A Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single and Multiple Ascending Doses of APL-1501 Extended Release (ER) Capsules Compared to APL-1202 Immediate Release (IR) Tablets in Healthy Volunteers

NCT06034015 | Unknown Phase 1 DMC

• 1 other identifier: YHGT-PN-02
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

This is an integrated Phase 1, single centre, 2-part, open-label, dose-escalation study conducted in healthy volunteers to assess the safety, tolerability, and PK of APL-1501 ER capsules in comparison to APL-1202 IR tablets.

Conditions

Bladder Cancer

Outcome Measures

Primary Outcomes (3)

• Adverse Events (AEs)

  Number of participants with AEs

  Part A: upto Day 11 post dose follow up; Part B: Upto Day 20 post dose follow up

• Serious Adverse Events (SAEs)

  Number of participants with SAEs

  Part A: upto Day 11 post dose follow up; Part B: Upto Day 20 post dose follow up

• Treatement Emergent Adverse Events (TEAEs)

  Number of participants with TEAEs

  Part A: upto Day 11 post dose follow up; Part B: Upto Day 20 post dose follow up

Secondary Outcomes (8)

• PK parameters: area under the curve (AUC)

  up to 120 hours post dose in each treatment period

• PK parameters: maximum concentration (Cmax)

  up to 120 hours post dose in each treatment period

• PK parameters: Tmax

  up to 120 hours post dose in each treatment period

• PK parameters: half-life (t1/2)

  up to 120 hours post dose in each treatment period

• Urine PK parameters: Renal clearance (CLr)

  up to 120 hours post dose in each treatment period

Study Arms (2)

Part A

ACTIVE COMPARATOR

Drug: APL-1202 and APL-1501 (Single ascending dose)

Part B

ACTIVE COMPARATOR

Drug: APL-1202 and APL-1501 (Multiple Ascending dose)

Interventions

APL-1202 and APL-1501 (Single ascending dose) DRUG

Period 1 drug adminstration (APL-1202 IR tablet , single dose of 375mg will be administered orally on Day 1; washout period of 72 hrs; Period 2 drug administration (APL-1501 ER capsules of 764mg, 1146 mg and 1528 mg will be administered as single dose on Day 4.

Part A

APL-1202 and APL-1501 (Multiple Ascending dose) DRUG

Period 1 drug adminstration (APL-1202 IR of 375mg will be administered thrice a day (TID) orally from Day 1 to Day 5; washout period of 72 hrs; Period 2 drug administration (APL-1501 ER capsules of 764mg, 1146 mg and 1528 mg will be administered twice daily (BID) from Day 9 to 13.

Part B

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy male or female 18 to 65 years of age (inclusive at the time of informed consent).
• In good general health, with no significant medical history and no clinically significant abnormalities on physical examination, 12-lead ECG, vital signs and oximetry measurements at Screening and/or before the first administration of Investigational Products (IP), as determined by the Principal Investigator or designee.
• Clinical laboratory values within normal range as specified by the testing laboratory, at Screening and/or before the first administration of IP unless deemed not clinically significant (NCS) by the Principal Investigator or designee.
• Body-mass index (BMI) between ≥ 18.0 and ≤ 32.0 kg/m2 at Screening and weight ≥ 50 kg.
• Current non-smoker or casual smoker who used no more than 5 cigarettes (or equivalent quantity of any other nicotine-containing products eg, snuff, chewing tobacco, cigars, cigarettes, pipes, e-cigarettes \[Vaping\] etc.) per week for 3 months prior to Screening. Participants must abstain from smoking and abstain from using nicotine-containing products (eg, nicotine chewing gum, nicotine plasters, or other product used for smoking cessation) for 2 weeks prior to admission and throughout the study period, and test negative at Screening and on Day -1 for urinary cotinine.
• No relevant dietary restrictions.
• Females must not be pregnant or lactating, and must use acceptable, highly effective double contraception from Screening until 30 days after study completion, including the Follow-up period.
• Males must be surgically sterile (\> 90 days since vasectomy with no viable sperm), or if engaged in sexual relations with a women of child bearing potential (WOCBP), his partner must be either surgically sterile (eg, hysterectomy, bilateral salpingectomy, bilateral oophorectomy), or use an acceptable, highly effective contraceptive method (see Section 7.3.3) from Screening until 90 days after study completion, including the Follow-up period.
• Able and willing to attend the necessary visits to the study site.
• Able and willing to provide written informed consent after the nature of the study has been explained and prior to the commencement of any study procedures.

You may not qualify if:

• Underlying physical or psychological medical condition that, in the opinion of the PI, would make it unlikely for the participant to comply with the protocol or complete the study per protocol.
• Receipt of blood products, or significant blood loss deemed to be CTCAE Grade 3 or Grade 4 within 6 weeks prior to the first administration of IP.
• Plasma donation within 7 days prior to the first administration of IP, or platelet/blood donation within 4 weeks prior to the first administration of IP
• Fever (body temperature \> 38°C) or symptomatic viral or bacterial infection within 2 weeks prior to the first administration of IP.
• Poor pill swallowing ability.
• History of severe allergic or anaphylactic reactions, or sensitivity to the IP or its constituents, including lactose intolerance/allergy.
• History of malignancy, except for non-melanoma skin cancer, excised more than 1 year prior to Screening and cervical intraepithelial neoplasia that has been successfully cured more than 5 years prior to Screening.
• History or presence of a condition associated with significant immunosuppression.
• History of life-threatening infection (eg, meningitis). Severe infections within 4 weeks prior to the first administration of IP including but not limited to hospitalisation for complications of infection, bacteraemia, or severe pneumonia.
• Infections requiring parenteral antibiotics within 6 months prior to the first administration of IP.
• Vaccination with a live vaccine within 4 weeks prior to the first administration of IP. COVID-19 or influenza can be exempted.
• Exposure to any significantly immune suppressing drug (including experimental therapies as part of a clinical study) within 4 months prior to the first administration of IP or 5-half-lives, whichever is longer.
• Positive test for hepatitis C virus antibody (HCVAb), hepatitis B virus surface antigen (HBsAg), human Immunodeficiency virus (HIV) antibody, or COVID-19 at Screening and Day-1.
• History of tuberculosis (TB) or positive QuantiFERON®-TB Gold test at Screening or 2 successive indeterminate QuantiFERON-TB Gold test results.
• Positive toxicology screening panel (urine test including qualitative identification of barbiturates, tetrahydrocannabinol, amphetamines, benzodiazepines, opiates, cocaine and tricyclic antidepressants), or alcohol breath test at Screening and Day-1.

Sponsors & Collaborators

• Jiangsu Yahong Meditech Co., Ltd aka Asieris: lead

Study Sites (1)

Nucleus Network Pty Ltd

Melbourne, Victoria, 3004, Australia

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Central Study Contacts

Qiuyue Qu

CONTACT

+86 021 68583863; qyqu@asieris.cn

Zoey Zhao

CONTACT

+86 021 68583863; vzhao@asieris.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 29, 2023
• First Posted: September 13, 2023
• Study Start: September 9, 2023
• Primary Completion: January 19, 2024
• Study Completion: February 7, 2024
• Last Updated: September 13, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)