Everett

Researchers are evaluating a new care strategy for people at increased risk of atherosclerotic cardiovascular disease ASCVD but without symptoms. The study compares a Cleerly Coronary Artery Disease CAD Staging System-based care approach against the usual risk factor-based care to see if it better reduces cardiovascular events. This pragmatic, randomized trial addresses the need for improved methods to identify and personalize treatment for asymptomatic individuals at risk due to age, diabetes, prediabetes, or metabolic syndrome. Participants are randomly assigned to one of two groups. The risk factor-based care group receives usual care managed by their providers, while a cardiology team monitors and supports guideline-based treatment without revealing certain imaging results during the study. The Cleerly stage-based care group gets personalized management from a remote cardiologist-led team using the Cleerly CAD Staging System, which includes imaging to assess coronary atherosclerosis and guides pharmacotherapy and education. Treatment intensity may increase if plaque worsens after 24 months. During the study, participants will have assessments to monitor heart health and treatment adherence over an average of 3.5 years. Researchers will measure cardiovascular events and other related health outcomes to compare the two care strategies. The study involves ongoing medication monitoring, lab tests, and feedback to optimize prevention, with the goal of improving personalized care for cardiovascular risk management.

Researchers are evaluating the effects of azetukalner in adults diagnosed with bipolar I or II disorder who are currently experiencing a depressive episode, also known as bipolar depression. This Phase 3, multicenter, randomized, double-blind, placebo-controlled study aims to assess the safety and efficacy of azetukalner in this population. Participants must have had their first major depressive episode before age 50 and meet specific diagnostic criteria confirmed by clinical interview. Participants will be randomly assigned to receive either azetukalner 20 mg or a placebo orally once daily with food, preferably with the evening meal, for six weeks. The study has two groups one receiving the experimental drug and one receiving a placebo, both taken over the same period. The study is designed to keep participants and researchers unaware of the group assignments to ensure unbiased results. Throughout the trial, participants will be evaluated using various measures, including changes in depression severity assessed by the Montgomery-sberg Depression Rating Scale MADRS at baseline and at week 6, along with other scales at different time points. Safety and response will be monitored regularly during the six-week treatment period. The entire participation period is focused on this treatment phase, with assessments conducted to measure changes in symptoms and overall condition.

Researchers are evaluating azetukalner as a monotherapy in adults diagnosed with Major Depressive Disorder MDD. This Phase 3, multicenter, randomized, double-blind, placebo-controlled study aims to assess the clinical efficacy, safety, and tolerability of azetukalner compared to placebo in adults with moderate-to-severe MDD. Participants are adults aged 18 to 74 years with a current major depressive episode lasting between 6 weeks and 24 months. Participants will be randomly assigned to receive either azetukalner 20 mg or placebo, both taken orally once daily with food, preferably with the evening meal, for 6 weeks. The study uses a parallel design and includes a placebo comparator. Azetukalner and placebo are administered as daily oral doses over the treatment period. During the study, participants will undergo assessments including the Hamilton Depression Rating Scale HAMD-17 at baseline, Week 1, and Week 6, the Snaith-Hamilton Pleasure Scale SHAPS, and the Clinical Global Impression of Severity CGI-S score at Week 6. Safety and tolerability are monitored from screening through 8 weeks after the final dose. The primary outcome is the change from baseline in HAMD-17 at Week 6. Total participation may last several months, including screening, treatment, and follow-up periods.

Researchers are evaluating the effectiveness and safety of combining inavolisib with a cyclin-dependent kinase 4 and 6 inhibitor CDK46i and letrozole compared to placebo plus CDK46i and letrozole in adults with endocrine-sensitive PIK3CA-mutated hormone receptor-positive HR, HER2-negative advanced breast cancer. This phase III, randomized, double-blind study focuses on participants who have measurable disease and meet specific hormone receptor and HER2 status criteria. Participants are randomly assigned to receive either oral inavolisib once daily along with letrozole and CDK46i or placebo once daily with letrozole and CDK46i. The CDK46i is given on a schedule of either Days 1-21 or Days 1-28 of each 28-day cycle. The study includes parallel groups to compare these treatment combinations over time. During the study, participants will be monitored for progression-free survival, overall survival, response rates, duration of response, clinical benefit, and changes in pain, physical function, and global health status. Safety will be assessed by tracking adverse events and patient-reported treatment side effects using questionnaires. The study will follow participants for up to seven years, with regular evaluations to track disease status and quality of life.

Researchers are studying the effects of CYB003, a deuterated psilocin analog, compared to a matching placebo as an additional treatment for adults with Major Depressive Disorder MDD. This Phase III study aims to evaluate the safety, tolerability, and effectiveness of two different doses of CYB003 alongside participants current antidepressant medications and psychological support. Participants will be randomly assigned to one of three groups one receiving 8 mg of CYB003, another receiving 16 mg of CYB003, or a placebo group. Each participant will undergo two dosing sessions about three weeks apart while continuing their usual antidepressant treatment and receiving manualized psychological support from a facilitator. Non-responders in the placebo group may have the chance to receive CYB003 in an extension trial. During the study, participants will complete several assessments including the Montgomery-Asberg Depression Scale MADRS, Beck Depression Inventory-II BDI-II, Clinical Global Impression Scale CGI-S, Generalized Anxiety Disorder 7-Item Scale GAD-7, and Quality of Life Enjoyment and Satisfaction Questionnaire Q-LES-Q-SF. These evaluations occur at multiple timepoints from screening through the end of the trial. Safety and tolerability will be closely monitored throughout the study, with the total duration lasting approximately 12 weeks from baseline to study end.

Researchers are evaluating the anti-tumor activity and safety of amivantamab administered as a subcutaneous co-formulation with recombinant human hyaluronidase PH20 rHuPH20 in participants with advanced or metastatic solid tumors, including non-small cell lung cancer NSCLC with specific EGFR mutations. This study focuses on various cohorts, some receiving combination treatments, and others monitoring safety of the co-formulation alone. Participants receive amivantamab subcutaneously at doses adjusted by body weight, combined with treatments such as lazertinib orally, pemetrexed and carboplatin intravenously, or anticoagulants as appropriate. Dosing schedules vary by cohort, typically involving initial frequent doses followed by maintenance cycles every 21 or 28 days. Some participants may enter a long-term extension phase to continue receiving study treatments. During the study, participants undergo evaluations including tumor response assessments using RECIST 1.1 criteria, safety monitoring through adverse event tracking, laboratory tests, and patient-reported outcomes. Follow-up assessments occur up to several years depending on cohort. Participants eligibility includes confirmed NSCLC with specific EGFR mutations and adequate organ function, with monitoring of treatment safety and efficacy throughout their participation.

Researchers are evaluating the addition of Tersolisib LY4064809STX-478 to other anti-cancer drugs as a first treatment for adults with advanced hormone receptor-positive HRhuman epidermal growth factor receptor 2-negative HER2- breast cancer that has a PIK3CA mutation. This Phase 3 randomized, double-blind, placebo-controlled trial aims to understand the efficacy and safety of this combination compared to placebo, focusing on improving outcomes for patients with this specific genetic change. Participants receive LY4064809 orally in one of two doses combined with a CDK46 inhibitor such as Ribociclib, Palbociclib, or Abemaciclib and endocrine therapy ET administered orally or via intramuscular injection. The comparison group receives a placebo combined with the same CDK46 inhibitor and ET. The study includes two parts Part 1 explores dose optimization, and Part 2 evaluates the treatment combinations effectiveness and safety as a first-line therapy. During the study, participants will have regular assessments to monitor cancer response, progression, and safety over an estimated period of up to 5 years or more. Researchers will measure outcomes such as overall response rate, progression-free survival, duration of response, overall survival, and quality of life. Treatment continues as long as the cancer benefits without intolerable side effects. Safety monitoring, laboratory tests, and quality of life questionnaires are part of the participant involvement throughout the trial.

Researchers are evaluating whether combining tucatinib with trastuzumab and mFOLFOX6 works better than standard treatments for people with HER2 positive colorectal cancer that has spread or cannot be removed by surgery. This Phase 3 study also aims to learn about the side effects that may occur when taking this combination of drugs. Participants have metastatic or unresectable colorectal cancer and are randomly assigned to different treatment groups. Participants are randomly placed in one of two study groups. One group receives tucatinib taken orally twice daily along with trastuzumab given intravenously every 3 weeks and mFOLFOX6 chemotherapy every 2 weeks. The other group receives standard care, which may be mFOLFOX6 alone or combined with bevacizumab or cetuximab, both given intravenously on different schedules. Tissue samples and biopsies are collected before treatment to confirm HER2 positivity and other markers. During the study, participants will have regular evaluations including imaging scans to measure cancer progression, blood tests, and assessments of side effects and quality of life. Progression-free survival is the primary outcome measured for up to about 3 years, with other outcomes like overall survival and response rate also tracked. Safety monitoring continues for about one year after the last treatment. The study lasts several years, with ongoing follow-up to understand long-term effects and benefits.

This research aims to evaluate the safety and effectiveness of Icalcaprant in adults diagnosed with bipolar I or II disorder, specifically focusing on depressive episodes. Bipolar disorder is a chronic mood condition affecting a significant portion of the adult and pediatric populations in the United States. The study targets approximately 195 adult participants across about 35 sites in the U.S., aiming to understand how Icalcaprant impacts disease activity and adverse events. Participants are randomly assigned to one of three groups two groups receive different doses of oral Icalcaprant once daily for 6 weeks, and one group receives a matching placebo daily for the same period. After the treatment phase, all participants enter a 4-week safety follow-up period. The study uses a parallel design with quadruple masking to compare the effects of the investigational drug versus placebo. During the study, participants will attend regular visits at hospitals or clinics where they undergo medical assessments, blood tests, and complete questionnaires to monitor side effects and treatment effects. Researchers will measure changes from baseline to week 6 in depression severity using the Montgomery-sberg Depression Rating Scale and the Clinician Global Impression of Severity for bipolar disorder. Safety will be monitored up to approximately 10 weeks, ensuring participant well-being throughout the trial.

Bipolar disorder is a serious, long-lasting mood condition affecting both adults and children. This research focuses on studying the effects and safety of cariprazine, a medication approved for adults, in treating depressive episodes linked to bipolar I disorder in children and adolescents aged 10 to 17. The study aims to better understand how this drug impacts the pediatric population, where treatment options are currently limited. Participants will be randomly assigned to one of two groups one receiving cariprazine at flexible doses adjusted by age and weight, and the other receiving a placebo. The treatment lasts six weeks, with dose adjustments at week 3 depending on response. Following treatment, there is a four-week safety follow-up period. Weekly visits at clinics or hospitals will support monitoring and treatment. During the study, participants will undergo medical assessments, blood tests, questionnaires, and side effect checks to evaluate the drugs impact. Researchers will track changes in mood symptoms using scales like the Childrens Depression Rating Scale and monitor safety through vital signs, lab tests, and movement assessments. The total study participation spans around 10 weeks, including treatment and follow-up.