A Phase 1, Open-Label, Randomized, Crossover Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single Ascending Doses of APL-1501 ER Capsules Compared to APL-1202 IR Tablets in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Number of Participants With Abnormal Clinical Laboratory Values
研究概览
简要总结
The primary objective of the study is to assess safety and tolerability following administration of single doses of APL-1202 (immediate release) IR tablets and APL-1501 extended release (ER) capsules in healthy participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Participants must meet all of the following criteria to be included in the study:
- •Male, >=18 and less than or equal to (<=) 65 years of age, with body mass index (BMI) greater than (>) 18.5 and less than (<) 32.0 kilogram per square meter (kg/m^2) and body weight >=50.0 kilogram (kg).
- •Non-smoker (no use of tobacco or nicotine products, example, snuff, chewing tobacco, cigars, cigarettes, pipes, e-cigarettes [vaping] etc. within 3 months prior to screening).
- •Healthy as defined by:
- •the absence of clinically significant illness and surgery within 4 weeks prior to study drug administration.
- •the absence of clinically significant history of neurological, endocrine, cardiovascular, respiratory, hematological, immunological, psychiatric, gastrointestinal, renal, hepatic, and metabolic disease.
- •Sexually active non-sterile males must be willing to use an acceptable contraceptive method throughout the study.
- •Able to understand the study procedures and provide signed informed consent to participate in the study.
排除标准
- •Participants to whom any of the following applies will be excluded from the study:
- •Any clinically significant abnormal finding at physical examination.
- •Clinically significant abnormal laboratory test results or positive serology test results for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV) antibody, or Human immunodeficiency virus (HIV) antigen and antibody.
- •Positive urine drug screen, cotinine test, or alcohol breath test.
- •History of significant allergic reactions (example, anaphylactic reaction, hypersensitivity, angioedema) to any drug.
- •Clinically significant Electrocardiograms (ECG) abnormalities or vital signs abnormalities (systolic blood pressure [BP] lower than 90 or over 140 millimeters of mercury [mmHg], diastolic BP lower than 50 or over 90 mmHg, heart rate [HR] less than 40 or over 100 beats per minute [bpm], or RR less than 10 or over 25 bpm) at screening.
- •History of drug abuse within 1 year prior to screening or recreational use of marijuana within 1 month or other illegal drugs such as cocaine, phencyclidine [PCP], crack, opioid derivatives including heroin, and amphetamine derivatives within 3 months prior to screening.
- •History of alcohol abuse within 1 year prior to screening or regular use of alcohol within 6 months prior to screening that exceeds 10 units of alcohol per week (1 unit = 375 milliliter [mL] of beer 3.5 percent (%), or 100 mL of wine 13.5%, or 30 mL of distilled alcohol 40%).
- •Use of medications within the timeframes specified in section.
- •Participation in a clinical research study involving the administration of an investigational or marketed drug or device within 30 days prior to the first dosing, administration of a biological product in the context of a clinical research study within 90 days prior to the first dosing, or concomitant participation in an investigational study involving no drug or device administration.
- •Donation of plasma within 7 days prior to dosing or donation or loss of 500 mL or more of whole blood within 8 weeks prior to dosing.
- •Optic nerve disease, cataracts, or a history of related conditions.
- •Any reason which, in the opinion of the Investigator, would prevent the participant from participating in the study.
研究组 & 干预措施
Cohort 1, Sequence 1, R1T1: APL-1202 IR 375 mg + APL-1501 ER 764 mg
Participants will receive APL-1202 375 milligram (mg) IR tablets, orally, once on Day 1 of Period 1 (Treatment R1), followed by T1 APL-1501 764 mg ER capsules, orally, once, on Day 4 of Period 2 (Treatment T1). A washout period of more than or equal to (>=) 72 hours will be maintained in between Period 1 and 2.
干预措施: APL-1202 (Drug)
Cohort 1, Sequence 1, R1T1: APL-1202 IR 375 mg + APL-1501 ER 764 mg
Participants will receive APL-1202 375 milligram (mg) IR tablets, orally, once on Day 1 of Period 1 (Treatment R1), followed by T1 APL-1501 764 mg ER capsules, orally, once, on Day 4 of Period 2 (Treatment T1). A washout period of more than or equal to (>=) 72 hours will be maintained in between Period 1 and 2.
干预措施: APL-1501 (Drug)
Cohort 1, Sequence 2, T1R1: APL-1501 ER 764 mg + APL-1202 IR 375 mg
Participants will receive APL-1501 764 mg ER capsules, orally, once on Day 1 of Period 1 (Treatment T1), followed by APL-1202 375 mg IR tablets, orally, once, on Day 4 of Period 2 (Treatment R1). A washout period of >=72 hours will be maintained in between Period 1 and 2.
干预措施: APL-1202 (Drug)
Cohort 1, Sequence 2, T1R1: APL-1501 ER 764 mg + APL-1202 IR 375 mg
Participants will receive APL-1501 764 mg ER capsules, orally, once on Day 1 of Period 1 (Treatment T1), followed by APL-1202 375 mg IR tablets, orally, once, on Day 4 of Period 2 (Treatment R1). A washout period of >=72 hours will be maintained in between Period 1 and 2.
干预措施: APL-1501 (Drug)
Cohort 2, Sequence 1, R1T2: APL-1202 IR 375 mg + APL-1501 ER 1146 mg
Participants will receive APL-1202 375 mg IR tablets, orally, once on Day 1 of Period 1 (Treatment R1), followed by APL-1501 1146 mg ER capsules, orally, once, on Day 4 of Period 2 (Treatment T2). A washout period of >=72 hours will be maintained in between Period 1 and 2.
干预措施: APL-1202 (Drug)
Cohort 2, Sequence 1, R1T2: APL-1202 IR 375 mg + APL-1501 ER 1146 mg
Participants will receive APL-1202 375 mg IR tablets, orally, once on Day 1 of Period 1 (Treatment R1), followed by APL-1501 1146 mg ER capsules, orally, once, on Day 4 of Period 2 (Treatment T2). A washout period of >=72 hours will be maintained in between Period 1 and 2.
干预措施: APL-1501 (Drug)
Cohort 2, Sequence 2, T2R1: APL-1501 ER 1146 mg + APL-1202 IR 375 mg
Participants will receive APL-1501 1146 mg ER capsules, orally, once on Day 1 of Period 1 (Treatment T2), followed by APL-1202 375 mg IR tablets, orally, once, on Day 4 of Period 2 (Treatment R1). A washout period of >=72 hours will be maintained in between Period 1 and 2.
干预措施: APL-1202 (Drug)
Cohort 2, Sequence 2, T2R1: APL-1501 ER 1146 mg + APL-1202 IR 375 mg
Participants will receive APL-1501 1146 mg ER capsules, orally, once on Day 1 of Period 1 (Treatment T2), followed by APL-1202 375 mg IR tablets, orally, once, on Day 4 of Period 2 (Treatment R1). A washout period of >=72 hours will be maintained in between Period 1 and 2.
干预措施: APL-1501 (Drug)
Cohort 3: APL-1501 ER 1528 mg
Participants will receive APL-1501 1528 mg ER capsules, orally, once on Day 1.
干预措施: APL-1501 (Drug)
结局指标
主要结局
Number of Participants With Abnormal Clinical Laboratory Values
时间窗: From Baseline up to Day 9
Number of Participants With Adverse Events (AEs)
时间窗: From Baseline up to Day 9
Number of Participants With Abnormal Vital Sign Measurements
时间窗: From Baseline up to Day 9
Number of Participants With Abnormal 12-Lead Electrocardiogram (ECGs) Recordings
时间窗: From Baseline up to Day 9
Number of Participants With Abnormal Physical Examinations
时间窗: From Baseline up to Day 9
次要结局
- AUC0-inf: Area Under the Concentration-time Curve From Time Zero to Infinity of APL-1202, and ASN-1651 (Metabolite) Following APL-1501 ER Capsules(Cohorts 1 and 2 - Days 1 and 4: Pre-dose and up to 24 hours post-dose; Cohort 3 - Day 1: Pre-dose and up to 24 hours post-dose)
- Cmax: Maximal Observed Concentration of APL-1202, and ASN-1651 (Metabolite) Following APL-1501 ER Capsules(Cohorts 1 and 2 - Days 1 and 4: Pre-dose and up to 24 hours post-dose; Cohort 3 - Day 1: Pre-dose and up to 24 hours post-dose)
- Tlast: Time When the Last Concentration is Observed of APL-1202, and ASN-1651 (Metabolite) Following APL-1501 ER Capsules(Cohorts 1 and 2 - Days 1 and 4: Pre-dose and up to 24 hours post-dose; Cohort 3 - Day 1: Pre-dose and up to 24 hours post-dose)
- Tmax: Time When the Cmax is Observed of APL-1202, and ASN-1651 (Metabolite) Following APL-1501 ER Capsules(Cohorts 1 and 2 - Days 1 and 4: Pre-dose and up to 24 hours post-dose; Cohort 3 - Day 1: Pre-dose and up to 24 hours post-dose)
- Residual Area of APL-1202, and ASN-1651 (Metabolite) Following APL-1501 ER Capsules(Cohorts 1 and 2 - Days 1 and 4: Pre-dose and up to 24 hours post-dose; Cohort 3 - Day 1: Pre-dose and up to 24 hours post-dose)
- T½ el: Terminal Elimination Half-life of APL-1202, and ASN-1651 (Metabolite) Following APL-1501 ER Capsules(Cohorts 1 and 2 - Days 1 and 4: Pre-dose and up to 24 hours post-dose; Cohort 3 - Day 1: Pre-dose and up to 24 hours post-dose)
- Kel: Terminal Elimination Rate Constant of APL-1202, and ASN-1651 (Metabolite) Following APL-1501 ER Capsules(Cohorts 1 and 2 - Days 1 and 4: Pre-dose and up to 24 hours post-dose; Cohort 3 - Day 1: Pre-dose and up to 24 hours post-dose)
- AUC0-t: Area Under the Concentration-time Curve From Time Zero Until the Last Observed Concentration of APL-1202, and ASN-1651 (Metabolite) Following APL-1501 ER Capsules(Cohorts 1 and 2 - Days 1 and 4: Pre-dose and up to 24 hours post-dose; Cohort 3 - Day 1: Pre-dose and up to 24 hours post-dose)
- Cl/F: Apparent Clearance of APL-1202, and ASN-1651 (Metabolite) Following APL-1501 ER Capsules(Cohorts 1 and 2 - Days 1 and 4: Pre-dose and up to 24 hours post-dose; Cohort 3 - Day 1: Pre-dose and up to 24 hours post-dose)
- Vz/F: Apparent Volume of Distribution of APL-1202, and ASN-1651 (Metabolite) Following APL-1501 ER Capsules(Cohorts 1 and 2 - Days 1 and 4: Pre-dose and up to 24 hours post-dose; Cohort 3 - Day 1: Pre-dose and up to 24 hours post-dose)
- DNAUC0-inf: Dose Normalized AUC0-inf of APL-1202, and ASN-1651 (Metabolite) Following APL-1501 ER Capsules(Cohorts 1 and 2 - Days 1 and 4: Pre-dose and up to 24 hours post-dose; Cohort 3 - Day 1: Pre-dose and up to 24 hours post-dose)
- DNCmax: Dose Normalized Cmax of APL-1202, and ASN-1651 (Metabolite) Following APL-1501 ER Capsules(Cohorts 1 and 2 - Days 1 and 4: Pre-dose and up to 24 hours post-dose; Cohort 3 - Day 1: Pre-dose and up to 24 hours post-dose)
- Geometric Mean Ratio of Cmax of APL-1501 ER Capsules in Reference to APL-1202 IR Tablets(Cohorts 1 and 2 - Days 1 and 4: Pre-dose and up to 24 hours post-dose; Cohort 3 - Day 1: Pre-dose and up to 24 hours post-dose)
- Geometric Mean Ratio of AUC0-t of APL-1501 ER Capsules in Reference to APL-1202 IR Tablets(Cohorts 1 and 2 - Days 1 and 4: Pre-dose and up to 24 hours post-dose; Cohort 3 - Day 1: Pre-dose and up to 24 hours post-dose)
- Geometric Mean Ratio of AUC0-inf of APL-1501 ER Capsules in Reference to APL-1202 IR Tablets(Cohorts 1 and 2 - Days 1 and 4: Pre-dose and up to 24 hours post-dose; Cohort 3 - Day 1: Pre-dose and up to 24 hours post-dose)
- Frel: Relative Bioavailability of APL-1501 ER Capsules and APL-1202 IR Tablets(Cohorts 1 and 2 - Days 1 and 4: Pre-dose and up to 24 hours post-dose; Cohort 3 - Day 1: Pre-dose and up to 24 hours post-dose)
- Dose Proportionality of Cmax(Cohorts 1 and 2 - Days 1 and 4: Pre-dose and up to 24 hours post-dose; Cohort 3 - Day 1: Pre-dose and up to 24 hours post-dose)
- Dose Proportionality of AUC0-t(Cohorts 1 and 2 - Days 1 and 4: Pre-dose and up to 24 hours post-dose; Cohort 3 - Day 1: Pre-dose and up to 24 hours post-dose)
- Dose Proportionality of AUC0-inf(Cohorts 1 and 2 - Days 1 and 4: Pre-dose and up to 24 hours post-dose; Cohort 3 - Day 1: Pre-dose and up to 24 hours post-dose)