Clinical trial NCT06308523: A Study to Evaluate the Safety, Tolerability, PK and PD of AP303 in Healthy Chinese Participants
Official title: A Randomized, Double-blind, Placebo-controlled Multiple-ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AP303 Following 2-week Oral Administration in Healthy Chinese Participants.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Lead sponsor: Alebund Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2024-03-13
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The study will be a single center, double-blind, randomized, placebo-controlled, multiple-ascending-dose study to evaluate the safety, tolerability, PK and PD of AP303 following 2-week oral administration to healthy Chinese participants.

Detailed description: Eligible study participants will be enrolled and randomized into one of the two dose cohorts, each cohort will include 9 participants randomized to AP303 and placebo at 2:1 ratio (6 on AP303 and 3 on placebo).

Eligibility criteria: Important Inclusion Criteria:

1. Healthy male and female participants, 18-50 years of age.
2. BMI (body mass index) 18-27 kg/m2.

Important Exclusion criteria:

1. History or symptoms of any clinically significant kidney, liver, broncho-pulmonary, gastrointestinal, neurological, psychiatric, cardiovascular, endocrine/metabolic, hematological disease or cancer.
2. Personal history of congenital long QT syndrome or family history of sudden death.
3. People with a history of specific severe allergies, or severe allergic conditions or known allergies to the study or any of its ingredients or excipients as judged by the investigator, or any acute confirmed significant allergic reactions to any drug, or multiple drug severe allergies (non-active hay fever is acceptable). Allowing for childhood asthma, history of mild eczema that has had no flare ups for ≥5 years or is fully resolved.
4. History of having received or currently receiving any systemic anti-neoplastic or immunomodulatory treatment (including systemic oral or inhaled corticosteroids) ≤6 months prior to the first dose of study drug or the expectation that such treatment will be needed at any time during the study.
5. Participants who have had significant acute infection, e.g., COVID-19, influenza, local infection, acute gastrointestinal symptoms or any other clinically significant illness within two weeks before study drug administration.
6. Confirmed systolic BP greater than 140 or less than 90 mmHg, and diastolic BP greater than 90 or less than 50 mmHg at screening.
7. Abnormalities of ECG parameters and abnormal shape of ECG wave on screening ECG.
8. Implantation of cardiac pacemaker or clinically significant arrhythmias.
9. Estimated glomerular filtration rate (eGFR) \<90 mL/min/1.73 m2 (using the CKD-EPI equation).
10. Positive test at screening of any of the following: Hepatitis B (HBsAg), Hepatitis C (HCVAb), human immunodeficiency virus (HIV Ab) or syphilis AB.
11. ALT or AST \>1.5 × ULN, or any other clinically significant abnormalities in laboratory test results at screening.
12. Dosed with a small-molecule or biologic investigational drug within 30 days or 90 days, respectively, or 5 half-lives whichever is the longer) prior to first dose of this study.
13. Donation of component (plasma or platelet) or whole blood ≥200 mL within 4 weeks prior to screening.
14. Receipt of a live vaccine within 4 weeks of prior to screening (Influenza and COVID-19 vaccines are allowed).
15. Positive urine test for drugs of abus.
16. History of drug and/or alcohol abuse or addiction.
17. History (within 3 months of screening) of alcohol consumption exceeding 2 standard drinks per day on average (1 standard drink = 10 grams of alcohol). Alcohol consumption within 48 hours before screening.
18. Use of \>5 cigarettes or equivalent nicotine-containing product per day.
19. Taking any prescribed or over-the-counter medications (including vitamins or herbal remedies) within 30 days or 5 half-lives (whichever is the longer) of the first dose of study drug. Occasional paracetamol is allowed (see section on Permitted Therapy). Exceptions may be made on a case-by-case basis following discussion and agreement between the investigator and the sponsor.
20. Medical or social conditions that would potentially interfere with the participant's ability to comply with the study visit schedule or the study assessments.

Primary outcomes:
measure: Cmax
timeFrame: Day 1, Day 3-14
measure: Tmax
timeFrame: Day 1, Day 3-14
measure: AUC0-24h
timeFrame: Day 1
measure: AUC0-last
timeFrame: Day 1
measure: AUC0-inf
timeFrame: Day 1
measure: AUC0-t
timeFrame: Day 3-14
measure: t1/2
timeFrame: Day 1, Day 3-14
measure: CL/F
timeFrame: Day 1
measure: V/F
timeFrame: Day 1, Day 3-14
measure: Cav
timeFrame: Day 3-14
measure: Ctrough
timeFrame: Day 3-14
measure: Rac
timeFrame: Day 3-14
measure: Incidence and severity of adverse events
timeFrame: Day 1-28
measure: Incidence of laboratory abnormalities, based on hematology, clinical chemistry, coagulation and urinalysis test results
timeFrame: Day 1-28
measure: Effect of AP303 on ECG parameters
timeFrame: Day 1-28
measure: Effect of AP303 on ECG parameters
timeFrame: Day 1-28
measure: Effect of AP303 on ECG parameters
timeFrame: Day 1-28
measure: Effect of AP303 on ECG parameters
timeFrame: Day 1-28
measure: Effect of AP303 on ECG parameters
timeFrame: Day 1-28
measure: Effect of AP303 on ECG parameters
timeFrame: Day 1-28
measure: Vital signs
timeFrame: Day 1-28
measure: Effect of AP303 on physical examination result
timeFrame: Day 1-28
measure: body weight
timeFrame: Day 1-28
Secondary outcomes:
measure: Fasting glucose
timeFrame: Baseline, Days 5, 10, 14 and 28
measure: Fasting lipid profile
timeFrame: Baseline, Days 5, 10, 14 and 28
measure: Serum creatinine
timeFrame: Baseline, Days 5, 10, 14 and 28
measure: eGFR
timeFrame: Baseline, Days 5, 10, 14 and 28
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University Third Hospital
Study officials:
References: