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

A Single-center Randomized Double-blind Placebo-controlled Study to Investigate the Safety Tolerability and PK of SAD and MAD of AP303 Following Oral Administration and the Effect of Food on the PK of AP303 in Healthy Subjects

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.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: AP303 50 μg; Drug: AP303 150 μg; Drug: AP303 300 μg; Drug: AP303 600 μg; Drug: Placebo 50 μg; Drug: Placebo 150 μg; Drug: Placebo 300 μg; Drug: Placebo 600 μg

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 Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Nucleus Network Pty Ltd

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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 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 50 μg; Placebo tablet; Drug: Placebo 150 μg; Placebo tablet; Drug: Placebo 300 μg; Placebo tablet; Drug: Placebo 600 μg; Placebo tablet
Experimental: AP303	Drug: AP303 50 μg; AP303 tablet; Drug: AP303 150 μg; AP303 tablet; Drug: AP303 300 μg; AP303 tablet; Drug: AP303 600 μg; AP303 tablet

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Alebund Pty Ltd
• Investigators: Principal Investigator: Sam Francis, Doctor, Nucleus Network

Study record dates

Study Major Dates

• Study Start (Actual): December 6, 2022
• Primary Completion (Actual): June 16, 2023
• Study Completion (Actual): July 7, 2023

Study Registration Dates

• First Submitted: August 15, 2022
• First Submitted That Met QC Criteria: August 15, 2022
• First Posted (Actual): August 17, 2022

Study Record Updates

• Last Update Posted (Actual): July 14, 2023
• Last Update Submitted That Met QC Criteria: July 13, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Safety, Tolerability, Pharmacokinetics, AP303, Healthy Subjects
• Other Study ID Numbers: AP303-PK-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No