Plettenberg Bay

Researchers are evaluating the pharmacokinetics, safety, and efficacy of doravirine DOR and a fixed-dose combination of doravirinelamivudinetenofovir disoproxil fumarate DOR3TCTDF in children aged 4 weeks to under 12 years who weigh less than 45 kg and are infected with human immunodeficiency virus type 1 HIV-1. The study includes participants who are either treatment-naive or have been virologically suppressed on stable combination antiretroviral therapy for at least 3 months without treatment failure. The goal is to understand how DOR behaves in the body and its safety when used with other antiretrovirals in this pediatric population. Participants receive DOR doses ranging from 7.2 mg to 100 mg based on weight, combined with two nucleosidenucleotide analog reverse transcriptase inhibitors NRTIs as per local guidelines, or a fixed-dose combination of DOR3TCTDF tailored to weight. Treatment lasts for 96 weeks, and those completing the Week 96 visit may join an extension study to continue receiving DOR for up to 224 additional weeks or until it becomes commercially available. Throughout the study, participants undergo intensive pharmacokinetic sampling to measure drug concentrations at specific time points, safety monitoring for adverse events, and evaluations of HIV-1 viral load and immune cell counts at various weeks up to Week 96. Researchers also assess adherence to the medication regimens and the palatability of the oral pellets or granules. The total duration of participation can extend up to several years, including the extension phase.

Researchers are evaluating whether adding zilebesiran to standard antihypertensive treatment can reduce major cardiovascular events in adults with hypertension that is not well controlled and who either have established cardiovascular disease or are at high risk for it. This phase 3, randomized, double-blind study aims to determine if zilebesiran lowers the risk of cardiovascular death, heart attacks, strokes, or heart failure events compared to placebo. The study will continue until a targeted number of these events have occurred, which may take up to about 5 years. Participants will be randomly assigned to receive either 300 mg of zilebesiran or a placebo, both given as subcutaneous injections every 6 months, alongside their usual blood pressure medications. The study uses a parallel design and includes careful monitoring of blood pressure and cardiovascular events over time. Both groups will continue their standard antihypertensive therapies, including at least two medications where one must be a diuretic. During the study, participants will be regularly assessed for cardiovascular events such as heart attacks, strokes, heart failure hospitalizations, and cardiovascular death. Blood pressure measurements will be taken at baseline and at 6 months, among other times. The primary outcome is the time until the first occurrence of a major cardiovascular event, with secondary outcomes including changes in blood pressure and other cardiovascular events. Participants will be followed for up to approximately 5 years to monitor these outcomes and overall survival.