Idiopathic Pulmonary Fibrosis, Pulmonary Hypertension, Safety Issues, Tolerance
Conditions
Brief summary
This is a FIH, double-blind, placebo-controlled, within-group randomised, trial designed to evaluate the safety, tolerability, and pharmacokinetics (PK) of single and multiple ascending oral doses of compound 106 (C106) in healthy females of non-childbearing potential and healthy males. The trial will be conducted in 2 parts: Part A, single ascending dose (SAD) including a food interaction cohort: safety, tolerability, and PK in healthy males and healthy females of non-childbearing potential receiving single ascending doses of C106. Part B, multiple ascending dose (MAD): safety, tolerability, and PK in healthy males and healthy females of non-childbearing potential receiving twice daily multiple ascending doses of C106 for 8 days.
Interventions
DRUGC106 solution
selective nonpeptide angiotensin II type 2 receptor (AT2R) agonist
DRUGPlacebo
Placebo for C106 solution
Sponsors
Vicore Pharma AB
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The IMP, i.e., the C106 and the placebo oral solutions, are identical in appearance. Both solutions are colourless to yellow. Hence, it is expected that the subjects, Investigator and other site personnel will remain unaware of treatment allocation.
Intervention model description
Part A, single ascending dose (SAD) including a food interaction cohort Part B, multiple ascending dose (MAD)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. Willing and able to give written informed consent for participation in the trial. 2. Healthy males and females of non-childbearing potential aged 18-65 years inclusive. 3. Body Mass Index (BMI) ≥ 18.5 and ≤ 30.0 kg/m2 4. Clinically normal medical history, physical findings, vital signs, ECG, and laboratory values at the time of screening, as judged by the Investigator 5. Women of non-childbearing potential, defined as pre-menopausal females who are sterilized (tubal ligation or permanent bilateral occlusion of fallopian tubes); or females who have undergone hysterectomy or bilateral oophorectomy; or post-menopausal defined as 12 months of amenorrhea (in questionable cases a blood sample with simultaneous detection of follicle stimulating hormone \[FSH\] ≥ 25 IU/L is confirmatory). Male subjects must be willing to use condom or be vasectomised or practice sexual abstinence to prevent pregnancy and drug exposure of a partner and refrain from donating sperm from the date of dosing until 3 months after (last) dosing with the IMP. Their female partner of child-bearing potential must use highly effective contraceptive methods with a failure rate of \< 1% to prevent pregnancy (combined \[oestrogen and progestogen containing\] hormonal contraception associated with inhibition of ovulation \[oral, intravaginal, transdermal\], progestogen-only hormonal contraception associated with inhibition of ovulation \[oral, injectable, implantable\], intrauterine device \[IUD\]or intrauterine hormone-releasing system \[IUS\]) from at least 4 weeks prior to dose to 3 months after last dose.
Exclusion criteria
1. History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the trial, or influence the results or the subject's ability to participate in the trial. 2. Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP. 3. Malignancy within the past 5 years except for in situ removal of basal cell carcinoma. 4. Any planned major surgery within the duration of the trial. 5. Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody and Human Immunodeficiency Virus (HIV). 6. After 10 minutes supine rest at the time of screening, any vital signs values outside the following ranges: * Systolic blood pressure \<90 or \>140 mmHg, or * Diastolic blood pressure \<50 or \>90 mmHg, or * Pulse \<40 or \>90 bpm 7. Prolonged QTcF (\>450 ms), PR interval \< 120 ms or \> 240 ms, QRS\>115 ms, clinically significant cardiac arrhythmias or any clinically significant abnormalities in the resting ECG at the time of screening, as judged by the Investigator. 8. History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the Investigator, or history of hypersensitivity to drugs with a similar chemical structure or class to C106. 9. Regular use of any prescribed or non-prescribed medication including antacids, analgesics, herbal remedies, vitamins and minerals within 2 weeks prior to the (first) administration of IMP, at the discretion of the Investigator. 10. Planned treatment or treatment with another investigational drug within 3 months prior to Day -1. Subjects consented and screened but not dosed in previous clinical trials are not excluded. 11. Current smokers or users of nicotine products. Irregular use of nicotine (e.g., smoking, snuffing, chewing tobacco) less than three times per week is allowed before screening visit. 12. Positive screen for drugs of abuse or alcohol at screening or on admission to the unit prior to administration of the IMP. 13. History of alcohol abuse or excessive intake of alcohol, as judged by the Investigator. 14. Presence or history of drug abuse, as judged by the Investigator. 15. History of, or current use of, anabolic steroids. 16. Excessive caffeine consumption defined by a daily intake of \>5 cups of caffeine containing beverages. 17. Plasma donation within one month of screening or blood donation (or corresponding blood loss) during the three months prior to screening. 18. Investigator considers the subject unlikely to comply with trial procedures, restrictions, and requirements.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Number of Treatment Emergent Adverse Events (AEs) and Serious AEs (SAEs) | From date of signing informed consent until End of Study, assessed up to Day 22 | AE reporting and questioning. AEs must be recorded in the AE Log of the eCRF. The Investigator must provide information on the AE, preferably with a diagnosis or at least with signs and symptoms; start and stop dates, start and stop time; intensity; causal relationship to IMP; action taken, and outcome. If the AE is serious, this must be indicated in the eCRF. AEs, including out-of-range clinically significant clinical safety laboratory values, must be recorded individually, except when considered manifestations of the same medical condition or disease state; in such cases, they must be recorded under a single diagnosis. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0. The causal relationship between AEs and the IMP was assessed as related, not related or not applicable. |
| Number of Reported Clinically Significant Changes From Baseline in 12-lead Electrocardiograms (ECGs) | Part A: Up to Day 10. Part B: Up to Day 22. | Single 12-lead ECG will be recorded in supine position after 10 minutes of rest using an ECG machine. Abnormalities will be specified and documented as clinically significant or not clinically significant. Heart rate (HR) and PR, QRS, QT, and QTcF intervals were recorded. |
| Number of Reported Clinically Significant Changes in Vital Signs | Part A: Up to Day 3, Part B: Up to Day 10. Vital signs were measured at pre-defined timepoints during the trial. | Systolic and diastolic blood pressure and pulse were measured in supine position after 10 minutes of rest. The respiratory rate was assessed. Body temperature was measured using a digital thermometer on Day -1 of each part. |
| Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis) | Part A: Up to Day 3, Part B: Up to Day 10. Safety laboratory samples were collected at pre-defined timepoints during the trial. | Blood samples for analysis of clinical chemistry, haematology, and coagulation parameters were collected through venepuncture or an indwelling venous catheter. |
| Number of Reported Clinically Significant Changes in Physical Examinations. | Physical examination was performed at pre-defined timepoints during the trial. Part A: Day 7, Part B: Day 22 | Any abnormalities will be specified and documented as clinically significant or not clinically significant. Abnormal findings assessed as clinically significant will be reported as AEs. A complete physical examination will include assessments of the head, eyes, ears, nose, throat, skin, neurological, lungs, cardiovascular, and abdomen. . |
Countries
Sweden
Participant flow
Recruitment details
The subjects were recruited from CTC's database of healthy volunteers and patients, as well as from strategic marketing campaigns. Advertisements in social media and other media. Single ascending dose (SAD) part: First subject screened: 08-Jun-2022 Last subject completed: 09-May-2023 Multiple ascending dose (MAD) part: First subject screened: 19-Aug-2022 Last subject completed: 22-Jun-2023
Pre-assignment details
SAD part: Screened - 92 subjects, included - 48 subjects. Subjects in the SAD Part Cohort 4, dose 180 mg group were supposed to completed additional trial visits exploring single dose administration of C106 under fed conditions, this group is called SAD Part Cohort 4, dose 180 mg fasted first, then Dose 180 mg Fed. MAD part: Screened - 77 subjects, included 32 subjects. 28 subjects completed all 3 trial visits (multiple dose administration of C106). 4 subjects were withdrawn from the trial.
Participants by arm
| Arm | Count |
|---|---|
| SAD Part Cohort 1, Dose 5 mg Oral administration, Single dose 5 mg oral solution
C106 solution: selective nonpeptide angiotensin II type 2 receptor (AT2R) agonist | 6 |
| SAD Part Cohort 2, Dose 30 mg Oral administration, Single dose 30 mg oral solution
C106 solution: selective nonpeptide angiotensin II type 2 receptor (AT2R) agonist | 6 |
| SAD Part Cohort 3, Dose 60 mg Oral administration, Single dose 60 mg oral solution
C106 solution: selective nonpeptide angiotensin II type 2 receptor (AT2R) agonist | 6 |
| SAD Part Cohort 4, Dose 180 mg, Fasted First, Then Dose 180 mg Fed Oral administration, Single dose 180 mg oral solution, Fasted First, Then Dose 180 mg Fed
C106 solution: selective nonpeptide angiotensin II type 2 receptor (AT2R) agonist | 6 |
| SAD Part Cohort 5, Dose 240 mg Oral administration, Single dose 240 mg oral solution
C106 solution: selective nonpeptide angiotensin II type 2 receptor (AT2R) agonist | 6 |
| SAD Part, Cohort 6, Dose 300 mg Oral administration, Single dose 300 mg oral solution
C106 solution: selective nonpeptide angiotensin II type 2 receptor (AT2R) agonist | 6 |
| SAD Part, Placebo Oral administration, Single dose placebo oral solution | 12 |
| MAD Part, Dose 40mg Oral administration dose 40 mg twice daily for 8 days
C106 solution: selective nonpeptide angiotensin II type 2 receptor (AT2R) agonist | 6 |
| MAD Part, Dose 100mg Oral administration dose 100 mg twice daily for 8 days
C106 solution: selective nonpeptide angiotensin II type 2 receptor (AT2R) agonist | 6 |
| MAD Part, Dose 140mg Oral administration dose 140 mg twice daily for 8 days
C106 solution: selective nonpeptide angiotensin II type 2 receptor (AT2R) agonist | 6 |
| MAD Part, Dose 180mg Oral administration dose 180 mg twice daily for 8 days
C106 solution: selective nonpeptide angiotensin II type 2 receptor (AT2R) agonist | 6 |
| MAD Part, Placebo Oral administration of placebo oral solution twice daily for 8 days | 8 |
| Total | 80 |
Baseline characteristics
| Characteristic | Total | SAD Part Cohort 3, Dose 60 mg | SAD Part Cohort 4, Dose 180 mg, Fasted First, Then Dose 180 mg Fed | SAD Part Cohort 5, Dose 240 mg | SAD Part Cohort 2, Dose 30 mg | SAD Part, Cohort 6, Dose 300 mg | SAD Part, Placebo | MAD Part, Dose 40mg | MAD Part, Dose 100mg | MAD Part, Dose 140mg | SAD Part Cohort 1, Dose 5 mg | MAD Part, Dose 180mg | MAD Part, Placebo |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 80 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 12 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 8 Participants |
| Age, Continuous | 39.7 years STANDARD_DEVIATION 13 | 35.0 years STANDARD_DEVIATION 9.4 | 40.2 years STANDARD_DEVIATION 16.2 | 38.7 years STANDARD_DEVIATION 14 | 47.2 years STANDARD_DEVIATION 12.9 | 50.8 years STANDARD_DEVIATION 17 | 46.5 years STANDARD_DEVIATION 14.4 | 39.3 years STANDARD_DEVIATION 10.6 | 29.0 years STANDARD_DEVIATION 5.3 | 31.3 years STANDARD_DEVIATION 7.1 | 38.5 years STANDARD_DEVIATION 11.7 | 37.2 years STANDARD_DEVIATION 9.9 | 36.6 years STANDARD_DEVIATION 13 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 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 | 0 Participants | 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 75 Participants | 6 Participants | 6 Participants | 6 Participants | 5 Participants | 6 Participants | 11 Participants | 6 Participants | 6 Participants | 4 Participants | 6 Participants | 5 Participants | 8 Participants |
| Region of Enrollment Sweden | 80 participants | 6 participants | 6 participants | 6 participants | 6 participants | 6 participants | 12 participants | 6 participants | 6 participants | 6 participants | 6 participants | 6 participants | 8 participants |
| Sex: Female, Male Female | 14 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 4 Participants | 3 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 66 Participants | 6 Participants | 5 Participants | 5 Participants | 5 Participants | 2 Participants | 9 Participants | 5 Participants | 6 Participants | 5 Participants | 6 Participants | 5 Participants | 7 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 | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 5 | 0 / 6 | 0 / 6 | 0 / 12 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 8 |
| other Total, other adverse events | 2 / 6 | 2 / 6 | 2 / 6 | 2 / 6 | 2 / 5 | 2 / 6 | 4 / 6 | 4 / 12 | 4 / 6 | 5 / 6 | 5 / 6 | 4 / 6 | 8 / 8 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 5 | 0 / 6 | 0 / 6 | 0 / 12 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 8 |
Outcome results
Primary
Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis)
Blood samples for analysis of clinical chemistry, haematology, and coagulation parameters were collected through venepuncture or an indwelling venous catheter.
Time frame: Part A: Up to Day 3, Part B: Up to Day 10. Safety laboratory samples were collected at pre-defined timepoints during the trial.
Population: Data were presented using summary statistics.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SAD Part Cohort 1, Dose 5 mg | Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis) | Coagulation | 0 Number of events |
| SAD Part Cohort 1, Dose 5 mg | Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis) | Haematology | 0 Number of events |
| SAD Part Cohort 1, Dose 5 mg | Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis) | Urinalysis | 0 Number of events |
| SAD Part Cohort 1, Dose 5 mg | Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis) | Clinical chemistry | 0 Number of events |
| SAD Part Cohort 2, Dose 30 mg | Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis) | Haematology | 0 Number of events |
| SAD Part Cohort 2, Dose 30 mg | Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis) | Coagulation | 0 Number of events |
| SAD Part Cohort 2, Dose 30 mg | Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis) | Urinalysis | 0 Number of events |
| SAD Part Cohort 2, Dose 30 mg | Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis) | Clinical chemistry | 0 Number of events |
| SAD Part Cohort 3, Dose 60 mg | Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis) | Coagulation | 0 Number of events |
| SAD Part Cohort 3, Dose 60 mg | Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis) | Urinalysis | 0 Number of events |
| SAD Part Cohort 3, Dose 60 mg | Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis) | Haematology | 0 Number of events |
| SAD Part Cohort 3, Dose 60 mg | Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis) | Clinical chemistry | 0 Number of events |
| SAD Part Cohort 4, Dose 180 mg | Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis) | Coagulation | 0 Number of events |
| SAD Part Cohort 4, Dose 180 mg | Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis) | Urinalysis | 0 Number of events |
| SAD Part Cohort 4, Dose 180 mg | Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis) | Haematology | 0 Number of events |
| SAD Part Cohort 4, Dose 180 mg | Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis) | Clinical chemistry | 0 Number of events |
| SAD Part Cohort 4, Dose 180 mg Fed | Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis) | Clinical chemistry | 0 Number of events |
| SAD Part Cohort 4, Dose 180 mg Fed | Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis) | Urinalysis | 0 Number of events |
| SAD Part Cohort 4, Dose 180 mg Fed | Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis) | Haematology | 0 Number of events |
| SAD Part Cohort 4, Dose 180 mg Fed | Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis) | Coagulation | 0 Number of events |
| SAD Part Cohort 5, Dose 240 mg | Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis) | Coagulation | 0 Number of events |
| SAD Part Cohort 5, Dose 240 mg | Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis) | Clinical chemistry | 1 Number of events |
| SAD Part Cohort 5, Dose 240 mg | Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis) | Haematology | 0 Number of events |
| SAD Part Cohort 5, Dose 240 mg | Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis) | Urinalysis | 0 Number of events |
| SAD Part, Cohort 6, Dose 300 mg | Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis) | Urinalysis | 0 Number of events |
| SAD Part, Cohort 6, Dose 300 mg | Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis) | Clinical chemistry | 0 Number of events |
| SAD Part, Cohort 6, Dose 300 mg | Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis) | Haematology | 0 Number of events |
| SAD Part, Cohort 6, Dose 300 mg | Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis) | Coagulation | 0 Number of events |
| SAD Part, Placebo | Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis) | Haematology | 0 Number of events |
| SAD Part, Placebo | Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis) | Coagulation | 0 Number of events |
| SAD Part, Placebo | Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis) | Urinalysis | 0 Number of events |
| SAD Part, Placebo | Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis) | Clinical chemistry | 0 Number of events |
| MAD Part, Dose 40mg | Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis) | Urinalysis | 0 Number of events |
| MAD Part, Dose 40mg | Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis) | Clinical chemistry | 0 Number of events |
| MAD Part, Dose 40mg | Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis) | Coagulation | 0 Number of events |
| MAD Part, Dose 40mg | Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis) | Haematology | 0 Number of events |
| MAD Part, Dose 100mg | Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis) | Haematology | 0 Number of events |
| MAD Part, Dose 100mg | Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis) | Coagulation | 0 Number of events |
| MAD Part, Dose 100mg | Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis) | Urinalysis | 0 Number of events |
| MAD Part, Dose 100mg | Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis) | Clinical chemistry | 0 Number of events |
| MAD Part, Dose 140mg | Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis) | Coagulation | 0 Number of events |
| MAD Part, Dose 140mg | Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis) | Clinical chemistry | 0 Number of events |
| MAD Part, Dose 140mg | Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis) | Urinalysis | 0 Number of events |
| MAD Part, Dose 140mg | Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis) | Haematology | 0 Number of events |
| MAD Part, Dose 180mg | Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis) | Coagulation | 0 Number of events |
| MAD Part, Dose 180mg | Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis) | Clinical chemistry | 0 Number of events |
| MAD Part, Dose 180mg | Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis) | Haematology | 0 Number of events |
| MAD Part, Dose 180mg | Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis) | Urinalysis | 0 Number of events |
| MAD Part, Placebo | Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis) | Haematology | 0 Number of events |
| MAD Part, Placebo | Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis) | Urinalysis | 0 Number of events |
| MAD Part, Placebo | Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis) | Coagulation | 0 Number of events |
| MAD Part, Placebo | Number of Clinically Significant Changes in Laboratory Safety Variables (Haematology, Coagulation, Clinical Chemistry and Urine Analysis) | Clinical chemistry | 0 Number of events |
Primary
Number of Reported Clinically Significant Changes From Baseline in 12-lead Electrocardiograms (ECGs)
Single 12-lead ECG will be recorded in supine position after 10 minutes of rest using an ECG machine. Abnormalities will be specified and documented as clinically significant or not clinically significant. Heart rate (HR) and PR, QRS, QT, and QTcF intervals were recorded.
Time frame: Part A: Up to Day 10. Part B: Up to Day 22.
Population: Data were presented using summary statistics..
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SAD Part Cohort 1, Dose 5 mg | Number of Reported Clinically Significant Changes From Baseline in 12-lead Electrocardiograms (ECGs) | 0 Number of events |
| SAD Part Cohort 2, Dose 30 mg | Number of Reported Clinically Significant Changes From Baseline in 12-lead Electrocardiograms (ECGs) | 0 Number of events |
| SAD Part Cohort 3, Dose 60 mg | Number of Reported Clinically Significant Changes From Baseline in 12-lead Electrocardiograms (ECGs) | 1 Number of events |
| SAD Part Cohort 4, Dose 180 mg | Number of Reported Clinically Significant Changes From Baseline in 12-lead Electrocardiograms (ECGs) | 0 Number of events |
| SAD Part Cohort 4, Dose 180 mg Fed | Number of Reported Clinically Significant Changes From Baseline in 12-lead Electrocardiograms (ECGs) | 0 Number of events |
| SAD Part Cohort 5, Dose 240 mg | Number of Reported Clinically Significant Changes From Baseline in 12-lead Electrocardiograms (ECGs) | 1 Number of events |
| SAD Part, Cohort 6, Dose 300 mg | Number of Reported Clinically Significant Changes From Baseline in 12-lead Electrocardiograms (ECGs) | 0 Number of events |
| SAD Part, Placebo | Number of Reported Clinically Significant Changes From Baseline in 12-lead Electrocardiograms (ECGs) | 0 Number of events |
| MAD Part, Dose 40mg | Number of Reported Clinically Significant Changes From Baseline in 12-lead Electrocardiograms (ECGs) | 0 Number of events |
| MAD Part, Dose 100mg | Number of Reported Clinically Significant Changes From Baseline in 12-lead Electrocardiograms (ECGs) | 0 Number of events |
| MAD Part, Dose 140mg | Number of Reported Clinically Significant Changes From Baseline in 12-lead Electrocardiograms (ECGs) | 1 Number of events |
| MAD Part, Dose 180mg | Number of Reported Clinically Significant Changes From Baseline in 12-lead Electrocardiograms (ECGs) | 0 Number of events |
| MAD Part, Placebo | Number of Reported Clinically Significant Changes From Baseline in 12-lead Electrocardiograms (ECGs) | 0 Number of events |
Primary
Number of Reported Clinically Significant Changes in Physical Examinations.
Any abnormalities will be specified and documented as clinically significant or not clinically significant. Abnormal findings assessed as clinically significant will be reported as AEs. A complete physical examination will include assessments of the head, eyes, ears, nose, throat, skin, neurological, lungs, cardiovascular, and abdomen. .
Time frame: Physical examination was performed at pre-defined timepoints during the trial. Part A: Day 7, Part B: Day 22
Population: Data were presented using summary statistics.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SAD Part Cohort 1, Dose 5 mg | Number of Reported Clinically Significant Changes in Physical Examinations. | 0 Number of events |
| SAD Part Cohort 2, Dose 30 mg | Number of Reported Clinically Significant Changes in Physical Examinations. | 0 Number of events |
| SAD Part Cohort 3, Dose 60 mg | Number of Reported Clinically Significant Changes in Physical Examinations. | 0 Number of events |
| SAD Part Cohort 4, Dose 180 mg | Number of Reported Clinically Significant Changes in Physical Examinations. | 0 Number of events |
| SAD Part Cohort 4, Dose 180 mg Fed | Number of Reported Clinically Significant Changes in Physical Examinations. | 0 Number of events |
| SAD Part Cohort 5, Dose 240 mg | Number of Reported Clinically Significant Changes in Physical Examinations. | 0 Number of events |
| SAD Part, Cohort 6, Dose 300 mg | Number of Reported Clinically Significant Changes in Physical Examinations. | 0 Number of events |
| SAD Part, Placebo | Number of Reported Clinically Significant Changes in Physical Examinations. | 0 Number of events |
| MAD Part, Dose 40mg | Number of Reported Clinically Significant Changes in Physical Examinations. | 0 Number of events |
| MAD Part, Dose 100mg | Number of Reported Clinically Significant Changes in Physical Examinations. | 0 Number of events |
| MAD Part, Dose 140mg | Number of Reported Clinically Significant Changes in Physical Examinations. | 0 Number of events |
| MAD Part, Dose 180mg | Number of Reported Clinically Significant Changes in Physical Examinations. | 0 Number of events |
| MAD Part, Placebo | Number of Reported Clinically Significant Changes in Physical Examinations. | 0 Number of events |
Primary
Number of Reported Clinically Significant Changes in Vital Signs
Systolic and diastolic blood pressure and pulse were measured in supine position after 10 minutes of rest. The respiratory rate was assessed. Body temperature was measured using a digital thermometer on Day -1 of each part.
Time frame: Part A: Up to Day 3, Part B: Up to Day 10. Vital signs were measured at pre-defined timepoints during the trial.
Population: Data were presented using summary statistics.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SAD Part Cohort 1, Dose 5 mg | Number of Reported Clinically Significant Changes in Vital Signs | Respiratory rate | 0 Number of events |
| SAD Part Cohort 1, Dose 5 mg | Number of Reported Clinically Significant Changes in Vital Signs | Blood pressure | 0 Number of events |
| SAD Part Cohort 1, Dose 5 mg | Number of Reported Clinically Significant Changes in Vital Signs | Pulse | 0 Number of events |
| SAD Part Cohort 2, Dose 30 mg | Number of Reported Clinically Significant Changes in Vital Signs | Respiratory rate | 0 Number of events |
| SAD Part Cohort 2, Dose 30 mg | Number of Reported Clinically Significant Changes in Vital Signs | Pulse | 0 Number of events |
| SAD Part Cohort 2, Dose 30 mg | Number of Reported Clinically Significant Changes in Vital Signs | Blood pressure | 0 Number of events |
| SAD Part Cohort 3, Dose 60 mg | Number of Reported Clinically Significant Changes in Vital Signs | Pulse | 0 Number of events |
| SAD Part Cohort 3, Dose 60 mg | Number of Reported Clinically Significant Changes in Vital Signs | Blood pressure | 0 Number of events |
| SAD Part Cohort 3, Dose 60 mg | Number of Reported Clinically Significant Changes in Vital Signs | Respiratory rate | 0 Number of events |
| SAD Part Cohort 4, Dose 180 mg | Number of Reported Clinically Significant Changes in Vital Signs | Blood pressure | 0 Number of events |
| SAD Part Cohort 4, Dose 180 mg | Number of Reported Clinically Significant Changes in Vital Signs | Respiratory rate | 0 Number of events |
| SAD Part Cohort 4, Dose 180 mg | Number of Reported Clinically Significant Changes in Vital Signs | Pulse | 0 Number of events |
| SAD Part Cohort 4, Dose 180 mg Fed | Number of Reported Clinically Significant Changes in Vital Signs | Pulse | 0 Number of events |
| SAD Part Cohort 4, Dose 180 mg Fed | Number of Reported Clinically Significant Changes in Vital Signs | Blood pressure | 0 Number of events |
| SAD Part Cohort 4, Dose 180 mg Fed | Number of Reported Clinically Significant Changes in Vital Signs | Respiratory rate | 0 Number of events |
| SAD Part Cohort 5, Dose 240 mg | Number of Reported Clinically Significant Changes in Vital Signs | Respiratory rate | 0 Number of events |
| SAD Part Cohort 5, Dose 240 mg | Number of Reported Clinically Significant Changes in Vital Signs | Blood pressure | 1 Number of events |
| SAD Part Cohort 5, Dose 240 mg | Number of Reported Clinically Significant Changes in Vital Signs | Pulse | 0 Number of events |
| SAD Part, Cohort 6, Dose 300 mg | Number of Reported Clinically Significant Changes in Vital Signs | Pulse | 0 Number of events |
| SAD Part, Cohort 6, Dose 300 mg | Number of Reported Clinically Significant Changes in Vital Signs | Blood pressure | 1 Number of events |
| SAD Part, Cohort 6, Dose 300 mg | Number of Reported Clinically Significant Changes in Vital Signs | Respiratory rate | 0 Number of events |
| SAD Part, Placebo | Number of Reported Clinically Significant Changes in Vital Signs | Blood pressure | 0 Number of events |
| SAD Part, Placebo | Number of Reported Clinically Significant Changes in Vital Signs | Pulse | 0 Number of events |
| SAD Part, Placebo | Number of Reported Clinically Significant Changes in Vital Signs | Respiratory rate | 0 Number of events |
| MAD Part, Dose 40mg | Number of Reported Clinically Significant Changes in Vital Signs | Blood pressure | 0 Number of events |
| MAD Part, Dose 40mg | Number of Reported Clinically Significant Changes in Vital Signs | Pulse | 0 Number of events |
| MAD Part, Dose 40mg | Number of Reported Clinically Significant Changes in Vital Signs | Respiratory rate | 2 Number of events |
| MAD Part, Dose 100mg | Number of Reported Clinically Significant Changes in Vital Signs | Pulse | 0 Number of events |
| MAD Part, Dose 100mg | Number of Reported Clinically Significant Changes in Vital Signs | Respiratory rate | 1 Number of events |
| MAD Part, Dose 100mg | Number of Reported Clinically Significant Changes in Vital Signs | Blood pressure | 0 Number of events |
| MAD Part, Dose 140mg | Number of Reported Clinically Significant Changes in Vital Signs | Pulse | 0 Number of events |
| MAD Part, Dose 140mg | Number of Reported Clinically Significant Changes in Vital Signs | Blood pressure | 1 Number of events |
| MAD Part, Dose 140mg | Number of Reported Clinically Significant Changes in Vital Signs | Respiratory rate | 0 Number of events |
| MAD Part, Dose 180mg | Number of Reported Clinically Significant Changes in Vital Signs | Blood pressure | 0 Number of events |
| MAD Part, Dose 180mg | Number of Reported Clinically Significant Changes in Vital Signs | Respiratory rate | 1 Number of events |
| MAD Part, Dose 180mg | Number of Reported Clinically Significant Changes in Vital Signs | Pulse | 0 Number of events |
| MAD Part, Placebo | Number of Reported Clinically Significant Changes in Vital Signs | Respiratory rate | 2 Number of events |
| MAD Part, Placebo | Number of Reported Clinically Significant Changes in Vital Signs | Pulse | 0 Number of events |
| MAD Part, Placebo | Number of Reported Clinically Significant Changes in Vital Signs | Blood pressure | 0 Number of events |
Primary
Total Number of Treatment Emergent Adverse Events (AEs) and Serious AEs (SAEs)
AE reporting and questioning. AEs must be recorded in the AE Log of the eCRF. The Investigator must provide information on the AE, preferably with a diagnosis or at least with signs and symptoms; start and stop dates, start and stop time; intensity; causal relationship to IMP; action taken, and outcome. If the AE is serious, this must be indicated in the eCRF. AEs, including out-of-range clinically significant clinical safety laboratory values, must be recorded individually, except when considered manifestations of the same medical condition or disease state; in such cases, they must be recorded under a single diagnosis. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0. The causal relationship between AEs and the IMP was assessed as related, not related or not applicable.
Time frame: From date of signing informed consent until End of Study, assessed up to Day 22
Population: SAD: The withdrawn subject was part of Cohort 4 fed condition. .The subject was excluded from the trial before completing the food interaction visit.~MAD: Two (2) subjects in the 100 mg C106 dose group had AEs (common cold) that lead to subject withdrawal from the trial.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SAD Part Cohort 1, Dose 5 mg | Total Number of Treatment Emergent Adverse Events (AEs) and Serious AEs (SAEs) | Serious Adverse events | 0 Number of events |
| SAD Part Cohort 1, Dose 5 mg | Total Number of Treatment Emergent Adverse Events (AEs) and Serious AEs (SAEs) | Adverse events | 5 Number of events |
| SAD Part Cohort 2, Dose 30 mg | Total Number of Treatment Emergent Adverse Events (AEs) and Serious AEs (SAEs) | Adverse events | 5 Number of events |
| SAD Part Cohort 2, Dose 30 mg | Total Number of Treatment Emergent Adverse Events (AEs) and Serious AEs (SAEs) | Serious Adverse events | 0 Number of events |
| SAD Part Cohort 3, Dose 60 mg | Total Number of Treatment Emergent Adverse Events (AEs) and Serious AEs (SAEs) | Adverse events | 3 Number of events |
| SAD Part Cohort 3, Dose 60 mg | Total Number of Treatment Emergent Adverse Events (AEs) and Serious AEs (SAEs) | Serious Adverse events | 0 Number of events |
| SAD Part Cohort 4, Dose 180 mg | Total Number of Treatment Emergent Adverse Events (AEs) and Serious AEs (SAEs) | Serious Adverse events | 0 Number of events |
| SAD Part Cohort 4, Dose 180 mg | Total Number of Treatment Emergent Adverse Events (AEs) and Serious AEs (SAEs) | Adverse events | 2 Number of events |
| SAD Part Cohort 4, Dose 180 mg Fed | Total Number of Treatment Emergent Adverse Events (AEs) and Serious AEs (SAEs) | Adverse events | 2 Number of events |
| SAD Part Cohort 4, Dose 180 mg Fed | Total Number of Treatment Emergent Adverse Events (AEs) and Serious AEs (SAEs) | Serious Adverse events | 0 Number of events |
| SAD Part Cohort 5, Dose 240 mg | Total Number of Treatment Emergent Adverse Events (AEs) and Serious AEs (SAEs) | Adverse events | 7 Number of events |
| SAD Part Cohort 5, Dose 240 mg | Total Number of Treatment Emergent Adverse Events (AEs) and Serious AEs (SAEs) | Serious Adverse events | 0 Number of events |
| SAD Part, Cohort 6, Dose 300 mg | Total Number of Treatment Emergent Adverse Events (AEs) and Serious AEs (SAEs) | Serious Adverse events | 0 Number of events |
| SAD Part, Cohort 6, Dose 300 mg | Total Number of Treatment Emergent Adverse Events (AEs) and Serious AEs (SAEs) | Adverse events | 8 Number of events |
| SAD Part, Placebo | Total Number of Treatment Emergent Adverse Events (AEs) and Serious AEs (SAEs) | Serious Adverse events | 0 Number of events |
| SAD Part, Placebo | Total Number of Treatment Emergent Adverse Events (AEs) and Serious AEs (SAEs) | Adverse events | 4 Number of events |
| MAD Part, Dose 40mg | Total Number of Treatment Emergent Adverse Events (AEs) and Serious AEs (SAEs) | Serious Adverse events | 0 Number of events |
| MAD Part, Dose 40mg | Total Number of Treatment Emergent Adverse Events (AEs) and Serious AEs (SAEs) | Adverse events | 11 Number of events |
| MAD Part, Dose 100mg | Total Number of Treatment Emergent Adverse Events (AEs) and Serious AEs (SAEs) | Adverse events | 10 Number of events |
| MAD Part, Dose 100mg | Total Number of Treatment Emergent Adverse Events (AEs) and Serious AEs (SAEs) | Serious Adverse events | 0 Number of events |
| MAD Part, Dose 140mg | Total Number of Treatment Emergent Adverse Events (AEs) and Serious AEs (SAEs) | Serious Adverse events | 0 Number of events |
| MAD Part, Dose 140mg | Total Number of Treatment Emergent Adverse Events (AEs) and Serious AEs (SAEs) | Adverse events | 15 Number of events |
| MAD Part, Dose 180mg | Total Number of Treatment Emergent Adverse Events (AEs) and Serious AEs (SAEs) | Adverse events | 7 Number of events |
| MAD Part, Dose 180mg | Total Number of Treatment Emergent Adverse Events (AEs) and Serious AEs (SAEs) | Serious Adverse events | 0 Number of events |
| MAD Part, Placebo | Total Number of Treatment Emergent Adverse Events (AEs) and Serious AEs (SAEs) | Adverse events | 21 Number of events |
| MAD Part, Placebo | Total Number of Treatment Emergent Adverse Events (AEs) and Serious AEs (SAEs) | Serious Adverse events | 0 Number of events |