Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Cross Research S.A. | INDUSTRY |
Not provided
Not provided
Not provided
Not provided
Objectives:
The objective of the study was to investigate the bioequivalence between two formulations containing ketoprofen lysine salt (KLS) when administered as single oral doses in two consecutive study periods to healthy male and female volunteers under fasting conditions.
Primary end-point: to evaluate the bioequivalent rate (Cmax) and extent (AUC0-t) of absorption of ketoprofen after single dose administration of test and reference products.
Secondary end-points:
This was a single centre, single dose, open, randomised, two-way cross-over, two-stage bioequivalence study. According to the two-stage design of the study, an initial group of subjects was treated in study stage 1 and data were analysed. Since bioequivalence was demonstrated, according to the protocol the study was terminated after stage 1, and stage 2 was not performed.
The study was conducted as planned and consisted of a screening visit, a treatment phase of 2 study periods separated by a wash-out interval of at least 4 days and a final visit / early termination visit (ETV).
Considering the lack of information about the PK profile of the new formulation, it was decided to use a "two stage" bioequivalence study design, that allows a re-calculation of the sample size in case the number of subjects initially enrolled in the study is not large enough to provide a reliable answer to the questions addressed, due to a possible underestimation of the variability or misleading estimation of the point estimate for the test/reference ratio of the geometric means.
The sequence of treatments in the two study periods was assigned to each randomised subject according to a computer generated randomisation list.
A wash-out period of at least 4 days between the two administrations is justified by the elimination half-life of the ketoprofen (1-2 h).
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Test - Reference (KSL 40 mg - OKi® 80 mg) | Experimental | In this arm, a single dose of the test product (1 tablet; 40 mg KLS) was orally administered, under fasting conditions, in the first study period (day 1, 08:00±1h), and, after a wash-out period of at least 4 days, a single dose of the reference product OKi® 80 mg (half a sachet, 40 mg KLS) was orally administered, under fasting conditions, in the second study period (day 1, Visit 5, 08:00 ±1h). |
|
| Reference - Test (OKi® 80 mg - KSL 40 mg) | Experimental | In this arm, a single dose of the reference product OKi® 80 mg (half a sachet, 40 mg KLS) was orally administered, under fasting conditions, in the first study period (day 1, Visit 3, 08:00 ±1h) and, after a wash-out period of at least 4 days, a single dose of the test product (1 tablet; 40 mg KLS) was orally administered, under fasting conditions, in the second study period (day 1, Visit 5, 08:00±1h). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| KSL 40 mg | Drug | Ketoprofen lysine salt (KLS) immediate release oral tablets 40 mg, corresponding to 25 mg of ketoprofen free acid. Ketoprofen lysine salt was administered according to the randomisation list and the cross-over design. One (1) tablet of test formulation was administered to the subjects in the morning with 240 mL of still mineral water. Afterwards, no fluid intake was permitted for 2 h. All subjects were under fasting conditions from the evening before investigational product administration (i.e. for at least 10 h, overnight). |
| Measure | Description | Time Frame |
|---|---|---|
| Ketoprofen Plasma PK Parameters: Cmax | 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. | 0, 1, 2, 3, 4, 5, 6, 7 and 8 hours post-dose |
| Ketoprofen Plasma PK Parameters: AUC0-t | 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. | pre-dose (0), 5, 15, 30, 45 min, 1, 1.5, 2, 3, 4, 5, 6 and 8 h post-dose. |
| Measure | Description | Time Frame |
|---|---|---|
| Ketoprofen Plasma PK Parameters: AUC0-∞ | 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. |
Not provided
Inclusion Criteria:
To be enrolled in this study, subjects must fulfil all these criteria:
Informed consent: signed written informed consent before inclusion in the study
Sex and Age: males/females, 18-55 years old inclusive
Body Mass Index (BMI): 18.5-30 kg/m2 inclusive
Vital signs: systolic blood pressure (SBP) 100-139 mmHg, diastolic blood pressure (DBP) 50-89 mmHg, pulse rate (PR) 50-90 bpm and body temperature (BT) ≤ 37.5° C, measured after 5 min of rest in the sitting position;
Full comprehension: ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to co-operate with the investigator and to comply with the requirements of the entire study
Contraception and fertility (females only): females of child-bearing potential and with an active sexual life must be using at least one of the following reliable methods of contraception:
Female participants of non-child-bearing potential or in post-menopausal status for at least 1 year will be admitted. For all female subjects, pregnancy test result must be negative at screening.
Exclusion Criteria:
Subjects meeting any of these criteria will not be enrolled in the study:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Milko Radicioni, MD | CROSS Research S.A., Phase I Unit | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CROSS Research S.A., Phase I Unit | Arzo | CH-6864 | Switzerland |
Not provided
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.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| FG001 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Treatment Period |
| |||||||||||||
| Washout Period (at Least 4 Days) |
| |||||||||||||
| Second Treatment Period |
|
The 30 randomised subjects completed the study per protocol and were included in the PK and Safety sets.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | All Study 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Ketoprofen Plasma PK Parameters: Cmax | 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. | 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. | Posted | Mean | Standard Deviation | μg/mL | 0, 1, 2, 3, 4, 5, 6, 7 and 8 hours post-dose |
|
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
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | KSL 40 mg | 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. |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dizziness | Nervous system disorders | MedDRA (17.1) | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Development & Operations | Dompé farmaceutici SpA | +39 02 583831 | clinical.trials@dompe.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Apr 22, 2015 | Jul 28, 2022 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 13, 2015 | Jul 28, 2022 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D013001 | Somatoform Disorders |
| D006261 | Headache |
| D014098 | Toothache |
| D009437 | Neuralgia |
| D004412 | Dysmenorrhea |
| ID | Term |
|---|---|
| D001523 | Mental Disorders |
| D010146 | Pain |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
|
| OKi® 80 mg | Drug | 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). Ketoprofen lysine salt was administered according to the randomisation list and the cross-over design. The content of half sachet of the reference formulation was dissolved in 190 mL of still mineral water. The subject drank the entire solution immediately. Then the glass was rinsed with 50 mL of still mineral water and the subject drank the rinse immediately. Afterwards, no fluid intake was permitted for 2 h. All subjects were under fasting conditions from the evening before investigational product administration (i.e. for at least 10 h, overnight). |
|
|
| pre-dose (0), 5, 15, 30, 45 min, 1, 1.5, 2, 3, 4, 5, 6 and 8 h post-dose |
| Ketoprofen Plasma PK Parameters: Tmax | 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. | pre-dose (0), 5, 15, 30, 45 min, 1, 1.5, 2, 3, 4, 5, 6 and 8 h post-dose. |
| Ketoprofen Plasma PK Parameters: T1/2 | 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. | pre-dose (0), 5, 15, 30, 45 min, 1, 1.5, 2, 3, 4, 5, 6 and 8 h post-dose. |
| Ketoprofen Plasma PK Parameters: Frel | Frel = Relative bioavailability, calculated as ratio AUC0-t (test)/ AUC0-t (reference) | 0, 1, 2, 3, 4, 5, 6, 7 and 8 hours post-dose |
| Number of TEAEs | 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. | From Day -14 to Day 1 of period 2 (Final visit/ETV), approximately 1 month |
| NOT COMPLETED |
|
| NOT COMPLETED |
|
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | 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. |
|
|
|
| Primary | Ketoprofen Plasma PK Parameters: AUC0-t | 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. | 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. | Posted | Mean | Standard Deviation | h*μg/mL | pre-dose (0), 5, 15, 30, 45 min, 1, 1.5, 2, 3, 4, 5, 6 and 8 h post-dose. |
|
|
|
|
| Secondary | Ketoprofen Plasma PK Parameters: AUC0-∞ | 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. | 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. | Posted | Mean | Standard Deviation | h*μg/mL | pre-dose (0), 5, 15, 30, 45 min, 1, 1.5, 2, 3, 4, 5, 6 and 8 h post-dose |
|
|
|
|
| Secondary | Ketoprofen Plasma PK Parameters: Tmax | 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. | 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. | Posted | Mean | Standard Deviation | h | pre-dose (0), 5, 15, 30, 45 min, 1, 1.5, 2, 3, 4, 5, 6 and 8 h post-dose. |
|
|
|
|
| Secondary | Ketoprofen Plasma PK Parameters: T1/2 | 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. | 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. | Posted | Mean | Standard Deviation | h | pre-dose (0), 5, 15, 30, 45 min, 1, 1.5, 2, 3, 4, 5, 6 and 8 h post-dose. |
|
|
|
| Secondary | Ketoprofen Plasma PK Parameters: Frel | Frel = Relative bioavailability, calculated as ratio AUC0-t (test)/ AUC0-t (reference) | 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. | Posted | Mean | Standard Deviation | % of bioavailability | 0, 1, 2, 3, 4, 5, 6, 7 and 8 hours post-dose |
|
|
|
| Secondary | Number of TEAEs | 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. | Safety Set: all subjects who received at least one dose of investigational medicinal product. | Posted | Number | number of events | From Day -14 to Day 1 of period 2 (Final visit/ETV), approximately 1 month |
|
|
|
| 0 |
| 30 |
| 0 |
| 30 |
| 1 |
| 30 |
| EG001 | OKi® 80 mg | 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. | 0 | 30 | 0 | 30 | 2 | 30 |
| Headache | Nervous system disorders | MedDRA (17.1) | Systematic Assessment |
|
Not provided
Not provided
| D013568 |
| Pathological Conditions, Signs and Symptoms |
| D014076 | Tooth Diseases |
| D009057 | Stomatognathic Diseases |
| D005157 | Facial Pain |
| D010523 | Peripheral Nervous System Diseases |
| D009468 | Neuromuscular Diseases |
| D009422 | Nervous System Diseases |
| D008599 | Menstruation Disturbances |
| D010335 | Pathologic Processes |
| D017699 | Pelvic Pain |
| mild |
|
| moderate |
|
| severe |
|
| TEAE leading to discontinuation |
|
| serious TEAE |
|