Trial Outcomes & Findings for A Single Dose Study About the Influence of Food on the Oral Bioavailability of Ladarixin Capsule in Healthy Volunteers (NCT NCT04854642)

NCT ID: NCT04854642

Last Updated: 2024-01-17

Results Overview

PK parameters were assessed after single dose administration of 400 mg of ladarixin under fed and fasting conditions. Cmax = maximum plasma concentration

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 36 participants
• Primary outcome timeframe: 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)
• Results posted on: 2024-01-17

Participant Flow

Thirty-six (36) subjects were enrolled in the study, as planned, and 32 of them completed the study as per protocol.

Participant milestones

Measure	T - R (Fed Then Fasting Condition) 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. 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.	R - T (Fasting Then Fed Condition) 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. 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.
Overall Study STARTED	18	18
Overall Study Safety Set	18	18
Overall Study PK Set 1	18	18
Overall Study PK Set 2	18	18
Overall Study COMPLETED	17	15
Overall Study NOT COMPLETED	1	3

Reasons for withdrawal

Measure	T - R (Fed Then Fasting Condition) 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. 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.	R - T (Fasting Then Fed Condition) 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. 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.
Overall Study Adverse Event	1	2
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Enrolled and Safety Set, PK Set 1 and PK Set 2 n=36 Participants 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".
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	36 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	36.0 years STANDARD_DEVIATION 11.6 • n=5 Participants
Sex: Female, Male Female	18 Participants n=5 Participants
Sex: Female, Male Male	18 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	1 Participants n=5 Participants
Race (NIH/OMB) White	35 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	36 participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

PK parameters were assessed after single dose administration of 400 mg of ladarixin under fed and fasting conditions.

Cmax = maximum plasma concentration

Outcome measures

Measure	Ladarixin Fed (T) n=33 Participants Ladarixin - Fed Condition: 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) condition.	Ladarixin Fasting (R) n=35 Participants Ladarixin - Fasting condition: A single oral dose of 400 mg of ladarixin (two 200 mg capsules) was administered to healthy male and female volunteers under fasting (Reference treatment) condition.
Cmax of Plasma DF 2156Y	67.345 μg/mL Standard Deviation 11.426	95.982 μg/mL Standard Deviation 14.257

PRIMARY outcome

Timeframe: 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.

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

Outcome measures

Measure	Ladarixin Fed (T) n=33 Participants Ladarixin - Fed Condition: 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) condition.	Ladarixin Fasting (R) n=35 Participants Ladarixin - Fasting condition: A single oral dose of 400 mg of ladarixin (two 200 mg capsules) was administered to healthy male and female volunteers under fasting (Reference treatment) condition.
AUC0-t of Plasma DF 2156Y	1422.500 h*μg/mL Standard Deviation 362.265	1564.189 h*μg/mL Standard Deviation 364.099

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Measure	Ladarixin Fed (T) n=33 Participants Ladarixin - Fed Condition: 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) condition.	Ladarixin Fasting (R) n=35 Participants Ladarixin - Fasting condition: A single oral dose of 400 mg of ladarixin (two 200 mg capsules) was administered to healthy male and female volunteers under fasting (Reference treatment) condition.
AUC0-∞ of Plasma DF 2156Y	1533.432 h*μg/mL Standard Deviation 442.119	1677.749 h*μg/mL Standard Deviation 434.421

SECONDARY outcome

Timeframe: 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.

PK parameters were assessed after single dose administration of 400 mg of ladarixin under fed and fasting conditions.

tmax = time to maximum plasma concentration

Outcome measures

Measure	Ladarixin Fed (T) n=33 Participants Ladarixin - Fed Condition: 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) condition.	Ladarixin Fasting (R) n=35 Participants Ladarixin - Fasting condition: A single oral dose of 400 mg of ladarixin (two 200 mg capsules) was administered to healthy male and female volunteers under fasting (Reference treatment) condition.
Tmax of Plasma DF 2156Y	5.485 h Standard Deviation 0.939	1.914 h Standard Deviation 1.197

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Measure	Ladarixin Fed (T) n=33 Participants Ladarixin - Fed Condition: 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) condition.	Ladarixin Fasting (R) n=35 Participants Ladarixin - Fasting condition: A single oral dose of 400 mg of ladarixin (two 200 mg capsules) was administered to healthy male and female volunteers under fasting (Reference treatment) condition.
t1/2 of Plasma DF 2156Y	16.918 h Standard Deviation 5.797	17.087 h Standard Deviation 5.349

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Measure	Ladarixin Fed (T) n=33 Participants Ladarixin - Fed Condition: 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) condition.	Ladarixin Fasting (R) n=35 Participants Ladarixin - Fasting condition: A single oral dose of 400 mg of ladarixin (two 200 mg capsules) was administered to healthy male and female volunteers under fasting (Reference treatment) condition.
Lambda-zeta of Plasma DF 2156Y	0.046 1/h Standard Deviation 0.015	0.045 1/h Standard Deviation 0.015

SECONDARY outcome

Timeframe: 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.

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)

Outcome measures

Measure	Ladarixin Fed (T) n=32 Participants Ladarixin - Fed Condition: 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) condition.	Ladarixin Fasting (R) Ladarixin - Fasting condition: A single oral dose of 400 mg of ladarixin (two 200 mg capsules) was administered to healthy male and female volunteers under fasting (Reference treatment) condition.
Frel of Plasma DF 2156Y	93.721 percentage of bioavailability Standard Deviation 21.605	—

SECONDARY outcome

Timeframe: 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.

PK parameters were assessed after single dose of 400 mg of ladarixin under fed and fasting conditions.

Cmax = maximum plasma concentration

Outcome measures

Measure	Ladarixin Fed (T) n=33 Participants Ladarixin - Fed Condition: 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) condition.	Ladarixin Fasting (R) n=35 Participants Ladarixin - Fasting condition: A single oral dose of 400 mg of ladarixin (two 200 mg capsules) was administered to healthy male and female volunteers under fasting (Reference treatment) condition.
Cmax of Plasma DF 2108Y (DF 2156Y Metabolite)	0.940 μg/mL Standard Deviation 0.292	0.972 μg/mL Standard Deviation 0.210

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Measure	Ladarixin Fed (T) n=33 Participants Ladarixin - Fed Condition: 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) condition.	Ladarixin Fasting (R) n=35 Participants Ladarixin - Fasting condition: A single oral dose of 400 mg of ladarixin (two 200 mg capsules) was administered to healthy male and female volunteers under fasting (Reference treatment) condition.
AUC0-t of Plasma DF 2108Y (DF 2156Y Metabolite)	47.013 (h*μg/mL Standard Deviation 13.822	50.462 (h*μg/mL Standard Deviation 11.636

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Measure	Ladarixin Fed (T) n=33 Participants Ladarixin - Fed Condition: 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) condition.	Ladarixin Fasting (R) n=35 Participants Ladarixin - Fasting condition: A single oral dose of 400 mg of ladarixin (two 200 mg capsules) was administered to healthy male and female volunteers under fasting (Reference treatment) condition.
AUC0-∞ of Plasma DF 2108Y (DF 2156Y Metabolite)	78.549 h*μg/mL Standard Deviation 48.921	77.220 h*μg/mL Standard Deviation 29.818

SECONDARY outcome

Timeframe: 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.

PK parameters were assessed after single dose of 400 mg of ladarixin under fed and fasting conditions.

tmax = time to maximum plasma concentration

Outcome measures

Measure	Ladarixin Fed (T) n=33 Participants Ladarixin - Fed Condition: 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) condition.	Ladarixin Fasting (R) n=35 Participants Ladarixin - Fasting condition: A single oral dose of 400 mg of ladarixin (two 200 mg capsules) was administered to healthy male and female volunteers under fasting (Reference treatment) condition.
Tmax of Plasma DF 2108Y (DF 2156Y Metabolite)	28.364 h Standard Deviation 5.667	24.343 h Standard Deviation 9.474

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Measure	Ladarixin Fed (T) n=33 Participants Ladarixin - Fed Condition: 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) condition.	Ladarixin Fasting (R) n=35 Participants Ladarixin - Fasting condition: A single oral dose of 400 mg of ladarixin (two 200 mg capsules) was administered to healthy male and female volunteers under fasting (Reference treatment) condition.
t1/2 of Plasma DF 2108Y (DF 2156Y Metabolite)	40.637 h Standard Deviation 28.192	36.444 h Standard Deviation 16.315

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Ladarixin Fed (T) n=33 Participants Ladarixin - Fed Condition: 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) condition.	Ladarixin Fasting (R) n=35 Participants Ladarixin - Fasting condition: A single oral dose of 400 mg of ladarixin (two 200 mg capsules) was administered to healthy male and female volunteers under fasting (Reference treatment) condition.
Lambda-zeta of Plasma DF2108Y (DF 2156Y Metabolite)	0.022 1/h Standard Deviation 0.010	0.023 1/h Standard Deviation 0.010

SECONDARY outcome

Timeframe: 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.

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)

Outcome measures

Measure	Ladarixin Fed (T) n=32 Participants Ladarixin - Fed Condition: 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) condition.	Ladarixin Fasting (R) Ladarixin - Fasting condition: A single oral dose of 400 mg of ladarixin (two 200 mg capsules) was administered to healthy male and female volunteers under fasting (Reference treatment) condition.
Frel of Plasma DF2108Y (DF 2156Y Metabolite)	95.569 percentage of bioavailability Standard Deviation 20.352	—

SECONDARY outcome

Timeframe: 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.

PK parameters were assessed after single dose of 400 mg of ladarixin under fed and fasting conditions.

Cmax = maximum plasma concentration

Outcome measures

Measure	Ladarixin Fed (T) n=33 Participants Ladarixin - Fed Condition: 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) condition.	Ladarixin Fasting (R) n=35 Participants Ladarixin - Fasting condition: A single oral dose of 400 mg of ladarixin (two 200 mg capsules) was administered to healthy male and female volunteers under fasting (Reference treatment) condition.
Cmax of Plasma DF2227Y (DF 2156Y Metabolite)	0.882 μg/mL Standard Deviation 0.195	0.964 μg/mL Standard Deviation 0.192

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Measure	Ladarixin Fed (T) n=33 Participants Ladarixin - Fed Condition: 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) condition.	Ladarixin Fasting (R) n=35 Participants Ladarixin - Fasting condition: A single oral dose of 400 mg of ladarixin (two 200 mg capsules) was administered to healthy male and female volunteers under fasting (Reference treatment) condition.
AUC0-t of Plasma DF2227Y (DF 2156Y Metabolite)	52.928 h*μg/mL Standard Deviation 10.877	58.465 h*μg/mL Standard Deviation 10.884

SECONDARY outcome

Timeframe: 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

PK parameters were assessed after single dose of 400 mg of ladarixin under fed and fasting conditions.

tmax = time to maximum plasma concentration

Outcome measures

Measure	Ladarixin Fed (T) n=33 Participants Ladarixin - Fed Condition: 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) condition.	Ladarixin Fasting (R) n=35 Participants Ladarixin - Fasting condition: A single oral dose of 400 mg of ladarixin (two 200 mg capsules) was administered to healthy male and female volunteers under fasting (Reference treatment) condition.
Tmax of Plasma DF2227Y (DF 2156Y Metabolite)	36.606 hours Standard Deviation 19.349	31.657 hours Standard Deviation 23.849

SECONDARY outcome

Timeframe: 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.

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)

Outcome measures

Measure	Ladarixin Fed (T) n=32 Participants Ladarixin - Fed Condition: 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) condition.	Ladarixin Fasting (R) Ladarixin - Fasting condition: A single oral dose of 400 mg of ladarixin (two 200 mg capsules) was administered to healthy male and female volunteers under fasting (Reference treatment) condition.
Frel of Plasma DF222Y (DF 2156Y Metabolite)	92.745 percentage of bioavailability Standard Deviation 13.340	—

Adverse Events

Ladarixin Fed (T)

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Ladarixin Fasting (R)

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Ladarixin Fed (T) n=33 participants at risk Ladarixin - Fed Conditions: 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) conditions.	Ladarixin Fasting (R) n=35 participants at risk Ladarixin - Fasting conditions: A single oral dose of 400 mg of ladarixin (two 200 mg capsules) was administered to healthy male and female volunteers under fasting (Reference treatment) conditions.
Nervous system disorders Headache	3.0% 1/33 • Number of events 1 • Throughout the study, from screening to final visit /ETV (at day 4 of period 2 or early termination up to 22 days) The TEAE were calculated based on the safety set. The Safety set consists of all subjects who received at least one dose of study treatments. This analysis set was used for the safety and tolerability analyses.	8.6% 3/35 • Number of events 3 • Throughout the study, from screening to final visit /ETV (at day 4 of period 2 or early termination up to 22 days) The TEAE were calculated based on the safety set. The Safety set consists of all subjects who received at least one dose of study treatments. This analysis set was used for the safety and tolerability analyses.
Nervous system disorders Presyncope	6.1% 2/33 • Number of events 2 • Throughout the study, from screening to final visit /ETV (at day 4 of period 2 or early termination up to 22 days) The TEAE were calculated based on the safety set. The Safety set consists of all subjects who received at least one dose of study treatments. This analysis set was used for the safety and tolerability analyses.	0.00% 0/35 • Throughout the study, from screening to final visit /ETV (at day 4 of period 2 or early termination up to 22 days) The TEAE were calculated based on the safety set. The Safety set consists of all subjects who received at least one dose of study treatments. This analysis set was used for the safety and tolerability analyses.
Gastrointestinal disorders Nausea	0.00% 0/33 • Throughout the study, from screening to final visit /ETV (at day 4 of period 2 or early termination up to 22 days) The TEAE were calculated based on the safety set. The Safety set consists of all subjects who received at least one dose of study treatments. This analysis set was used for the safety and tolerability analyses.	8.6% 3/35 • Number of events 3 • Throughout the study, from screening to final visit /ETV (at day 4 of period 2 or early termination up to 22 days) The TEAE were calculated based on the safety set. The Safety set consists of all subjects who received at least one dose of study treatments. This analysis set was used for the safety and tolerability analyses.
Gastrointestinal disorders Toothache	3.0% 1/33 • Number of events 2 • Throughout the study, from screening to final visit /ETV (at day 4 of period 2 or early termination up to 22 days) The TEAE were calculated based on the safety set. The Safety set consists of all subjects who received at least one dose of study treatments. This analysis set was used for the safety and tolerability analyses.	0.00% 0/35 • Throughout the study, from screening to final visit /ETV (at day 4 of period 2 or early termination up to 22 days) The TEAE were calculated based on the safety set. The Safety set consists of all subjects who received at least one dose of study treatments. This analysis set was used for the safety and tolerability analyses.
Gastrointestinal disorders Vomiting	0.00% 0/33 • Throughout the study, from screening to final visit /ETV (at day 4 of period 2 or early termination up to 22 days) The TEAE were calculated based on the safety set. The Safety set consists of all subjects who received at least one dose of study treatments. This analysis set was used for the safety and tolerability analyses.	2.9% 1/35 • Number of events 1 • Throughout the study, from screening to final visit /ETV (at day 4 of period 2 or early termination up to 22 days) The TEAE were calculated based on the safety set. The Safety set consists of all subjects who received at least one dose of study treatments. This analysis set was used for the safety and tolerability analyses.
Investigations SARS-CoV-2 test positive	0.00% 0/33 • Throughout the study, from screening to final visit /ETV (at day 4 of period 2 or early termination up to 22 days) The TEAE were calculated based on the safety set. The Safety set consists of all subjects who received at least one dose of study treatments. This analysis set was used for the safety and tolerability analyses.	2.9% 1/35 • Number of events 1 • Throughout the study, from screening to final visit /ETV (at day 4 of period 2 or early termination up to 22 days) The TEAE were calculated based on the safety set. The Safety set consists of all subjects who received at least one dose of study treatments. This analysis set was used for the safety and tolerability analyses.
Musculoskeletal and connective tissue disorders Neck pain	3.0% 1/33 • Number of events 1 • Throughout the study, from screening to final visit /ETV (at day 4 of period 2 or early termination up to 22 days) The TEAE were calculated based on the safety set. The Safety set consists of all subjects who received at least one dose of study treatments. This analysis set was used for the safety and tolerability analyses.	0.00% 0/35 • Throughout the study, from screening to final visit /ETV (at day 4 of period 2 or early termination up to 22 days) The TEAE were calculated based on the safety set. The Safety set consists of all subjects who received at least one dose of study treatments. This analysis set was used for the safety and tolerability analyses.

Additional Information

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Email: clinical.trials@dompe.com

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• Principal investigator is a sponsor employee
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