Effect of Alpelisib in Healthy Volunteers

NCT05733455 | Completed Phase 1 FDA Drug FDA Device

• 1 other identifier: AAAU3423
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief 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 72 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).

Conditions

Insulin Resistance; Hyperinsulinemia; Dyslipidemias

Keywords

Insulin resistance; Hyperinsulinemia; Diabetes; Non-alcoholic fatty liver disease

Outcome Measures

Primary Outcomes (3)

• Fasting plasma glucose

  Fasting plasma glucose (units: mg/dL) after a single dose of alpelisib vs placebo.

  Day 4 (10 hours after dose)

• Fasting serum insulin

  Fasting serum insulin (units: micro-international units per milliliter, µIU/mL) levels after a single dose of alpelisib vs placebo.

  Day 4 (10 hours after dose)

• Fasting serum C-peptide

  Fasting serum C-peptide (units: ng/mL) after a single dose of alpelisib vs placebo.

  Day 4 (10 hours after dose)

Secondary Outcomes (11)

• Overnight glucose profile

  Days 3-4 (Approximately 24 hours)

• Plasma glucose levels during OGTT

  Day 4 (Up to 180 minutes from the start of the procedure)

• Plasma glucose area under the curve (AUC) during OGTT

  Day 4 (Up to 180 minutes from the start of the procedure)

• Serum insulin levels during OGTT

  Day 4 (Up to 180 minutes from the start of the procedure)

• Serum insulin area under the curve (AUC) during OGTT

  Day 4 (Up to 180 minutes from the start of the procedure)

Study Arms (2)

Alpelisib treatment

EXPERIMENTAL

Participants will ingest a single dose of alpelisib 300 mg (two overencapsulated 150-mg tablets)

Drug: Alpelisib 150 mg [Piqray], 2 overencapsulated tablets (total: 300 mg); Device: FreeStyle Libre Pro; Diagnostic Test: Oral glucose tolerance test (OGTT) with Trutol glucose beverage; Dietary Supplement: BOOST Plus nutritional beverage

Placebo treatment

PLACEBO COMPARATOR

Participants will ingest a single dose of placebo (two capsules filled with microcrystalline cellulose)

Drug: Placebo (microcrystalline cellulose), 2 capsules; Device: FreeStyle Libre Pro; Diagnostic Test: Oral glucose tolerance test (OGTT) with Trutol glucose beverage; Dietary Supplement: BOOST Plus nutritional beverage

Interventions

Alpelisib 150 mg [Piqray], 2 overencapsulated tablets (total: 300 mg) DRUG

Participants will ingest two overencapsulated tablets of alpelisib at 23:00, along with a saltine cracker.

Also known as: Piqray

Alpelisib treatment

Placebo (microcrystalline cellulose), 2 capsules DRUG

Participants will ingest two capsules filled with microcrystalline cellulose at 23:00, along with a saltine cracker.

Placebo treatment

FreeStyle Libre Pro DEVICE

Continuous glucose monitoring for 24 hours (double blinded)

Alpelisib treatment; Placebo treatment

Oral glucose tolerance test (OGTT) with Trutol glucose beverage DIAGNOSTIC_TEST

Participants will drink Trutol glucose beverage (D-glucose 75 g in 10 fl oz) and blood will be sampled at baseline and at 15, 30, 60, 90, 120, 150, and 180 minutes.

Alpelisib treatment; Placebo treatment

BOOST Plus nutritional beverage DIETARY_SUPPLEMENT

Participants will consume a quantity of BOOST Plus calculated to match their daily caloric needs, divided over three liquid meals.

Alpelisib treatment; Placebo treatment

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Inability to provide informed consent in English or Spanish
• 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

Sponsors & Collaborators

• Columbia University: lead

Study Sites (1)

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Insulin Resistance; Hyperinsulinism; Dyslipidemias; Diabetes Mellitus; Non-alcoholic Fatty Liver Disease

Interventions

Alpelisib; microcrystalline cellulose; Glucose Tolerance Test

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders; Endocrine System Diseases; Fatty Liver; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Blood Chemical Analysis; Clinical Chemistry Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Endocrine; Investigative Techniques

Study Officials

• Joshua R Cook, MD, PhD

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: February 3, 2023
• First Posted: February 17, 2023
• Study Start: May 9, 2023
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2023
• Last Updated: December 21, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Indefinitely following study completion.

Locations

US (1)