Testing Mitapivat for anemia

Exclusion

• −History of drug-induced cholestatic hepatitis.
• −g. Positive test for HBsAg or HCVAb with signs of active hepatitis B or C virus infection. Subjects with hepatitis C may be rescreened after receiving appropriate hepatitis C treatment.
• −i. Positive test for HIV-1 or -2 antibodies. j. Active infection requiring the use of parenteral antimicrobial agents or Grade ≥3 in severity (per NCI CTCAE) within 2 months prior to the first dose of study treatment.
• −\. Known allergy to mitapivat or its excipients (microcrystalline cellulose, croscarmellose sodium, sodium stearyl fumarate, and mannitol) or history of acute allergic reaction to drugs characterized by acute hemolytic anemia, drug-induced liver injury, anaphylaxis, rash of erythema multiforme type or Stevens-Johnson syndrome, cholestatic hepatitis, or other serious clinical manifestations.
• −Known history of pyruvate kinase deficiency (decreased PKPharmacokineticsThe study of how the body absorbs, distributes, and clears a treatment.Read more → activity or two pathogenic PKLR alleles). PK activity and PKLR testing is not required.
• −Receiving regularly scheduled blood (RBC) transfusion therapy (also termed chronic, prophylactic or preventive transfusion), defined as more than 5 transfusion episodes in the 12-month period up to the first day of study treatment, and/or have received a transfusion within the past 3 months prior to the first day of study treatment.
• −Have a significant medical condition that confers an unacceptable risk to participating in the study, and/or that could confound interpretation of the study data. Such significant medical conditions include, but are not limited to:
• −Poorly controlled hypertension (defined as systolic blood pressure \>150 mm Hg or diastolic blood pressure \>90 mm Hg) refractory to medical management.
• −Any history of congestive heart failure; myocardial infarction or unstable angina pectoris; hemorrhagic, embolic, or thrombotic stroke; or recent (\< 6 months prior to signing informed consentInformed consentThe process of being told what taking part involves, then choosing freely.Read more →) deep venous thrombosis; or pulmonary or arterial embolism.
• −Cardiac dysrhythmias judged as clinically significant by the InvestigatorPrincipal investigatorThe doctor or researcher responsible for running the study at a site.Read more →.
• −Clinically symptomatic cholelithiasis or cholecystitis. Prior cholecystectomy is not exclusionary. Subjects with symptomatic cholelithiasis or cholecystitis may be rescreened once the disorder has been treated and clinical symptoms have resolved.
• −Severe iron overload as evaluated by the Investigator. This includes cardiac (eg, clinically significant impaired left ventricular ejection fraction) or hepatic (eg, fibrosis, cirrhosis) dysfunction.
• −Have a diagnosis of any other congenital or acquired blood disorder or any other hemolytic process, except mild allo-immunization, as a consequence of transfusion therapy.
• −k. Diabetes mellitus judged to be under poor controlControl groupThe group a new treatment is measured against.Read more → by the Investigator or requiring \>3 antidiabetic agents, including insulin (all insulins are considered 1 agent); use of insulin per se is not exclusionary.
• −l. History of any primary malignancy, with the exception of: curatively treated non-melanomatous skin cancer; curatively treated cervical or breast carcinoma in situ; or other primary tumor treated with curative intent, no known active disease present, and no treatment administered during the last 3 years.
• −m. Unstable extramedullary hematopoiesis that could pose a risk of imminent neurologic compromise.
• −n. Severe hepatic issues such as liver fibrosis (F3 or worse), significant cirrhosis or non-alcoholic fatty liver disease (NASH).
• −o. Current or recent history of psychiatric disorder that, in the opinion of the Investigator, could compromise the ability of the subject to cooperate with study visits and procedures.
• −p. Alcohol use disorder.
• −\. Are currently enrolledEnrolmentThe number of participants a study plans to include, or has included.Read more → in another therapeutic clinical trialInterventional studyA study where participants are given something to see what happens.Read more → involving ongoing therapy with any investigational or marketed product or placeboPlaceboA dummy treatment with no active medicine, used for comparison.Read more →. Participation in registry studies is allowed.
• −\. Have exposure to any investigational drug, device, or procedure within 5 half-lives or 3 months (whichever is longer) to the first dose of study treatment.
• −\. Have had any prior treatment with a pyruvate kinase activator.
• −\. Have a prior bone marrow or stem cell transplant.
• −\. Are currently receiving medications that are strong inhibitors of CYP3A4 and strong inducers of CYP3A4 that have not been stopped for a duration of at least 5 days or a timeframe equivalent to 5 half-lives (whichever is longer) prior to the first dose of study treatment.
• −\. Are currently receiving hematopoietic stimulating agents (eg, erythropoietins, granulocyte colony stimulating factors, thrombopoietins) that have not been stopped for a duration of at least 28 days prior to the first dose of study treatment.
• −\. Are currently receiving herbal or dietary supplements that have not been stable in dose and preparation for \>8 weeks prior to randomizationRandomisedWhich group you go into is decided by chance, not by you or your doctor.Read more →.
• −\. Are currently pregnant or breastfeeding or planning to become pregnant during the course of the study.
• −\. For men and women of reproductive potential: unwillingness to be abstinent or use double anticonception during the trial period.
• −\. Have a history of major surgery within 6 months prior to signing informed consent. Note that procedures such as laparoscopic gallbladder surgery are not considered major in this context.