Exclusion criteria
bladder tumors, fever, malignancy, stroke, unstable angina, ventricular rhythm disturbances, psychiatric, nausea,, depression, only).Donation, abdominal pain, basal cell carcinoma, TG, hepatitis, vomiting, infection, prolonged QT, heart failure, myocardial infarction, cardiovascular or coronary artery disease, pain, jaundice, Brugada syndrome, atrial arrhythmias
BLADDER TUMORS, CARDIOVASCULAR DISEASE, SQUAMOUS CELL SKIN CANCER, STROKE, UNSTABLE ANGINA, ASYMPTOMATIC BRADYCARDIA, HEART, 3RD DEGREE HEART BLOCK, VENTRICULAR TACHYCARDIA, HEPATITIS, BASAL CELL CARCINOMAS, BLEEDING DIATHESIS, HEPATITIS B, TORSADES DE POINTES, ATRIAL ARRHYTHMIA, INFECTION, MALIGNANCIES, HEPATITIS C, COAGULOPATHY, UNSTABLE DIABETES MELLITUS, HEART FAILURE, CONGENITAL LONG QT SYNDROME, FIBRILLATION, SUDDEN CARDIAC DEATH, VIRUS, UNCONTROLLED HYPERTENSION, MYOCARDIAL INFARCTION, TRANSIENT ISCHEMIC ATTACK (TIA), METASTATIC DISEASE, CEREBROVASCULAR ACCIDENT, CERVICAL CANCER, BRUGADA SYNDROME
Participants who met any of the following criteria at screening were not eligible to participate in the study:Female participants with a positive pregnancy test or who were lactating.Acute signs of hepatitis (for example, moderate fever, jaundice, nausea, vomiting and abdominal pain) at screening or at baseline.Use of prescription medication that, in the opinion of the study investigator or the sponsor, would interfere with study conduct. Stable regimens to lower LDL-C or TG or to treat cardiovascular disease, stable regimens of anti-hypertensives and stable regimens of anti-platelet agents or anti-coagulants were acceptable for cohorts 5, 6, 7 and 8 as long as the participant met other criteria. Stable regimen was defined as on treatment for at least 3 months. Topical products without systemic absorption, over-the-counter and prescription pain medication or hormonal contraceptives (female participants) were acceptable at the investigator’s discretion.Use of more than two tobacco/nicotine-containing or cannabis products (for example, two cigarettes) per month within 6 months before the first intraperitoneal administration (applicable only to HP cohorts 1, 2, 3, 4, 2b, 3b and 4b).HIV infection, as shown by the presence of anti-HIV antibody (seropositive).Seropositive for hepatitis B virus or hepatitis C virus (HCV) (HCV seropositivity required positive test for antibodies confirmed with positive test for HCV RNA).Had uncontrolled hypertension, defined as blood pressure >170/100 mmHg at screening, confirmed by repeat.A history of torsades de pointes, ventricular rhythm disturbances (for example, ventricular tachycardia or fibrillation), pathologic symptomatic bradycardia, 2nd degree or 3rd degree heart block, congenital long QT syndrome, prolonged QT interval due to medications or new elevation or depression in the part of an ECG immediately after the QRS complex and merging into the T wave (ST segment) or new pathologic inverted T waves or new pathologic Q waves on ECG that were deemed clinically significant in the opinion of the PI. Participants with a history of atrial arrhythmias could be discussed with the Sponsor Medical Monitor and the CRO Medical Monitor.A family history of congenital long QT syndrome, Brugada syndrome or unexplained sudden cardiac death.Symptomatic heart failure (per New York Heart Association guidelines), unstable angina, myocardial infarction, severe cardiovascular disease (ejection fraction <20%), transient ischemic attack (TIA) or cerebrovascular accident (CVA) within 6 months before study entry. For cohorts 7, 7b, 7c and 8, known stable (no clinically significant adverse change in last 6 months) cardiovascular or coronary artery disease was acceptable.History of malignancy within the last 1 year except for basal cell carcinoma, squamous cell skin cancer, superficial bladder tumors or in situ cervical cancer. Participants with other treated malignancies who had no evidence of metastatic disease and more than 1 year without evidence of active malignancy could be entered after approval by the Sponsor Medical Monitor.History of major surgery within 3 months of screening.Regular use of alcohol within 1 month before the screening visit (that is, more than 14 units for women and 21 units for men per week (1 unit = 150 ml of wine, 360 ml of beer or 45 ml of 40% alcohol)).Cardiac troponin (troponin I) above ULN at screening.Recent (within 3 months) use of illicit drugs (such as cocaine, phencyclidine or and 3,4-methylenedioxy methamphetamine (MDMA)) or positive test for such drugs of abuse at screening. Participants who were on prescription medications that caused a positive result on urine drug screen were not excluded. Participants with a positive urine drug screen for cannabinoids were not excluded.Use of an investigational agent or device within 30 days before dosing or current participation in an investigational study.Any concomitant medical or psychiatric condition or social situation or any other situation that would make it difficult to comply with protocol requirements or put the participant at additional safety risk (for cohorts 5, 6, 7 and 8, stable diabetes mellitus based on principal investigator discretion, requiring or not requiring insulin, was not exclusionary.)Had a history of clinically meaningful coagulopathy, bleeding diathesis, stroke or myocardial infarction within 6 months of baseline and/or concurrent anti-coagulant medication(s).Participants with any of the following laboratory abnormalities:International normalized ratio >1.5× ULN at screeningPlatelets <100,000 per microliter at screeningParticipants who were unable to return for all scheduled study visits.Participants with any contraindications to MRI (cohort 5 only).Donation or loss of whole blood (excluding the volume of blood that was to be drawn during the screening procedures of the study) before administration of the study treatment as follows: 50–499 ml of whole blood within 30 days, or more than 499 ml of whole blood within 56 days, before study treatment administration.When laboratory value cutoffs were used for inclusion or exclusion, up to two repeat tests (after the initial screening test) were acceptable, and values from repeat testing could be used to determine study eligibility.