Vratsa

Researchers are evaluating the safety and effectiveness of oral AP1189 combined with methotrexate (MTX) in adults with early rheumatoid arthritis (RA) who have not previously taken disease-modifying anti-rheumatic drugs (DMARDs). This phase II, randomized, double-blind, placebo-controlled study aims to understand how different doses of AP1189 affect disease activity and inflammation in participants with active RA symptoms. The study involves four groups of 60 participants each, receiving either AP1189 at doses of 40 mg, 70 mg, 100 mg, or a placebo, all alongside oral methotrexate. Treatments are given daily for 12 weeks. Participants will be randomly assigned to one of these groups to compare the dose response and safety of AP1189 combined with methotrexate versus methotrexate alone. Participants will attend scheduled visits to monitor their disease activity, safety, and tolerability of the treatment. Assessments include measuring changes in the Disease Activity Score 28 using C-Reactive Protein (DAS28-CRP) at week 12. The study also involves physical exams, joint assessments, blood tests for inflammation markers and antibodies, and safety monitoring. The total treatment period lasts 12 weeks, with ongoing evaluations throughout this time.

Researchers are studying the effectiveness and safety of a combination inhaler containing fluticasone propionate and albuterol sulfate delivered through a multidose dry powder inhaler with an electronic module (Fp/ABS eMDPI). This Phase 3 trial focuses on people aged 12 years and older who have asthma. The study also looks at the safety and tolerability of this inhaler when used four times daily over four weeks, as well as the pharmacokinetics of the combination and its individual components after a single dose. Participants will be randomly assigned to receive either the Fp/ABS combination inhaler, fluticasone propionate alone, albuterol sulfate alone, or a placebo inhaler. All treatments are given as inhalation powders. The main treatment period lasts four weeks, during which the inhalers are taken four times a day. The total study duration for each participant is about 10 weeks, not counting an optional prescreening visit. Throughout the study, researchers will measure lung function changes, specifically forced expiratory volume in one second (FEV1), from baseline to week 4. Participants will undergo assessments including lung function tests and safety evaluations. The study monitors how the inhaler affects breathing over time and checks for any side effects or tolerability issues during the treatment period.

Researchers are evaluating the effect of a triple therapy inhaler called BGF MDI containing budesonide, glycopyrronium, and formoterol fumarate compared with a dual therapy inhaler called GFF MDI containing glycopyrronium and formoterol fumarate in people with Chronic Obstructive Pulmonary Disease (COPD) who have a higher risk of heart and lung problems. This Phase III randomized, double-blind, parallel group study takes place at multiple centers and focuses on cardiopulmonary outcomes in these patients. Participants receive either the BGF MDI 320/14.4/9.6 micrograms twice daily or the GFF MDI 14.4/9.6 micrograms twice daily. The treatments are inhaled using metered dose inhalers. The study compares these two therapies over time to see how they affect the time until the first severe heart or lung event occurs. The study design ensures that neither participants nor researchers know which treatment is given to reduce bias. During the study, participants will have regular visits to the study site or virtual visits to complete assessments. Researchers will monitor lung function, symptoms, and blood tests, including blood eosinophil counts and COPD assessment test scores. The main outcome measured is the time to the first severe cardiac or COPD event, with follow-up lasting up to three years. Safety and adherence to treatment will also be closely observed throughout the study period.

Researchers are evaluating the effectiveness of camizestrant compared to standard endocrine therapy in patients with early breast cancer that is estrogen receptor positive (ER+) and human epidermal growth factor receptor 2 negative (HER2-). These patients have an intermediate or high risk of cancer recurrence and have already completed local treatments such as surgery and possibly chemotherapy, alongside at least 2 years and up to 5 years of standard adjuvant endocrine therapy. The study is a Phase III, open-label trial designed to assess outcomes over a long term. Participants will be randomly assigned to receive either camizestrant, an oral selective estrogen receptor degrader, or one of several standard endocrine therapies including tamoxifen, anastrozole, letrozole, or exemestane, administered according to local approved guidelines. The treatment duration for both groups is planned to last 60 months. Eligible patients may have previously used CDK4/6 inhibitors, and the study will specifically include those with intermediate or high risk of recurrence as determined by clinical and biological markers. During the study, participants will be monitored for up to 10 years from the last patient's randomization to evaluate invasive breast cancer-free survival. Additional outcomes include invasive disease-free survival, distant relapse-free survival, overall survival, safety, and clinical outcome assessments. The study involves ongoing assessments of health status, treatment effects, and safety to determine the long-term benefits and risks of camizestrant compared to standard therapies.

Researchers are evaluating the safety and effectiveness of KarXT in preventing relapse of psychosis symptoms in people aged 55 to 90 years who have psychosis associated with Alzheimer's Disease. This Phase 3 study is randomized, double-blind, placebo-controlled, and conducted at multiple outpatient centers. The main goal is to compare relapse prevention between KarXT treatment and placebo over 38 weeks, while also assessing time to discontinuation, safety, and tolerability. Participants receive either KarXT in varying doses (ranging from 20 mg/2 mg to 66.7 mg/6.67 mg taken three times daily) or placebo capsules. The study lasts 38 weeks, during which participants remain on assigned treatment in an outpatient setting. The randomized, double-blind design ensures neither participants nor researchers know who receives KarXT or placebo during the study. Throughout the study, participants will visit the clinic regularly for assessments of their psychosis symptoms, safety checks, and overall health. Researchers will track the time to relapse of psychosis symptoms as the primary outcome. They will also monitor safety and tolerability through clinical examinations and other evaluations. The total duration of participation is 38 weeks from randomization to the end of the study period.

Researchers are evaluating the effectiveness, safety, and tolerability of ITI-1284 compared to a placebo in treating psychosis associated with Alzheimer's disease. This Phase 2, multicenter, randomized, double-blind, placebo-controlled study focuses on patients aged 55 and older who meet specific clinical criteria for Alzheimer's disease and psychosis. The study aims to assess changes in psychosis symptoms using the BEHAVE-AD psychosis subscale score after 6 weeks of treatment. Participants will be randomly assigned in equal numbers to receive either ITI-1284 or a placebo. ITI-1284 is administered as a rapidly disintegrating tablet taken once daily under the tongue at doses of 10 mg or 20 mg. The study includes three periods: up to 4 weeks of screening to determine eligibility, a 6-week double-blind treatment phase where participants receive their assigned medication, and a 30-day safety follow-up after the last dose to monitor any adverse effects. During the study, participants will undergo assessments to confirm Alzheimer's disease diagnosis and psychosis presence, including biomarker tests, clinical rating scales, and cognitive evaluations. Caregivers will be involved as designated support persons. Researchers will monitor symptom changes, safety, and tolerability throughout the treatment and follow-up periods. The primary outcome is the psychosis subscale score measured at week 6, with safety follow-up visits approximately 30 days after treatment ends.

Researchers are evaluating the long-term safety and tolerability of KarXT in treating mania or mania with mixed features in adults with Bipolar-I disorder. This phase 3, open-label extension study aims to better understand how KarXT performs over an extended period in this population. The study includes participants who either completed previous double-blind placebo-controlled studies or are newly diagnosed with Bipolar-I disorder experiencing manic symptoms. Participants receive KarXT at specified doses on certain days, with some also taking therapeutic doses of Lithium, Valproate, or Lamotrigine as part of their treatment. The study does not mention a placebo group during this extension, focusing instead on monitoring the long-term effects of KarXT alone or in combination with these established therapies. During the study, participants are monitored for adverse events up to week 54 to assess safety. Evaluations include psychiatric assessments using scales such as the Young Mania Rating Scale and CGI-BP score at screening and baseline. Researchers will track treatment-emergent adverse events and overall tolerability throughout the study duration, which lasts up to 54 weeks for each participant.

Researchers are evaluating the efficacy, pharmacokinetics, safety, and immunogenicity of MB04, a proposed etanercept biosimilar, compared to Enbrel4 (EU-sourced) in adults aged 18 to 75 years with active moderate to severe rheumatoid arthritis despite methotrexate therapy. This Phase 3 study includes approximately 458 patients who have been on a stable methotrexate dose for at least 8 weeks before randomization. The goal is to compare these treatments over time to understand their effects in this patient population. Participants will be randomly assigned in a 1:1 ratio to receive either MB04 or EU-sourced Enbrel4 as a 50 mg subcutaneous injection once weekly during the main treatment period. After completing 24 weeks of treatment, those initially receiving Enbrel4 will be re-randomized to either continue Enbrel4 or switch to MB04 until week 36. Patients who started on MB04 will continue the same treatment through week 36. All participants will continue their stable methotrexate and folic acid regimen throughout the study. Participants will undergo screening within 28 days before randomization and will be monitored through week 40, including a 4-week safety follow-up after treatment ends. Researchers will assess treatment response using the American College of Rheumatology 20% Response Criteria (ACR20) at week 24, along with safety, pharmacokinetics, and immunogenicity evaluations. Regular assessments and monitoring will help determine how patients respond to the treatments and ensure their safety throughout the study.

Researchers are evaluating the effectiveness of DT-101 in treating adults with Major Depressive Disorder (MDD). This Phase 2 clinical trial compares DT-101 to a placebo to understand its impact on depression symptoms and evaluates the safety and tolerability of the study drug. Participants have recurrent depression diagnosed by the latest DSM manual and are between 18 and 75 years old. Participants will receive either DT-101 or placebo in a double-blind, randomized manner. The study includes physical and neurological examinations, blood and urine sample collections, and clinical assessments to monitor ongoing suitability and gather data on the drug's effects. Blood samples will also be used to study how DT-101 is absorbed and metabolized and to explore genetic factors that may influence treatment response. During the study, participants will visit the clinic every few weeks to undergo general health checks and complete questionnaires. Researchers will measure changes in depression using the Montgomery Åsberg Depression Rating Scale (MADRS) from the start of the study to Day 42. Safety and adherence will be closely monitored throughout the trial, ensuring participant well-being and data accuracy.

Researchers are investigating the safety and effectiveness of KarXT in treating manic episodes in adults with Bipolar-I Disorder. This Phase 3 study focuses on individuals experiencing acute mania or mania with mixed features who require hospitalization. The study aims to compare KarXT with a placebo to see how well it reduces manic symptoms during a three-week inpatient period. Participants will be randomly assigned to receive either KarXT or a placebo at specified doses during the inpatient treatment phase. The study is double-blind, so neither the participants nor the researchers know who receives which treatment. The total study duration, including screening, treatment, and safety follow-up, will not exceed seven weeks. During the study, participants will be closely monitored through psychiatric evaluations and rating scales, including the Young Mania Rating Scale (YMRS) to measure changes in mania symptoms by week 3. Other assessments include the Clinical Global Impressions-Bipolar scale and safety evaluations. Researchers will track adherence, symptoms, and any side effects throughout the study period.