A Single Dose Study About the Influence of Food on the Oral Bioavailability of Ladarixin Capsule in Healthy Volunteers

Phase 1

Completed

Conditions: no Condition

Interventions: Drug: Ladarixin

Registration Number: NCT04854642

Lead Sponsor: Dompé Farmaceutici S.p.A

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 36

Inclusion Criteria

Informed consent: signed written informed consent before inclusion in the study
Sex and Age: men/women, 18-55 years old inclusive
Body Mass Index: 18.5-30 kg/m2 inclusive
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
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 (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

Electrocardiogram (ECG) 12-leads (supine position): clinically significant abnormalities
Physical findings: clinically significant abnormal physical findings which could interfere with the objectives of the study
Laboratory analyses: clinically significant abnormal laboratory values indicative of physical illness
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
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
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.
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
Blood donation: blood donations for 3 months before this study
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)
SARS-COV2 test: positive SARS-COV2 test on day -3 or -2 of each study period
Virology: positive Hepatitis B (HBs antigen), Hepatitis C (HCV antibodies), HIV 1/2 (HIV Ag/Ab combo) at screening.
Drug test: positive result at the drug test at screening or day -1 of each study period
Alcohol test: positive alcohol breath test at screening or day -1 of each study period
Diet: abnormal diets (<1600 or >3500 kcal/day) or substantial changes in eating habits in the 4 weeks before this study; vegetarians; vegans
Pregnancy (women only): positive or missing pregnancy test at screening or day -1 of each study period, pregnant or lactating women

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
R - T (fasting then fed condition)	Ladarixin	Subjects were assigned to the sequence of treatments RT to receive Ladarixin ini fasting conditions (R treatment) in period 1 and in fed conditions (T treatment) during period 2.
T - R (fed then fasting condition)	Ladarixin	Subjects were assigned to the sequence of treatments TR to receive Ladarixin in fed conditions (T treatment) during period 1 and in fasting conditions (R treatment) in period 2.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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
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
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-∞ 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
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
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
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)
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
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)
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)
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
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 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