A Phase I, Two-phase, Crossover Study to Evaluate the Safety, Tolerability and Pharmacokinetics of APL-1501 ER Tablets

A Phase I, Open-Label, Randomized, Two-phase, Crossover Study to Evaluate the Safety, Tolerability and Pharmacokinetics of APL-1501 ER Tablets 2, APL1501 ER Tablets 3, and APL-1202 in Healthy Volunteers

A two-phase study design will be used for this pilot study. In the first phase, a 2×2 crossover study will be used to evaluate the safety, tolerability and PK characteristic of APL-1202 and APL-1501 ER Tablets 3. Twelve healthy subjects will be in ratio 1:1 randomly assigned to two groups, randomization will be stratified by gender (male, female) in ratio 1:1. Each group will be dosed with APL-1202, APL-1501 ER Tablets 3 in a cross-over way. A 7-day (±1 day) washout will be required before next period of drug administration. The samples in first phase will be sent to bioanalysis lab for PK research at the end of first phase. The initiate of second phase will depend on the results of first phase within 30 days and not less than 7 days after the first phase.

Study Overview

• Status: Completed
• Conditions: Bladder Cancer
• Intervention / Treatment: Drug: APL-1202+APL-1501 ER Tablets 3+APL-1501 ER Tablets 2; Drug: APL-1501 ER Tablets 3+APL-1202+APL-1501 ER Tablets 2

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Randwick, New South Wales, Australia, 2031
      • Scientia Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. The subject must have informed consent before the trial, and have a full understanding of the content, process and possible adverse reactions of the trial, and voluntarily signed a written informed consent form
2. The subject is able to communicate well with the researchers and is able to complete the trial in accordance with the protocol
3. 18 to 45 years old (including 18 and 45 years old)
4. Postmenopausal females or sterilized participant must be at least 6 months post-menopausal, surgically sterile; the postmenopausal/sterilization should be confirmed by FSH testing
5. The body weight of male subjects are ≥ 50 kg, and that of female subjects are ≥ 45 kg, and the body mass index (BMI) are between 18.0 and 30.0 kg/m2, including the boundary value. BMI= weight (kg) / height2 (m2)

6. Must have normal organ functions, including the following:

   1. Bone marrow reserve: within normal range or deemed NCS by the treating investigator
   2. Hepatic: total bilirubin within normal range or deemed NCS by the treating investigator; aspartate transaminase (AST) and/or alanine aminotransferase (ALT) ≤ 1.5x ULN
   3. Renal: serum creatinine ≤ ULN Confidential Page 7 of 61
   4. Prothrombin time (PT) and partial thromboplastin time (PTT) ≤ ULN or deemed NCS by the treating investigator
   5. QTCF≤450 msec for males and 470 msec for females
7. Healthy as determined by physician, based on a medical evaluation including Physical examination and vital signs, hematology, biochemistry, coagulation, urinalysis, and 12-lead Electrocardiograms (ECGs)
8. Willingness for subjects of reproductive potential to use highly effective methods of contraception from the beginning of the study screening to the end of study follow up period a. A highly effective method of contraception is defined as one that results in a low failure rate (i.e., less than 1% per year, when used consistently and correctly)

Exclusion Criteria:

1. History of allergy to any research drug components, similar drugs or their excipients
2. History of optic nerve disorder, malignancy, anemia or gastrointestinal, liver and kidney diseases that may affect the pharmacokinetics of the investigational drugs
3. Subject who is positive in one or more of the tests of hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV), and AIDS antibody (HIV)
4. Subject who is positive for urine drug screening or who with a history of drug abuse
5. Subject who smoked more than 5 cigarettes per day in the 3 months before the trial, and/or disagreed to avoid using any tobacco products 24 hours before administration and during hospitalization
6. Regular drinkers within 6 months before the trial, that is, those who drank more than 14 units of alcohol per week (1 unit = 10 g pure alcohol), and/or those who do not agree to stop alcohol intake 24 hours before administration and during hospitalization, and/or positive in breath alcohol test. STANDARD DRINK= Volume of Alcoholic Drinks x Concentration of Alcoholic Drinks x 0.789/pure alcohol
7. Systemic treatment on any investigational clinical trial within 28 days (or 5 half-lives of that agent, whichever is greater) prior to enrollment
8. Subject who take strong inducers or inhibitors of metabolism enzymes or transporter within 48 h before the study, including but not limited to caffeine, xanthine, grapefruit, grapefruit juice or grapefruit-related citrus fruits (e.g. Seville oranges, pomelos) etc.
9. Pregnancy or lactation
10. Any other reason that in the opinion of the Investigator or Sponsor would prevent the patient from completing participation or following the study schedule

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A	Drug: APL-1202+APL-1501 ER Tablets 3+APL-1501 ER Tablets 2; Phase1: Period 1 drug administration( APL-1202 50 mg, 3 tablets, orally );Washout( 7± 1 day) ; Period 2 drug administration(1501 ER Tablets 3 382 mg ASN-1324, 1 tablet); Phase2:Washout(The initiation of second phase will depend on the results of first phase within 30 days and not less than 7 days after the first phase ); Period 3 (APL-1501 ER Tablets 2,382 mg ASN-1324, 1 tablet)
Experimental: Group B	Drug: APL-1501 ER Tablets 3+APL-1202+APL-1501 ER Tablets 2; Phase1: Period 1 drug administration( 1501 ER Tablets 3 382 mg ASN-1324, 1 tablet );Washout( 7± 1 day) ; Period 2 drug administration(APL-1202 50 mg, 3 tablets, orally); Phase2:Washout(The initiation of second phase will depend on the results of first phase within 30 days and not less than 7 days after the first phase ); Period 3 (APL-1501 ER Tablets 2,382 mg ASN-1324, 1 tablet)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AEs	Number of subjects with AEs,	6 months
SAEs	Number of subjects with SAEs	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK parameters: area under the curve (AUC)	Area under the curve (AUC) of APL-1501 ER Tablets, and APL-1202 Tablets	6 months
PK parameters: maximum concentration (Cmax)	maximum concentration (Cmax), of APL-1501 ER Tablets, and APL-1202 Tablets	6 months
PK parameters: Tmax	Tmax of APL-1501 ER Tablets, and APL-1202 Tablets	6 months
PK parameters: half-life	apparent t1/2 of APL-1501 ER Tablets, and APL-1202 Tablets	6 months
Urine concentration	Urine concentration of APL-1501 ER Tablets 2, APL-1501 ER Tablets 3, and APL-1202 Tablets.	6 months
Accumulated excretion rate (Ae%)	Accumulated excretion rate (Ae%) of APL-1501 ER Tablets 2, APL-1501 ER Tablets 3, and APL-1202 Tablets.	6 months

Collaborators and Investigators

• Sponsor: Asieris Pharmaceuticals (AUS) Pty Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2020
• Primary Completion (Actual): December 18, 2020
• Study Completion (Actual): February 1, 2021

Study Registration Dates

• First Submitted: October 20, 2020
• First Submitted That Met QC Criteria: October 20, 2020
• First Posted (Actual): October 26, 2020

Study Record Updates

• Last Update Posted (Actual): June 30, 2021
• Last Update Submitted That Met QC Criteria: June 25, 2021
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Urinary Bladder Neoplasms
• Other Study ID Numbers: YHGT-PN-01

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