Clinical trial NCT06717269: Relative Bioavailability of NX-5948 Tablets Vs Capsules and the Effect of Covariates on the PK of NX-5948 Tablets
Official title: A Phase 1, Open-Label Study in Healthy Volunteers to Evaluate the Relative Bioavailability of NX-5948 Tablets Compared to Capsules, and the Effect of Food and an Acid-reducing Agent on the Pharmacokinetics of NX-5948
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Healthy Volunteer
Lead sponsor: Nurix Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2024-12-04
Enrollment: 18
Sex: ALL
Minimum age (years): 19
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a 2-cohort, fixed-sequence, 3-period, relative bioavailability, food-effect, and drug-drug interaction study, which will enroll 18 volunteers. A total of 48 healthy, adult male and female (of non-childbearing potential) volunteers are planned to be enrolled.
Primary purpose: TREATMENT

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.

Eligibility criteria: Key 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.

Primary outcomes:
measure: Assessment of PK parameters in 18 healthy volunteers of NX-5948 tablets versus capsules
timeFrame: 9 weeks
measure: Food effect and effect of esomeprazole on AUC0-t for single-dose NX-5948 tablet
timeFrame: 9 weeks
measure: Food effect and effect of esomeprazole on AUC0-inf for single-dose NX-5948 tablet
timeFrame: 9 weeks
measure: Food effect and effect of esomeprazole on Cmax for single-dose NX-5948 tablet
timeFrame: 9 weeks
measure: Assessment of PK parameters in 18 healthy volunteers of NX-5948 tablets versus capsules
timeFrame: 9 weeks
measure: Assessment of PK parameters in 18 healthy volunteers of NX-5948 tablets versus capsules
timeFrame: 9 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Lincoln
country: United States
facility: Celerion
state: Nebraska
Study officials:
affiliation: Nurix Therapeutics
name: Sarah Injac, MD
role: STUDY_DIRECTOR
References: