no Condition
Conditions
Brief summary
Primary objective: \- to investigate the effect of food on the bioavailability of DF 2156Y after single dose administration of 400 mg of ladarixin to healthy male and female volunteers under fed and fasting conditions. Secondary objectives: * to investigate the effect of gender on the bioavailability of DF 2156Y and its metabolites (DF 2108Y and DF 2227Y) after single dose administration of 400 mg of ladarixin to healthy male and female volunteers * to evaluate safety and tolerability of a single dose administration of ladarixin 400 mg to healthy male and female volunteers.
Detailed description
This is a Single center, single dose, open label, randomized, two-way, crossover, food effect on bioavailability study. More precisely, a single oral dose of 400 mg of ladarixin (two 200 mg capsules) was administered to healthy male and female volunteers under fed (Test treatment) and fasting (Reference treatment) conditions in two consecutive study periods, according to a two-way crossover design, with a wash-out interval of at least 14 days between the two administrations.
Interventions
DRUGLadarixin
A single oral dose of 400 mg of ladarixin (two 200 mg capsules) was administered to healthy male and female volunteers under fed (Test treatment) and fasting (Reference treatment) conditions in two consecutive study periods, according to a two-way crossover design, with a wash-out interval of at least 14 days between the two administrations.
Sponsors
Dompé Farmaceutici S.p.A
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Masking description
This is an open-label trial. No masking procedure will be applied since an open-label design was considered adequate for evaluating objective measures such as pharmacokinetic parameters.
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Informed consent: signed written informed consent before inclusion in the study 2. Sex and Age: men/women, 18-55 years old inclusive 3. Body Mass Index: 18.5-30 kg/m2 inclusive 4. Vital signs: systolic blood pressure 100-139 mmHg, diastolic blood pressure 50-89 mmHg, pulse rate 50-90 bpm and body temperature 35.5-37.5° C, measured after 5 min at rest in the sitting position 5. 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 6. Contraception and fertility (women only): women of child-bearing potential must not wish to get pregnant within 30 days after the end of the study and must be using at least one of the following reliable methods of contraception: 1. Hormonal oral, implantable, transdermal, or injectable contraceptives for at least 2 months before the screening visit until 30 days after final visit 2. A non-hormonal intrauterine device or female condom with spermicide or contraceptive sponge with spermicide or diaphragm with spermicide or cervical cap with spermicide for at least 2 months before the screening visit until 30 days after final visit 3. A male sexual partner who agrees to use a male condom with spermicide until 30 days after final visit 4. A sterile sexual partner Women participants of non-childbearing potential or in post-menopausal status for at least one year will be admitted. For all women, pregnancy test result must be negative at screening and day -1.
Exclusion criteria
1. Electrocardiogram (ECG) 12-leads (supine position): clinically significant abnormalities 2. Physical findings: clinically significant abnormal physical findings which could interfere with the objectives of the study 3. Laboratory analyses: clinically significant abnormal laboratory values indicative of physical illness 4. Allergy: ascertained or presumptive hypersensitivity to the active principles (ladarixin or derivatives) and/or formulations' ingredients; known hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs); history of hypersensitivity to drugs (in particular methanesulfonyl propanamide) or allergic reactions in general, which the Investigator considers may affect the outcome of the study 5. Diseases: hypoalbuminemia or significant history of renal, hepatic, gastrointestinal, respiratory, skin, hematological, endocrine, neurological or cardiovascular diseases that may interfere with the aim of the study 6. Medications: medications, including over the counter drugs (in particular nonsteroidal anti-inflammatory drugs), herbal remedies and food supplements taken 14 days before the start of the study (in any case at least 5 times the half-life of the drug or a minimum of 14 days, whichever is longer), with the exception of paracetamol. Hormonal contraceptives and hormonal replacement therapy for women will be allowed. 7. Investigative drug studies: participation in the evaluation of any investigational product for 3 months before this study. The 3-month interval is calculated as the time between the first calendar day of the month that follows the last visit of the previous study and the first day of the present study 8. Blood donation: blood donations for 3 months before this study 9. Drug, alcohol, caffeine, tobacco: history of drug, alcohol (\>1 drink/day for women and \>2 drinks/day for men, defined according to the USDA Dietary Guidelines 2015-2020), caffeine (\>5 cups coffee/tea/day) or tobacco abuse (≥10 cigarettes/day) 10. SARS-COV2 test: positive SARS-COV2 test on day -3 or -2 of each study period 11. Virology: positive Hepatitis B (HBs antigen), Hepatitis C (HCV antibodies), HIV 1/2 (HIV Ag/Ab combo) at screening. 12. Drug test: positive result at the drug test at screening or day -1 of each study period 13. Alcohol test: positive alcohol breath test at screening or day -1 of each study period 14. Diet: abnormal diets (\<1600 or \>3500 kcal/day) or substantial changes in eating habits in the 4 weeks before this study; vegetarians; vegans 15. Pregnancy (women only): positive or missing pregnancy test at screening or day -1 of each study period, pregnant or lactating women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax of Plasma DF 2156Y | At day 1 (15 min, 30 min, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 and 18 hours postdose); at days 2 and 3 (24, 30, 36, 48, 54 and 60 hours post-dose); at day 4 (72 hours post-dose) | PK parameters were assessed after single dose administration of 400 mg of ladarixin under fed and fasting conditions. Cmax = maximum plasma concentration |
| AUC0-t of Plasma DF 2156Y | At day 1 (15 min, 30 min, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 and 18 hours postdose); at days 2 and 3 (24, 30, 36, 48, 54 and 60 hours post-dose); at day 4 (72 hours post-dose) | PK parameters were assessed after single dose administration of 400 mg of ladarixin under fed and fasting conditions. AUC0-t = area under the concentration-time curve (AUC) from zero to the last quantifiable concentrations |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| t1/2 of Plasma DF 2156Y | At day 1 (15 min, 30 min, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 and 18 hours postdose); at days 2 and 3 (24, 30, 36, 48, 54 and 60 hours post-dose); at day 4 (72 hours post-dose) | PK parameters were assessed after single dose administration of 400 mg of ladarixin under fed and fasting conditions. t1/2 = half life, is the time required for a quantity to reduce to half of its initial value |
| Lambda-zeta of Plasma DF 2156Y | At day 1 (15 min, 30 min, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 and 18 hours postdose); at days 2 and 3 (24, 30, 36, 48, 54 and 60 hours post-dose); at day 4 (72 hours post-dose) | PK parameters were assessed after single dose administration of 400 mg of ladarixin under fed and fasting conditions. lambda-zeta is the Individual estimate of the terminal elimination rate constant, calculated using log-linear regression of the terminal portions of the plasma concentration-versus-time curves |
| Frel of Plasma DF 2156Y | At day 1 (15 min, 30 min, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 and 18 hours postdose); at days 2 and 3 (24, 30, 36, 48, 54 and 60 hours post-dose); at day 4 (72 hours post-dose) | PK parameters were assessed after single dose administration of 400 mg of ladarixin under fed and fasting conditions. Frel: Relative bioavailability, calculated as ratio AUC0-t (T)/ AUC0-t (R) (multiplicated by 100) |
| Cmax of Plasma DF 2108Y (DF 2156Y Metabolite) | At day 1 (15 min, 30 min, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 and 18 hours postdose); at days 2 and 3 (24, 30, 36, 48, 54 and 60 hours post-dose); at day 4 (72 hours post-dose) | PK parameters were assessed after single dose of 400 mg of ladarixin under fed and fasting conditions. Cmax = maximum plasma concentration |
| AUC0-t of Plasma DF 2108Y (DF 2156Y Metabolite) | At day 1 (15 min, 30 min, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 and 18 hours postdose); at days 2 and 3 (24, 30, 36, 48, 54 and 60 hours post-dose); at day 4 (72 hours post-dose) | PK parameters were assessed after single dose of 400 mg of ladarixin under fed and fasting conditions. AUC0-t = area under the concentration-time curve (AUC) from zero to the last quantifiable concentrations |
| AUC0-∞ of Plasma DF 2108Y (DF 2156Y Metabolite) | At day 1 (15 min, 30 min, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 and 18 hours postdose); at days 2 and 3 (24, 30, 36, 48, 54 and 60 hours post-dose); at day 4 (72 hours post-dose) | PK parameters were assessed after single dose of 400 mg of ladarixin under fed and fasting conditions. AUC0-∞ = area under the concentration-time curve (AUC) from zero to infinity |
| Tmax of Plasma DF 2108Y (DF 2156Y Metabolite) | At day 1 (15 min, 30 min, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 and 18 hours postdose); at days 2 and 3 (24, 30, 36, 48, 54 and 60 hours post-dose); at day 4 (72 hours post-dose) | PK parameters were assessed after single dose of 400 mg of ladarixin under fed and fasting conditions. tmax = time to maximum plasma concentration |
| AUC0-∞ of Plasma DF 2156Y | At day 1 (15 min, 30 min, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 and 18 hours postdose); at days 2 and 3 (24, 30, 36, 48, 54 and 60 hours post-dose); at day 4 (72 hours post-dose) | PK parameters were assessed after single dose administration of 400 mg of ladarixin under fed and fasting conditions: AUC0-∞ = area under the concentration-time curve (AUC) from zero to infinity |
| Lambda-zeta of Plasma DF2108Y (DF 2156Y Metabolite) | At day 1 (15 min, 30 min, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 and 18 hours postdose); at days 2 and 3 (24, 30, 36, 48, 54 and 60 hours post-dose); at day 4 (72 hours post-dose) | PK parameters were assessed after single dose administration of 400 mg of ladarixin under fed and fasting conditions. Lambda-zeta is the individual estimate of the terminal elimination rate constant, calculated using log-linear regression of the terminal portions of the plasma concentration-versus-time curves. |
| Frel of Plasma DF2108Y (DF 2156Y Metabolite) | At day 1 (15 min, 30 min, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 and 18 hours postdose); at days 2 and 3 (24, 30, 36, 48, 54 and 60 hours post-dose); at day 4 (72 hours post-dose) | PK parameters were assessed after single dose administration of 400 mg of ladarixin under fed and fasting conditions. Frel: Relative bioavailability, calculated as ratio AUC0-t (T)/ AUC0-t (R) (multiplicated by 100) |
| Cmax of Plasma DF2227Y (DF 2156Y Metabolite) | At day 1 (15 min, 30 min, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 and 18 hours postdose); at days 2 and 3 (24, 30, 36, 48, 54 and 60 hours post-dose); at day 4 (72 hours post-dose) | PK parameters were assessed after single dose of 400 mg of ladarixin under fed and fasting conditions. Cmax = maximum plasma concentration |
| AUC0-t of Plasma DF2227Y (DF 2156Y Metabolite) | At day 1 (15 min, 30 min, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 and 18 hours postdose); at days 2 and 3 (24, 30, 36, 48, 54 and 60 hours post-dose); at day 4 (72 hours post-dose) | PK parameters were assessed after single dose of 400 mg of ladarixin under fed and fasting conditions. AUC0-t = area under the concentration-time curve (AUC) from zero to the last quantifiable concentrations |
| Tmax of Plasma DF2227Y (DF 2156Y Metabolite) | At day 1 (15 min, 30 min, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 and 18 hours postdose); at days 2 and 3 (24, 30, 36, 48, 54 and 60 hours post-dose); at day 4 (72 hours post-dose) | PK parameters were assessed after single dose of 400 mg of ladarixin under fed and fasting conditions. tmax = time to maximum plasma concentration |
| Frel of Plasma DF222Y (DF 2156Y Metabolite) | At day 1 (15 min, 30 min, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 and 18 hours postdose); at days 2 and 3 (24, 30, 36, 48, 54 and 60 hours post-dose); at day 4 (72 hours post-dose) | PK parameters were assessed after single dose administration of 400 mg of ladarixin under fed and fasting conditions. Frel: Relative bioavailability, calculated as ratio AUC0-t (T)/ AUC0-t (R) (multiplicated by 100) |
| t1/2 of Plasma DF 2108Y (DF 2156Y Metabolite) | At day 1 (15 min, 30 min, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 and 18 hours postdose); at days 2 and 3 (24, 30, 36, 48, 54 and 60 hours post-dose); at day 4 (72 hours post-dose) | PK parameters were assessed after single dose of 400 mg of ladarixin under fed and fasting conditions. t1/2 = half life, is the time required for a quantity to reduce to half of its initial value |
| Tmax of Plasma DF 2156Y | At day 1 (15 min, 30 min, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 and 18 hours postdose); at days 2 and 3 (24, 30, 36, 48, 54 and 60 hours post-dose); at day 4 (72 hours post-dose) | PK parameters were assessed after single dose administration of 400 mg of ladarixin under fed and fasting conditions. tmax = time to maximum plasma concentration |
Countries
Switzerland
Participant flow
Recruitment details
Thirty-six (36) subjects were enrolled in the study, as planned, and 32 of them completed the study as per protocol.
Participants by arm
| Arm | Count |
|---|---|
| Enrolled and Safety Set, PK Set 1 and PK Set 2 Demographics are reported for the enrolled set (N=36), which has the same number of participants of the safety set, the PK set 1, and the PK set 2. | 36 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Enrolled and Safety Set, PK Set 1 and PK Set 2 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 36 Participants |
| Age, Continuous | 36.0 years STANDARD_DEVIATION 11.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 35 Participants |
| Region of Enrollment Switzerland | 36 participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 33 | 0 / 35 |
| other Total, other adverse events | 4 / 33 | 4 / 35 |
| serious Total, serious adverse events | 0 / 33 | 0 / 35 |
Outcome results
Primary
AUC0-t of Plasma DF 2156Y
PK parameters were assessed after single dose administration of 400 mg of ladarixin under fed and fasting conditions. AUC0-t = area under the concentration-time curve (AUC) from zero to the last quantifiable concentrations
Time frame: At day 1 (15 min, 30 min, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 and 18 hours postdose); at days 2 and 3 (24, 30, 36, 48, 54 and 60 hours post-dose); at day 4 (72 hours post-dose)
Population: PK set 1: all subjects randomised who fulfilled the study protocol requirements in terms of IMP intake and had evaluable PK data readouts for DF 2156Y with no major deviations that could affect the PK results. This analysis set was used for the statistical analysis of the PK results for DF 2156Y.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ladarixin Fed (T) | AUC0-t of Plasma DF 2156Y | 1422.500 h*μg/mL | Standard Deviation 362.265 |
| Ladarixin Fasting (R) | AUC0-t of Plasma DF 2156Y | 1564.189 h*μg/mL | Standard Deviation 364.099 |
p-value: 0.01790% CI: [85.3, 96.93]ANOVA
Primary
Cmax of Plasma DF 2156Y
PK parameters were assessed after single dose administration of 400 mg of ladarixin under fed and fasting conditions. Cmax = maximum plasma concentration
Time frame: At day 1 (15 min, 30 min, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 and 18 hours postdose); at days 2 and 3 (24, 30, 36, 48, 54 and 60 hours post-dose); at day 4 (72 hours post-dose)
Population: PK set 1: all subjects randomised who fulfilled the study protocol requirements in terms of IMP intake and had evaluable PK data readouts for DF 2156Y with no major deviations that could affect the PK results. This analysis set was used for the statistical analysis of the PK results for DF 2156Y.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ladarixin Fed (T) | Cmax of Plasma DF 2156Y | 67.345 μg/mL | Standard Deviation 11.426 |
| Ladarixin Fasting (R) | Cmax of Plasma DF 2156Y | 95.982 μg/mL | Standard Deviation 14.257 |
p-value: <0.000190% CI: [68.13, 75.29]ANOVA
Secondary
AUC0-∞ of Plasma DF 2108Y (DF 2156Y Metabolite)
PK parameters were assessed after single dose of 400 mg of ladarixin under fed and fasting conditions. AUC0-∞ = area under the concentration-time curve (AUC) from zero to infinity
Time frame: At day 1 (15 min, 30 min, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 and 18 hours postdose); at days 2 and 3 (24, 30, 36, 48, 54 and 60 hours post-dose); at day 4 (72 hours post-dose)
Population: PK set 2: all subjects randomised who fulfilled the study protocol requirements in terms of IMP intake and had evaluable PK data readouts for DF 2108Y and DF 2227Y, with no major deviations that could affect the PK results. This analysis set was used for the statistical analysis of the PK results for DF 2108Y and DF 2227Y.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ladarixin Fed (T) | AUC0-∞ of Plasma DF 2108Y (DF 2156Y Metabolite) | 78.549 h*μg/mL | Standard Deviation 48.921 |
| Ladarixin Fasting (R) | AUC0-∞ of Plasma DF 2108Y (DF 2156Y Metabolite) | 77.220 h*μg/mL | Standard Deviation 29.818 |
Secondary
AUC0-∞ of Plasma DF 2156Y
PK parameters were assessed after single dose administration of 400 mg of ladarixin under fed and fasting conditions: AUC0-∞ = area under the concentration-time curve (AUC) from zero to infinity
Time frame: At day 1 (15 min, 30 min, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 and 18 hours postdose); at days 2 and 3 (24, 30, 36, 48, 54 and 60 hours post-dose); at day 4 (72 hours post-dose)
Population: PK set 1: all subjects randomised who fulfilled the study protocol requirements in terms of IMP intake and had evaluable PK data readouts for DF 2156Y with no major deviations that could affect the PK results. This analysis set was used for the statistical analysis of the PK results for DF 2156Y.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ladarixin Fed (T) | AUC0-∞ of Plasma DF 2156Y | 1533.432 h*μg/mL | Standard Deviation 442.119 |
| Ladarixin Fasting (R) | AUC0-∞ of Plasma DF 2156Y | 1677.749 h*μg/mL | Standard Deviation 434.421 |
p-value: 0.021390% CI: [85.04, 97.16]ANOVA
Secondary
AUC0-t of Plasma DF 2108Y (DF 2156Y Metabolite)
PK parameters were assessed after single dose of 400 mg of ladarixin under fed and fasting conditions. AUC0-t = area under the concentration-time curve (AUC) from zero to the last quantifiable concentrations
Time frame: At day 1 (15 min, 30 min, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 and 18 hours postdose); at days 2 and 3 (24, 30, 36, 48, 54 and 60 hours post-dose); at day 4 (72 hours post-dose)
Population: PK set 2: all subjects randomised who fulfilled the study protocol requirements in terms of IMP intake and had evaluable PK data readouts for DF 2108Y and DF 2227Y, with no major deviations that could affect the PK results. This analysis set was used for the statistical analysis of the PK results for DF 2108Y and DF 2227Y.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ladarixin Fed (T) | AUC0-t of Plasma DF 2108Y (DF 2156Y Metabolite) | 47.013 (h*μg/mL | Standard Deviation 13.822 |
| Ladarixin Fasting (R) | AUC0-t of Plasma DF 2108Y (DF 2156Y Metabolite) | 50.462 (h*μg/mL | Standard Deviation 11.636 |
Secondary
AUC0-t of Plasma DF2227Y (DF 2156Y Metabolite)
PK parameters were assessed after single dose of 400 mg of ladarixin under fed and fasting conditions. AUC0-t = area under the concentration-time curve (AUC) from zero to the last quantifiable concentrations
Time frame: At day 1 (15 min, 30 min, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 and 18 hours postdose); at days 2 and 3 (24, 30, 36, 48, 54 and 60 hours post-dose); at day 4 (72 hours post-dose)
Population: PK set 2: all subjects randomised who fulfilled the study protocol requirements in terms of IMP intake and had evaluable PK data readouts for DF 2108Y and DF 2227Y, with no major deviations that could affect the PK results. This analysis set was used for the statistical analysis of the PK results for DF 2108Y and DF 2227Y.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ladarixin Fed (T) | AUC0-t of Plasma DF2227Y (DF 2156Y Metabolite) | 52.928 h*μg/mL | Standard Deviation 10.877 |
| Ladarixin Fasting (R) | AUC0-t of Plasma DF2227Y (DF 2156Y Metabolite) | 58.465 h*μg/mL | Standard Deviation 10.884 |
Secondary
Cmax of Plasma DF 2108Y (DF 2156Y Metabolite)
PK parameters were assessed after single dose of 400 mg of ladarixin under fed and fasting conditions. Cmax = maximum plasma concentration
Time frame: At day 1 (15 min, 30 min, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 and 18 hours postdose); at days 2 and 3 (24, 30, 36, 48, 54 and 60 hours post-dose); at day 4 (72 hours post-dose)
Population: PK set 2: all subjects randomised who fulfilled the study protocol requirements in terms of IMP intake and had evaluable PK data readouts for DF 2108Y and DF 2227Y, with no major deviations that could affect the PK results. This analysis set was used for the statistical analysis of the PK results for DF 2108Y and DF 2227Y.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ladarixin Fed (T) | Cmax of Plasma DF 2108Y (DF 2156Y Metabolite) | 0.940 μg/mL | Standard Deviation 0.292 |
| Ladarixin Fasting (R) | Cmax of Plasma DF 2108Y (DF 2156Y Metabolite) | 0.972 μg/mL | Standard Deviation 0.21 |
Secondary
Cmax of Plasma DF2227Y (DF 2156Y Metabolite)
PK parameters were assessed after single dose of 400 mg of ladarixin under fed and fasting conditions. Cmax = maximum plasma concentration
Time frame: At day 1 (15 min, 30 min, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 and 18 hours postdose); at days 2 and 3 (24, 30, 36, 48, 54 and 60 hours post-dose); at day 4 (72 hours post-dose)
Population: PK set 2: all subjects randomised who fulfilled the study protocol requirements in terms of IMP intake and had evaluable PK data readouts for DF 2108Y and DF 2227Y, with no major deviations that could affect the PK results. This analysis set was used for the statistical analysis of the PK results for DF 2108Y and DF 2227Y.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ladarixin Fed (T) | Cmax of Plasma DF2227Y (DF 2156Y Metabolite) | 0.882 μg/mL | Standard Deviation 0.195 |
| Ladarixin Fasting (R) | Cmax of Plasma DF2227Y (DF 2156Y Metabolite) | 0.964 μg/mL | Standard Deviation 0.192 |
Secondary
Frel of Plasma DF2108Y (DF 2156Y Metabolite)
PK parameters were assessed after single dose administration of 400 mg of ladarixin under fed and fasting conditions. Frel: Relative bioavailability, calculated as ratio AUC0-t (T)/ AUC0-t (R) (multiplicated by 100)
Time frame: At day 1 (15 min, 30 min, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 and 18 hours postdose); at days 2 and 3 (24, 30, 36, 48, 54 and 60 hours post-dose); at day 4 (72 hours post-dose)
Population: PK sets 1 and 2 : PK set 1: all subjects randomised who fulfilled the study protocol requirements in terms of IMP intake and had evaluable PK data readouts for DF 2156Y with no major deviations that could affect the PK results.~PK set 2: all subjects randomised who fulfilled the study protocol requirements in terms of IMP intake and had evaluable PK data readouts for DF 2108Y and DF 2227Y, with no major deviations that could affect the PK results.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ladarixin Fed (T) | Frel of Plasma DF2108Y (DF 2156Y Metabolite) | 95.569 percentage of bioavailability | Standard Deviation 20.352 |
Secondary
Frel of Plasma DF 2156Y
PK parameters were assessed after single dose administration of 400 mg of ladarixin under fed and fasting conditions. Frel: Relative bioavailability, calculated as ratio AUC0-t (T)/ AUC0-t (R) (multiplicated by 100)
Time frame: At day 1 (15 min, 30 min, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 and 18 hours postdose); at days 2 and 3 (24, 30, 36, 48, 54 and 60 hours post-dose); at day 4 (72 hours post-dose)
Population: PK sets 1 and 2 : PK set 1: all subjects randomised who fulfilled the study protocol requirements in terms of IMP intake and had evaluable PK data readouts for DF 2156Y with no major deviations that could affect the PK results.~PK set 2: all subjects randomised who fulfilled the study protocol requirements in terms of IMP intake and had evaluable PK data readouts for DF 2108Y and DF 2227Y, with no major deviations that could affect the PK results.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ladarixin Fed (T) | Frel of Plasma DF 2156Y | 93.721 percentage of bioavailability | Standard Deviation 21.605 |
Secondary
Frel of Plasma DF222Y (DF 2156Y Metabolite)
PK parameters were assessed after single dose administration of 400 mg of ladarixin under fed and fasting conditions. Frel: Relative bioavailability, calculated as ratio AUC0-t (T)/ AUC0-t (R) (multiplicated by 100)
Time frame: At day 1 (15 min, 30 min, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 and 18 hours postdose); at days 2 and 3 (24, 30, 36, 48, 54 and 60 hours post-dose); at day 4 (72 hours post-dose)
Population: PK sets 1 and 2 : PK set 1: all subjects randomised who fulfilled the study protocol requirements in terms of IMP intake and had evaluable PK data readouts for DF 2156Y with no major deviations that could affect the PK results.~PK set 2: all subjects randomised who fulfilled the study protocol requirements in terms of IMP intake and had evaluable PK data readouts for DF 2108Y and DF 2227Y, with no major deviations that could affect the PK results.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ladarixin Fed (T) | Frel of Plasma DF222Y (DF 2156Y Metabolite) | 92.745 percentage of bioavailability | Standard Deviation 13.34 |
Secondary
Lambda-zeta of Plasma DF2108Y (DF 2156Y Metabolite)
PK parameters were assessed after single dose administration of 400 mg of ladarixin under fed and fasting conditions. Lambda-zeta is the individual estimate of the terminal elimination rate constant, calculated using log-linear regression of the terminal portions of the plasma concentration-versus-time curves.
Time frame: At day 1 (15 min, 30 min, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 and 18 hours postdose); at days 2 and 3 (24, 30, 36, 48, 54 and 60 hours post-dose); at day 4 (72 hours post-dose)
Population: PK set 2: all subjects randomised who fulfilled the study protocol requirements in terms of IMP intake and had evaluable PK data readouts for DF 2108Y and DF 2227Y, with no major deviations that could affect the PK results. This analysis set was used for the statistical analysis of the PK results for DF 2108Y and DF 2227Y.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ladarixin Fed (T) | Lambda-zeta of Plasma DF2108Y (DF 2156Y Metabolite) | 0.022 1/h | Standard Deviation 0.01 |
| Ladarixin Fasting (R) | Lambda-zeta of Plasma DF2108Y (DF 2156Y Metabolite) | 0.023 1/h | Standard Deviation 0.01 |
Secondary
Lambda-zeta of Plasma DF 2156Y
PK parameters were assessed after single dose administration of 400 mg of ladarixin under fed and fasting conditions. lambda-zeta is the Individual estimate of the terminal elimination rate constant, calculated using log-linear regression of the terminal portions of the plasma concentration-versus-time curves
Time frame: At day 1 (15 min, 30 min, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 and 18 hours postdose); at days 2 and 3 (24, 30, 36, 48, 54 and 60 hours post-dose); at day 4 (72 hours post-dose)
Population: PK set 1: all subjects randomised who fulfilled the study protocol requirements in terms of IMP intake and had evaluable PK data readouts for DF 2156Y with no major deviations that could affect the PK results. This analysis set was used for the statistical analysis of the PK results for DF 2156Y.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ladarixin Fed (T) | Lambda-zeta of Plasma DF 2156Y | 0.046 1/h | Standard Deviation 0.015 |
| Ladarixin Fasting (R) | Lambda-zeta of Plasma DF 2156Y | 0.045 1/h | Standard Deviation 0.015 |
Secondary
t1/2 of Plasma DF 2108Y (DF 2156Y Metabolite)
PK parameters were assessed after single dose of 400 mg of ladarixin under fed and fasting conditions. t1/2 = half life, is the time required for a quantity to reduce to half of its initial value
Time frame: At day 1 (15 min, 30 min, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 and 18 hours postdose); at days 2 and 3 (24, 30, 36, 48, 54 and 60 hours post-dose); at day 4 (72 hours post-dose)
Population: PK set 2: all subjects randomised who fulfilled the study protocol requirements in terms of IMP intake and had evaluable PK data readouts for DF 2108Y and DF 2227Y, with no major deviations that could affect the PK results. This analysis set was used for the statistical analysis of the PK results for DF 2108Y and DF 2227Y.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ladarixin Fed (T) | t1/2 of Plasma DF 2108Y (DF 2156Y Metabolite) | 40.637 h | Standard Deviation 28.192 |
| Ladarixin Fasting (R) | t1/2 of Plasma DF 2108Y (DF 2156Y Metabolite) | 36.444 h | Standard Deviation 16.315 |
Secondary
t1/2 of Plasma DF 2156Y
PK parameters were assessed after single dose administration of 400 mg of ladarixin under fed and fasting conditions. t1/2 = half life, is the time required for a quantity to reduce to half of its initial value
Time frame: At day 1 (15 min, 30 min, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 and 18 hours postdose); at days 2 and 3 (24, 30, 36, 48, 54 and 60 hours post-dose); at day 4 (72 hours post-dose)
Population: PK set 1: all subjects randomised who fulfilled the study protocol requirements in terms of IMP intake and had evaluable PK data readouts for DF 2156Y with no major deviations that could affect the PK results. This analysis set was used for the statistical analysis of the PK results for DF 2156Y.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ladarixin Fed (T) | t1/2 of Plasma DF 2156Y | 16.918 h | Standard Deviation 5.797 |
| Ladarixin Fasting (R) | t1/2 of Plasma DF 2156Y | 17.087 h | Standard Deviation 5.349 |
Secondary
Tmax of Plasma DF 2108Y (DF 2156Y Metabolite)
PK parameters were assessed after single dose of 400 mg of ladarixin under fed and fasting conditions. tmax = time to maximum plasma concentration
Time frame: At day 1 (15 min, 30 min, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 and 18 hours postdose); at days 2 and 3 (24, 30, 36, 48, 54 and 60 hours post-dose); at day 4 (72 hours post-dose)
Population: PK set 2: all subjects randomised who fulfilled the study protocol requirements in terms of IMP intake and had evaluable PK data readouts for DF 2108Y and DF 2227Y, with no major deviations that could affect the PK results. This analysis set was used for the statistical analysis of the PK results for DF 2108Y and DF 2227Y.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ladarixin Fed (T) | Tmax of Plasma DF 2108Y (DF 2156Y Metabolite) | 28.364 h | Standard Deviation 5.667 |
| Ladarixin Fasting (R) | Tmax of Plasma DF 2108Y (DF 2156Y Metabolite) | 24.343 h | Standard Deviation 9.474 |
Secondary
Tmax of Plasma DF 2156Y
PK parameters were assessed after single dose administration of 400 mg of ladarixin under fed and fasting conditions. tmax = time to maximum plasma concentration
Time frame: At day 1 (15 min, 30 min, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 and 18 hours postdose); at days 2 and 3 (24, 30, 36, 48, 54 and 60 hours post-dose); at day 4 (72 hours post-dose)
Population: PK set 1: all subjects randomised who fulfilled the study protocol requirements in terms of IMP intake and had evaluable PK data readouts for DF 2156Y with no major deviations that could affect the PK results. This analysis set was used for the statistical analysis of the PK results for DF 2156Y.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ladarixin Fed (T) | Tmax of Plasma DF 2156Y | 5.485 h | Standard Deviation 0.939 |
| Ladarixin Fasting (R) | Tmax of Plasma DF 2156Y | 1.914 h | Standard Deviation 1.197 |
p-value: <0.0001Wilcoxon (Mann-Whitney)
Secondary
Tmax of Plasma DF2227Y (DF 2156Y Metabolite)
PK parameters were assessed after single dose of 400 mg of ladarixin under fed and fasting conditions. tmax = time to maximum plasma concentration
Time frame: At day 1 (15 min, 30 min, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 and 18 hours postdose); at days 2 and 3 (24, 30, 36, 48, 54 and 60 hours post-dose); at day 4 (72 hours post-dose)
Population: PK set 2: all subjects randomised who fulfilled the study protocol requirements in terms of IMP intake and had evaluable PK data readouts for DF 2108Y and DF 2227Y, with no major deviations that could affect the PK results. This analysis set was used for the statistical analysis of the PK results for DF 2108Y and DF 2227Y
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ladarixin Fed (T) | Tmax of Plasma DF2227Y (DF 2156Y Metabolite) | 36.606 hours | Standard Deviation 19.349 |
| Ladarixin Fasting (R) | Tmax of Plasma DF2227Y (DF 2156Y Metabolite) | 31.657 hours | Standard Deviation 23.849 |