subjects who received at least one dose of investigational medicinal product.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
30 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
38.7 years
STANDARD_DEVIATION 8.2 • n=5 Participants
|
|
Sex: Female, Male
Female
|
15 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
15 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
30 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
Switzerland
|
30 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 0, 1, 2, 3, 4, 5, 6, 7 and 8 hours post-dosePopulation: PK set: all randomised subjects who fulfilled the study protocol requirements in terms of investigational medicinal products intake and have evaluable PK data readouts for the planned treatment comparisons, with no major deviations that could affect the PK results.
Cmax = maximum plasma concentration. Cmax a of ketoprofen was calculated from plasma concentrations after single oral dose of test and reference products. Plasma concentrations of ketoprofen were measured in each study period at the timepoints hereunder reported. Arithmetic means + standard deviation are reported hereunder.
Outcome measures
| Measure |
KSL 40 mg (Test Product)
n=30 Participants
Ketoprofen lysine salt (KLS) immediate release tablets 40 mg, corresponding to 25 mg of ketoprofen free acid. A single dose of the test product (1 tablet; 40 mg KLS) was orally administered, under fasting conditions, in one of the two consecutive study periods (day 1, 08:00±1h), according to the study randomised cross-over design.
KSL 40 mg: Ketoprofen lysine salt oral immediate release tablets 40 mg. The two single dose administrations (test and reference) in the two study periods were separated by a wash-out interval of at least 4 days.
|
OKi® 80 mg (Reference Product)
n=30 Participants
OKi® 80 mg granules for oral solution (bipartite sachets: each half sachet containing 40 mg of KLS corresponding to 25 mg of ketoprofen free acid). A single dose of the reference product (half a sachet, 40 mg KLS) was orally administered, under fasting conditions, in one of the two consecutive study periods (day 1, 08:00 ±1h), according to the study randomised cross-over design.
OKi® 80 mg: Ketoprofen lysine salt granules for oral solution 40 mg (half of a bipartite sachet).The two single dose administrations (reference and test) in the two study periods were separated by a wash-out interval of at least 4 days.
|
|---|---|---|
|
Ketoprofen Plasma PK Parameters: Cmax
|
3.61 μg/mL
Standard Deviation 1.17
|
3.40 μg/mL
Standard Deviation 1.38
|
PRIMARY outcome
Timeframe: pre-dose (0), 5, 15, 30, 45 min, 1, 1.5, 2, 3, 4, 5, 6 and 8 h post-dose.Population: PK set: all randomised subjects who fulfilled the study protocol requirements in terms of investigational medicinal products intake and have evaluable PK data readouts for the planned treatment comparisons, with no major deviations that could affect the PK results.
AUC0-t = Area under the concentration-time curve from administration to the last observed concentration time t, calculated with the linear trapezoidal method. AUC0-t of ketoprofen was calculated from plasma concentrations after single oral dose of test and reference products. Plasma concentrations of ketoprofen were measured in each study period at the timepoints hereunder specified. Please note that AUC0-t was considered a reliable estimate of the extent of absorption if the ratio AUC0-t/AUC0-∞ equalled or exceeded a factor of 0.8, i.e. if %AUCextra was \< 20%. Arithmetic means + standard deviation are reported hereunder.
Outcome measures
| Measure |
KSL 40 mg (Test Product)
n=30 Participants
Ketoprofen lysine salt (KLS) immediate release tablets 40 mg, corresponding to 25 mg of ketoprofen free acid. A single dose of the test product (1 tablet; 40 mg KLS) was orally administered, under fasting conditions, in one of the two consecutive study periods (day 1, 08:00±1h), according to the study randomised cross-over design.
KSL 40 mg: Ketoprofen lysine salt oral immediate release tablets 40 mg. The two single dose administrations (test and reference) in the two study periods were separated by a wash-out interval of at least 4 days.
|
OKi® 80 mg (Reference Product)
n=30 Participants
OKi® 80 mg granules for oral solution (bipartite sachets: each half sachet containing 40 mg of KLS corresponding to 25 mg of ketoprofen free acid). A single dose of the reference product (half a sachet, 40 mg KLS) was orally administered, under fasting conditions, in one of the two consecutive study periods (day 1, 08:00 ±1h), according to the study randomised cross-over design.
OKi® 80 mg: Ketoprofen lysine salt granules for oral solution 40 mg (half of a bipartite sachet).The two single dose administrations (reference and test) in the two study periods were separated by a wash-out interval of at least 4 days.
|
|---|---|---|
|
Ketoprofen Plasma PK Parameters: AUC0-t
|
4.53 h*μg/mL
Standard Deviation 1.35
|
4.12 h*μg/mL
Standard Deviation 1.35
|
SECONDARY outcome
Timeframe: pre-dose (0), 5, 15, 30, 45 min, 1, 1.5, 2, 3, 4, 5, 6 and 8 h post-dosePopulation: PK set: all randomised subjects who fulfilled the study protocol requirements in terms of investigational medicinal products intake and have evaluable PK data readouts for the planned treatment comparisons, with no major deviations that could affect the PK results.
AUC0-∞ = Area under the concentration-time curve extrapolated to infinity, calculated, if feasible, as AUC0-t + Ct/λz, where Ct is the last measurable drug concentration. AUC0-∞ of ketoprofen was calculated from plasma concentrations after single oral dose of test and reference products. Plasma concentrations of ketoprofen were measured in each study period at the timepoints hereunder reported. Arithmetic means + standard deviation are reported hereunder.
Outcome measures
| Measure |
KSL 40 mg (Test Product)
n=30 Participants
Ketoprofen lysine salt (KLS) immediate release tablets 40 mg, corresponding to 25 mg of ketoprofen free acid. A single dose of the test product (1 tablet; 40 mg KLS) was orally administered, under fasting conditions, in one of the two consecutive study periods (day 1, 08:00±1h), according to the study randomised cross-over design.
KSL 40 mg: Ketoprofen lysine salt oral immediate release tablets 40 mg. The two single dose administrations (test and reference) in the two study periods were separated by a wash-out interval of at least 4 days.
|
OKi® 80 mg (Reference Product)
n=30 Participants
OKi® 80 mg granules for oral solution (bipartite sachets: each half sachet containing 40 mg of KLS corresponding to 25 mg of ketoprofen free acid). A single dose of the reference product (half a sachet, 40 mg KLS) was orally administered, under fasting conditions, in one of the two consecutive study periods (day 1, 08:00 ±1h), according to the study randomised cross-over design.
OKi® 80 mg: Ketoprofen lysine salt granules for oral solution 40 mg (half of a bipartite sachet).The two single dose administrations (reference and test) in the two study periods were separated by a wash-out interval of at least 4 days.
|
|---|---|---|
|
Ketoprofen Plasma PK Parameters: AUC0-∞
|
4.64 h*μg/mL
Standard Deviation 1.40
|
4.22 h*μg/mL
Standard Deviation 1.39
|
SECONDARY outcome
Timeframe: pre-dose (0), 5, 15, 30, 45 min, 1, 1.5, 2, 3, 4, 5, 6 and 8 h post-dose.Population: PK set: all randomised subjects who fulfilled the study protocol requirements in terms of investigational medicinal products intake and have evaluable PK data readouts for the planned treatment comparisons, with no major deviations that could affect the PK results.
Tmax = Time to achieve Cmax. Tmax (0-8 hours) of ketoprofen calculated from plasma concentrations after single oral dose of test and reference. Plasma concentrations of ketoprofen were measured in each study period at the following timepoints: pre-dose (0), 5, 15, 30, 45 min, 1, 1.5, 2, 3, 4, 5, 6 and 8 h post-dose.
Outcome measures
| Measure |
KSL 40 mg (Test Product)
n=30 Participants
Ketoprofen lysine salt (KLS) immediate release tablets 40 mg, corresponding to 25 mg of ketoprofen free acid. A single dose of the test product (1 tablet; 40 mg KLS) was orally administered, under fasting conditions, in one of the two consecutive study periods (day 1, 08:00±1h), according to the study randomised cross-over design.
KSL 40 mg: Ketoprofen lysine salt oral immediate release tablets 40 mg. The two single dose administrations (test and reference) in the two study periods were separated by a wash-out interval of at least 4 days.
|
OKi® 80 mg (Reference Product)
n=30 Participants
OKi® 80 mg granules for oral solution (bipartite sachets: each half sachet containing 40 mg of KLS corresponding to 25 mg of ketoprofen free acid). A single dose of the reference product (half a sachet, 40 mg KLS) was orally administered, under fasting conditions, in one of the two consecutive study periods (day 1, 08:00 ±1h), according to the study randomised cross-over design.
OKi® 80 mg: Ketoprofen lysine salt granules for oral solution 40 mg (half of a bipartite sachet).The two single dose administrations (reference and test) in the two study periods were separated by a wash-out interval of at least 4 days.
|
|---|---|---|
|
Ketoprofen Plasma PK Parameters: Tmax
|
0.39 h
Standard Deviation 0.19
|
0.30 h
Standard Deviation 0.10
|
SECONDARY outcome
Timeframe: pre-dose (0), 5, 15, 30, 45 min, 1, 1.5, 2, 3, 4, 5, 6 and 8 h post-dose.Population: PK set: all randomised subjects who fulfilled the study protocol requirements in terms of investigational medicinal products intake and have evaluable PK data readouts for the planned treatment comparisons, with no major deviations that could affect the PK results.
T1/2 = Half-life, calculated, if feasible, as ln2/λz. T1/2 (0-8 hours) of ketoprofen was calculated from plasma concentrations after single oral dose of test and reference. Plasma concentrations of ketoprofen were measured in each study period at the following timepoints: pre-dose (0), 5, 15, 30, 45 min, 1, 1.5, 2, 3, 4, 5, 6 and 8 h post-dose.
Outcome measures
| Measure |
KSL 40 mg (Test Product)
n=30 Participants
Ketoprofen lysine salt (KLS) immediate release tablets 40 mg, corresponding to 25 mg of ketoprofen free acid. A single dose of the test product (1 tablet; 40 mg KLS) was orally administered, under fasting conditions, in one of the two consecutive study periods (day 1, 08:00±1h), according to the study randomised cross-over design.
KSL 40 mg: Ketoprofen lysine salt oral immediate release tablets 40 mg. The two single dose administrations (test and reference) in the two study periods were separated by a wash-out interval of at least 4 days.
|
OKi® 80 mg (Reference Product)
n=30 Participants
OKi® 80 mg granules for oral solution (bipartite sachets: each half sachet containing 40 mg of KLS corresponding to 25 mg of ketoprofen free acid). A single dose of the reference product (half a sachet, 40 mg KLS) was orally administered, under fasting conditions, in one of the two consecutive study periods (day 1, 08:00 ±1h), according to the study randomised cross-over design.
OKi® 80 mg: Ketoprofen lysine salt granules for oral solution 40 mg (half of a bipartite sachet).The two single dose administrations (reference and test) in the two study periods were separated by a wash-out interval of at least 4 days.
|
|---|---|---|
|
Ketoprofen Plasma PK Parameters: T1/2
|
1.64 h
Standard Deviation 0.17
|
1.64 h
Standard Deviation 0.17
|
SECONDARY outcome
Timeframe: 0, 1, 2, 3, 4, 5, 6, 7 and 8 hours post-dosePopulation: PK set: all randomised subjects who fulfilled the study protocol requirements in terms of investigational medicinal products intake and have evaluable PK data readouts for the planned treatment comparisons, with no major deviations that could affect the PK results.
Frel = Relative bioavailability, calculated as ratio AUC0-t (test)/ AUC0-t (reference)
Outcome measures
| Measure |
KSL 40 mg (Test Product)
n=30 Participants
Ketoprofen lysine salt (KLS) immediate release tablets 40 mg, corresponding to 25 mg of ketoprofen free acid. A single dose of the test product (1 tablet; 40 mg KLS) was orally administered, under fasting conditions, in one of the two consecutive study periods (day 1, 08:00±1h), according to the study randomised cross-over design.
KSL 40 mg: Ketoprofen lysine salt oral immediate release tablets 40 mg. The two single dose administrations (test and reference) in the two study periods were separated by a wash-out interval of at least 4 days.
|
OKi® 80 mg (Reference Product)
OKi® 80 mg granules for oral solution (bipartite sachets: each half sachet containing 40 mg of KLS corresponding to 25 mg of ketoprofen free acid). A single dose of the reference product (half a sachet, 40 mg KLS) was orally administered, under fasting conditions, in one of the two consecutive study periods (day 1, 08:00 ±1h), according to the study randomised cross-over design.
OKi® 80 mg: Ketoprofen lysine salt granules for oral solution 40 mg (half of a bipartite sachet).The two single dose administrations (reference and test) in the two study periods were separated by a wash-out interval of at least 4 days.
|
|---|---|---|
|
Ketoprofen Plasma PK Parameters: Frel
|
112.07 % of bioavailability
Standard Deviation 18.70
|
—
|
SECONDARY outcome
Timeframe: From Day -14 to Day 1 of period 2 (Final visit/ETV), approximately 1 monthPopulation: Safety Set: all subjects who received at least one dose of investigational medicinal product.
TEAE = Treatment Emergent Adverse Events. TEAEs were assessed throughout the study, from informed consent up to the final visit / early termination visit (ETV), which takes place after visit 5 on day 1 of period 2, more precisely after the 8 h blood sampling and vital signs check.
Outcome measures
| Measure |
KSL 40 mg (Test Product)
n=30 Participants
Ketoprofen lysine salt (KLS) immediate release tablets 40 mg, corresponding to 25 mg of ketoprofen free acid. A single dose of the test product (1 tablet; 40 mg KLS) was orally administered, under fasting conditions, in one of the two consecutive study periods (day 1, 08:00±1h), according to the study randomised cross-over design.
KSL 40 mg: Ketoprofen lysine salt oral immediate release tablets 40 mg. The two single dose administrations (test and reference) in the two study periods were separated by a wash-out interval of at least 4 days.
|
OKi® 80 mg (Reference Product)
n=30 Participants
OKi® 80 mg granules for oral solution (bipartite sachets: each half sachet containing 40 mg of KLS corresponding to 25 mg of ketoprofen free acid). A single dose of the reference product (half a sachet, 40 mg KLS) was orally administered, under fasting conditions, in one of the two consecutive study periods (day 1, 08:00 ±1h), according to the study randomised cross-over design.
OKi® 80 mg: Ketoprofen lysine salt granules for oral solution 40 mg (half of a bipartite sachet).The two single dose administrations (reference and test) in the two study periods were separated by a wash-out interval of at least 4 days.
|
|---|---|---|
|
Number of TEAEs
TEAE related to treatment
|
1 number of events
|
2 number of events
|
|
Number of TEAEs
mild
|
1 number of events
|
2 number of events
|
|
Number of TEAEs
serious TEAE
|
0 number of events
|
0 number of events
|
|
Number of TEAEs
TEAE not related to treatment
|
0 number of events
|
0 number of events
|
|
Number of TEAEs
moderate
|
0 number of events
|
0 number of events
|
|
Number of TEAEs
severe
|
0 number of events
|
0 number of events
|
|
Number of TEAEs
TEAE leading to discontinuation
|
0 number of events
|
0 number of events
|
Adverse Events
KSL 40 mg
OKi® 80 mg
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
KSL 40 mg
n=30 participants at risk
Ketoprofen lysine salt (KLS) immediate release tablets 40 mg, corresponding to 25 mg of ketoprofen free acid. A single dose of the test product (1 tablet; 40 mg KLS) was orally administered, under fasting conditions, in one of the two consecutive study periods (day 1, 08:00±1h), according to the study randomised cross-over design.
KSL 40 mg: Ketoprofen lysine salt oral immediate release tablets 40 mg. The two single dose administrations (test and reference) in the two study periods were separated by a wash-out interval of at least 4 days.
|
OKi® 80 mg
n=30 participants at risk
OKi® 80 mg granules for oral solution (bipartite sachets: each half sachet containing 40 mg of KLS corresponding to 25 mg of ketoprofen free acid). A single dose of the reference product (half a sachet, 40 mg KLS) was orally administered, under fasting conditions, in one of the two consecutive study periods (day 1, 08:00 ±1h), according to the study randomised cross-over design.
OKi® 80 mg: Ketoprofen lysine salt granules for oral solution 40 mg (half of a bipartite sachet).The two single dose administrations (reference and test) in the two study periods were separated by a wash-out interval of at least 4 days.
|
|---|---|---|
|
Nervous system disorders
Dizziness
|
3.3%
1/30 • Number of events 1 • TEAEs were assessed throughout the study, from informed consent up to the final visit / early termination visit (ETV), which takes place after visit 5 on day 1 of period 2, more precisely after the 8 h blood sampling and vital signs check. From Day -14 to Day 1 of period 2 (Final visit/ETV), approximately 1 month.
More specifically, adverse events are assessed at: Visit 1: days -14/-2 Visit 2: day -1 Visit 3: day 1 Visit 4: Day -1 Visit 5: day 1 From Period 1 to Period 2 : wash-out period of at least 4 days
|
3.3%
1/30 • Number of events 1 • TEAEs were assessed throughout the study, from informed consent up to the final visit / early termination visit (ETV), which takes place after visit 5 on day 1 of period 2, more precisely after the 8 h blood sampling and vital signs check. From Day -14 to Day 1 of period 2 (Final visit/ETV), approximately 1 month.
More specifically, adverse events are assessed at: Visit 1: days -14/-2 Visit 2: day -1 Visit 3: day 1 Visit 4: Day -1 Visit 5: day 1 From Period 1 to Period 2 : wash-out period of at least 4 days
|
|
Nervous system disorders
Headache
|
0.00%
0/30 • TEAEs were assessed throughout the study, from informed consent up to the final visit / early termination visit (ETV), which takes place after visit 5 on day 1 of period 2, more precisely after the 8 h blood sampling and vital signs check. From Day -14 to Day 1 of period 2 (Final visit/ETV), approximately 1 month.
More specifically, adverse events are assessed at: Visit 1: days -14/-2 Visit 2: day -1 Visit 3: day 1 Visit 4: Day -1 Visit 5: day 1 From Period 1 to Period 2 : wash-out period of at least 4 days
|
3.3%
1/30 • Number of events 1 • TEAEs were assessed throughout the study, from informed consent up to the final visit / early termination visit (ETV), which takes place after visit 5 on day 1 of period 2, more precisely after the 8 h blood sampling and vital signs check. From Day -14 to Day 1 of period 2 (Final visit/ETV), approximately 1 month.
More specifically, adverse events are assessed at: Visit 1: days -14/-2 Visit 2: day -1 Visit 3: day 1 Visit 4: Day -1 Visit 5: day 1 From Period 1 to Period 2 : wash-out period of at least 4 days
|
Additional Information
Clinical Development & Operations
Dompé farmaceutici SpA
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place