Healthy Subjects
Conditions
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).
Interventions
DRUGAP303 150 μg
AP303 Tablet 150 μg QD
DRUGPlacebo 150 μg
Placebo Tablet 150 μg QD
DRUGAP303 300 μg
AP303 Tablet 300 μg QD
DRUGPlacebo 300 μg
Placebo Tablet 300 μg QD
Sponsors
Alebund Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| body weight | Day 1-28 | Effect of AP303 on body weight, e.g. change of body weight after administration of AP303 |
| Cav | Day 3-14 | average plasma concentration |
| Ctrough | Day 3-14 | Trough plasma concentration |
| Rac | Day 3-14 | Ratio of accumulation |
| Incidence and severity of adverse events | Day 1-28 | Incidence and severity of adverse events |
| Effect of AP303 on ECG parameters | Day 1-28 | Heart rate in beats/min |
| Vital signs | Day 1-28 | Effect of AP303 on vital signs, e.g. blood pressure |
| Effect of AP303 on physical examination result | Day 1-28 | nature, frequency, and severity of abnormality of physical examination result |
| V/F | Day 1, Day 3-14 | Apparent volume of distribution of oral drug |
| Cmax | Day 1, Day 3-14 | Maximum observed plasma concentration |
| Tmax | Day 1, Day 3-14 | Time to maximum observed plasma concentration |
| AUC0-24h | Day 1 | Area under the plasma concentration versus time curve up to 24 hours |
| AUC0-last | Day 1 | Area under the plasma concentration versus time curve up to the last measurable concentration |
| AUC0-inf | Day 1 | Area under the plasma concentration versus time curve extrapolated to infinity |
| AUC0-t | Day 3-14 | Area under the plasma concentration-time curve for a dosing interval |
| t1/2 | Day 1, Day 3-14 | Apparent terminal half-life, computed as ln(2)/λz |
| CL/F | Day 1 | Apparent oral clearance calculated from Dose/ AUC0-inf |
| Incidence of laboratory abnormalities, based on hematology, clinical chemistry, coagulation and urinalysis test results | Day 1-28 | Incidence of laboratory abnormalities, based on hematology, clinical chemistry, coagulation and urinalysis test results |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fasting glucose | Baseline, Days 5, 10, 14 and 28 | Fasting glucose |
| Fasting lipid profile | Baseline, Days 5, 10, 14 and 28 | Triglyceride, HDL-C, LDL-C, Total cholesterol |
| Serum creatinine | Baseline, Days 5, 10, 14 and 28 | Serum creatinine |
| eGFR | Baseline, Days 5, 10, 14 and 28 | Estimated glomerular filtration rate |
Countries
China
Outcome results
None listed