Trial Outcomes & Findings for Ascending Dose Tolerability Trial and PK Assessment in Healthy Volunteers After Single & Multiple Oral Intake of DF2755A (NCT NCT04803396)

NCT ID: NCT04803396

Last Updated: 2024-04-26

Results Overview

Adverse Event (AE), is defined as any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment/product. Serious Adverse Event or Reaction, is any untoward medical occurrence, that: * Results in death; * Is life-threatening * Requires in patient hospitalization or prolongation of existing hospitalization * Results in persistent or significant disability or incapacity * an important medical event/reaction that may jeopardize the patient and require medical / surgical intervention to prevent one of the outcomes above. Any AE (including laboratory test abnormalities, intercurrent illnesses or injuries, and/or study procedures related AE) reported spontaneously by the subjects, or observed by the Investigator, was recorded according to the procedures in force at Eurofins Optimed.

• Recruitment status: TERMINATED
• Study phase: PHASE1
• Target enrollment: 32 participants
• Primary outcome timeframe: Throughout the study, up to Day 4
• Results posted on: 2024-04-26

Participant Flow

60 subjects were screened in this study. 32 subjects were included: 24 males and 8 females. All subjects completed the part A of the study.

Participant milestones

Measure	Placebo Placebo was administered once a day (oad) as matching oral capsules. The administration took place at around 8:00 a.m with 200 mL of tap water, in sitting position, in fasting conditions.	50 mg DF2755A The experimental drug was administered once a day (oad) as one oral capsule of 50 mg. The administration took place at around 8:00 a.m with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 300 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	150 mg DF2755A The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 300 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	300 mg DF2755A The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 300 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	600 mg DF2755A The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 300 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.
Overall Study STARTED	8	6	6	6	6
Overall Study COMPLETED	8	6	6	6	6
Overall Study NOT COMPLETED	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Ascending Dose Tolerability Trial and PK Assessment in Healthy Volunteers After Single & Multiple Oral Intake of DF2755A

Baseline characteristics by cohort

Measure	Placebo n=8 Participants Placebo was administered once a day (oad) as matching oral capsules. The administration took place at around 8:00 a.m with 200 mL of tap water, in sitting position, in fasting conditions.	50 mg DF2755A n=6 Participants The experimental drug was administered once a day (oad) as one oral capsule of 50 mg. The administration took place at around 8:00 a.m with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 300 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	150 mg DF2755A n=6 Participants The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 300 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	300 mg DF2755A n=6 Participants The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 300 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	600 mg DF2755A n=6 Participants The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 300 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	Total n=32 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Age, Categorical Between 18 and 65 years	8 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	6 Participants n=4 Participants	6 Participants n=21 Participants	32 Participants n=8 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Age, Continuous	46.1 years STANDARD_DEVIATION 11.9 • n=5 Participants	46.3 years STANDARD_DEVIATION 8.8 • n=7 Participants	48.8 years STANDARD_DEVIATION 7.8 • n=5 Participants	45.8 years STANDARD_DEVIATION 5.8 • n=4 Participants	36.5 years STANDARD_DEVIATION 13.3 • n=21 Participants	44.8 years STANDARD_DEVIATION 10.3 • n=8 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants	8 Participants n=8 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants	5 Participants n=4 Participants	5 Participants n=21 Participants	24 Participants n=8 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	2 Participants n=8 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	6 Participants n=4 Participants	6 Participants n=21 Participants	30 Participants n=8 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Region of Enrollment France	8 participants n=5 Participants	6 participants n=7 Participants	6 participants n=5 Participants	6 participants n=4 Participants	6 participants n=21 Participants	32 participants n=8 Participants

PRIMARY outcome

Timeframe: Throughout the study, up to Day 4

Population: Safety set: defined as all included subjects having taken at least one dose of study drug.

Adverse Event (AE), is defined as any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment/product.

Serious Adverse Event or Reaction, is any untoward medical occurrence, that:

• Results in death;
• Is life-threatening
• Requires in patient hospitalization or prolongation of existing hospitalization
• Results in persistent or significant disability or incapacity
• an important medical event/reaction that may jeopardize the patient and require medical / surgical intervention to prevent one of the outcomes above.

Any AE (including laboratory test abnormalities, intercurrent illnesses or injuries, and/or study procedures related AE) reported spontaneously by the subjects, or observed by the Investigator, was recorded according to the procedures in force at Eurofins Optimed.

Outcome measures

Measure	Placebo n=8 Participants Placebo was administered once a day (oad) as matching oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	50 mg DF2755A n=6 Participants The experimental drug was administered once a day (oad) as one oral capsule of 50 mg. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	150 mg DF2755A n=6 Participants The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	300 mg DF2755A n=6 Participants The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	600 mg DF2755A n=6 Participants The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.
Number of Adverse Events by Severity Mild	0 events	0 events	0 events	1 events	0 events
Number of Adverse Events by Severity Severe	0 events	0 events	0 events	0 events	0 events
Number of Adverse Events by Severity Moderate	2 events	3 events	0 events	1 events	0 events

SECONDARY outcome

Timeframe: Day 1 (0,5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 h post-dose); Day 2 (24, 36, 40h post-dose); Day 3 (48, 60 h post-dose); Day 4 (72 h post dose)

Population: The pharmacokinetic set (PKS) was defined as all the included subjects who have taken at least one dose of study drug without major protocol deviations affecting pharmacokinetics and with available data.

Cmax is the observed maximum plasma concentration of a product.

Outcome measures

Measure	Placebo n=6 Participants Placebo was administered once a day (oad) as matching oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	50 mg DF2755A n=6 Participants The experimental drug was administered once a day (oad) as one oral capsule of 50 mg. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	150 mg DF2755A n=6 Participants The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	300 mg DF2755A n=6 Participants The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	600 mg DF2755A The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.
Cmax of DF2755A	1943 ng/mL Geometric Coefficient of Variation 39.0	6324 ng/mL Geometric Coefficient of Variation 28.7	16081 ng/mL Geometric Coefficient of Variation 20.2	26145 ng/mL Geometric Coefficient of Variation 32.0	—

SECONDARY outcome

Timeframe: Day 1 (0,5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 h post-dose); Day 2 (24, 36, 40h post-dose); Day 3 (48, 60 h post-dose); Day 4 (72 h post dose)

Population: The pharmacokinetic set (PKS) was defined as all the included subjects who have taken at least one dose of study drug without major protocol deviations affecting pharmacokinetics and with available data.

It is the first time to reach Cmax.

Outcome measures

Measure	Placebo n=6 Participants Placebo was administered once a day (oad) as matching oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	50 mg DF2755A n=6 Participants The experimental drug was administered once a day (oad) as one oral capsule of 50 mg. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	150 mg DF2755A n=6 Participants The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	300 mg DF2755A n=6 Participants The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	600 mg DF2755A The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.
Tmax	0.50 Hours Interval 0.5 to 1.0	0.50 Hours Interval 0.5 to 0.5	0.50 Hours Interval 0.5 to 0.53	0.77 Hours Interval 0.5 to 3.0	—

SECONDARY outcome

Timeframe: Day 1 (0,5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 h post-dose); Day 2 (24, 36, 40h post-dose); Day 3 (48, 60 h post-dose); Day 4 (72 h post dose)

Population: The pharmacokinetic set (PKS) was defined as all the included subjects who have taken at least one dose of study drug without major protocol deviations affecting pharmacokinetics and with available data.

It is the plasma concentration half life.

Outcome measures

Measure	Placebo n=6 Participants Placebo was administered once a day (oad) as matching oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	50 mg DF2755A n=5 Participants The experimental drug was administered once a day (oad) as one oral capsule of 50 mg. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	150 mg DF2755A n=5 Participants The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	300 mg DF2755A n=5 Participants The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	600 mg DF2755A The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.
t1/2	1.49 Hours Geometric Coefficient of Variation 54.2	1.62 Hours Geometric Coefficient of Variation 42.6	3.19 Hours Geometric Coefficient of Variation 43.9	4.05 Hours Geometric Coefficient of Variation 52.5	—

SECONDARY outcome

Timeframe: Day 1 (0,5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 h post-dose); Day 2 (24, 36, 40h post-dose); Day 3 (48, 60 h post-dose); Day 4 (72 h post dose)

Population: The pharmacokinetic set (PKS) was defined as all the included subjects who have taken at least one dose of study drug without major protocol deviations affecting pharmacokinetics and with available data.

The area under the concentration vs. time curve from time zero (pre-dose) to the time of last quantifiable concentration was calculated using a linear trapezoidal method.

Outcome measures

Measure	Placebo n=6 Participants Placebo was administered once a day (oad) as matching oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	50 mg DF2755A n=6 Participants The experimental drug was administered once a day (oad) as one oral capsule of 50 mg. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	150 mg DF2755A n=6 Participants The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	300 mg DF2755A n=6 Participants The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	600 mg DF2755A The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.
AUC0-t	3314.54 h*ng/mL Geometric Coefficient of Variation 38.9	9498.72 h*ng/mL Geometric Coefficient of Variation 30.2	25354.16 h*ng/mL Geometric Coefficient of Variation 12.2	75915.63 h*ng/mL Geometric Coefficient of Variation 26.9	—

SECONDARY outcome

Timeframe: Day 1 (0,5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 h post-dose); Day 2 (24, 36, 40h post-dose); Day 3 (48, 60 h post-dose); Day 4 (72 h post dose)

Population: The pharmacokinetic set (PKS) was defined as all the included subjects who have taken at least one dose of study drug without major protocol deviations affecting pharmacokinetics and with available data.

It is the area under the plasma concentration-time curve from administration up to infinity with extrapolation of the terminal phase.

Outcome measures

Measure	Placebo n=4 Participants Placebo was administered once a day (oad) as matching oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	50 mg DF2755A n=5 Participants The experimental drug was administered once a day (oad) as one oral capsule of 50 mg. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	150 mg DF2755A n=5 Participants The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	300 mg DF2755A n=5 Participants The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	600 mg DF2755A The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.
AUC 0-inf	4005.92 h*ng/mL Geometric Coefficient of Variation 39.7	9126.11 h*ng/mL Geometric Coefficient of Variation 13.2	26102.10 h*ng/mL Geometric Coefficient of Variation 13.8	81580.67 h*ng/mL Geometric Coefficient of Variation 26.4	—

SECONDARY outcome

Timeframe: Day 1 (0,5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 h post-dose); Day 2 (24, 36, 40h post-dose); Day 3 (48, 60 h post-dose); Day 4 (72 h post dose)

Population: The pharmacokinetic set (PKS) was defined as all the included subjects who have taken at least one dose of study drug without major protocol deviations affecting pharmacokinetics and with available data.

It is the apparent volume of distribution during terminal phase after non-intravenous administration.

Outcome measures

Measure	Placebo n=6 Participants Placebo was administered once a day (oad) as matching oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	50 mg DF2755A n=5 Participants The experimental drug was administered once a day (oad) as one oral capsule of 50 mg. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	150 mg DF2755A n=5 Participants The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	300 mg DF2755A n=5 Participants The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	600 mg DF2755A The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.
Vz/F	27.74 liters Geometric Coefficient of Variation 48.6	38.33 liters Geometric Coefficient of Variation 32.7	52.98 liters Geometric Coefficient of Variation 36.1	42.98 liters Geometric Coefficient of Variation 31.2	—

SECONDARY outcome

Timeframe: Day 1 (0,5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 h post-dose); Day 2 (24, 36, 40h post-dose); Day 3 (48, 60 h post-dose); Day 4 (72 h post dose)

Population: The pharmacokinetic set (PKS) was defined as all the included subjects who have taken at least one dose of study drug without major protocol deviations affecting pharmacokinetics and with available data.

It is the apparent oral clearance of the drug, where CL = clearance and F = bioavailability.

Outcome measures

Measure	Placebo n=6 Participants Placebo was administered once a day (oad) as matching oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	50 mg DF2755A n=5 Participants The experimental drug was administered once a day (oad) as one oral capsule of 50 mg. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	150 mg DF2755A n=5 Participants The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	300 mg DF2755A n=5 Participants The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	600 mg DF2755A The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.
CL/F	12.87 L/hours Geometric Coefficient of Variation 31.2	16.44 L/hours Geometric Coefficient of Variation 14.5	11.49 L/hours Geometric Coefficient of Variation 13.4	7.35 L/hours Geometric Coefficient of Variation 27.7	—

SECONDARY outcome

Timeframe: 0-24 h post-dose; 24-48 h post-dose, 48-72 h post dose

Population: The pharmacokinetic set (PKS) was defined as all the included subjects who have taken at least one dose of study drug without major protocol deviations affecting pharmacokinetics and with available data.

After oral administration, the individual amount of the drug excreted in faeces as DF2755Y is measured by the tracing of the radiolabelled compound [14C]DF2755A.

Outcome measures

Measure	Placebo n=4 Participants Placebo was administered once a day (oad) as matching oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	50 mg DF2755A n=5 Participants The experimental drug was administered once a day (oad) as one oral capsule of 50 mg. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	150 mg DF2755A n=5 Participants The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	300 mg DF2755A n=6 Participants The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	600 mg DF2755A The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.
Ae,f(0-72) Total Amount in Faeces	50.04 μg Geometric Coefficient of Variation 81.2	220.92 μg Geometric Coefficient of Variation 78.5	425.62 μg Geometric Coefficient of Variation 61.1	316.38 μg Geometric Coefficient of Variation 83	—

SECONDARY outcome

Timeframe: 0-24 h post-dose; 24-48 h post-dose, 48-72 h post dose

Population: The pharmacokinetic set (PKS) was defined as all the included subjects who have taken at least one dose of study drug without major protocol deviations affecting pharmacokinetics and with available data.

The individual corresponding fraction of DF2755A dose excreted in faeces as DF2755Y over time in the whole sampling window is reported.

Outcome measures

Measure	Placebo n=4 Participants Placebo was administered once a day (oad) as matching oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	50 mg DF2755A n=5 Participants The experimental drug was administered once a day (oad) as one oral capsule of 50 mg. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	150 mg DF2755A n=5 Participants The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	300 mg DF2755A n=6 Participants The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	600 mg DF2755A The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.
Fe,f(0-72)	0.11 percentage of value Geometric Coefficient of Variation 81.2	0.17 percentage of value Geometric Coefficient of Variation 78.5	0.16 percentage of value Geometric Coefficient of Variation 61.1	0.06 percentage of value Geometric Coefficient of Variation 83	—

SECONDARY outcome

Timeframe: 0-6 h post-dose; 6-10 h post-dose; 10-16h post-dose; 16-24h post-dose; 24-48h post-dose; 48-72h post-dose

Population: The pharmacokinetic set (PKS) was defined as all the included subjects who have taken at least one dose of study drug without major protocol deviations affecting pharmacokinetics and with available data.

The individual amount of DF2755A excreted in urine as DF2755Y over time in the whole sampling window is reported.

Outcome measures

Measure	Placebo n=6 Participants Placebo was administered once a day (oad) as matching oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	50 mg DF2755A n=6 Participants The experimental drug was administered once a day (oad) as one oral capsule of 50 mg. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	150 mg DF2755A n=6 Participants The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	300 mg DF2755A n=6 Participants The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	600 mg DF2755A The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.
Ae,ur(0-72)	3612.8 μg Geometric Coefficient of Variation 32.7	3556.2 μg Geometric Coefficient of Variation 38.1	12110.41 μg Geometric Coefficient of Variation 74.1	20018.07 μg Geometric Coefficient of Variation 27	—

SECONDARY outcome

Timeframe: 0-6 h post-dose; 6-10 h post-dose; 10-16h post-dose; 16-24h post-dose; 24-48h post-dose; 48-72h post-dose

Population: The pharmacokinetic set (PKS) was defined as all the included subjects who have taken at least one dose of study drug without major protocol deviations affecting pharmacokinetics and with available data.

The individual corresponding fraction of DF2755A dose excreted in urine as DF2755Y over time in the whole sampling window is reported.

Outcome measures

Measure	Placebo n=6 Participants Placebo was administered once a day (oad) as matching oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	50 mg DF2755A n=6 Participants The experimental drug was administered once a day (oad) as one oral capsule of 50 mg. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	150 mg DF2755A n=6 Participants The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	300 mg DF2755A n=6 Participants The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	600 mg DF2755A The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.
Fe,ur(0-72)	8.14 percentage of value Geometric Coefficient of Variation 32.7	2.67 percentage of value Geometric Coefficient of Variation 38.1	4.55 percentage of value Geometric Coefficient of Variation 74.1	3.76 percentage of value Geometric Coefficient of Variation 27	—

SECONDARY outcome

Timeframe: 0-6 h post-dose; 6-10 h post-dose; 10-16h post-dose; 16-24h post-dose; 24-48h post-dose; 48-72h post-dose

Population: The pharmacokinetic set (PKS) was defined as all the included subjects who have taken at least one dose of study drug without major protocol deviations affecting pharmacokinetics and with available data.

It is the renal clearance of DF2755Y.

Outcome measures

Measure	Placebo n=6 Participants Placebo was administered once a day (oad) as matching oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	50 mg DF2755A n=6 Participants The experimental drug was administered once a day (oad) as one oral capsule of 50 mg. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	150 mg DF2755A n=6 Participants The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	300 mg DF2755A n=6 Participants The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	600 mg DF2755A The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.
CLR	1.09 L/hours Geometric Coefficient of Variation 34	0.37 L/hours Geometric Coefficient of Variation 50.4	0.48 L/hours Geometric Coefficient of Variation 70.1	0.26 L/hours Geometric Coefficient of Variation 27.8	—

SECONDARY outcome

Timeframe: day -1 (pre treatment), day 3 (last visit after treatment)

Population: The Safety set (SS) was defined as all included subjects having taken at least one dose of study drug.

12-lead ECG included the assessment of the following parameters: HR, PR, QRS, QT, and QTcF. Here heart rate (HR) is reported. Heart rate (or pulse rate is the frequency of the heartbeat measured by the number of contractions (beats) of the heart per minute (bpm). The heart rate can vary according to the body's physical needs, including the need to absorb oxygen and excrete carbon dioxide, but is also modulated by numerous factors, including, but not limited to, genetics, physical fitness, stress or psychological status, diet, drugs, hormonal status, environment, and disease/illness as well as the interaction between and among these factors. It is usually equal or close to the pulse measured at any peripheral point.

Outcome measures

Measure	Placebo n=8 Participants Placebo was administered once a day (oad) as matching oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	50 mg DF2755A n=6 Participants The experimental drug was administered once a day (oad) as one oral capsule of 50 mg. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	150 mg DF2755A n=6 Participants The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	300 mg DF2755A n=6 Participants The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	600 mg DF2755A n=6 Participants The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.
12-lead ECG (HR) D-1	67.8 bpm Standard Deviation 10.7	66.7 bpm Standard Deviation 6.3	59.3 bpm Standard Deviation 4.4	65.2 bpm Standard Deviation 7.4	60.7 bpm Standard Deviation 12.7
12-lead ECG (HR) D3	61.3 bpm Standard Deviation 8.3	58.2 bpm Standard Deviation 4.4	55.0 bpm Standard Deviation 6.4	62.2 bpm Standard Deviation 4.6	58.8 bpm Standard Deviation 12.4

SECONDARY outcome

Timeframe: day -1 (pre treatment), day 3 (last visit after treatment)

Population: The Safety set (SS) was defined as all included subjects having taken at least one dose of study drug

It included the assessment of the following parameters: PR, QRS, QT, and QTcF. PR=PR interval measured on ECG; it is the period, measured in milliseconds, that extends from the beginning of the P wave (the onset of atrial depolarization) until the beginning of the QRS complex (the onset of ventricular depolarization).

QRS=QRS interval measured on ECG; It's the combination of 3 of the graphical deflections seen on a typical ECG. It corresponds to the depolarization of the right and left ventricles of the heart and contraction of the large ventricular muscles.

QT=QT interval; it is used to assess some of the electrical heart properties, calculated as the time from the start of the Q wave to the end of the T wave, and approximates to the time taken from when the cardiac ventricles start to contract to when they finish relaxing.

QtcF=QT interval corrected for heart rate using Fridericia's formula; it's measured with a "QT/QTcF semiautomated triplicate averaging method" (TAM).

Outcome measures

Measure	Placebo n=8 Participants Placebo was administered once a day (oad) as matching oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	50 mg DF2755A n=6 Participants The experimental drug was administered once a day (oad) as one oral capsule of 50 mg. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	150 mg DF2755A n=6 Participants The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	300 mg DF2755A n=6 Participants The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	600 mg DF2755A n=6 Participants The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.
12-lead ECG PR, QRS, QT, and QTcF QRS D-1	85.8 ms Standard Deviation 8.3	87.7 ms Standard Deviation 9.1	90.0 ms Standard Deviation 8.2	88.3 ms Standard Deviation 15.6	91.3 ms Standard Deviation 13.7
12-lead ECG PR, QRS, QT, and QTcF QRS D3	83.5 ms Standard Deviation 8.8	82.7 ms Standard Deviation 5.0	87.7 ms Standard Deviation 9.4	87.3 ms Standard Deviation 13.0	90.0 ms Standard Deviation 12.8
12-lead ECG PR, QRS, QT, and QTcF QT D-1	383.5 ms Standard Deviation 35.7	380.7 ms Standard Deviation 10.5	390.3 ms Standard Deviation 24.1	399.7 ms Standard Deviation 23.3	397.3 ms Standard Deviation 27.4
12-lead ECG PR, QRS, QT, and QTcF PR D-1	164.3 ms Standard Deviation 19.7	187.0 ms Standard Deviation 14.7	166.3 ms Standard Deviation 15.5	156.7 ms Standard Deviation 20.7	160.3 ms Standard Deviation 27.6
12-lead ECG PR, QRS, QT, and QTcF PR D3	167.3 ms Standard Deviation 18.1	192.7 ms Standard Deviation 15.9	170.3 ms Standard Deviation 24.8	166.0 ms Standard Deviation 19.8	162.3 ms Standard Deviation 20.6
12-lead ECG PR, QRS, QT, and QTcF QT D3	394.5 ms Standard Deviation 33.6	386.3 ms Standard Deviation 12.1	404.0 ms Standard Deviation 21.1	401.3 ms Standard Deviation 16.0	400.7 ms Standard Deviation 29.4
12-lead ECG PR, QRS, QT, and QTcF QTcF D-1	397.1 ms Standard Deviation 26.7	394.0 ms Standard Deviation 8.6	388.0 ms Standard Deviation 17.7	410.2 ms Standard Deviation 18.2	400.2 ms Standard Deviation 25.7
12-lead ECG PR, QRS, QT, and QTcF QTcF D3	395.9 ms Standard Deviation 27.5	381.5 ms Standard Deviation 11.3	391.5 ms Standard Deviation 15.5	406.0 ms Standard Deviation 13.2	395.0 ms Standard Deviation 14.0

SECONDARY outcome

Timeframe: day -1 (pre treatment), day 2 (post-treatment)

Population: The Safety set (SS) was defined as all included subjects having taken at least one dose of study drug.

Vital signs included SBP and DBP in both supine position (after 10 minutes rest) and standing position (after 2 minutes).

SBP= Systolic Blood Pressure is the maximum pressure during one heartbeat. DBP= Diastolic Blood Pressure minimum is the pressure between two heartbeats.

Outcome measures

Measure	Placebo n=8 Participants Placebo was administered once a day (oad) as matching oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	50 mg DF2755A n=6 Participants The experimental drug was administered once a day (oad) as one oral capsule of 50 mg. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	150 mg DF2755A n=6 Participants The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	300 mg DF2755A n=6 Participants The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	600 mg DF2755A n=6 Participants The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.
Systolic and Diastolic Blood Pressure (SBP, DBP) Standing SBP D2	107.0 mmHg Standard Deviation 14.4	101.8 mmHg Standard Deviation 12.0	118.2 mmHg Standard Deviation 15.9	111.2 mmHg Standard Deviation 13.2	112.7 mmHg Standard Deviation 11.8
Systolic and Diastolic Blood Pressure (SBP, DBP) Standing DBP D-1	75.8 mmHg Standard Deviation 5.6	72.2 mmHg Standard Deviation 7.2	74.0 mmHg Standard Deviation 4.4	72.7 mmHg Standard Deviation 11.6	78.7 mmHg Standard Deviation 7.0
Systolic and Diastolic Blood Pressure (SBP, DBP) Supine SBP D-1	110.4 mmHg Standard Deviation 13.7	112.2 mmHg Standard Deviation 11.5	114.2 mmHg Standard Deviation 14.1	108.2 mmHg Standard Deviation 6.7	113.8 mmHg Standard Deviation 8.8
Systolic and Diastolic Blood Pressure (SBP, DBP) Supine SBP D2	110.8 mmHg Standard Deviation 9.8	106.0 mmHg Standard Deviation 6.8	113.0 mmHg Standard Deviation 15.9	102.8 mmHg Standard Deviation 12.1	104.8 mmHg Standard Deviation 5.0
Systolic and Diastolic Blood Pressure (SBP, DBP) Standing SBP D-1	111.6 mmHg Standard Deviation 12.6	116.3 mmHg Standard Deviation 16.5	120.5 mmHg Standard Deviation 8.7	115.7 mmHg Standard Deviation 9.5	115.2 mmHg Standard Deviation 2.6
Systolic and Diastolic Blood Pressure (SBP, DBP) Supine DBP D-1	65.3 mmHg Standard Deviation 7.6	64.7 mmHg Standard Deviation 3.3	65.0 mmHg Standard Deviation 5.2	64.7 mmHg Standard Deviation 8.9	61.0 mmHg Standard Deviation 6.7
Systolic and Diastolic Blood Pressure (SBP, DBP) Supine DBP D2	64.3 mmHg Standard Deviation 6.2	63.5 mmHg Standard Deviation 2.6	69.8 mmHg Standard Deviation 9.4	64.5 mmHg Standard Deviation 11.7	63.3 mmHg Standard Deviation 6.0
Systolic and Diastolic Blood Pressure (SBP, DBP) Standing DBP D2	74.0 mmHg Standard Deviation 5.5	71.7 mmHg Standard Deviation 5.4	77.3 mmHg Standard Deviation 8.0	72.0 mmHg Standard Deviation 9.9	73.3 mmHg Standard Deviation 7.3

SECONDARY outcome

Timeframe: day -1 (pre treatment), day 3 (last visit after treatment)

Population: The Safety set (SS) was defined as all included subjects having taken at least one dose of study drug.

Vital signs included HR in both supine position (after 10 minutes rest) and standing position (after 2 minutes).

HR: Heart Rate(or pulse rate) is the frequency of the heartbeat measured by the number of contractions (beats) of the heart per minute (bpm).

Outcome measures

Measure	Placebo n=8 Participants Placebo was administered once a day (oad) as matching oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	50 mg DF2755A n=6 Participants The experimental drug was administered once a day (oad) as one oral capsule of 50 mg. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	150 mg DF2755A n=6 Participants The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	300 mg DF2755A n=6 Participants The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	600 mg DF2755A n=6 Participants The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.
Heart Rate (HR) Supine HR D-1	65.8 bpm Standard Deviation 6.5	63.3 bpm Standard Deviation 5.9	63.3 bpm Standard Deviation 4.7	65.3 bpm Standard Deviation 8.7	57.3 bpm Standard Deviation 7.8
Heart Rate (HR) Supine HR D3	64.0 bpm Standard Deviation 6.5	61.3 bpm Standard Deviation 5.3	63.3 bpm Standard Deviation 4.7	56.3 bpm Standard Deviation 6.3	58.2 bpm Standard Deviation 11.2
Heart Rate (HR) Standing HR D-1	76.3 bpm Standard Deviation 7.9	74.3 bpm Standard Deviation 3.2	76.7 bpm Standard Deviation 6.8	69.5 bpm Standard Deviation 11.1	70.7 bpm Standard Deviation 10.6
Heart Rate (HR) Standing HR D3	73.6 bpm Standard Deviation 5.9	74.0 bpm Standard Deviation 11.0	70.3 bpm Standard Deviation 8.0	66.7 bpm Standard Deviation 6.7	72.8 bpm Standard Deviation 10.2

SECONDARY outcome

Timeframe: day -1 (pre treatment), day 2 (post-treatment)

Population: The Safety set (SS) was defined as all included subjects having taken at least one dose of study drug

The oral body temperature is the measurement of the body temperature placing the thermometer under one side of the back of the tongue. Human body temperature varies. It depends on sex, age, time of day, exertion level, health status (such as illness and menstruation), what part of the body the measurement is taken at, state of consciousness (waking, sleeping, sedated), and emotions. Body temperature range in this study was 36.3 to 37.5 °C.

Outcome measures

Measure	Placebo n=8 Participants Placebo was administered once a day (oad) as matching oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	50 mg DF2755A n=6 Participants The experimental drug was administered once a day (oad) as one oral capsule of 50 mg. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	150 mg DF2755A n=6 Participants The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	300 mg DF2755A n=6 Participants The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	600 mg DF2755A n=6 Participants The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m. with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 600 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.
Oral Body Temperature Oral Temperature D-1	36.41 °C Standard Deviation 0.24	36.32 °C Standard Deviation 0.20	36.38 °C Standard Deviation 0.13	36.40 °C Standard Deviation 0.23	36.32 °C Standard Deviation 0.37
Oral Body Temperature Oral Temperature D2	36.38 °C Standard Deviation 0.27	36.40 °C Standard Deviation 0.14	36.30 °C Standard Deviation 0.30	36.28 °C Standard Deviation 0.23	36.13 °C Standard Deviation 0.27

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

50 mg DF2755A

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

150 mg DF2755A

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

300 mg DF2755A

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

600 mg DF2755A

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Placebo n=8 participants at risk Placebo was administered once a day (oad) as matching oral capsules. The administration took place at around 8:00 a.m with 200 mL of tap water, in sitting position, in fasting conditions. Hence, only part A of the study was accomplished.	50 mg DF2755A n=6 participants at risk The experimental drug was administered once a day (oad) as one oral capsule of 50 mg. The administration took place at around 8:00 a.m with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 300 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	150 mg DF2755A n=6 participants at risk The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 300 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	300 mg DF2755A n=6 participants at risk The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 300 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.	600 mg DF2755A n=6 participants at risk The experimental drug was administered once a day (oad) as oral capsules. The administration took place at around 8:00 a.m with 200 mL of tap water, in sitting position, in fasting conditions. DF2755A: DF2755A was planned to be administered in two different parts: Part A: Single oral dose administration on D1 according to the randomization (50, 150, 300 and 300 mg oad). Part B: was planned (100 mg bid, 200 mg bid or 300 mg bid) not performed (repeated oral administration from Day 1 to Day 14). Hence, only part A of the study was accomplished.
Gastrointestinal disorders Nausea	0.00% 0/8 • adverse event data were collected from baseline (day -21) up to end of study visit (day 4) All subjects who received a dose of the study drug were included in the safety evaluation (Safety Set N=32).	0.00% 0/6 • adverse event data were collected from baseline (day -21) up to end of study visit (day 4) All subjects who received a dose of the study drug were included in the safety evaluation (Safety Set N=32).	0.00% 0/6 • adverse event data were collected from baseline (day -21) up to end of study visit (day 4) All subjects who received a dose of the study drug were included in the safety evaluation (Safety Set N=32).	16.7% 1/6 • Number of events 1 • adverse event data were collected from baseline (day -21) up to end of study visit (day 4) All subjects who received a dose of the study drug were included in the safety evaluation (Safety Set N=32).	0.00% 0/6 • adverse event data were collected from baseline (day -21) up to end of study visit (day 4) All subjects who received a dose of the study drug were included in the safety evaluation (Safety Set N=32).
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/8 • adverse event data were collected from baseline (day -21) up to end of study visit (day 4) All subjects who received a dose of the study drug were included in the safety evaluation (Safety Set N=32).	16.7% 1/6 • Number of events 1 • adverse event data were collected from baseline (day -21) up to end of study visit (day 4) All subjects who received a dose of the study drug were included in the safety evaluation (Safety Set N=32).	0.00% 0/6 • adverse event data were collected from baseline (day -21) up to end of study visit (day 4) All subjects who received a dose of the study drug were included in the safety evaluation (Safety Set N=32).	0.00% 0/6 • adverse event data were collected from baseline (day -21) up to end of study visit (day 4) All subjects who received a dose of the study drug were included in the safety evaluation (Safety Set N=32).	0.00% 0/6 • adverse event data were collected from baseline (day -21) up to end of study visit (day 4) All subjects who received a dose of the study drug were included in the safety evaluation (Safety Set N=32).
Musculoskeletal and connective tissue disorders Limb discomfort	12.5% 1/8 • Number of events 1 • adverse event data were collected from baseline (day -21) up to end of study visit (day 4) All subjects who received a dose of the study drug were included in the safety evaluation (Safety Set N=32).	0.00% 0/6 • adverse event data were collected from baseline (day -21) up to end of study visit (day 4) All subjects who received a dose of the study drug were included in the safety evaluation (Safety Set N=32).	0.00% 0/6 • adverse event data were collected from baseline (day -21) up to end of study visit (day 4) All subjects who received a dose of the study drug were included in the safety evaluation (Safety Set N=32).	0.00% 0/6 • adverse event data were collected from baseline (day -21) up to end of study visit (day 4) All subjects who received a dose of the study drug were included in the safety evaluation (Safety Set N=32).	0.00% 0/6 • adverse event data were collected from baseline (day -21) up to end of study visit (day 4) All subjects who received a dose of the study drug were included in the safety evaluation (Safety Set N=32).
Nervous system disorders Headache	12.5% 1/8 • Number of events 1 • adverse event data were collected from baseline (day -21) up to end of study visit (day 4) All subjects who received a dose of the study drug were included in the safety evaluation (Safety Set N=32).	16.7% 1/6 • Number of events 2 • adverse event data were collected from baseline (day -21) up to end of study visit (day 4) All subjects who received a dose of the study drug were included in the safety evaluation (Safety Set N=32).	0.00% 0/6 • adverse event data were collected from baseline (day -21) up to end of study visit (day 4) All subjects who received a dose of the study drug were included in the safety evaluation (Safety Set N=32).	16.7% 1/6 • Number of events 1 • adverse event data were collected from baseline (day -21) up to end of study visit (day 4) All subjects who received a dose of the study drug were included in the safety evaluation (Safety Set N=32).	0.00% 0/6 • adverse event data were collected from baseline (day -21) up to end of study visit (day 4) All subjects who received a dose of the study drug were included in the safety evaluation (Safety Set N=32).

Additional Information

dr. Mauro P. Ferrari

Dompé farmaceutici SpA

Phone: +39 02 583831

Email: clinops@pec.dompe.it

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place