CompletedPhase 1ACTRN12624000116527

A study to evaluate safety, tolerability and pharmacokinetics of ELVN-001 in Normal Healthy Participants- Part B

A study to Evaluate the Safety, Tolerability, and Pharmacokinetics of ELVN-001 Following Single Doses of Capsule and Tablet Administration in the Presence or Absence of High-Fat Food and/or Proton Pump Inhibitors (PPI) in Normal Healthy Participants- Part B

Sponsor

Enliven Therapeutics, Inc.

Enrollment

15 participants

Start Date

Jan 14, 2025

Study Type

Interventional

Conditions

Parkinson's Disease (PD)Chronic Myeloid Leukaemia (CML)

Summary

The current study is being conducted in healthy participants to understand the appropriate drug dosage form and administration of ELVN-001. This study plans to assess the relative bioavailability of ELVN-001 in capsule and tablet forms, the safety profile of ELVN-001, and the effects of food and/or proton pump inhibitors (PPIs) on ELVN-001. Who is it for? Participants who provide written informed consent will undergo screening evaluations and only eligible participants will be admitted to the clinical research unit (CRU) from Day -1 until the End of Confinement Visit/End of Study (EOS) or withdrawal from the study, whichever comes first. Study details Participants are healthy participants between age of 18-60yrs with the BMI of more than equal to 18.5 and less than equal to 32 kg/m2 inclusive, and weigh between more than equal to 50 kg and less than equal to 100 kg, inclusive, at Screening. The study will be conducted in healthy participants (15 in Part B). All doses of ELVN-001 for Part B and esomeprazole will be administered at the CRU in the presence of the PI or their designee. Study duration It is estimated that overall study duration to be approximately 9 months. Estimated study duration for each participant (including the screening period) is approximately 48 days. It is hoped that this research will help determine the appropriate drug dosage form and administration of ELVN-001 and inform further clinical use of ELVN-001 in patients with CML and other therapeutic areas, such as PD.

Eligibility

Sex: Both males and femalesMin Age: 18 YearssMax Age: 60 Yearss

Inclusion Criteria18

Participants more than equal to 18 and less than equal to 60 years of age at time of informed consent.
Normal healthy male and female participants with no clinically significant medical history, and no clinically significant abnormalities on physical examination at Screening and/or before the first administration of IP at the discretion of the PI or designee.
Able to provide written informed consent to participate in this study.
Healthy and free from clinically significant illness or disease with clinical laboratory values at Screening and Day -1 (including haematology, biochemistry, coagulation, and urinalysis) within normal range as specified by the testing laboratory, unless deemed not clinically significant by the PI or designee.
Has a body mass index (BMI) more than equal to 18.5 and less than equal to 32 kg/metre square, inclusive, and weigh between more than equal to 50 kg and less than equal to 100 kg, inclusive, at Screening.
Able to understand the nature of the study and any risks associated with participation and willing to cooperate and comply with protocol restrictions and requirements.
Agrees to the meals, dietary and lifestyle requirements as outlined in the protocol.
Estimated glomerular filtration rate (eGFR): more than equal to 80 mL/min/1.73 metre square for all participants using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation.
Systolic blood pressure more than equal to 90 and less than equal to 140 mmHg and diastolic blood pressure more than equal to 40 and less than equal to 90 mmHg.
Resting heart rate more than equal to 45 and less than equal to 100 beats per minute (bpm).
A male participant must agree to use contraception, as detailed in protocol during the treatment period and for at least 90 days after the last dose of IP and refrain from donating sperm during this period or has vasectomised since at least 6 months prior to first IP administration. Male participants whose partners are woman of childbearing potential (WOCBP) can be eligible if they use condoms during intercourse and their WOCBP partners use 1 of the following contraceptive measures for at least 90 days following the last dose of IP:
Hormonal contraception (oral, implant, or injectable),
Intrauterine device (IUD) or intrauterine system (IUS),
Tubal ligation, hysterectomy, bilateral salpingectomy, bilateral oophorectomy, or
Diaphragm or cervical cap.
A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies:
Not a woman of childbearing potential, OR
Must agree to use contraception, as detailed in protocol, during the treatment period and for at least 90 days after the last dose of IP

Exclusion Criteria20

Previous participating in a trial with ELVN-001 or participating in another clinical trial within 30 days prior to first dose of the IP.
Received any prescribed systemic or topical medications, or live vaccination within 30 days (or less than 5 half-lives, whichever is longer) or any inactivated vaccination within 72 hours prior to first dose of the IP.
Potential participant has used any other IP or investigational medical device within 30 days prior to Screening.
Family history (biological relatives [ie, parents, siblings]) of long or short QT syndrome or Torsades de Pointes.
Abnormal ECG findings at Screening or Day -1 (eg, repeated demonstration of a QTc interval > 450 msec [male] or > 470 msec [female] corrected by Fridericia’s formula [QTcF] or Bazett’s formula [QTcB]) that are considered by the PI or designee to be clinically significant.
Presence or history of drug and or alcohol abuse including a positive result on the urine drug screen or alcohol breath test at Screening or Day -1.
Excessive intake of caffeine-containing drinks or food as judged by the PI. Excessive intake is defined as more than 400 mg of caffeine per day (equivalent to 4 or 5 cups of brewed coffee).
Use of tobacco or nicotine-containing products (including e-cigarettes) within 3 months prior to first dose of IP and during the course of the study.
Test positive for hepatitis B surface antigen, hepatitis B core antibody, hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) 1 and HIV 2 antibodies. If a participant tests positive for HCV antibodies, they may still be allowed into the trial if HCV ribonucleic acid (RNA) is undetectable in a Follow-up assessment.
Plasma donation within 30 days of Screening or any blood/loss or donation more than 500 mL during the 90 days prior to Screening.
History or presence of gastrointestinal (including a previous episode of pancreatitis), hepatic, or renal disease, or any other conditions known to interfere with absorption, distribution, metabolism, or excretion of drugs.
Unwillingness to refrain from strenuous exercise 48 hours prior to CRU confinement and for the duration of the study.
Positive cotinine test at Screening and Day -1.
Is at suicidal risk in the opinion of the PI as per the following criteria:
Any suicidal attempts within 12 months prior to Screening.
Any suicidal intent including a plan or Columbia-Suicide Severity Rating Scale (C-SSRS) answer of “YES” on suicidal ideation currently or within 3 months.
Is unable to consume a high-fat, high-calorie meal.
Unwillingness to abstain from concomitant therapy for the duration of the study (with the exception of medications used to treat adverse symptoms associated with ELVN-001
administration and permitted contraception [outlined in protocol. Over the counter (OTC) medications, topical medications, herbal remedies, supplements, or vitamins are not permitted for 7 days prior to dosing, and during the study without prior approval of the PI or designee.
Has hypersensitivities and/or intolerance for PPIs

Interested in this trial?

Get notified about updates and connect with the research team.

Interventions

The study is composed of 2 parts: This registration captures the details of PART B • Part B (PPI (Proton pump inhibitors) + FE (food effect)) will be conducted to assess the PK (pharmacokinetics), safety, and tolerability of ELVN-001 in healthy participants receiving single doses of ELVN-001 in tablet form following PPI treatment for a total of 14 days, in the presence or absence of high-fat, high-calorie food. An example of a high-fat, high-calorie meal would be two eggs fried in butter, two strips of bacon, two slices of toast with butter, four ounces of hash brown potatoes and eight ounces of whole milk. Treatment Duration: Part B: 15 Participants will receive a single dose of 80 mg ELVN-001 tablet on Days 1 (tablet-fasted), 8 (tablet-fasted), and 15 (tablet-fed). In addition, participants will receive 40 mg esomeprazole (oral tablet) from Day 2 to Day 15. Mode of administration: Tablet form. Orally with 240ml of water Participants who provide written informed consent will undergo Screening evaluations to determine eligibility within 28 days prior to Day -1. Eligible participants will be admitted to the clinical research unit (CRU) from Day -1 until the End of Confinement Visit/End of Study (EOS) or withdrawal from the study, whichever comes first. All the IP administrations will be done in the clinic under PI/delegate supervision who will monitor adherance to protocol.