First-in-human Trial to Evaluate the Safety, Tolerability... | NCT05427253

NCT05427253

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

Status Module

Label	Type	Description	Intervention Names
C106 solution	Experimental	Part A: Oral administration start dose, Single dose 5 mg Part B: Oral administration start dose 20 mg twice daily for 8 days	Drug: C106 solution
Placebo	Placebo Comparator	Part A and B: Placebo to C106 without the active pharmaceutical ingredient	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
C106 solution	Drug	selective nonpeptide angiotensin II type 2 receptor (AT2R) agonist	C106 solution

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.	From date of signing informed consent until End of Study, assessed up to Day 22
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.	Part A: Up to Day 10. Part B: Up to Day 22.
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.	Part A: Up to Day 3, Part B: Up to Day 10. Vital signs were measured at pre-defined timepoints during the trial.
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.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Willing and able to give written informed consent for participation in the trial.
Healthy males and females of non-childbearing potential aged 18-65 years inclusive.
Body Mass Index (BMI) ≥ 18.5 and ≤ 30.0 kg/m2
Clinically normal medical history, physical findings, vital signs, ECG, and laboratory values at the time of screening, as judged by the Investigator
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:

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.
Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP.
Malignancy within the past 5 years except for in situ removal of basal cell carcinoma.
Any planned major surgery within the duration of the trial.
Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody and Human Immunodeficiency Virus (HIV).
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
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.
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.
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.
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.
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.
Positive screen for drugs of abuse or alcohol at screening or on admission to the unit prior to administration of the IMP.
History of alcohol abuse or excessive intake of alcohol, as judged by the Investigator.
Presence or history of drug abuse, as judged by the Investigator.
History of, or current use of, anabolic steroids.
Excessive caffeine consumption defined by a daily intake of >5 cups of caffeine containing beverages.
Plasma donation within one month of screening or blood donation (or corresponding blood loss) during the three months prior to screening.
Investigator considers the subject unlikely to comply with trial procedures, restrictions, and requirements.

Name	Affiliation	Role
Måns Jergil, PhD	CTC Clinical Trial Consultants AB (CTC)	Study Director
Helena Litorp, MD, PhD	CTC Clinical Trial Consultants AB (CTC)	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
CTC Clinical Trial Consultants AB		Uppsala		SE-752 37	Sweden

Arm/Group Information

ID	Title	Description
FG000	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
FG001	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
FG002	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
FG003	SAD Part Cohort 4, Dose 180 mg Fasted First, Then Dose 180 mg Fed	Oral administration, Single dose 180 mg oral solution Subjects proceed from the SAD Part Cohort 4, dose 180 mg fasting after a washout period of at least 5 half-lives of C106 to a second period where the intervention of 180 mg is given under fed condition. C106 solution: selective nonpeptide angiotensin II type 2 receptor (AT2R) agonist
FG004	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
FG005	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
FG006	SAD Part, Placebo	Oral administration, Single dose placebo oral solution
FG007	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
FG008	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
FG009	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
FG010	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
FG011	MAD Part, Placebo	Oral administration of placebo oral solution twice daily for 8 days

ID	Title	Description
BG000	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
BG001	SAD Part Cohort 2, Dose 30 mg

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Categorical			Count of Participants

Outcome Measures Module

Outcome Measures

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	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.	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.	Posted		Number		Number of events		From date of signing informed consent until End of Study, assessed up to Day 22

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Dizziness	Nervous system disorders		Systematic Assessment

Title	Organization	Phone	Extension	Email
Cecilia Ganslandt, MD, MSc, Global Medical Director	Vicore Pharma AB	+46 317880560		info@vicorepharma.com

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Feb 27, 2023	May 17, 2024	Prot_SAP_000.pdf

ID	Term
D054990	Idiopathic Pulmonary Fibrosis
D006976	Hypertension, Pulmonary

ID	Term
D011658	Pulmonary Fibrosis
D017563	Lung Diseases, Interstitial
D008171	Lung Diseases
D012140	Respiratory Tract Diseases

ID	Title	Description
OG000	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
OG001	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
OG002	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
OG003	SAD Part Cohort 4, Dose 180 mg	Oral administration, Single dose 180 mg oral solution C106 solution: selective nonpeptide angiotensin II type 2 receptor (AT2R) agonist
OG004	SAD Part Cohort 4, Dose 180 mg Fed	Oral administration, Single dose 180 mg oral solution in fed condition. C106 solution: selective nonpeptide angiotensin II type 2 receptor (AT2R) agonist
OG005	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
OG006	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
OG007	SAD Part, Placebo	Oral administration, Single dose placebo oral solution
OG008	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
OG009	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
OG010	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
OG011	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
OG012	MAD Part, Placebo	Oral administration of placebo oral solution twice daily for 8 days