A Pharmacodynamic Effect Study of AP301 in Healthy Volunteers

Study Overview
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Brief Summary
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This is a randomized, open-label, parallel-group, phase 1 study to evaluate the PD effect of AP301 capsule in healthy volunteers. The study is planned to have 4 treatment arms: Arm 1: 2.10 g/day; arm 2: 4.20 g/day; arm 3: 6.30 g/day; arm 4: 8.40 g/day.

Detailed Description
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A total of 32 participants will participate in this study and the study consists of 3 periods such as screening period, hospitalization period and follow up period.

Official Title
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A Randomized, Open-Label, Parallel Group, Phase 1 Study to Assess the Pharmacodynamic Effect of AP301 on Urinary Phosphorus Excretion in Healthy Volunteers

Conditions
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Healthy Subjects

Intervention / Treatment
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* Drug: AP301


Participation Criteria
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Eligibility Criteria
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Important Inclusion Criteria: Healthy male volunteers, 18-55 years of age Body mass index (BMI) 18-30 kg/m2 (exclusive) at screening. Important Exclusion Criteria: Serum phosphorus is below 1.00 mmol/L at screening. History of significant gastrointestinal disease or disorder, major gastrointestinal surgeries, or cholecystectomy History or symptoms of any clinically significant kidney, liver, broncho-pulmonary, gastrointestinal, neurological, psychiatric, cardiovascular, endocrine/metabolic, hematological diseases, or cancer. History of specific allergies or allergic conditions or known allergies to the study drug as judged by the investigator, or any confirmed significant allergic reactions (urticaria or anaphylaxis) to any drug, or multiple drug 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. Known history of allergy to common food like milk or gluten, or lactose intolerance, or special diet habit for religious/life-style reasons, which might potentially jeopardize the participant's compliance of study diet. Any clinically significant concomitant disease, or condition or treatment that could interfere with the conduct of the study. Confirmed (based on the average of 3 separate resting blood pressure measurements, after at least 5 minutes rest) systolic blood pressure (BP) greater than 150 or less than 90 mmHg, and diastolic BP greater than 90 or less than 50 mmHg at screening. Clinically relevant ECG abnormalities on screening ECG. Estimated glomerular filtration rate (eGFR) ≤ 70 mL/min/1.73 m2. Positive test at screening of any of the following: Hepatitis B (HBsAg), Hepatitis C (HCV Ab) or human immunodeficiency virus (HIV-1 or HIV-2 Ab). Alanine aminotransferase (ALT) or aspartate transaminase (AST) > 1.5 × upper limit of normal (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. Positive urine test for drugs of abuse and/or positive alcohol test at screening. Any medical or social conditions that, in the view of investigator, might potentially jeopardize the participant's compliance of study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 2.10 g/day of AP301<br> | Drug: AP301<br>* Orally administered<br>|
| Experimental: 4.20 g/day of AP301<br> | Drug: AP301<br>* Orally administered<br>|
| Experimental: 6.30 g/day of AP301<br> | Drug: AP301<br>* Orally administered<br>|
| Experimental: 8.40 g.day of AP301<br> | Drug: AP301<br>* Orally administered<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary phosphorus excretion during AP301 administration | Average daily urinary phosphorus excretion during the 3 consecutive days of AP301 treatment | From the Day 1 to Day 4 after dosing, assessed up to 3 days | 
| Effect of AP301 on urinary phosphorus excretion | Change of average daily urinary phosphorus excretion from 3 days before treatment to 3 days during treatment. | From Day -3 to Day 4 after dosing, assessed up to 6 days | 
| Urinary calcium excretion during AP301 administration | Average daily urinary calcium excretion during the 3 consecutive days of AP301 treatment. | From the Day 1 to Day 4 after dosing, assessed up to 3 days | 
| Effect of AP301 on urinary calcium excretion | Change of average daily urinary calcium excretion from 3 days before treatment to 3 days during treatment. | From Day -3 to Day 4 after dosing, assessed up to 6 days | 
| Effect of AP301 on serum phosphorus and calcium | Changes of serum phosphorus and serum calcium from baseline to end of treatment. | From Day -3 to Day 4 after dosing, assessed up to 6 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of adverse events (AEs) | Number of participants with adverse events (AEs) and the intensity of adverse events. Number of participants with serious adverse events (SAEs) and the intensity of adverse events. | From screening to hospitalization and follow up periods, assessed up to 43 days | 
| Changes in clinical laboratory values | Changes and their clinical meaningfulness in clinical laboratory values: Hematology, Biochemistry, Urinalysis | From screening to hospitalization and follow up periods, assessed up to 43 days | 
| Abnormal electrocardiogram (ECG) readings and their clinical meaningfulness | ECG intervals (PR [PQ], QRS, QT, QTcF) and heart rate | From screening to hospitalization and follow up periods, assessed up to 43 days | 
| Changes of ECG parameters and their clinical meaningfulness | ECG intervals (PR [PQ], QRS, QT, QTcF), heart rate, T-wave morphology and U-wave morphology. | From screening to hospitalization and follow up periods, assessed up to 43 days | 
| Abnormal vital signs and their clinical meaningfulness | Blood pressure, heart rate and body temperature | From screening to hospitalization and follow up periods, assessed up to 43 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pharmacodynamic, safety, tolerability, AP301, Healthy subjects