Muscat

Researchers are evaluating the safety and activity of a new medicine called etavopivat in children aged 12 to 16 years with sickle cell disease who are at higher risk for stroke. The study focuses on how etavopivat affects blood flow velocity in brain arteries, measured by transcranial Doppler (TCD) ultrasound. Participants are divided into two groups based on their TCD results and whether they are receiving hydroxyurea, a medication commonly used in sickle cell disease treatment. The study is a Phase 2, open-label trial aiming to better understand etavopivat’s effects in this pediatric population. Participants will take 400 mg of etavopivat daily, given as two 200 mg tablets by mouth, which can be taken with or without food. The treatment period lasts 52 weeks (one year). One group includes participants with conditional or abnormal TCD results who are not taking hydroxyurea, while the other includes those with similar TCD results who are on a stable dose of hydroxyurea. After the 52-week treatment, participants may have the option to join a 48-week extension phase to continue evaluating the safety of etavopivat. If appropriate, participants might also be offered to join a separate study to keep receiving etavopivat after completing these phases. Throughout the study, participants will visit the clinic regularly for assessments, including TCD ultrasound to measure blood flow velocities in specific brain arteries at baseline and week 12. Researchers will monitor safety and treatment effects closely. The primary outcome is the change in the highest blood flow velocity measured by TCD in any of the left or right internal carotid or middle cerebral arteries. Caregivers and participants will be involved in ongoing evaluations to ensure safety and adherence during the study's full duration and optional extension period.

Researchers are evaluating the long-term safety and effectiveness of etavopivat, a new oral medicine being developed to treat inherited blood disorders such as sickle cell disease and thalassemia. These disorders affect hemoglobin, the protein responsible for carrying oxygen in the body. This phase 3 study aims to monitor how well etavopivat works and its safety profile over an extended period. Participants will receive one of three forms of etavopivat (A, B, or C) as oral doses. The study is open-label and multicenter, involving adults, adolescents, and children who have previously completed treatment in an etavopivat parent study and continue to benefit clinically. The treatment period can last up to 264 weeks but may end earlier if etavopivat is approved in the participant's country. During the study, researchers will track the number of treatment-emergent adverse events and adverse reactions for each participant by indication and age group from baseline through the end of the study, which can last up to 316 weeks. Participants' safety and response to long-term treatment will be closely monitored throughout this period.

Researchers are evaluating how well etavopivat works to reduce the number of vaso-occlusive crises (painful blood vessel blockages) in adolescents and adults living with sickle cell disease. The study also aims to assess if etavopivat can decrease organ damage, improve exercise tolerance, and reduce fatigue. This is a global Phase 3 study involving participants aged 12 years and older with confirmed sickle cell disease. The study is randomized, double-blind, and placebo-controlled to ensure accurate evaluation of the treatment effects. Participants will receive either etavopivat or a matching placebo by mouth. Which treatment they receive is determined randomly. The study will last about two years, during which participants will take the assigned medication and be monitored closely. Etavopivat is an investigational drug currently under evaluation in multiple studies for sickle cell disease. During the study, participants will have regular assessments including documentation of vaso-occlusive crisis events, blood tests, and physical evaluations. Researchers will track the number of crises that require medical attention over a 52-week period, as well as measures of organ health, exercise ability, and fatigue. Safety and overall health will be monitored throughout the study, with the total participation time lasting approximately two years.

Researchers are evaluating the efficacy and safety of inavolisib combined with Phesgo compared to placebo with Phesgo as maintenance therapy in participants who have previously untreated HER2-positive advanced breast cancer with PIK3CA mutations. This Phase III, multicenter, randomized, double-blind, placebo-controlled study focuses on participants with locally advanced or metastatic breast cancer, aiming to understand the treatment impact after initial induction therapy. Participants will receive inavolisib orally once daily on Days 1 to 21 of each 21-day cycle, starting on Day 1 of Cycle 1 during maintenance treatment. Phesgo will be administered subcutaneously every three weeks on Day 1 of each cycle. The study includes an induction therapy phase where taxane-based chemotherapy is given after Phesgo. Optional endocrine therapy such as tamoxifen, aromatase inhibitors, or fulvestrant may be used based on the investigator's choice, with luteinizing hormone-releasing hormone agonists administered according to local guidelines. During the study, participants will be monitored for progression-free survival for up to approximately 40 months. Assessments include evaluation of heart function, organ function, and overall health status. Researchers will track the safety and effectiveness of the treatment combination through regular clinical evaluations and laboratory tests. The total duration includes maintenance treatment cycles and follow-up to measure outcomes and monitor safety.

Researchers are evaluating the effects of an herbal extract called Aescin (Reparil) compared to Ibuprofen for managing pain and swelling after surgical removal of impacted lower wisdom teeth. The study focuses on adults aged 18 to 40 years undergoing this common oral surgery. The goal is to see if Aescin can reduce postoperative pain, facial swelling, and limited mouth opening (trismus) with fewer side effects than Ibuprofen, a commonly used anti-inflammatory drug with known risks. Participants will be randomly assigned to one of two groups. One group will take Reparil tablets containing 20 mg of Aescin three times daily for five days after surgery. The other group will take 400 mg Ibuprofen tablets three times daily for the same duration. Both groups will follow standardized surgical procedures to remove the impacted mandibular third molars. Rescue pain medication will be available if needed. During the study, pain levels will be recorded using a visual scale, facial swelling will be measured with a 3D facial scanner, and mouth opening will be checked with a digital caliper at baseline, day 2, and day 7 after surgery. Safety and side effects will be monitored throughout. Participants must attend follow-up visits on days 2 and 7 post-surgery. The total involvement lasts for one week after their operation.

Researchers are evaluating the effectiveness of two doses of dexamethasone, 4 mg and 8 mg, compared to a placebo in reducing pain after dental implant surgery. This randomized, double-blind, phase 3 trial aims to determine the best dose of dexamethasone to manage postoperative pain. The study also explores how preoperative anxiety may relate to the level of pain experienced after surgery. Participants will be randomly assigned to one of three groups: 4 mg dexamethasone, 8 mg dexamethasone, or a placebo (normal saline). Each participant will receive a submucosal injection near the surgical site in the buccal vestibule using a concealed syringe. This injection is given during the dental implant procedure. After surgery, pain will be measured using a Visual Analog Scale at 6 hours post-operation and then once daily for six days. The number of pain-relief tablets taken will also be recorded. Participants will complete a Generalized Anxiety Disorder-7 questionnaire before surgery to assess anxiety levels. The study will help identify the optimal dexamethasone dose for pain control following dental implant surgery.

Researchers are evaluating the effectiveness of three medications—metoclopramide, promethazine, and prochloroperazine—in treating adults aged 18 to 60 who come to the emergency department with acute peripheral vertigo. Peripheral vertigo is a common cause of dizziness often accompanied by nausea or vomiting, and this study aims to identify which medication provides the best relief with the fewest side effects. The study is a Phase 3, multi-center, randomized, triple-blind controlled trial conducted across three hospitals in Oman from February 2022 to August 2024. Participants will receive one of the three medications through an injection administered by the emergency doctor, who will not know which medication is given to maintain blinding. The medications are prepared in identical syringes labeled A, B, or C. The patient's symptoms will be assessed before treatment and again one hour after the medication. If needed, rescue medications such as betahistine or ondansetron or maneuvers like the Epley maneuver may be used. During the study, researchers will collect data on symptom severity using a visual analog scale and track any side effects or additional treatments required. The primary outcome is the effectiveness of the medication in relieving vertigo symptoms within one hour. Patient information, symptom scores, and treatment details will be recorded and reviewed weekly by the principal investigators at each center. Participation lasts for the duration of the emergency visit and treatment evaluation.

Researchers are evaluating the long-term safety, tolerability, and effectiveness of marstacimab as a preventative treatment for people with severe hemophilia A or moderately severe to severe hemophilia B, including those with or without inhibitors. This open-label extension study includes participants from two earlier Phase 3 studies: one with adolescents and adults aged 12 to under 75 years, and another ongoing study with pediatric participants under 18 years old. The goal is to continue monitoring these participants who did not require early termination in the prior studies. Participants will receive marstacimab administered by subcutaneous injection using a prefilled pen or syringe. Dosage varies by age group: those 12 years and older start with a 300 mg loading dose followed by 150 mg weekly, with the option to increase to 300 mg weekly if needed. Children aged 6 to under 12 years receive a 150 mg loading dose followed by 75 mg weekly, with possible escalation to 150 mg weekly. The study allows use of prefilled syringes where pens are not available, and includes an optional substudy for some participants from the earlier adult study. Throughout the study, participants will attend scheduled visits for assessments including physical exams, laboratory tests, and safety monitoring lasting up to 7 years. Researchers will track adverse events, serious side effects, thrombotic events, injection site reactions, immune responses to the drug, and changes in vital signs or lab values. This extended observation helps to understand marstacimab’s long-term effects and supports safer dosing decisions across different age groups.

Researchers are evaluating the natural progression of ENPP1 Deficiency and the infantile-onset form of ABCC6 Deficiency, both rare genetic disorders. ENPP1 Deficiency can cause serious complications such as rickets in children and bone softening in adults, with a high risk of early mortality in infants. Infantile-onset ABCC6 Deficiency shares similar acute symptoms and may involve cerebrovascular disease. This international, multicenter, prospective registry aims to collect detailed genetic, biochemical, anatomical, and functional information over time to better understand these diseases and their impact on patients' lives. The study is observational with no interventions or treatments administered. Participants include patients with confirmed genetic diagnoses of ENPP1 or ABCC6 Deficiency, including symptomatic individuals with one ENPP1 mutation and children under 18 with ABCC6 Deficiency. The study includes a Screening Period, where retrospective and baseline data from medical records and standard care visits are collected, followed by an Observational Period during which patient information is gathered at routine clinical visits. Optional blood samples may be taken to measure inorganic pyrophosphate levels at these visits. Participants will be monitored annually up to 10 years for disease progression using various assessments including laboratory tests, radiographic evaluations, bone mineralization studies, and patient-reported outcome questionnaires measuring functional changes and quality of life. Data on healthcare use and physician and caregiver reports will also be collected. This comprehensive follow-up aims to provide a clear picture of the burden and course of these rare conditions over time.

Researchers are evaluating the effectiveness and safety of plozasiran in about 288 adults who have severe hypertriglyceridemia (high levels of triglycerides in the blood) and a history of at least two acute pancreatitis events, with at least one occurring within the last year before screening. This Phase 3 study compares plozasiran to a placebo in a double-blind manner to better understand its impact on reducing pancreatitis risk in this population. Participants will be randomly assigned to receive either plozasiran 25 mg or a matching placebo through subcutaneous injections every three months. They will be advised to continue a low-fat diet and maintain their usual lipid- and triglyceride-lowering medications throughout the study. After completing the double-blind treatment period or experiencing an acute pancreatitis event, participants will enter a 12-month open-label phase where all receive plozasiran 25 mg injections every three months. During the study, participants will be monitored for the time until their first confirmed acute pancreatitis event starting more than 10 days after the first dose, with follow-up lasting up to approximately 50 months. Researchers will assess treatment effects, safety, adherence to diet and medications, and overall participant health. The study includes regular evaluations to ensure participant safety and collect data on the treatment's impact on severe hypertriglyceridemia and pancreatitis risk.