A Phase 1, Two-Part, Open-Label Study to Evaluate the Safety, Tolerability and Pharmacokinetics (PK) of Single Ascending Doses of APL-1501 Extended Release (ER) Capsules Compared to APL-1202 Immediate Release (IR) Tablets in Healthy Volunteers (Part A) and Multiple Ascending Doses of APL-1501 ER Capsules Compared to APL-1202 IR Tablets in Healthy Volunteers (Part B)
Overview
- Phase
- Phase 1
- Intervention
- APL-1202 and APL-1501 (Single ascending dose)
- Conditions
- Bladder Cancer
- Sponsor
- Jiangsu Yahong Meditech Co., Ltd aka Asieris
- Enrollment
- 48
- Locations
- 1
- Primary Endpoint
- Serious Adverse Events (SAEs)
- Status
- Not yet recruiting
- Last Updated
- 2 years ago
Overview
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.
Detailed Description
The study will have 2 parts: Each study part will comprise 2 dosing periods with a 72-hour washout period in between: Period 1: APL-1202 IR tablet dosing and Period 2: APL-1501 ER capsule dosing. In Part A dosing will be single day/single dosing for the APL-1202 IR tablets, and single day/single dosing the APL-1501 ER capsules with 24 participants in 3 sequential cohorts, Cohorts A1, A2, and A3. Each cohort will enrol 8 participants, with male to female participants in a 1:1 ratio. In Period 1/Day 1, participants in all cohorts will be dosed with single dose of 375 mg APL-1202 IR tablets which will followed by a washout period of at least 72 hours, after which participants will be dosed with single dose of APL-1501 ER capsules in Period 2/Day 4, . In Part B dosing will be multi-day/TID dosing for the APL-1202 IR tablets, and multi-day/BID dosing the APL-1501 ER capsules with 24 participants in 2 sequential cohorts, Cohorts B1 and B2. Each cohort will enrol 12 participants, with male to female participants in a 1:1 ratio and in each of the 2 study periods, participants will be administered IP for 5 days. In period 1, participants will administered with APL-1202 IR tablet (TID) on Day 1, Day 2, Day 3, Day 4, and Day 5 and period 2 with APL-1501 ER capsule (BID) dosing on Day 9, Day 10, Day 11, Day 12, and morning of Day 13.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
Exclusion Criteria
- •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.
Arms & Interventions
Part A
Intervention: APL-1202 and APL-1501 (Single ascending dose)
Part B
Intervention: APL-1202 and APL-1501 (Multiple Ascending dose)
Outcomes
Primary Outcomes
Serious Adverse Events (SAEs)
Time Frame: Part A: upto Day 11 post dose follow up; Part B: Upto Day 20 post dose follow up
Number of participants with SAEs
Adverse Events (AEs)
Time Frame: Part A: upto Day 11 post dose follow up; Part B: Upto Day 20 post dose follow up
Number of participants with AEs
Treatement Emergent Adverse Events (TEAEs)
Time Frame: Part A: upto Day 11 post dose follow up; Part B: Upto Day 20 post dose follow up
Number of participants with TEAEs
Secondary Outcomes
- PK parameters: area under the curve (AUC)(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: Apparent terminal volume of distribution (Vz/F)(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: 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)
- PK Parameters: Apparent total plasma clearance (CL/F)(up to 120 hours post dose in each treatment period)
- Urine PK parameters: Total amount of the APL-1202 excreted in urine from time t1 to t2 hours (Aet1-t2)(up to 120 hours post dose in each treatment period)