Ensayos clínicos

Inclusion Criteria:

• Subjects must have the ability to understand, and sign written informed consent, which must be obtained prior to any study-related procedures being completed;
• Adult female subjects of non-childbearing potential may participate in the study if they are either surgically sterile (hysterectomy, bilateral tubal ligation, salpingectomy, and/or bilateral oophorectomy at least 26 weeks before the Screening Visit) or are post-menopausal, defined as spontaneous amenorrhea for at least 2 years as of screening visit;
• Sexually active female subjects of childbearing potential (i.e., ovulating, pre-menopausal, and not surgically sterile) or sexually active male subjects may participate in the study if they agree to use a medically accepted contraceptive regimen during their participation in the study and for 90 days after the last administration of study drug. Medically accepted contraceptive methods are defined as those with 90% or greater efficacy and include;
  • For male subjects enrolled in the study include the following:
    • Condoms with spermicide, or
    • Surgical sterilization of subject at least 26 weeks before the Screening Visit (vasectomy)
  • For female subjects enrolled in the study include the following:
    • Intrauterine device for at least 12 weeks before the Screening Visit;
    • Hormonal contraception (oral, implant, injection, ring, or patch) for at least 12 weeks before the Screening Visit;
    • Diaphragm used in combination with spermicide; or
    • Male partner: condom with spermicide;
• Male subjects must agree to abstain from sperm donation and not plan to father a child (including sperm donation) through 90 days after administration of the last dose of study drug;
• Female subjects may not be pregnant, lactating, or breast-feeding or plan to become pregnant (including ova donation) within 90 days of last study drug administration;
• Female subjects must have a negative result for the urine pregnancy test at the Study Visit #1 (screen and enrollment) and within 24-48 hours of each visit where exercise and hypoxia are involved;
• Subjects must have a negative test result for hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCVAb), and human immunodeficiency virus (HIV) antibody at the Screening Visit or documented in the medical chart within the last 1 year;
• Subjects must be willing and able to abide by all study requirements (including the ability to swallow study tablets) and restrictions;
• Subjects must be adult males or females between 18 and 50 years of age (inclusive) at the time of the screening visit;
• Subjects must be in general good health, based upon the results of medical history and a physical examination performed by a physician, with vital signs, laboratory profile, and a 12-lead ECG, as judged by the Investigator at Screening and first period Check-in. Screening assessments may be repeated once (blood pressure may be repeated twice) at the Investigator’s discretion;
• Subjects must have a body mass index (BMI) within the range of 18 kg/m2 to 33 kg/m2 (inclusive) and a minimum body weight of 50 kg at the Screening Visit; All participants will be evaluated on a case-by-case basis and inclusion in the study will be up to the discretion of the principal investigator;
• Subjects must be physically active, including ≥3 days per week of structured aerobic (endurance) exercise or cross-training (resistance training + aerobic) type exercise for a combined 90+ minutes per week
• Subjects must refrain from vigorous exercise and alcohol for 24 hours and caffeine 12 hours before study visits.
• Subjects must have a negative urine test for drugs of abuse (opiates, benzodiazepines, amphetamines,  cocaine, barbiturates, and phencyclidine), cotinine, and alcohol at the Screening Visit.
• For Phase 2 only, participants must have a negative COVID-19 test prior to Study Visits #2 and #4 per Institutional Guidelines for Aerosol Generating Procedures. The study team will follow institutional requirements throughout the study, and COVID test will be removed if institutional guidelines change.

Exclusion Criteria:

• History of gastrointestinal (GI) surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs, with the exception of appendectomy;
• History of malignancy within previous 5 years (other than successfully treated basal cell or squamous cell skin cancer, or carcinoma-in-situ of the cervix);includes prostatic intraepithelial neoplasia (PIN)
• History of clinically significant arrhythmia, left or right bundle branch block, 2nd or 3rd degree atrioventricular (AV) block, pacemaker or implantable cardioverter-defibrillator;
• Abnormal and clinically significant 12-lead ECG, including QT interval corrected for heart rate according to Fridericia’s formula (QTcF) > 450 ms, QRS interval ≥ 120 ms, PR interval > 220 ms, based on average of triplicated ECG, assessed at Screening and first study (pre-treatment) visit. If any of these test results are out of range the test can be repeated once;
• Systolic blood pressure < 90 or > 150 mmHg (or >95th percentile for age) or diastolic blood pressure < 50 or > 95 mmHg (or > 95th percentile for age), at Screening and first period Check-in. If blood pressure is out of range, up to two repeated assessments are permitted;
• A family history of QT prolongation or sudden cardiac death;
• History of severe allergic reaction (including anaphylaxis) to any substance, or previous status asthmaticus;
• Has had an acute illness considered clinically significant by the Investigator within 14 days prior to the study drug administration;
• History of alcohol abuse or dependence within one year prior to Screening (self report more than 14 units of alcohol per week; one unit = 150 mL wine, 360 mL beer or 45 mL of 40% alcohol)or positive for ethanol in urine screening test (cutoff >10mg/dL)
• Concerns for nicotine dependence or recent use prior to screening or intention to use nicotine products during the course of the study; or positive for nicotine and metabolites (cotinine, nornicotine, anabasine) in the urine screening test. 
• Use of a prohibited prescription or non-prescription drugs and dietary supplements (including herbal and alternative medications), as specified in Section 6.2;
• Has received an investigational drug, including vaccines (COVID-19 vaccines and booster shots), within five times the elimination half-life (if known) or within 30 days (if the elimination half-life is unknown) prior to first drug administration or is concurrently enrolled in any research judged not to be scientifically or medically compatible with this study;
• History of allergy or hypersensitivity to etavopivat or excipients;
• Subject has a history of chronic skin conditions including psoriasis, eczema or any recurring rash/dermatitis requiring oral or topical corticosteroids or chronic skin softeners within 12 months prior to screening;
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• Difficulty with venous or arterial access or unsuitable or unwilling to undergo intravenous or intra-arterial catheter insertion.
• Has lost or donated > 550 mL (or > 10 mL/kg if < 18 yrs) of whole blood or blood products within 12 weeks prior to study drug administration;
• Investigator has reason to believe that the subject may be unable to fulfill the protocol visit schedule or requirements;
• Has any finding that, in the view of the Investigator, would compromise the subject’s safety requirements;
• Evidence of clinically significant (or undergoing active medical treatment) hematologic, renal, endocrine, pulmonary, cardiac, GI, hepatic, psychiatric, neurologic, immunologic, allergic disease (including multiple or clinically significant drug allergies), or any other condition that, in the opinion of the Investigator, might significantly interfere with the absorption, distribution, metabolism, or excretion of study drug, or place the subject at an unacceptable risk as a participant in this study;
• Laboratory results (serum chemistry, hematology) outside the normal range at the Screening Visit that are considered clinically significant in the opinion of the Investigator. One retest of an exclusionary laboratory result is allowed at the discretion of the Investigator;
• Iron deficiency anemia (as evidenced by abnormal iron level, and/or serum ferritin with reduced hemoglobin)
•  Any elevation of aspartate aminotransferase and alanine aminotransferase 
• > 1.5× the upper limit of normal (ULN), and bilirubin greater than ULN at the Screening Visit is exclusionary; or
• Currently prescribed or taking any medications or supplements (see Section 6.2.1). Any over-the-counter medications or supplements will be evaluated by the primary investigator/sponsor medical monitor on a case-by-case basis.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 2/15/23. Questions regarding updates should be directed to the study team contact.