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| ID | Type | Description | Link |
|---|---|---|---|
| 2016-003629-41 | EudraCT Number |
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The Sponsor decided to not proceed from SAD to MAD to explore the possibility of further studying PD.
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Primary objective:
•To evaluate the tolerability and safety of ascending single doses of DF2755A in healthy adult male and female volunteers.
Secondary Objectives:
Please note that the study has been closed after Part A (single ascending doses), so all the objectives were revised accordingly.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo RS/PKS/PDS/SS | Placebo Comparator | 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 50 mg - RS/PKS/PDS/SS | Experimental | 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 150 mg - RS/PKS/PDS/SS | Experimental | 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 300 mg - RS/PKS/PDS/SS | Experimental | 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 600 mg - RS/PKS/PDS/SS | Experimental | 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| DF2755A | Drug | 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). |
| Measure | Description | Time Frame |
|---|---|---|
| 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:
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. | Throughout the study, up to Day 4 |
| Measure | Description | Time Frame |
|---|---|---|
| Cmax of DF2755A | Cmax is the observed maximum plasma concentration of a product. | 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) |
| Tmax |
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Inclusion Criteria:
For eligibility into the trial, subjects had to meet all the following inclusion criteria:
Healthy male subject, aged between 18 and 55 years inclusive;
Healthy female subject infertile or in post menopause for at least two years, aged between 18 and 60 years inclusive;
Body Mass Index (BMI) between 18.5 and 29.9 kg/m2 inclusive and weight ≤ 90kg;
Considered as healthy after a comprehensive clinical assessment (detailed medical history and complete physical examination);
Normal Blood Pressure (BP) and Heart Rate (HR) at the screening visit after 10 minutes in supine position:
Smoker < 5cigarettes per day who stop totally during the study;
Normal ECG recording on a 12-lead ECG at the screening visit:
Normal oral temperature;
36.3°C < oral body temperature < 37.5°C;
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;
Normal dietary habits;
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;
Covered by Health Insurance System and / or in compliance with the recommendations of National Law in force relating to biomedical research.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Yves Donazzolo, MD, MSc | Eurofins Optimed | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Eurofins Optimed | Gières | 38610 | France |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| FG002 | 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. |
| FG003 | 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. |
| FG004 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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The Randomized set (RS) was defined as all randomized subjects.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | 50 mg DF2755A |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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:
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. | Safety set: defined as all included subjects having taken at least one dose of study drug. | Posted | Number | events | Throughout the study, up to Day 4 |
|
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).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. Hence, only part A of the study was accomplished. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA (Unspecified) | Systematic Assessment |
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| dr. Mauro P. Ferrari | Dompé farmaceutici SpA | +39 02 583831 | clinops@pec.dompe.it |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 27, 2018 | Jan 24, 2023 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 5, 2019 | Dec 9, 2022 | SAP_001.pdf |
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| ID | Term |
|---|---|
| C000612078 | DF2755A |
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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.
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| Placebo | Other | Single oral dose administration on D1 |
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It is the first time to reach Cmax.
| 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) |
| t1/2 | It is the plasma concentration half life. | 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) |
| 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. | 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) |
| AUC 0-inf | It is the area under the plasma concentration-time curve from administration up to infinity with extrapolation of the terminal phase. | 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) |
| Vz/F | It is the apparent volume of distribution during terminal phase after non-intravenous administration. | 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) |
| CL/F | It is the apparent oral clearance of the drug, where CL = clearance and F = bioavailability. | 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) |
| 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. | 0-24 h post-dose; 24-48 h post-dose, 48-72 h post dose |
| 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. | 0-24 h post-dose; 24-48 h post-dose, 48-72 h post dose |
| Ae,ur(0-72) | The individual amount of DF2755A excreted in urine as DF2755Y over time in the whole sampling window is reported. | 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 |
| 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. | 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 |
| CLR | It is the renal clearance of DF2755Y. | 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 |
| 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. | day -1 (pre treatment), day 3 (last visit after treatment) |
| 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). | day -1 (pre treatment), day 3 (last visit after treatment) |
| 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. | day -1 (pre treatment), day 2 (post-treatment) |
| 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). | day -1 (pre treatment), day 3 (last visit after treatment) |
| 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. | day -1 (pre treatment), day 2 (post-treatment) |
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.
| BG002 | 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. |
| BG003 | 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. |
| BG004 | 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. |
| BG005 | Total | Total of all reporting groups |
| Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
|
| OG000 | 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. 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. |
| OG001 | 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 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. |
| OG002 | 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 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. |
| OG003 | 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 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. |
| OG004 | 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. |
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| Secondary | Cmax of DF2755A | Cmax is the observed maximum plasma concentration of a product. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 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) |
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| Secondary | Tmax | It is the first time to reach Cmax. | 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. | Posted | Median | Full Range | Hours | 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) |
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| Secondary | t1/2 | It is the plasma concentration half life. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours | 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) |
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | 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) |
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | 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) |
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| Secondary | Vz/F | It is the apparent volume of distribution during terminal phase after non-intravenous administration. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | liters | 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) |
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| Secondary | CL/F | It is the apparent oral clearance of the drug, where CL = clearance and F = bioavailability. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | L/hours | 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) |
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | μg | 0-24 h post-dose; 24-48 h post-dose, 48-72 h post dose |
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | percentage of value | 0-24 h post-dose; 24-48 h post-dose, 48-72 h post dose |
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| Secondary | Ae,ur(0-72) | The individual amount of DF2755A excreted in urine as DF2755Y over time in the whole sampling window is reported. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | μg | 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 |
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | percentage of value | 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 |
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| Secondary | CLR | It is the renal clearance of DF2755Y. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | L/hours | 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 |
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| 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. | The Safety set (SS) was defined as all included subjects having taken at least one dose of study drug. | Posted | Mean | Standard Deviation | bpm | day -1 (pre treatment), day 3 (last visit after treatment) |
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| 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). | The Safety set (SS) was defined as all included subjects having taken at least one dose of study drug | Posted | Mean | Standard Deviation | ms | day -1 (pre treatment), day 3 (last visit after treatment) |
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| 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. | The Safety set (SS) was defined as all included subjects having taken at least one dose of study drug. | Posted | Mean | Standard Deviation | mmHg | day -1 (pre treatment), day 2 (post-treatment) |
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| 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). | The Safety set (SS) was defined as all included subjects having taken at least one dose of study drug. | Posted | Mean | Standard Deviation | bpm | day -1 (pre treatment), day 3 (last visit after treatment) |
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| 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. | The Safety set (SS) was defined as all included subjects having taken at least one dose of study drug | Posted | Mean | Standard Deviation | °C | day -1 (pre treatment), day 2 (post-treatment) |
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| 0 |
| 8 |
| 0 |
| 8 |
| 2 |
| 8 |
| EG001 | 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. | 0 | 6 | 0 | 6 | 1 | 6 |
| EG002 | 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. | 0 | 6 | 0 | 6 | 0 | 6 |
| EG003 | 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. | 0 | 6 | 0 | 6 | 1 | 6 |
| EG004 | 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. | 0 | 6 | 0 | 6 | 0 | 6 |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
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| Limb discomfort | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
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Not provided
Not provided
| D3 |
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| PR D3 |
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| QRS D-1 |
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| QRS D3 |
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| QT D-1 |
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| QT D3 |
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| QTcF D-1 |
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| QTcF D3 |
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| Supine SBP D2 |
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| Standing SBP D-1 |
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| Standing SBP D2 |
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| Supine DBP D-1 |
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| Supine DBP D2 |
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| Standing DBP D-1 |
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| Standing DBP D2 |
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| Supine HR D3 |
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| Standing HR D-1 |
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| Standing HR D3 |
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| Oral Temperature D2 |
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