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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
QUADRUPLE
Enrollment
80
selective nonpeptide angiotensin II type 2 receptor (AT2R) agonist
Placebo for C106 solution
CTC Clinical Trial Consultants AB
Uppsala, Sweden
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
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.
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.
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.
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
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