A Study to Evaluate the Safety, Tolerability, PK and PD of AP303 in Healthy Chinese Participants

Healthy Subjects Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06308523
• Other study ID #: AP303-PK-02
• Status: Completed
• Phase: Phase 1
• Start date: March 18, 2024
• Est. completion date: May 13, 2024

Study information

• Verified date: May 2024
• Source: Alebund Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: May 13, 2024
• Est. primary completion date: May 8, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Subjects

Intervention

Drug:
• AP303 150 µg
AP303 Tablet 150 µg QD
• Placebo 150 µg
Placebo Tablet 150 µg QD
• AP303 300 µg
AP303 Tablet 300 µg QD
• Placebo 300 µg
Placebo Tablet 300 µg QD

Locations

Country	Name	City	State
China	Peking University Third Hospital	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Alebund Pharmaceuticals

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cmax	Maximum observed plasma concentration	Day 1, Day 3-14
Primary	Tmax	Time to maximum observed plasma concentration	Day 1, Day 3-14
Primary	AUC0-24h	Area under the plasma concentration versus time curve up to 24 hours	Day 1
Primary	AUC0-last	Area under the plasma concentration versus time curve up to the last measurable concentration	Day 1
Primary	AUC0-inf	Area under the plasma concentration versus time curve extrapolated to infinity	Day 1
Primary	AUC0-t	Area under the plasma concentration-time curve for a dosing interval	Day 3-14
Primary	t1/2	Apparent terminal half-life, computed as ln(2)/?z	Day 1, Day 3-14
Primary	CL/F	Apparent oral clearance calculated from Dose/ AUC0-inf	Day 1
Primary	V/F	Apparent volume of distribution of oral drug	Day 1, Day 3-14
Primary	Cav	average plasma concentration	Day 3-14
Primary	Ctrough	Trough plasma concentration	Day 3-14
Primary	Rac	Ratio of accumulation	Day 3-14
Primary	Incidence and severity of adverse events	Incidence and severity of adverse events	Day 1-28
Primary	Incidence of laboratory abnormalities, based on hematology, clinical chemistry, coagulation and urinalysis test results	Incidence of laboratory abnormalities, based on hematology, clinical chemistry, coagulation and urinalysis test results	Day 1-28
Primary	Effect of AP303 on ECG parameters	Heart rate in beats/min	Day 1-28
Primary	Effect of AP303 on ECG parameters	QT in ms	Day 1-28
Primary	Effect of AP303 on ECG parameters	PR in ms	Day 1-28
Primary	Effect of AP303 on ECG parameters	QRS in ms	Day 1-28
Primary	Effect of AP303 on ECG parameters	QTcF in ms	Day 1-28
Primary	Effect of AP303 on ECG parameters	QTcB in ms	Day 1-28
Primary	Vital signs	Effect of AP303 on vital signs, e.g. blood pressure	Day 1-28
Primary	Effect of AP303 on physical examination result	nature, frequency, and severity of abnormality of physical examination result	Day 1-28
Primary	body weight	Effect of AP303 on body weight, e.g. change of body weight after administration of AP303	Day 1-28
Secondary	Fasting glucose	Fasting glucose	Baseline, Days 5, 10, 14 and 28
Secondary	Fasting lipid profile	Triglyceride, HDL-C, LDL-C, Total cholesterol	Baseline, Days 5, 10, 14 and 28
Secondary	Serum creatinine	Serum creatinine	Baseline, Days 5, 10, 14 and 28
Secondary	eGFR	Estimated glomerular filtration rate	Baseline, Days 5, 10, 14 and 28