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

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.

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.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: AP303 150 μg; Drug: AP303 300 μg; Drug: Placebo 150 μg; Drug: Placebo 300 μg

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).

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Peking University Third Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo 150 μg; Placebo Tablet 150 μg QD; Drug: Placebo 300 μg; Placebo Tablet 300 μg QD
Experimental: AP303	Drug: AP303 150 μg; AP303 Tablet 150 μg QD; Drug: AP303 300 μg; AP303 Tablet 300 μg QD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	Maximum observed plasma concentration	Day 1, Day 3-14
Tmax	Time to maximum observed plasma concentration	Day 1, Day 3-14
AUC0-24h	Area under the plasma concentration versus time curve up to 24 hours	Day 1
AUC0-last	Area under the plasma concentration versus time curve up to the last measurable concentration	Day 1
AUC0-inf	Area under the plasma concentration versus time curve extrapolated to infinity	Day 1
AUC0-t	Area under the plasma concentration-time curve for a dosing interval	Day 3-14
t1/2	Apparent terminal half-life, computed as ln(2)/λz	Day 1, Day 3-14
CL/F	Apparent oral clearance calculated from Dose/ AUC0-inf	Day 1
V/F	Apparent volume of distribution of oral drug	Day 1, Day 3-14
Cav	average plasma concentration	Day 3-14
Ctrough	Trough plasma concentration	Day 3-14
Rac	Ratio of accumulation	Day 3-14
Incidence and severity of adverse events	Incidence and severity of adverse events	Day 1-28
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
Effect of AP303 on ECG parameters	Heart rate in beats/min	Day 1-28
Effect of AP303 on ECG parameters	QT in ms	Day 1-28
Effect of AP303 on ECG parameters	PR in ms	Day 1-28
Effect of AP303 on ECG parameters	QRS in ms	Day 1-28
Effect of AP303 on ECG parameters	QTcF in ms	Day 1-28
Effect of AP303 on ECG parameters	QTcB in ms	Day 1-28
Vital signs	Effect of AP303 on vital signs, e.g. blood pressure	Day 1-28
Effect of AP303 on physical examination result	nature, frequency, and severity of abnormality of physical examination result	Day 1-28
body weight	Effect of AP303 on body weight, e.g. change of body weight after administration of AP303	Day 1-28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fasting glucose	Fasting glucose	Baseline, Days 5, 10, 14 and 28
Fasting lipid profile	Triglyceride, HDL-C, LDL-C, Total cholesterol	Baseline, Days 5, 10, 14 and 28
Serum creatinine	Serum creatinine	Baseline, Days 5, 10, 14 and 28
eGFR	Estimated glomerular filtration rate	Baseline, Days 5, 10, 14 and 28

Collaborators and Investigators

• Sponsor: Alebund Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): March 18, 2024
• Primary Completion (Actual): May 13, 2024
• Study Completion (Actual): May 13, 2024

Study Registration Dates

• First Submitted: February 20, 2024
• First Submitted That Met QC Criteria: March 6, 2024
• First Posted (Actual): March 13, 2024

Study Record Updates

• Last Update Posted (Actual): October 22, 2024
• Last Update Submitted That Met QC Criteria: October 18, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: AP303-PK-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No