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

NCT06308523 | Completed Phase 1 DMC

• 1 other identifier: AP303-PK-02
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Subjects

Outcome Measures

Primary Outcomes (23)

• 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 Outcomes (4)

• Fasting glucose

  Baseline, Days 5, 10, 14 and 28

• Fasting lipid profile

  Baseline, Days 5, 10, 14 and 28

• Serum creatinine

  Baseline, Days 5, 10, 14 and 28

• eGFR

  Baseline, Days 5, 10, 14 and 28

Study Arms (2)

AP303

EXPERIMENTAL

Drug: AP303 150 μg; Drug: AP303 300 μg

Placebo

PLACEBO COMPARATOR

Drug: Placebo 150 μg; Drug: Placebo 300 μg

Interventions

AP303 150 μg DRUG

AP303 Tablet 150 μg QD

AP303

Placebo 150 μg DRUG

Placebo Tablet 150 μg QD

Placebo

AP303 300 μg DRUG

AP303 Tablet 300 μg QD

AP303

Placebo 300 μg DRUG

Placebo Tablet 300 μg QD

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• History or symptoms of any clinically significant kidney, liver, broncho-pulmonary, gastrointestinal, neurological, psychiatric, cardiovascular, endocrine/metabolic, hematological disease or cancer.
• Personal history of congenital long QT syndrome or family history of sudden death.
• 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.
• 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.
• 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.
• Confirmed systolic BP greater than 140 or less than 90 mmHg, and diastolic BP greater than 90 or less than 50 mmHg at screening.
• Abnormalities of ECG parameters and abnormal shape of ECG wave on screening ECG.
• Implantation of cardiac pacemaker or clinically significant arrhythmias.
• Estimated glomerular filtration rate (eGFR) \<90 mL/min/1.73 m2 (using the CKD-EPI equation).
• Positive test at screening of any of the following: Hepatitis B (HBsAg), Hepatitis C (HCVAb), human immunodeficiency virus (HIV Ab) or syphilis AB.
• ALT or AST \>1.5 × ULN, or any other clinically significant abnormalities in laboratory test results at screening.
• 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.
• Donation of component (plasma or platelet) or whole blood ≥200 mL within 4 weeks prior to screening.
• Receipt of a live vaccine within 4 weeks of prior to screening (Influenza and COVID-19 vaccines are allowed).
• Positive urine test for drugs of abus.

Sponsors & Collaborators

• Alebund Pharmaceuticals: lead

Study Sites (1)

Peking University Third Hospital

Beijing, China

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 20, 2024
• First Posted: March 13, 2024
• Study Start: March 18, 2024
• Primary Completion: May 13, 2024
• Study Completion: May 13, 2024
• Last Updated: October 22, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)