Effect of Alpelisib in Healthy Volunteers

• Status: Recruiting
• Trial end date: 2024-04-01
• Target enrollment: 0
• Participant gender: All

Summary

The goal of this clinical trial is to test a single dose of the phosphoinositide-3-kinase (PI3K) inhibitor alpelisib versus placebo in healthy volunteers. The main questions it aims to answer are the impact of acute alpelisib-induced insulin resistance on parameters of glucose and lipid metabolism (how healthy people respond to temporary insulin resistance so that the investigators can see what happens to how the liver handles fat and sugar).

Participants will:

• Consume their total calculated daily caloric needs in nutritional supplements, divided in three meals, and otherwise fast for 24 hours

• Take a dose of alpelisib 300 mg or placebo at bedtime

• Wear a continuous glucose monitor for 24 hours

• Participate in an oral glucose tolerance test (OGTT)

Researchers will compare blood tests before and during OGTT in participants randomized (like the flip of a coin) to alpelisib versus placebo to see how the drug treatment affects plasma glucose, serum insulin, and serum lipid parameters (triglycerides, free fatty acids, and apolipoprotein B).

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Columbia University

Criteria

Inclusion Criteria:

1. Adults aged 18-65 years, using highly effective contraception if of childbearing potential

2. Able to understand written and spoken English and/or Spanish

3. Body mass index of 18.0-26.9 kg/m2

4. 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.

Exclusion Criteria:

1. Inability to provide informed consent in English or Spanish

2. Concerns arising at screening visit (any of the following):

i. Unwillingness to fast (except water) for up to 15 hours

ii. Documented weight change of ≥ 3.0% of baseline within the previous 6 months

iii. 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

iv. 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

v. 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

vi. Abnormal screening serum electrolytes and/or liver function tests

vii. Fasting serum insulin level ≥ 15 µIU/mL

viii. Laboratory evidence of prediabetic state or diabetes mellitus:

• Hemoglobin A1c ≥ 5.7%, and/or

• Fasting plasma glucose ≥ 100 mg/dL

ix. Abnormal fasting lipids at screening (either of the following)

• Triglycerides ≥ 150 mg/dL

• LDL-cholesterol ≥ 160 mg/dL

x. Abnormal screening thyroid-stimulating hormone (TSH) level

• Exempt from TSH screening if previously obtained value within 2 months of screening is available

xi. Positive qualitative human chorionic gonadotropin beta subunit (β-hCG) (i.e., pregnancy test) in women of childbearing potential

3. COVID-19 precautions

i. Not fully vaccinated against COVID-19 (4 doses if ages 50-65, 3 doses if ages 18-49)

ii. Unwillingness to comply with masking requirements per hospital policy

iii. Active, documented COVID-19 at any time after screening through study completion

4. Reproductive concerns

i. 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

ii. Women currently pregnant

iii. Women currently breastfeeding

5. 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

6. 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

7. 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)

8. Clinical concern for alcohol overuse, including phosphatidylethanol ≥ 0.05 µmol/L 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

9. Positive urine drug screen

10. Tobacco smoking currently or within the previous 6 months

11. History of or ongoing febrile illness within 30 days of screening

12. 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.

13. 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.

14. Dietary restrictions (e.g.., vegan, kosher, halal) on gelatin present in overencapsulation

15. 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.