Kropyvnytskyi

Researchers are evaluating new treatment options for adults with locally advanced or metastatic colorectal cancer that cannot be removed by surgery and has a specific KRAS G12C gene mutation. This study compares the safety and effectiveness of adding calderasib and cetuximab, both targeted therapies, to a standard chemotherapy regimen called mFOLFOX6. The goal is to see if this combination can help patients live longer without their cancer growing or spreading compared to current treatments that may include mFOLFOX6 with or without bevacizumab. The study has two parts. It involves treatment with calderasib taken as an oral tablet, cetuximab given according to standard procedures, and mFOLFOX6 chemotherapy combining oxaliplatin, leucovorin/levofolinate calcium, and 5-fluorouracil. Some participants may receive bevacizumab or a bevacizumab biosimilar as part of the comparison. The treatments are given following approved dosing schedules. This design allows researchers to assess the safety and tolerability of these drug combinations in treating this type of colorectal cancer with the KRAS G12C mutation. Participants will be monitored for side effects, treatment tolerability, and cancer progression over a period that may last up to about 44 months. Researchers will track outcomes such as how many participants experience dose-limiting toxicities or adverse events, how many stop treatment due to side effects, and progression-free survival time. Assessments include health evaluations, laboratory tests, and imaging to observe cancer status. This long-term follow-up aims to understand both safety and effectiveness of the treatment combinations.

Researchers are evaluating molnupiravir, a study medicine designed to stop the COVID-19 virus from multiplying, to see if it can prevent severe illness from COVID-19 more effectively than a placebo. This Phase 3 randomized, placebo-controlled, double-blind study focuses on non-hospitalized adults at high risk of severe disease progression due to COVID-19. The study addresses the need for alternative treatments for people who cannot take certain COVID-19 medications due to availability or potential drug interactions. Participants will receive either molnupiravir or a placebo, both given orally as two 400 mg film-coated tablets every 12 hours for 5 days, totaling 10 doses. Some participants may also receive remdesivir as part of standard care if clinically appropriate and available. The study compares the effects of molnupiravir with placebo in preventing severe illness outcomes. Throughout the study, participants will be monitored for outcomes such as hospitalization, death, or medically attended visits related to COVID-19 up to 29 days. Safety is assessed by tracking adverse events for up to about 5 months and discontinuation of study treatment due to adverse events for about 5 days. The study involves laboratory tests, symptom assessments, and safety evaluations to understand molnupiravir's impact on disease progression and participant health.

Researchers are evaluating the safety and effectiveness of KarXT combined with KarX-EC in adults aged 55 to 90 who have agitation related to Alzheimer's Disease. This phase 3 study aims to better understand how these treatments impact agitation symptoms in this population by comparing them to a placebo group. Participants must have a confirmed Alzheimer's diagnosis and meet specific criteria for agitation severity to join the study. Participants will receive either the Xanomeline/Trospium Chloride Capsule, Xanomeline Enteric Capsule, or a placebo, each given at specified doses on designated days. The study is randomized, double-blind, and placebo-controlled to ensure reliable comparison of treatment effects. The treatment period lasts through Week 14, during which dosing schedules are closely followed. Throughout the study, participants will be regularly assessed using the Cohen-Mansfield Agitation Inventory-International Psychogeriatric Association (CMAI-IPA) to measure changes in agitation levels from baseline to Week 14. Caregivers will provide reports on participant status and help ensure medication compliance. Safety and symptom changes will be carefully monitored to evaluate the treatments' effects during this period.

Researchers are evaluating the safety, how the body processes the drug, and the effectiveness of calderasib alone or combined with other treatments in adults with advanced solid tumors that have a specific KRAS G12C mutation. This is a Phase 1, open-label, multicenter study focusing on participants with this genetic mutation in their tumors, aiming to understand how calderasib works alone and with other drugs. Participants receive calderasib as an oral dose, and some may also receive other medications such as pembrolizumab through intravenous infusion, or drugs like carboplatin, pemetrexed, cetuximab, oxaliplatin, leucovorin, and 5-fluorouracil according to standard guidelines. The treatments may be given alone or in combination depending on the study arm, with dosing schedules following label instructions or protocol specifications. During the study, participants will be closely monitored for any dose-limiting toxicities and adverse events, including reasons for stopping treatment. Researchers will assess these effects for up to about 21 days for dose-limiting toxicities and up to 56 months for adverse events and treatment discontinuation. The study involves regular evaluations to track safety, tolerability, and how well the treatment works over time.

Researchers are evaluating the safety and effectiveness of calderasib combined with pembrolizumab as a first treatment in adults with locally advanced or metastatic non-small cell lung cancer (NSCLC) that has a specific KRAS G12C mutation and a PD-L1 tumor proportion score of 50% or higher. This Phase 3 trial aims to test if the combination of calderasib and pembrolizumab improves progression-free survival and overall survival compared to pembrolizumab with a placebo. Participants receive oral calderasib tablets or placebo along with pembrolizumab given by intravenous infusion. The study compares these two treatment groups to see which provides better outcomes. Treatments continue during the study, and there are no additional interventions described beyond these drugs. During the trial, participants undergo regular assessments including scans and tests to monitor their cancer's progression and overall health. The main outcomes measured are progression-free survival for up to about 42 months and overall survival for up to about 56 months. Safety is monitored throughout, and participants are followed for several years to evaluate long-term effects of the treatments.

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 safety and effectiveness of adding KarXT (Xanomeline/Trospium Chloride) to standard treatment for mania in adults with Bipolar-I Disorder. This Phase 3, randomized, double-blind study focuses on individuals experiencing acute manic episodes, with or without mixed features, who are already taking lithium, valproate, or lamotrigine. The study aims to measure changes in mania symptoms using the Young Mania Rating Scale at Week 5. Participants will be randomly assigned to receive either KarXT or a placebo alongside their stable dose of lithium, valproate, or lamotrigine. The doses of these medications are specified and given on set days during the study. Only those with stable mood stabilizer doses for at least two weeks prior to screening, and valproate treatment for at least seven months, are eligible. The treatment period lasts for 5 weeks. During the study, participants will be closely monitored through psychiatric evaluations and clinical assessments. Researchers will assess mania severity, safety, and any side effects. The main outcome is the change from baseline in the Young Mania Rating Scale score at Week 5. Participants’ physical health, including liver function and risk of urinary or gastrointestinal issues, will also be monitored to ensure safety throughout the trial.

This trial focuses on people aged 55 to 90 who have agitation related to Alzheimer's Disease and previously finished one of two earlier studies. It aims to assess the long-term safety and effectiveness of a combination treatment using xanomeline tartrate/trospium chloride immediate release capsules (KarXT) and xanomeline enteric capsules (KarX-EC) in these participants. The study is a Phase 3 open-label extension, meaning all participants receive the treatment while researchers observe effects over time. Participants receive specified doses of KarXT and KarX-EC on set days as part of the treatment regimen. The study follows those who completed the earlier parent studies CN012-0023 or CN012-0024, continuing to monitor their response to the combined medication over an extended period. Throughout the study, researchers evaluate the number of participants who experience any treatment-emergent adverse events up to about 30 weeks. Caregiver involvement is required, with at least one caregiver having regular contact of about 10 hours per week or more. Safety and tolerability are closely monitored to understand the long-term impact of the treatment in managing agitation associated with Alzheimer's Disease.

Researchers are investigating better treatments for people with advanced non-small cell lung cancer (NSCLC) that has specific genetic changes called HER2 mutations. Advanced NSCLC refers to lung cancers that have spread or are unlikely to be controlled with current treatments. HER2 is a protein that helps cells grow, and mutations cause abnormal HER2 leading to cancer growth. This Phase 3 study aims to compare the safety and effectiveness of a new drug, sevabertinib, against standard treatment in patients with this type of lung cancer. Participants will be randomly assigned to receive either sevabertinib tablets twice daily by mouth or standard treatment consisting of cycles of intravenous infusions including drugs like pembrolizumab, cisplatin, carboplatin, and pemetrexed every 21 days. Treatments continue as long as participants benefit without severe side effects or until they or their doctors decide to stop. Participants on standard treatment whose disease worsens may switch to sevabertinib and continue until progression, intolerable side effects, or decision to stop. During the study, participants will undergo imaging scans such as CT, PET, MRI, and X-rays to monitor cancer spread. Health checks include blood and urine tests, heart monitoring with ECG, and pregnancy tests for women. Researchers will ask about participants’ well-being and record any medical problems or side effects experienced. The main outcome measured is progression-free survival over up to about two years.

Researchers are evaluating the effects of an injected vitamin combination versus an oral vitamin B12 alone on vitamin B12 levels in adults with vitamin B12 deficiency. This phase 4 study aims to compare changes in serum vitamin B12 concentration after 28 days of treatment. The study also assesses other markers related to vitamin B12 status, methylation, and overall well-being, including serum holotranscobalamin, homocysteine, methylmalonic acid, vitamin B6, folic acid, and quality of life questionnaires. Participants receive either an intramuscular injection of a fixed vitamin combination containing vitamin B6, vitamin B12, and folic acid or take oral tablets of vitamin B12 alone. The treatment period lasts for 4 weeks (28 days). Safety and tolerability of both treatment methods are also monitored during this time. During the study, participants undergo blood tests to measure vitamin B12 and related markers at baseline and day 28. Pregnancy tests are done at screening and on days 0, 28, and 56 for women of childbearing potential. Well-being and health surveys are completed to evaluate quality of life. Participants are monitored for safety and treatment effects throughout the study period, which includes follow-up assessments after treatment completion.