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

no Condition Clinical Trial

Official title:

Influence of Food on the Oral Bioavailability of Ladarixin 200 mg Capsule in Healthy Volunteers of Both Sexes. A Single Dose (400 mg), Randomized, Open Label, Two-Way Crossover Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04854642
• Other study ID #: LDX0219
• Status: Completed
• Phase: Phase 1
• Start date: October 20, 2020
• Est. completion date: December 9, 2020

Study information

• Verified date: December 2023
• Source: Dompé Farmaceutici S.p.A
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: December 9, 2020
• Est. primary completion date: December 9, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• no Condition

Intervention

Drug:
• Ladarixin
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.

Locations

Country	Name	City	State
Switzerland	CROSS Research S.A., I Unit	Arzo	Canton Ticino

Sponsors (1)

Lead Sponsor	Collaborator
Dompé Farmaceutici S.p.A

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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	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)
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	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)
Secondary	AUC0-8 of Plasma DF 2156Y	PK parameters were assessed after single dose administration of 400 mg of ladarixin under fed and fasting conditions: AUC0-8 = area under the concentration-time curve (AUC) from zero to infinity	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)
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	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)
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	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)
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	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)
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)	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)
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	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)
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	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)
Secondary	AUC0-8 of Plasma DF 2108Y (DF 2156Y Metabolite)	PK parameters were assessed after single dose of 400 mg of ladarixin under fed and fasting conditions.; AUC0-8 = area under the concentration-time curve (AUC) from zero to infinity	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)
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	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)
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	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)
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.	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)
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)	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)
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	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)
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	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)
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	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)
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)	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)