Inclusion criteria
only).On, TG, birth controlIntrauterine
FAMILIAL HYPERCHOLESTEROLEMIA
Participants who met all of the following criteria at screening were eligible to participate in the study:Male or female participants 18–65 years of age. In cohorts 7, 7b, 7c, 8 and 9, participants up to age 70 years were eligible if otherwise healthy and at the discretion of the investigator.Able and willing to provide written informed consent before the performance of any study-specific procedures.Participants with a BMI between 19.0 kg mA 12-lead ECG at screening and pre-dose assessment that, in the opinion of the principal investigator, had no abnormalities that compromise participant safety in this study.Non-nursing women.Fasting serum TG >100 mg dlFasting serum LDL-C >70 mg dlParticipants using two highly effective forms of contraception (both male and female partners) during the study and for 3 months after the dose of ARO-ANG3. Men were not to donate sperm for at least 3 months after dose of the last study treatment. Male partners of female participants and female partners of male participants were also required to use contraception, if they were of childbearing potential. Women of childbearing potential were required to have a negative urine pregnancy test at screening and on day 1. Women not of childbearing potential were to be postmenopausal (defined as cessation of regular menstrual periods for at least 12 months), confirmed by FSH level in the postmenopausal reference range.Using twice the normal protection of birth control by using a condom and one of the following:Birth control pillsDepot or injectable birth controlIntrauterine deviceBirth control patch (for example, Othro Evra)Vaginal ring (for example, NuvaRing)Surgical sterilization (that is, tubal ligation or hysterectomy for women or vasectomy for men or other forms of surgical sterilization) that could be verified in the participant’s medical history was acceptable as a single form of contraception.Rhythm methods were not considered as highly effective methods of birth control. Participant abstinence for the duration of the study and 3 months after the dose of ARO-ANG3 was acceptable only when this method was in alignment with the normal lifestyle of the participant.Participants who were willing and able to comply with all study assessments and adhere to the protocol schedule.Must have had suitable venous access for blood sampling.Aspartate transaminase (AST) and ALT <1.5× ULN at screening for cohorts 1–4 and 2b through 4b (one repeat screen test was allowed).AST and ALT <3× ULN at screening for cohorts 5, 6, 7, 7b, 7c and 8 (one repeat screen test was allowed).Creatinine levels ≤ULN at screening (one repeat screen test was allowed).MRI-PDFF indicating a liver fat content of ≥10% (cohort 5 only).On a stable regimen of statin therapy for at least 6 months and LDL-C >70 mg dlDocumented genetic diagnosis consistent with familial hypercholesterolemia (homozygous or heterozygous) with genotype documented in a verifiable source document OR Dutch Lipid Clinic Network Score ≥6 (cohorts 7, 7b and 7c only).LDL-C >100 mg dlScreening fasting TG ≥300 mg dlCohort 9 only: must have had completed all doses in cohorts 7, 7b or 7c.