A Phase 1 Study in Healthy Volunteers to Evaluate the Safety and Tolerability of NX-5948 Tablets Following Single and Multiple Ascending Doses, the Relative Bioavailability of NX-5948 Tablets Compared to Capsules, the Effect of NX-5948 on the QT Interval, the Effect of Food on the Pharmacokinetics of NX-5948, Drug-Drug Interactions With NX-5948, and the Intra-Subject Variability of the Bioavailability of NX-5948 Capsules
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 223
- 试验地点
- 3
- 主要终点
- Area under the concentration-time curve from time 0 to last observed non-zero concentration (AUC0-t): NX-5948
研究概览
简要总结
This is a multiple part, multiple cohort study evaluating single and multiple ascending doses, relative bioavailability, food effect, and drug-drug interaction of NX-5948 in healthy volunteers.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 19 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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, or vital signs at the screening visit, as deemed by the Principal Investigator (PI) or designee
- •Understands the study procedures in the informed consent form (ICF) and be willing and able to comply with the protocol.
排除标准
- •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-
- •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.
- •Note: Other Inclusion/Exclusion criteria may apply as defined in the protocol.
研究组 & 干预措施
NX-5948 tablet and capsule under fasting and fed conditions; with and without placebo
干预措施: Placebo (Drug)
NX-5948 tablet and capsule under fasting and fed conditions; with and without placebo
干预措施: NX-5948 (Drug)
NX-5948 tablet and capsule with and without esomeprazole under fasting and fed conditions
干预措施: NX-5948 (Drug)
NX-5948 tablet and capsule with and without esomeprazole under fasting and fed conditions
干预措施: Esomeprazole (Drug)
NX-5948 with and without famotidine under fasting and fed conditions
干预措施: Famotidine (Drug)
NX-5948 with and without famotidine under fasting and fed conditions
干预措施: NX-5948 (Drug)
Midazolam with and without NX-5948
干预措施: Midazolam (Drug)
Midazolam with and without NX-5948
干预措施: NX-5948 (Drug)
Digoxin with and without NX-5948
干预措施: Digoxin (Drug)
Digoxin with and without NX-5948
干预措施: NX-5948 (Drug)
Rosuvastatin with and without NX-5948
干预措施: Rosuvastatin (Drug)
Rosuvastatin with and without NX-5948
干预措施: NX-5948 (Drug)
NX-5948 with and without quinidine
干预措施: Quinidine (Drug)
NX-5948 with and without quinidine
干预措施: NX-5948 (Drug)
结局指标
主要结局
Area under the concentration-time curve from time 0 to last observed non-zero concentration (AUC0-t): NX-5948
时间窗: 9 weeks
NX-5948 administered as a tablet or capsule under fasting and fed conditions; with and without esomeprazole, famotidine, or quinidine
Area under the concentration-time curve from time 0 extrapolated to infinity (AUC0-inf): NX-5948
时间窗: 9 weeks
NX-5948 administered as a tablet or capsule under fasting and fed conditions; with and without esomeprazole, famotidine, or quinidine
Maximum observed concentration (Cmax): NX-5948
时间窗: 9 weeks
NX-5948 administered as a tablet or capsule under fasting and fed conditions; with and without esomeprazole, famotidine, or quinidine
AUC0-t: Midazolam, rosuvastatin, or digoxin
时间窗: 9 weeks
Midazolam, rosuvastatin, or digoxin administered with and without NX-5948
AUC0-inf: Midazolam, rosuvastatin, or digoxin
时间窗: 9 weeks
Midazolam, rosuvastatin, or digoxin administered with and without NX-5948
Cmax: Midazolam, rosuvastatin, or digoxin
时间窗: 9 weeks
Midazolam, rosuvastatin, or digoxin administered with and without NX-5948
Placebo-corrected change from baseline QT interval (QTc) as measured by electrocardiogram
时间窗: Baseline, 9 weeks
Number of participants with treatment-emergent adverse events
时间窗: Up to 10 weeks
Assessment of PK parameters NX-5948 tablets versus capsules
时间窗: 9 weeks
Relative bioavailability of NX-5948 tablet, compared to capsule, will be measured using PK parameters (Tmax)
Food effect and effect of esomeprazole on AUC0-t for single-dose NX-5948 tablet
时间窗: 9 weeks
Evaluate the effect of food and the effect of multiple doses of esomeprazole on the single-dose PK of NX-5948 tablet
Food effect and effect of esomeprazole on AUC0-inf for single-dose NX-5948 tablet
时间窗: 9 weeks
Evaluate the effect of food and the effect of multiple doses of esomeprazole on the single-dose PK of NX-5948 tablet
Food effect and effect of esomeprazole on Cmax for single-dose NX-5948 tablet
时间窗: 9 weeks
Evaluate the effect of food and the effect of multiple doses of esomeprazole on the single-dose PK of NX-5948 tablet
Assessment of PK parameters: NX-5948 tablets versus capsules
时间窗: 9 weeks
Relative bioavailability of NX-5948 tablet, compared to capsule, will be measured using PK parameters (AUC)
次要结局
未报告次要终点