Effect of Alpelisib in Healthy Volunteers

Prior treatment

• Reproductive concerns
  • Women of childbearing potential not using highly effective contraception, defined as:
  • Surgical sterilization (e.g., bilateral tubal occlusion, bilateral oophorectomy and/or salpingectomy, hysterectomy)
  • Combined oral contraceptive pills taken daily, including during the study
  • Intrauterine device (levonorgestrel-eluting or copper) active at the time of the study
  • Medroxyprogesterone acetate (Depo-Provera®) injection active at the time of the study
  • Etonogestrel implants (e.g., Implanon®, etc.) active at the time of the study
  • Norelgestromin/ethinyl estradiol transdermal system (e.g., Ortho-Evra®) active at the time of the study
  • Women currently pregnant
  • Women currently breastfeeding
• Any clinically relevant history or the presence of any active or chronic disease, including respiratory, renal, hepatic, gastrointestinal, hematological, lymphatic, neurological, cardiovascular, psychiatric, etc. disease or diseases except for:
  • Osteoarthritis, not using chronic anti-inflammatory medications
  • Non-melanoma skin cancer, localized and not receiving systemic therapy
  • N.B. Minor chronic health problems that do not impair overall health/functional status and are judged unlikely to interfere with study conduct or data analysis may be permitted at the discretion of the PI
• Dermatologic concerns
  • History of cutaneous and/or mucosal eruptive reactions to food or drugs, including, but not limited to, rash or urticaria
  • Active skin conditions requiring ongoing care by a dermatologist except for localized non-melanoma skin cancer (not receiving systemic therapy)
• Current use of illicit drugs
• Tobacco smoking currently or within the previous 6 months
• Concurrent enrollment in another clinical study of any investigational drug therapy or use of any biologicals within 6 months prior to screening or within 5 half-lives of an investigational agent or biologic, whichever is longer.

Other illness

• COVID-19 precautions
  • Unwillingness to comply with masking requirements per hospital policy
  • Active, documented COVID-19 at any time after screening through study completion
• History of or ongoing febrile illness within 30 days of screening
• Known allergy/hypersensitivity to any component of the medicinal product formulations (including soy or cow dairy), other biologics, venipuncture materials, plastics, adhesive or silicone, or ongoing clinically important allergy/hypersensitivity as judged by the investigator.

Lab values

• Concerns arising at screening visit (any of the following):
  • Unwillingness to fast (except water) for up to 15 hours
  • Documented weight change of ≥ 3.0% of baseline within the previous 6 months
  • Abnormal blood pressure
  • Systolic blood pressure \< 90 mm Hg or \> 160 mm Hg, and/or
  • Diastolic blood pressure \< 60 mm Hg or \> 100 mm Hg
  • Abnormal resting heart rate ≤ 60 bpm or ≥ 100 bpm
  • Sinus tachycardia that has been extensively worked up and considered benign by the recruit's personal physician may be permitted at the PI's discretion
  • Abnormal screening electrocardiogram (or if on file, performed within previous 90 d)
  • Non-sinus rhythm
  • Significant QTc prolongation (≥ 480 ms)
  • New or previously unknown ischaemic changes that persist on repeat EKG:
  • ST elevations
  • T-wave inversions
  • Abnormal screening serum electrolytes and/or liver function tests
  • Laboratory evidence of prediabetic state or diabetes mellitus:
  • Hemoglobin A1c ≥ 5.7%, and/or
  • Fasting plasma glucose ≥ 100 mg/dL
  • Abnormal fasting lipids at screening (either of the following)
  • Triglycerides ≥ 150 mg/dL
  • LDL-cholesterol ≥ 160 mg/dL
  • Positive qualitative human chorionic gonadotropin beta subunit (β-hCG) (i.e., pregnancy test) in women of childbearing potential
• Currently taking any prescription medications other than vitamins or other nutritional supplements, subject to review by the PI
  • o Any participant using biotin (vitamin B7) at \>1000 international units per day must not take it for 3 d prior to any study blood draw due to interference with laboratory assays
• Any other disease or condition or laboratory value that, in the opinion of the investigator, would place the participant at an unacceptable risk and/or interfere with the analysis of study data.

Other

• Inability to provide informed consent in English or Spanish
• Clinical concern for alcohol overuse at screening and/or by participant's report of consuming more than 14 standard drinks per week for males or more than 7 standard drinks per week for females
• Dietary restrictions (e.g.., vegan, kosher, halal) on gelatin present in overencapsulation

• Adults aged 18-65 years, using highly effective contraception if of childbearing potential
• Able to understand written and spoken English and/or Spanish
• Body mass index of 18.0-26.9 kg/m2
• Healthy, as determined by screening assessments and Principal Investigator's (PI's) clinical/scientific judgment. "Healthy" status is defined by the absence of evidence of any active or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead EKG, and laboratory tests on blood and urine.