Relative Bioavailability of NX-5948 Tablets Vs Capsules and the Effect of Covariates on the PK of NX-5948 Tablets

Phase 1

Recruiting

• Conditions: Healthy Volunteer
• Interventions: Drug: NX-5948 capsule; Drug: NX-5948 tablet; Drug: Esomeprazole

• Registration Number: NCT06717269
• Lead Sponsor: Nurix Therapeutics, Inc.

Brief Summary

This is a 2-cohort, fixed-sequence, 3-period, relative bioavailability, food-effect, and drug-drug interaction study. It is an open-label study evaluating the relative bioavailability of NX-5948 tablets compared to capsules, and the effect of food and an acid-reducing agent on the pharmacokinetics (PK) of NX-5948.

Detailed Description

In Cohort 1, Period 1 volunteers will receive NX-5948 in a tablet form under fasting conditions. In Period 2, volunteers will receive NX-5948 in a capsule form under fasting conditions. In Period 3, volunteers will receive NX-5948 in a tablet form under fed conditions.

In Cohort 2, Period 1 volunteers will receive NX-5948 in a capsule form under fasting conditions. In Period 2, volunteers will receive NX-5948 in a tablet form under fasting conditions. In Period 3, esomeprazole will be administered once daily for 5 consecutive days with a single dose of NX-5948 tablet coadministered on Day 5.

In both cohorts, serial blood samples will be collected to assess PK.

Study Timeline

• Study Start: 2024-11-30
• Status Verified: 2024-12
• Study First Submitted: 2024-12-01
• Study First Submitted QC: 2024-12-01
• Study First Posted: 2024-12-04
• Last Update Submitted: 2024-12-13
• Last Update Posted: 2024-12-19
• Primary Completion: 2025-02-15
• Study Completion: 2025-03-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 18

Inclusion Criteria

• Healthy, adult, male or female 19-55 years of age
• Continuous non-smoker who has not used nicotine and tobacco-containing products for at least 3 months prior to the first dosing
• Body mass index (BMI) ≥ 18.0 and ≤ 32.0 kg/m2
• Medically healthy with no clinically significant medical history, physical examination, clinical laboratory profiles, vital signs, or 12-lead safety ECGs at the screening visit, as deemed by the PI or designee
• Understands the study procedures in the informed consent form (ICF) and be willing and able to comply with the protocol.

Key

Exclusion Criteria

• Mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study

• Clinically significant history or presence of respiratory, gastrointestinal, renal, hepatic, hematological, lymphatic, neoplastic myeloproliferative, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, endocrine or connective tissue diseases or disorders

• History of any gastrointestinal surgery or cholecystectomy that could impact the PK of NX-5948

• History or presence of alcohol or drug abuse within the past 2 years

• History or presence of hypersensitivity, angioedema, or idiosyncratic reaction to the study drug(s) or related compounds

• History or presence of:

  • Significant multiple and/or severe allergies, including anaphylactic reaction.
  • Personal or family history of prolonged QT syndrome or family history of sudden cardiac death.
  • Evidence of atrial fibrillation, atrial flutter, complete bundle branch block, Wolff Parkinson-White Syndrome, or cardiac pacemaker.
  • Adrenal insufficiency.
  • Skin infection.

• Female volunteers of childbearing potential

• Female volunteer with a positive pregnancy test

• Positive results for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) at the screening visit

• Donation of blood or significant blood loss within 56 days prior to the first dosing

• Plasma donation within 7 days prior to the first dosing

• History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the PI or designee.

• Previous exposure to NX-5948.

• Participation in another clinical study within 30 days or within 5 half-lives (if known), prior to the first dosing, whichever is longer. The 30-day window will be derived from the date of the last blood collection or dosing, whichever is later, in the previous study to Day 1 of Period 1 of the current study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
NX-5948 tablet combined with esomeprazole under fasted conditions	NX-5948 tablet	Cohort 2: Single dose of NX-5948 tablet combined with esomeprazole under fasted conditions. Also, a single dose of NX-5948 capsule under fasted conditions.
NX-5948 tablet combined with esomeprazole under fasted conditions	Esomeprazole	Cohort 2: Single dose of NX-5948 tablet combined with esomeprazole under fasted conditions. Also, a single dose of NX-5948 capsule under fasted conditions.
NX-5948 tablet combined with esomeprazole under fasted conditions	NX-5948 capsule	Cohort 2: Single dose of NX-5948 tablet combined with esomeprazole under fasted conditions. Also, a single dose of NX-5948 capsule under fasted conditions.
NX-5948 tablet and capsule under fasted and fed conditions	NX-5948 capsule	Cohort 1: Single dose of NX-5948 tablet under fasted and fed conditions. Also, single dose of NX-5948 capsule under fasted conditions.
NX-5948 tablet and capsule under fasted and fed conditions	NX-5948 tablet	Cohort 1: Single dose of NX-5948 tablet under fasted and fed conditions. Also, single dose of NX-5948 capsule under fasted conditions.

Primary Outcome Measures

Name	Time	Method
Assessment of PK parameters in 18 healthy volunteers of NX-5948 tablets versus capsules	9 weeks	Relative bioavailability of NX-5948 tablet, compared to capsule, will be measured using PK parameters (Tmax) in up to 18 healthy volunteers
Food effect and effect of esomeprazole on AUC0-t for single-dose NX-5948 tablet	9 weeks	Evaluate the effect of food and the effect of multiple doses of esomeprazole on the single-dose PK of NX-5948 tablet in healthy volunteers
Food effect and effect of esomeprazole on AUC0-inf for single-dose NX-5948 tablet	9 weeks	Evaluate the effect of food and the effect of multiple doses of esomeprazole on the single-dose PK of NX-5948 tablet in healthy volunteers
Food effect and effect of esomeprazole on Cmax for single-dose NX-5948 tablet	9 weeks	Evaluate the effect of food and the effect of multiple doses of esomeprazole on the single-dose PK of NX-5948 tablet in healthy volunteers

Trial Locations

Locations (1)

Celerion; 🇺🇸 Lincoln, Nebraska, United States