A Safety, Tolerability, and Pharmacokinetics Study of AP303 in Healthy Subjects

Phase 1

Completed

• Conditions: Healthy Subjects
• Interventions: Drug: Placebo 50 μg; Drug: AP303 50 μg; Drug: AP303 150 μg; Drug: Placebo 150 μg; Drug: AP303 300 μg; Drug: Placebo 300 μg; Drug: Placebo 600 μg; Drug: AP303 600 μg

• Registration Number: NCT05503693
• Lead Sponsor: Alebund Pty Ltd

Brief Summary

This is a single-center, randomized, double-blind, placebo-controlled, first-in-human study in which the safety, tolerability, and pharmacokinetics of orally administered AP303 will be assessed in healthy adult subjects.

Detailed Description

The study will consist of 2 parts: Part A is a single ascending doses (SAD) phase enrolling a total of 4 cohorts of healthy subjects; Part B is a multiple ascending doses (MAD) phase enrolling 3 cohorts of healthy subjects. One cohort of Part A will receive AP303 under both fasted and fed conditions to investigate the effect of food.

Study Timeline

• Study First Submitted: 2022-08-15
• Study First Submitted QC: 2022-08-15
• Study First Posted: 2022-08-17
• Study Start: 2022-12-06
• Primary Completion: 2023-07-21
• Study Completion: 2023-07-21
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-29
• Last Update Posted: 2024-05-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 62

Inclusion Criteria

1. Healthy male and female subjects, 18 to 55 years of age, inclusive.
2. Body Mas index(BMI) between 18 to 32 kg/m2 inclusive.
3. Female subjects of child-bearing potential must have a negative pregnancy test result and agree to use highly effective contraception consisting of two forms of birth control
4. Subjects and their partners of childbearing potential must use two medically approved methods of contraception and the subjects should refrain from sperm/egg donation for the duration of the study and for 3 months after drug administration

Exclusion Criteria

1. Pregnant (positive pregnancy test) or lactating women, and male subjects with partners who are or plan to be pregnant or lactating.
2. History or symptoms of any clinically significant gastrointestinal, renal, hepatic, broncho-pulmonary, neurological, psychiatric, cardio-vascular, endocrinological, ophthalmologic, hematological or allergic disease, metabolic disorder, cancer or cirrhosis.
3. People with a history of specific allergies, or allergic conditions or known allergies to any ingredient of the investigational medicinal product (IMP).
4. History of having received or currently receiving any systemic anti-neoplastic or immune-modulatory treatment ≤ 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. Positive test at screening of any of the following: Hepatitis B (HBsAg), Hepatitis C (HCVAb) or human immunodeficiency virus (HIV Ab).
6. Received an investigational drug within 30 days or 5 xT1/2 whichever is longer prior to the first dose of our study for small molecule; or within 90 days or 5 x T1/2 whichever is longer prior to the first dose of our study drug; or device study within 90 days prior to screening or more than 4 times per year.
7. History of drug and/or alcohol abuse or addiction.
8. Use of >5 cigarettes or equivalent nicotine-containing product per day.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
AP303	AP303 300 μg	AP303
Placebo	Placebo 50 μg	Placebo
AP303	AP303 50 μg	AP303
AP303	AP303 150 μg	AP303
Placebo	Placebo 600 μg	Placebo
AP303	AP303 600 μg	AP303
Placebo	Placebo 150 μg	Placebo
Placebo	Placebo 300 μg	Placebo

Primary Outcome Measures

Name	Time	Method
Multiple Dose Safety Outcome Measures	From baseline to Day 28	Incidence and severity of AEs, laboratory, ECG, and vital sign changes.
Cmax after single dose	Pre-dose to 96 hours post-dose	PK characteristics after single dose
Tmax after single dose	Pre-dose to 96 hours post-dose	PK characteristics after single dose
AUC0-last after single dose	Pre-dose to 96 hours post-dose	PK characteristics after single dose
Single Dose and Food Effect Safety Outcome Measures	From baseline to Day 14 (Day 29 for Food Effect)	Incidence and severity of adverse events (AEs), laboratory, ECG, and vital sign changes
Ae and CLR (if warranted) after single dose	Pre-dose to 96 hours post-dose	PK characteristics after single dose
t1/2 after multiple dose	Pre-dose to 12 hours post dose on Day 1; pre-dose to 96 hours post-dose on Day 14	PK characteristics after multiple dose
Ctrough after multiple dose	Pre-dose on Days 2, 3, 4, 5, 7, 12, and 13	PK characteristics after multiple dose
t1/2 after single dose	Pre-dose to 96 hours post-dose	PK characteristics after single dose
V/F after single dose	Pre-dose to 96 hours post-dose	PK characteristics after single dose
Tmax after multiple dose	Pre-dose to 12 hours post dose on Day 1; pre-dose to 96 hours post-dose on Day 14	PK characteristics after multiple dose
V/F after multiple dose	Pre-dose to 12 hours post dose on Day 1; pre-dose to 96 hours post-dose on Day 14	PK characteristics after multiple dose
AUC0-inf after single dose	Pre-dose to 96 hours post-dose	PK characteristics after single dose
Cmax after multiple dose	Pre-dose to 12 hours post dose on Day 1; pre-dose to 96 hours post-dose on Day 14	PK characteristics after multiple dose
AUC0-τ after multiple dose	Pre-dose to 12 hours post dose on Day 1; pre-dose to 96 hours post-dose on Day 14	PK characteristics after multiple dose
Cav after multiple dose	Pre-dose to 12 hours post dose on Day 1; pre-dose to 96 hours post-dose on Day 14	PK characteristics after multiple dose
Ae and CLR (if warranted) after multiple dose	Pre-dose to 12 hours post dose on Day 1; pre-dose to 96 hours post-dose on Day 14	PK characteristics after multiple dose
CL/F after single dose	Pre-dose to 96 hours post-dose	PK characteristics after single dose
Rac after multiple dose	Pre-dose to 12 hours post dose on Day 1; pre-dose to 96 hours post-dose on Day 14	PK characteristics after multiple dose

Secondary Outcome Measures

Name	Time	Method
Effect of Food on the single dose Tmax	Pre-dose to 96 hours post-dose	Effect of food on the single dose PK
Effect of Food on the single dose AUC0-last	Pre-dose to 96 hours post-dose	Effect of food on the single dose PK
Effect of Food on the single dose AUC0-inf	Pre-dose to 96 hours post-dose	Effect of food on the single dose PK
Effect of Food on the single dose t1/2	Pre-dose to 96 hours post-dose	Effect of food on the single dose PK
Effect of Food on the single dose Cmax	Pre-dose to 96 hours post-dose	Effect of food on the single dose PK
Effect of Food on the single dose CL/F	Pre-dose to 96 hours post-dose	Effect of food on the single dose PK
Effect of Food on the single dose Ae and CLR (if warranted)	Pre-dose to 96 hours post-dose	Effect of food on the single dose PK
Effect of Food on the single dose V/F	Pre-dose to 96 hours post-dose	Effect of food on the single dose PK

Trial Locations

Locations (1)

Nucleus Network Pty Ltd; 🇦🇺 Melbourne, Victoria, Australia