no Condition
Conditions
Keywords
Healthy volunteers
Brief summary
Primary objective: •To evaluate the tolerability and safety of ascending single doses of DF2755A in healthy adult male and female volunteers. Secondary Objectives: * To determine the pharmacokinetics parameters of DF2755A * To establish a dose concentration-response relationship over a wide range of doses in order to select a narrower range of dose and dosing regimen to be subsequently studied in patients after single administration * To evaluate the effect of ascending single doses on the pharmacodynamics parameters * To compare metabolites pathway in Human with the one observed in animals Please note that the study has been closed after Part A (single ascending doses), so all the objectives were revised accordingly.
Detailed description
The study was a phase I, single center, double-blind, placebo controlled, randomized, ascending single doses study in healthy male and female volunteers. The design consisted of a double blind comparison of the test compound versus placebo in which the dose is increased in successive treatment periods. The escalating dose had the aim of achieving enough safety information on an interval of doses possibly encompassing both the effective dose and the maximum tolerated dose (defined as the highest dose devoid of any clinical signs/symptoms). Practically, of the two Parts planned - part A and Part B - only the Part A took place. The Part A consisted of single doses of 50 mg oad, 150 mg oad, 450 mg oad or 700 mg oad of DF2755A tested in healthy male and female volunteers who were hospitalized approximately for 4 days (D-1 morning to D4 morning). The planned Part B should have consisted of repeated doses of 100 mg bid, 200 mg bid or 300 mg bid of DF2755A) but it was not performed. Hence, the study was terminated at the end of Part A and, consequently, both the methodology and the endpoints were revised accordingly.
Interventions
DRUGDF2755A
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) but not performed (repeated oral administration from Day 1 to Day 14).
OTHERPlacebo
Single oral dose administration on D1
Sponsors
Dompé Farmaceutici S.p.A
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
This study is a double blind study. The analytical centre as well as the Investigator and the team and the subjects were in blind conditions.
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* For eligibility into the trial, subjects had to meet all the following inclusion criteria: 1. Healthy male subject, aged between 18 and 55 years inclusive; 2. Healthy female subject infertile or in post menopause for at least two years, aged between 18 and 60 years inclusive; 3. Body Mass Index (BMI) between 18.5 and 29.9 kg/m2 inclusive and weight ≤ 90kg; 4. Considered as healthy after a comprehensive clinical assessment (detailed medical history and complete physical examination); 5. Normal Blood Pressure (BP) and Heart Rate (HR) at the screening visit after 10 minutes in supine position: * 90 mmHg ≤ Systolic Blood Pressure (SBP) ≤ 140 mmHg or 150mmHg for subject \> 45 years, * 50 mmHg ≤ Diastolic Blood Pressure (DBP) ≤ 90 mmHg, * 40 bpm ≤ HR ≤ 100 bpm, Or considered NCs by investigators; 6. Smoker \< 5cigarettes per day who stop totally during the study; 7. Normal ECG recording on a 12-lead ECG at the screening visit: * 120 \< PR \< 210 ms, * QRS \< 120 ms, * QTcf ≤ 430 ms for male and \< 450 ms for female, * No sign of any trouble of sinusal automatism, Or considered NCs by investigators; 8. Normal oral temperature; 9. 36.3°C \< oral body temperature \< 37.5°C; 10. Laboratory parameters within the normal range of the laboratory (haematological, blood chemistry tests, urinalysis). Individual values out of the normal range can be accepted if judged clinically non relevant by the Investigator; 11. Normal dietary habits; 12. Able to communicate well with the Investigator, understand and comply with the requirements of the study, and understand and sign a written informed consent prior to selection; 13. Covered by Health Insurance System and / or in compliance with the recommendations of National Law in force relating to biomedical research.
Exclusion criteria
1. Subject has had a clinically significant illness in the six weeks before screening in the opinion of the Investigator. 2. Subject has had a serious adverse reaction or significant hypersensitivity to any drug, has a known clinically significant allergy to anti-inflammatory drugs or chemically related compounds or has a clinically significant allergy to drugs, foods or other materials (in the opinion of the Investigator). However, subjects with mild hayfever may be included in the study. 3. Subject has used prescription medication in the 14 days prior to dosing or over-the-counter preparations for 7 days prior to dosing (including vitamin supplements and herbal remedies), with the exception of paracetamol which was allowed during the study (maximum 500 mg per administration, total daily dose maximum 2 grams). 4. Subject has a significant history of drug/solvent abuse or a positive drugs of abuse (DOA) test at any time during the study. 5. Subject has a history of alcohol abuse in the last 5 years or currently drinks in excess of 21 and 14 units per week for males and female, respectively, or has a positive alcohol breath test (ABT) at any time during the study. 6. Subject is not willing to refrain from caffeine/xanthine containing products in the 48 hours prior to admission to the clinical unit on Day -1 and for the duration of the residential period. 7. Subject who has a positive human immunodeficiency virus (HIV) screen, Hepatitis B screen or Hepatitis C screen. 8. Subject has donated blood or blood products (e.g., plasma or platelets) within the three months prior to screening. 9. Subject who is not suitable to participate in the study in the opinion of the Investigator; 10. Subject who has participated in any clinical study with an investigational drug/device within three months prior to the first day of dosing. 11. Subject who is in the exclusion period from another study. 12. Administrative or legal supervision. 13. Subject who would receive more than 4500 euros as indemnities for his participation in biomedical research within the 12 last months, including the indemnities for the present study. -
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Adverse Events by Severity | Throughout the study, up to Day 4 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tmax | 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) | It is the first time to reach Cmax. |
| t1/2 | 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) | It is the plasma concentration half life. |
| AUC0-t | 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) | 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. |
| AUC 0-inf | 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) | It is the area under the plasma concentration-time curve from administration up to infinity with extrapolation of the terminal phase. |
| Vz/F | 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) | It is the apparent volume of distribution during terminal phase after non-intravenous administration. |
| CL/F | 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) | It is the apparent oral clearance of the drug, where CL = clearance and F = bioavailability. |
| Ae,f(0-72) Total Amount in Faeces | 0-24 h post-dose; 24-48 h post-dose, 48-72 h post dose | 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. |
| Fe,f(0-72) | 0-24 h post-dose; 24-48 h post-dose, 48-72 h post dose | The individual corresponding fraction of DF2755A dose excreted in faeces as DF2755Y over time in the whole sampling window is reported. |
| Cmax of DF2755A | 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) | Cmax is the observed maximum plasma concentration of a product. |
| Fe,ur(0-72) | 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 | The individual corresponding fraction of DF2755A dose excreted in urine as DF2755Y over time in the whole sampling window is reported. |
| CLR | 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 | It is the renal clearance of DF2755Y. |
| 12-lead ECG (HR) | day -1 (pre treatment), day 3 (last visit after treatment) | 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. |
| 12-lead ECG PR, QRS, QT, and QTcF | day -1 (pre treatment), day 3 (last visit after treatment) | 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). |
| Systolic and Diastolic Blood Pressure (SBP, DBP) | day -1 (pre treatment), day 2 (post-treatment) | 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. |
| Heart Rate (HR) | day -1 (pre treatment), day 3 (last visit after treatment) | 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). |
| Oral Body Temperature | day -1 (pre treatment), day 2 (post-treatment) | 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. |
| Ae,ur(0-72) | 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 | The individual amount of DF2755A excreted in urine as DF2755Y over time in the whole sampling window is reported. |
Countries
France
Participant flow
Recruitment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 8 |
| 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. | 6 |
| 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. | 6 |
| 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. | 6 |
| 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. | 6 |
| Total | 32 |
Baseline characteristics
| Characteristic | 600 mg DF2755A | Total | 50 mg DF2755A | 150 mg DF2755A | Placebo | 300 mg DF2755A |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 32 Participants | 6 Participants | 6 Participants | 8 Participants | 6 Participants |
| Age, Continuous | 36.5 years STANDARD_DEVIATION 13.3 | 44.8 years STANDARD_DEVIATION 10.3 | 46.3 years STANDARD_DEVIATION 8.8 | 48.8 years STANDARD_DEVIATION 7.8 | 46.1 years STANDARD_DEVIATION 11.9 | 45.8 years STANDARD_DEVIATION 5.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 30 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants |
| Region of Enrollment France | 6 participants | 32 participants | 6 participants | 6 participants | 8 participants | 6 participants |
| Sex: Female, Male Female | 1 Participants | 8 Participants | 1 Participants | 1 Participants | 4 Participants | 1 Participants |
| Sex: Female, Male Male | 5 Participants | 24 Participants | 5 Participants | 5 Participants | 4 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 2 / 8 | 1 / 6 | 0 / 6 | 1 / 6 | 0 / 6 |
| serious Total, serious adverse events | 0 / 8 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Number of Adverse Events by Severity
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.
Time frame: Throughout the study, up to Day 4
Population: Safety set: defined as all included subjects having taken at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Adverse Events by Severity | Severe | 0 events |
| Placebo | Number of Adverse Events by Severity | Moderate | 2 events |
| Placebo | Number of Adverse Events by Severity | Mild | 0 events |
| 50 mg DF2755A | Number of Adverse Events by Severity | Severe | 0 events |
| 50 mg DF2755A | Number of Adverse Events by Severity | Moderate | 3 events |
| 50 mg DF2755A | Number of Adverse Events by Severity | Mild | 0 events |
| 150 mg DF2755A | Number of Adverse Events by Severity | Mild | 0 events |
| 150 mg DF2755A | Number of Adverse Events by Severity | Moderate | 0 events |
| 150 mg DF2755A | Number of Adverse Events by Severity | Severe | 0 events |
| 300 mg DF2755A | Number of Adverse Events by Severity | Severe | 0 events |
| 300 mg DF2755A | Number of Adverse Events by Severity | Moderate | 1 events |
| 300 mg DF2755A | Number of Adverse Events by Severity | Mild | 1 events |
| 600 mg DF2755A | Number of Adverse Events by Severity | Mild | 0 events |
| 600 mg DF2755A | Number of Adverse Events by Severity | Severe | 0 events |
| 600 mg DF2755A | Number of Adverse Events by Severity | Moderate | 0 events |
Secondary
12-lead ECG (HR)
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 12-lead ECG (HR) | D-1 | 67.8 bpm | Standard Deviation 10.7 |
| Placebo | 12-lead ECG (HR) | D3 | 61.3 bpm | Standard Deviation 8.3 |
| 50 mg DF2755A | 12-lead ECG (HR) | D-1 | 66.7 bpm | Standard Deviation 6.3 |
| 50 mg DF2755A | 12-lead ECG (HR) | D3 | 58.2 bpm | Standard Deviation 4.4 |
| 150 mg DF2755A | 12-lead ECG (HR) | D-1 | 59.3 bpm | Standard Deviation 4.4 |
| 150 mg DF2755A | 12-lead ECG (HR) | D3 | 55.0 bpm | Standard Deviation 6.4 |
| 300 mg DF2755A | 12-lead ECG (HR) | D3 | 62.2 bpm | Standard Deviation 4.6 |
| 300 mg DF2755A | 12-lead ECG (HR) | D-1 | 65.2 bpm | Standard Deviation 7.4 |
| 600 mg DF2755A | 12-lead ECG (HR) | D-1 | 60.7 bpm | Standard Deviation 12.7 |
| 600 mg DF2755A | 12-lead ECG (HR) | D3 | 58.8 bpm | Standard Deviation 12.4 |
Secondary
12-lead ECG PR, QRS, QT, and QTcF
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).
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 12-lead ECG PR, QRS, QT, and QTcF | PR D-1 | 164.3 ms | Standard Deviation 19.7 |
| Placebo | 12-lead ECG PR, QRS, QT, and QTcF | QRS D-1 | 85.8 ms | Standard Deviation 8.3 |
| Placebo | 12-lead ECG PR, QRS, QT, and QTcF | QRS D3 | 83.5 ms | Standard Deviation 8.8 |
| Placebo | 12-lead ECG PR, QRS, QT, and QTcF | QT D-1 | 383.5 ms | Standard Deviation 35.7 |
| Placebo | 12-lead ECG PR, QRS, QT, and QTcF | QT D3 | 394.5 ms | Standard Deviation 33.6 |
| Placebo | 12-lead ECG PR, QRS, QT, and QTcF | QTcF D-1 | 397.1 ms | Standard Deviation 26.7 |
| Placebo | 12-lead ECG PR, QRS, QT, and QTcF | QTcF D3 | 395.9 ms | Standard Deviation 27.5 |
| Placebo | 12-lead ECG PR, QRS, QT, and QTcF | PR D3 | 167.3 ms | Standard Deviation 18.1 |
| 50 mg DF2755A | 12-lead ECG PR, QRS, QT, and QTcF | QT D3 | 386.3 ms | Standard Deviation 12.1 |
| 50 mg DF2755A | 12-lead ECG PR, QRS, QT, and QTcF | PR D-1 | 187.0 ms | Standard Deviation 14.7 |
| 50 mg DF2755A | 12-lead ECG PR, QRS, QT, and QTcF | QT D-1 | 380.7 ms | Standard Deviation 10.5 |
| 50 mg DF2755A | 12-lead ECG PR, QRS, QT, and QTcF | QTcF D3 | 381.5 ms | Standard Deviation 11.3 |
| 50 mg DF2755A | 12-lead ECG PR, QRS, QT, and QTcF | QTcF D-1 | 394.0 ms | Standard Deviation 8.6 |
| 50 mg DF2755A | 12-lead ECG PR, QRS, QT, and QTcF | QRS D3 | 82.7 ms | Standard Deviation 5 |
| 50 mg DF2755A | 12-lead ECG PR, QRS, QT, and QTcF | PR D3 | 192.7 ms | Standard Deviation 15.9 |
| 50 mg DF2755A | 12-lead ECG PR, QRS, QT, and QTcF | QRS D-1 | 87.7 ms | Standard Deviation 9.1 |
| 150 mg DF2755A | 12-lead ECG PR, QRS, QT, and QTcF | QT D3 | 404.0 ms | Standard Deviation 21.1 |
| 150 mg DF2755A | 12-lead ECG PR, QRS, QT, and QTcF | QRS D-1 | 90.0 ms | Standard Deviation 8.2 |
| 150 mg DF2755A | 12-lead ECG PR, QRS, QT, and QTcF | QRS D3 | 87.7 ms | Standard Deviation 9.4 |
| 150 mg DF2755A | 12-lead ECG PR, QRS, QT, and QTcF | QT D-1 | 390.3 ms | Standard Deviation 24.1 |
| 150 mg DF2755A | 12-lead ECG PR, QRS, QT, and QTcF | PR D-1 | 166.3 ms | Standard Deviation 15.5 |
| 150 mg DF2755A | 12-lead ECG PR, QRS, QT, and QTcF | QTcF D-1 | 388.0 ms | Standard Deviation 17.7 |
| 150 mg DF2755A | 12-lead ECG PR, QRS, QT, and QTcF | QTcF D3 | 391.5 ms | Standard Deviation 15.5 |
| 150 mg DF2755A | 12-lead ECG PR, QRS, QT, and QTcF | PR D3 | 170.3 ms | Standard Deviation 24.8 |
| 300 mg DF2755A | 12-lead ECG PR, QRS, QT, and QTcF | QTcF D-1 | 410.2 ms | Standard Deviation 18.2 |
| 300 mg DF2755A | 12-lead ECG PR, QRS, QT, and QTcF | PR D-1 | 156.7 ms | Standard Deviation 20.7 |
| 300 mg DF2755A | 12-lead ECG PR, QRS, QT, and QTcF | QT D3 | 401.3 ms | Standard Deviation 16 |
| 300 mg DF2755A | 12-lead ECG PR, QRS, QT, and QTcF | QRS D-1 | 88.3 ms | Standard Deviation 15.6 |
| 300 mg DF2755A | 12-lead ECG PR, QRS, QT, and QTcF | QT D-1 | 399.7 ms | Standard Deviation 23.3 |
| 300 mg DF2755A | 12-lead ECG PR, QRS, QT, and QTcF | PR D3 | 166.0 ms | Standard Deviation 19.8 |
| 300 mg DF2755A | 12-lead ECG PR, QRS, QT, and QTcF | QTcF D3 | 406.0 ms | Standard Deviation 13.2 |
| 300 mg DF2755A | 12-lead ECG PR, QRS, QT, and QTcF | QRS D3 | 87.3 ms | Standard Deviation 13 |
| 600 mg DF2755A | 12-lead ECG PR, QRS, QT, and QTcF | QRS D3 | 90.0 ms | Standard Deviation 12.8 |
| 600 mg DF2755A | 12-lead ECG PR, QRS, QT, and QTcF | QT D3 | 400.7 ms | Standard Deviation 29.4 |
| 600 mg DF2755A | 12-lead ECG PR, QRS, QT, and QTcF | QTcF D3 | 395.0 ms | Standard Deviation 14 |
| 600 mg DF2755A | 12-lead ECG PR, QRS, QT, and QTcF | QTcF D-1 | 400.2 ms | Standard Deviation 25.7 |
| 600 mg DF2755A | 12-lead ECG PR, QRS, QT, and QTcF | QRS D-1 | 91.3 ms | Standard Deviation 13.7 |
| 600 mg DF2755A | 12-lead ECG PR, QRS, QT, and QTcF | PR D3 | 162.3 ms | Standard Deviation 20.6 |
| 600 mg DF2755A | 12-lead ECG PR, QRS, QT, and QTcF | PR D-1 | 160.3 ms | Standard Deviation 27.6 |
| 600 mg DF2755A | 12-lead ECG PR, QRS, QT, and QTcF | QT D-1 | 397.3 ms | Standard Deviation 27.4 |
Secondary
Ae,f(0-72) Total Amount in Faeces
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.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Ae,f(0-72) Total Amount in Faeces | 50.04 μg | Geometric Coefficient of Variation 81.2 |
| 50 mg DF2755A | Ae,f(0-72) Total Amount in Faeces | 220.92 μg | Geometric Coefficient of Variation 78.5 |
| 150 mg DF2755A | Ae,f(0-72) Total Amount in Faeces | 425.62 μg | Geometric Coefficient of Variation 61.1 |
| 300 mg DF2755A | Ae,f(0-72) Total Amount in Faeces | 316.38 μg | Geometric Coefficient of Variation 83 |
Secondary
Ae,ur(0-72)
The individual amount of DF2755A excreted in urine as DF2755Y over time in the whole sampling window is reported.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Ae,ur(0-72) | 3612.8 μg | Geometric Coefficient of Variation 32.7 |
| 50 mg DF2755A | Ae,ur(0-72) | 3556.2 μg | Geometric Coefficient of Variation 38.1 |
| 150 mg DF2755A | Ae,ur(0-72) | 12110.41 μg | Geometric Coefficient of Variation 74.1 |
| 300 mg DF2755A | Ae,ur(0-72) | 20018.07 μg | Geometric Coefficient of Variation 27 |
Secondary
AUC 0-inf
It is the area under the plasma concentration-time curve from administration up to infinity with extrapolation of the terminal phase.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | AUC 0-inf | 4005.92 h*ng/mL | Geometric Coefficient of Variation 39.7 |
| 50 mg DF2755A | AUC 0-inf | 9126.11 h*ng/mL | Geometric Coefficient of Variation 13.2 |
| 150 mg DF2755A | AUC 0-inf | 26102.10 h*ng/mL | Geometric Coefficient of Variation 13.8 |
| 300 mg DF2755A | AUC 0-inf | 81580.67 h*ng/mL | Geometric Coefficient of Variation 26.4 |
Secondary
AUC0-t
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.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | AUC0-t | 3314.54 h*ng/mL | Geometric Coefficient of Variation 38.9 |
| 50 mg DF2755A | AUC0-t | 9498.72 h*ng/mL | Geometric Coefficient of Variation 30.2 |
| 150 mg DF2755A | AUC0-t | 25354.16 h*ng/mL | Geometric Coefficient of Variation 12.2 |
| 300 mg DF2755A | AUC0-t | 75915.63 h*ng/mL | Geometric Coefficient of Variation 26.9 |
Secondary
CL/F
It is the apparent oral clearance of the drug, where CL = clearance and F = bioavailability.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | CL/F | 12.87 L/hours | Geometric Coefficient of Variation 31.2 |
| 50 mg DF2755A | CL/F | 16.44 L/hours | Geometric Coefficient of Variation 14.5 |
| 150 mg DF2755A | CL/F | 11.49 L/hours | Geometric Coefficient of Variation 13.4 |
| 300 mg DF2755A | CL/F | 7.35 L/hours | Geometric Coefficient of Variation 27.7 |
Secondary
CLR
It is the renal clearance of DF2755Y.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | CLR | 1.09 L/hours | Geometric Coefficient of Variation 34 |
| 50 mg DF2755A | CLR | 0.37 L/hours | Geometric Coefficient of Variation 50.4 |
| 150 mg DF2755A | CLR | 0.48 L/hours | Geometric Coefficient of Variation 70.1 |
| 300 mg DF2755A | CLR | 0.26 L/hours | Geometric Coefficient of Variation 27.8 |
Secondary
Cmax of DF2755A
Cmax is the observed maximum plasma concentration of a product.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Cmax of DF2755A | 1943 ng/mL | Geometric Coefficient of Variation 39 |
| 50 mg DF2755A | Cmax of DF2755A | 6324 ng/mL | Geometric Coefficient of Variation 28.7 |
| 150 mg DF2755A | Cmax of DF2755A | 16081 ng/mL | Geometric Coefficient of Variation 20.2 |
| 300 mg DF2755A | Cmax of DF2755A | 26145 ng/mL | Geometric Coefficient of Variation 32 |
Secondary
Fe,f(0-72)
The individual corresponding fraction of DF2755A dose excreted in faeces as DF2755Y over time in the whole sampling window is reported.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Fe,f(0-72) | 0.11 percentage of value | Geometric Coefficient of Variation 81.2 |
| 50 mg DF2755A | Fe,f(0-72) | 0.17 percentage of value | Geometric Coefficient of Variation 78.5 |
| 150 mg DF2755A | Fe,f(0-72) | 0.16 percentage of value | Geometric Coefficient of Variation 61.1 |
| 300 mg DF2755A | Fe,f(0-72) | 0.06 percentage of value | Geometric Coefficient of Variation 83 |
Secondary
Fe,ur(0-72)
The individual corresponding fraction of DF2755A dose excreted in urine as DF2755Y over time in the whole sampling window is reported.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Fe,ur(0-72) | 8.14 percentage of value | Geometric Coefficient of Variation 32.7 |
| 50 mg DF2755A | Fe,ur(0-72) | 2.67 percentage of value | Geometric Coefficient of Variation 38.1 |
| 150 mg DF2755A | Fe,ur(0-72) | 4.55 percentage of value | Geometric Coefficient of Variation 74.1 |
| 300 mg DF2755A | Fe,ur(0-72) | 3.76 percentage of value | Geometric Coefficient of Variation 27 |
Secondary
Heart Rate (HR)
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).
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Heart Rate (HR) | Supine HR D-1 | 65.8 bpm | Standard Deviation 6.5 |
| Placebo | Heart Rate (HR) | Supine HR D3 | 64.0 bpm | Standard Deviation 6.5 |
| Placebo | Heart Rate (HR) | Standing HR D-1 | 76.3 bpm | Standard Deviation 7.9 |
| Placebo | Heart Rate (HR) | Standing HR D3 | 73.6 bpm | Standard Deviation 5.9 |
| 50 mg DF2755A | Heart Rate (HR) | Supine HR D-1 | 63.3 bpm | Standard Deviation 5.9 |
| 50 mg DF2755A | Heart Rate (HR) | Standing HR D3 | 74.0 bpm | Standard Deviation 11 |
| 50 mg DF2755A | Heart Rate (HR) | Supine HR D3 | 61.3 bpm | Standard Deviation 5.3 |
| 50 mg DF2755A | Heart Rate (HR) | Standing HR D-1 | 74.3 bpm | Standard Deviation 3.2 |
| 150 mg DF2755A | Heart Rate (HR) | Standing HR D3 | 70.3 bpm | Standard Deviation 8 |
| 150 mg DF2755A | Heart Rate (HR) | Supine HR D3 | 63.3 bpm | Standard Deviation 4.7 |
| 150 mg DF2755A | Heart Rate (HR) | Standing HR D-1 | 76.7 bpm | Standard Deviation 6.8 |
| 150 mg DF2755A | Heart Rate (HR) | Supine HR D-1 | 63.3 bpm | Standard Deviation 4.7 |
| 300 mg DF2755A | Heart Rate (HR) | Supine HR D-1 | 65.3 bpm | Standard Deviation 8.7 |
| 300 mg DF2755A | Heart Rate (HR) | Supine HR D3 | 56.3 bpm | Standard Deviation 6.3 |
| 300 mg DF2755A | Heart Rate (HR) | Standing HR D3 | 66.7 bpm | Standard Deviation 6.7 |
| 300 mg DF2755A | Heart Rate (HR) | Standing HR D-1 | 69.5 bpm | Standard Deviation 11.1 |
| 600 mg DF2755A | Heart Rate (HR) | Standing HR D3 | 72.8 bpm | Standard Deviation 10.2 |
| 600 mg DF2755A | Heart Rate (HR) | Standing HR D-1 | 70.7 bpm | Standard Deviation 10.6 |
| 600 mg DF2755A | Heart Rate (HR) | Supine HR D3 | 58.2 bpm | Standard Deviation 11.2 |
| 600 mg DF2755A | Heart Rate (HR) | Supine HR D-1 | 57.3 bpm | Standard Deviation 7.8 |
Secondary
Oral Body Temperature
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.
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Oral Body Temperature | Oral Temperature D-1 | 36.41 °C | Standard Deviation 0.24 |
| Placebo | Oral Body Temperature | Oral Temperature D2 | 36.38 °C | Standard Deviation 0.27 |
| 50 mg DF2755A | Oral Body Temperature | Oral Temperature D-1 | 36.32 °C | Standard Deviation 0.2 |
| 50 mg DF2755A | Oral Body Temperature | Oral Temperature D2 | 36.40 °C | Standard Deviation 0.14 |
| 150 mg DF2755A | Oral Body Temperature | Oral Temperature D-1 | 36.38 °C | Standard Deviation 0.13 |
| 150 mg DF2755A | Oral Body Temperature | Oral Temperature D2 | 36.30 °C | Standard Deviation 0.3 |
| 300 mg DF2755A | Oral Body Temperature | Oral Temperature D2 | 36.28 °C | Standard Deviation 0.23 |
| 300 mg DF2755A | Oral Body Temperature | Oral Temperature D-1 | 36.40 °C | Standard Deviation 0.23 |
| 600 mg DF2755A | Oral Body Temperature | Oral Temperature D-1 | 36.32 °C | Standard Deviation 0.37 |
| 600 mg DF2755A | Oral Body Temperature | Oral Temperature D2 | 36.13 °C | Standard Deviation 0.27 |
Secondary
Systolic and Diastolic Blood Pressure (SBP, DBP)
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Systolic and Diastolic Blood Pressure (SBP, DBP) | Standing DBP D-1 | 75.8 mmHg | Standard Deviation 5.6 |
| Placebo | Systolic and Diastolic Blood Pressure (SBP, DBP) | Standing SBP D2 | 107.0 mmHg | Standard Deviation 14.4 |
| Placebo | Systolic and Diastolic Blood Pressure (SBP, DBP) | Supine DBP D-1 | 65.3 mmHg | Standard Deviation 7.6 |
| Placebo | Systolic and Diastolic Blood Pressure (SBP, DBP) | Supine SBP D2 | 110.8 mmHg | Standard Deviation 9.8 |
| Placebo | Systolic and Diastolic Blood Pressure (SBP, DBP) | Supine SBP D-1 | 110.4 mmHg | Standard Deviation 13.7 |
| Placebo | Systolic and Diastolic Blood Pressure (SBP, DBP) | Standing DBP D2 | 74.0 mmHg | Standard Deviation 5.5 |
| Placebo | Systolic and Diastolic Blood Pressure (SBP, DBP) | Supine DBP D2 | 64.3 mmHg | Standard Deviation 6.2 |
| Placebo | Systolic and Diastolic Blood Pressure (SBP, DBP) | Standing SBP D-1 | 111.6 mmHg | Standard Deviation 12.6 |
| 50 mg DF2755A | Systolic and Diastolic Blood Pressure (SBP, DBP) | Standing DBP D-1 | 72.2 mmHg | Standard Deviation 7.2 |
| 50 mg DF2755A | Systolic and Diastolic Blood Pressure (SBP, DBP) | Standing SBP D-1 | 116.3 mmHg | Standard Deviation 16.5 |
| 50 mg DF2755A | Systolic and Diastolic Blood Pressure (SBP, DBP) | Standing SBP D2 | 101.8 mmHg | Standard Deviation 12 |
| 50 mg DF2755A | Systolic and Diastolic Blood Pressure (SBP, DBP) | Supine SBP D-1 | 112.2 mmHg | Standard Deviation 11.5 |
| 50 mg DF2755A | Systolic and Diastolic Blood Pressure (SBP, DBP) | Supine DBP D-1 | 64.7 mmHg | Standard Deviation 3.3 |
| 50 mg DF2755A | Systolic and Diastolic Blood Pressure (SBP, DBP) | Standing DBP D2 | 71.7 mmHg | Standard Deviation 5.4 |
| 50 mg DF2755A | Systolic and Diastolic Blood Pressure (SBP, DBP) | Supine SBP D2 | 106.0 mmHg | Standard Deviation 6.8 |
| 50 mg DF2755A | Systolic and Diastolic Blood Pressure (SBP, DBP) | Supine DBP D2 | 63.5 mmHg | Standard Deviation 2.6 |
| 150 mg DF2755A | Systolic and Diastolic Blood Pressure (SBP, DBP) | Standing SBP D2 | 118.2 mmHg | Standard Deviation 15.9 |
| 150 mg DF2755A | Systolic and Diastolic Blood Pressure (SBP, DBP) | Supine DBP D-1 | 65.0 mmHg | Standard Deviation 5.2 |
| 150 mg DF2755A | Systolic and Diastolic Blood Pressure (SBP, DBP) | Supine SBP D-1 | 114.2 mmHg | Standard Deviation 14.1 |
| 150 mg DF2755A | Systolic and Diastolic Blood Pressure (SBP, DBP) | Standing DBP D-1 | 74.0 mmHg | Standard Deviation 4.4 |
| 150 mg DF2755A | Systolic and Diastolic Blood Pressure (SBP, DBP) | Supine SBP D2 | 113.0 mmHg | Standard Deviation 15.9 |
| 150 mg DF2755A | Systolic and Diastolic Blood Pressure (SBP, DBP) | Standing DBP D2 | 77.3 mmHg | Standard Deviation 8 |
| 150 mg DF2755A | Systolic and Diastolic Blood Pressure (SBP, DBP) | Standing SBP D-1 | 120.5 mmHg | Standard Deviation 8.7 |
| 150 mg DF2755A | Systolic and Diastolic Blood Pressure (SBP, DBP) | Supine DBP D2 | 69.8 mmHg | Standard Deviation 9.4 |
| 300 mg DF2755A | Systolic and Diastolic Blood Pressure (SBP, DBP) | Standing SBP D2 | 111.2 mmHg | Standard Deviation 13.2 |
| 300 mg DF2755A | Systolic and Diastolic Blood Pressure (SBP, DBP) | Standing DBP D2 | 72.0 mmHg | Standard Deviation 9.9 |
| 300 mg DF2755A | Systolic and Diastolic Blood Pressure (SBP, DBP) | Supine SBP D-1 | 108.2 mmHg | Standard Deviation 6.7 |
| 300 mg DF2755A | Systolic and Diastolic Blood Pressure (SBP, DBP) | Supine SBP D2 | 102.8 mmHg | Standard Deviation 12.1 |
| 300 mg DF2755A | Systolic and Diastolic Blood Pressure (SBP, DBP) | Standing SBP D-1 | 115.7 mmHg | Standard Deviation 9.5 |
| 300 mg DF2755A | Systolic and Diastolic Blood Pressure (SBP, DBP) | Supine DBP D-1 | 64.7 mmHg | Standard Deviation 8.9 |
| 300 mg DF2755A | Systolic and Diastolic Blood Pressure (SBP, DBP) | Supine DBP D2 | 64.5 mmHg | Standard Deviation 11.7 |
| 300 mg DF2755A | Systolic and Diastolic Blood Pressure (SBP, DBP) | Standing DBP D-1 | 72.7 mmHg | Standard Deviation 11.6 |
| 600 mg DF2755A | Systolic and Diastolic Blood Pressure (SBP, DBP) | Standing DBP D-1 | 78.7 mmHg | Standard Deviation 7 |
| 600 mg DF2755A | Systolic and Diastolic Blood Pressure (SBP, DBP) | Supine DBP D2 | 63.3 mmHg | Standard Deviation 6 |
| 600 mg DF2755A | Systolic and Diastolic Blood Pressure (SBP, DBP) | Standing SBP D-1 | 115.2 mmHg | Standard Deviation 2.6 |
| 600 mg DF2755A | Systolic and Diastolic Blood Pressure (SBP, DBP) | Supine SBP D2 | 104.8 mmHg | Standard Deviation 5 |
| 600 mg DF2755A | Systolic and Diastolic Blood Pressure (SBP, DBP) | Supine SBP D-1 | 113.8 mmHg | Standard Deviation 8.8 |
| 600 mg DF2755A | Systolic and Diastolic Blood Pressure (SBP, DBP) | Standing DBP D2 | 73.3 mmHg | Standard Deviation 7.3 |
| 600 mg DF2755A | Systolic and Diastolic Blood Pressure (SBP, DBP) | Supine DBP D-1 | 61.0 mmHg | Standard Deviation 6.7 |
| 600 mg DF2755A | Systolic and Diastolic Blood Pressure (SBP, DBP) | Standing SBP D2 | 112.7 mmHg | Standard Deviation 11.8 |
Secondary
t1/2
It is the plasma concentration half life.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | t1/2 | 1.49 Hours | Geometric Coefficient of Variation 54.2 |
| 50 mg DF2755A | t1/2 | 1.62 Hours | Geometric Coefficient of Variation 42.6 |
| 150 mg DF2755A | t1/2 | 3.19 Hours | Geometric Coefficient of Variation 43.9 |
| 300 mg DF2755A | t1/2 | 4.05 Hours | Geometric Coefficient of Variation 52.5 |
Secondary
Tmax
It is the first time to reach Cmax.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Tmax | 0.50 Hours |
| 50 mg DF2755A | Tmax | 0.50 Hours |
| 150 mg DF2755A | Tmax | 0.50 Hours |
| 300 mg DF2755A | Tmax | 0.77 Hours |
Secondary
Vz/F
It is the apparent volume of distribution during terminal phase after non-intravenous administration.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Vz/F | 27.74 liters | Geometric Coefficient of Variation 48.6 |
| 50 mg DF2755A | Vz/F | 38.33 liters | Geometric Coefficient of Variation 32.7 |
| 150 mg DF2755A | Vz/F | 52.98 liters | Geometric Coefficient of Variation 36.1 |
| 300 mg DF2755A | Vz/F | 42.98 liters | Geometric Coefficient of Variation 31.2 |