Clinical trial NCT06435039: A Study of APL-1501 Extended Release Capsules Compared to APL-1202 Immediate Release Tablets in Healthy Volunteers
Official title: A Phase 1, Open-Label, Randomized, Crossover Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single Ascending Doses of APL-1501 ER Capsules Compared to APL-1202 IR Tablets in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Bladder Cancer
Lead sponsor: Syneos Health
Sponsor class: OTHER
Collaborators: name: Asieris Pharmaceuticals (AUS) Pty Ltd.
First posted: 2024-05-30
Enrollment: 12
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The primary objective of the study is to assess safety and tolerability following administration of single doses of APL-1202 (immediate release) IR tablets and APL-1501 extended release (ER) capsules in healthy participants.


Eligibility criteria: Inclusion Criteria:

Participants must meet all of the following criteria to be included in the study:

1. Male, \>=18 and less than or equal to (\<=) 65 years of age, with body mass index (BMI) greater than (\>) 18.5 and less than (\<) 32.0 kilogram per square meter (kg/m\^2) and body weight \>=50.0 kilogram (kg).
2. Non-smoker (no use of tobacco or nicotine products, example, snuff, chewing tobacco, cigars, cigarettes, pipes, e-cigarettes \[vaping\] etc. within 3 months prior to screening).
3. Healthy as defined by:

   1. the absence of clinically significant illness and surgery within 4 weeks prior to study drug administration.
   2. the absence of clinically significant history of neurological, endocrine, cardiovascular, respiratory, hematological, immunological, psychiatric, gastrointestinal, renal, hepatic, and metabolic disease.
4. Sexually active non-sterile males must be willing to use an acceptable contraceptive method throughout the study.
5. Able to understand the study procedures and provide signed informed consent to participate in the study.

Exclusion Criteria:

Participants to whom any of the following applies will be excluded from the study:

1. Any clinically significant abnormal finding at physical examination.
2. Clinically significant abnormal laboratory test results or positive serology test results for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV) antibody, or Human immunodeficiency virus (HIV) antigen and antibody.
3. Positive urine drug screen, cotinine test, or alcohol breath test.
4. History of significant allergic reactions (example, anaphylactic reaction, hypersensitivity, angioedema) to any drug.
5. Clinically significant Electrocardiograms (ECG) abnormalities or vital signs abnormalities (systolic blood pressure \[BP\] lower than 90 or over 140 millimeters of mercury \[mmHg\], diastolic BP lower than 50 or over 90 mmHg, heart rate \[HR\] less than 40 or over 100 beats per minute \[bpm\], or RR less than 10 or over 25 bpm) at screening.
6. History of drug abuse within 1 year prior to screening or recreational use of marijuana within 1 month or other illegal drugs such as cocaine, phencyclidine \[PCP\], crack, opioid derivatives including heroin, and amphetamine derivatives within 3 months prior to screening.
7. History of alcohol abuse within 1 year prior to screening or regular use of alcohol within 6 months prior to screening that exceeds 10 units of alcohol per week (1 unit = 375 milliliter \[mL\] of beer 3.5 percent (%), or 100 mL of wine 13.5%, or 30 mL of distilled alcohol 40%).
8. Use of medications within the timeframes specified in section.
9. Participation in a clinical research study involving the administration of an investigational or marketed drug or device within 30 days prior to the first dosing, administration of a biological product in the context of a clinical research study within 90 days prior to the first dosing, or concomitant participation in an investigational study involving no drug or device administration.
10. Donation of plasma within 7 days prior to dosing or donation or loss of 500 mL or more of whole blood within 8 weeks prior to dosing.
11. Optic nerve disease, cataracts, or a history of related conditions.
12. Any reason which, in the opinion of the Investigator, would prevent the participant from participating in the study.

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs)
timeFrame: From Baseline up to Day 9
measure: Number of Participants With Abnormal Vital Sign Measurements
timeFrame: From Baseline up to Day 9
measure: Number of Participants With Abnormal 12-Lead Electrocardiogram (ECGs) Recordings
timeFrame: From Baseline up to Day 9
measure: Number of Participants With Abnormal Physical Examinations
timeFrame: From Baseline up to Day 9
measure: Number of Participants With Abnormal Clinical Laboratory Values
timeFrame: From Baseline up to Day 9
Secondary outcomes:
measure: AUC0-t: Area Under the Concentration-time Curve From Time Zero Until the Last Observed Concentration of APL-1202, and ASN-1651 (Metabolite) Following APL-1501 ER Capsules
timeFrame: Cohorts 1 and 2 - Days 1 and 4: Pre-dose and up to 24 hours post-dose; Cohort 3 - Day 1: Pre-dose and up to 24 hours post-dose
measure: AUC0-inf: Area Under the Concentration-time Curve From Time Zero to Infinity of APL-1202, and ASN-1651 (Metabolite) Following APL-1501 ER Capsules
timeFrame: Cohorts 1 and 2 - Days 1 and 4: Pre-dose and up to 24 hours post-dose; Cohort 3 - Day 1: Pre-dose and up to 24 hours post-dose
measure: Cmax: Maximal Observed Concentration of APL-1202, and ASN-1651 (Metabolite) Following APL-1501 ER Capsules
timeFrame: Cohorts 1 and 2 - Days 1 and 4: Pre-dose and up to 24 hours post-dose; Cohort 3 - Day 1: Pre-dose and up to 24 hours post-dose
measure: Tlast: Time When the Last Concentration is Observed of APL-1202, and ASN-1651 (Metabolite) Following APL-1501 ER Capsules
timeFrame: Cohorts 1 and 2 - Days 1 and 4: Pre-dose and up to 24 hours post-dose; Cohort 3 - Day 1: Pre-dose and up to 24 hours post-dose
measure: Tmax: Time When the Cmax is Observed of APL-1202, and ASN-1651 (Metabolite) Following APL-1501 ER Capsules
timeFrame: Cohorts 1 and 2 - Days 1 and 4: Pre-dose and up to 24 hours post-dose; Cohort 3 - Day 1: Pre-dose and up to 24 hours post-dose
measure: Residual Area of APL-1202, and ASN-1651 (Metabolite) Following APL-1501 ER Capsules
timeFrame: Cohorts 1 and 2 - Days 1 and 4: Pre-dose and up to 24 hours post-dose; Cohort 3 - Day 1: Pre-dose and up to 24 hours post-dose
measure: T½ el: Terminal Elimination Half-life of APL-1202, and ASN-1651 (Metabolite) Following APL-1501 ER Capsules
timeFrame: Cohorts 1 and 2 - Days 1 and 4: Pre-dose and up to 24 hours post-dose; Cohort 3 - Day 1: Pre-dose and up to 24 hours post-dose
measure: Kel: Terminal Elimination Rate Constant of APL-1202, and ASN-1651 (Metabolite) Following APL-1501 ER Capsules
timeFrame: Cohorts 1 and 2 - Days 1 and 4: Pre-dose and up to 24 hours post-dose; Cohort 3 - Day 1: Pre-dose and up to 24 hours post-dose
measure: Cl/F: Apparent Clearance of APL-1202, and ASN-1651 (Metabolite) Following APL-1501 ER Capsules
timeFrame: Cohorts 1 and 2 - Days 1 and 4: Pre-dose and up to 24 hours post-dose; Cohort 3 - Day 1: Pre-dose and up to 24 hours post-dose
measure: Vz/F: Apparent Volume of Distribution of APL-1202, and ASN-1651 (Metabolite) Following APL-1501 ER Capsules
timeFrame: Cohorts 1 and 2 - Days 1 and 4: Pre-dose and up to 24 hours post-dose; Cohort 3 - Day 1: Pre-dose and up to 24 hours post-dose
measure: DNAUC0-inf: Dose Normalized AUC0-inf of APL-1202, and ASN-1651 (Metabolite) Following APL-1501 ER Capsules
timeFrame: Cohorts 1 and 2 - Days 1 and 4: Pre-dose and up to 24 hours post-dose; Cohort 3 - Day 1: Pre-dose and up to 24 hours post-dose
measure: DNCmax: Dose Normalized Cmax of APL-1202, and ASN-1651 (Metabolite) Following APL-1501 ER Capsules
timeFrame: Cohorts 1 and 2 - Days 1 and 4: Pre-dose and up to 24 hours post-dose; Cohort 3 - Day 1: Pre-dose and up to 24 hours post-dose
measure: Geometric Mean Ratio of Cmax of APL-1501 ER Capsules in Reference to APL-1202 IR Tablets
timeFrame: Cohorts 1 and 2 - Days 1 and 4: Pre-dose and up to 24 hours post-dose; Cohort 3 - Day 1: Pre-dose and up to 24 hours post-dose
measure: Geometric Mean Ratio of AUC0-t of APL-1501 ER Capsules in Reference to APL-1202 IR Tablets
timeFrame: Cohorts 1 and 2 - Days 1 and 4: Pre-dose and up to 24 hours post-dose; Cohort 3 - Day 1: Pre-dose and up to 24 hours post-dose
measure: Geometric Mean Ratio of AUC0-inf of APL-1501 ER Capsules in Reference to APL-1202 IR Tablets
timeFrame: Cohorts 1 and 2 - Days 1 and 4: Pre-dose and up to 24 hours post-dose; Cohort 3 - Day 1: Pre-dose and up to 24 hours post-dose
measure: Frel: Relative Bioavailability of APL-1501 ER Capsules and APL-1202 IR Tablets
timeFrame: Cohorts 1 and 2 - Days 1 and 4: Pre-dose and up to 24 hours post-dose; Cohort 3 - Day 1: Pre-dose and up to 24 hours post-dose
measure: Dose Proportionality of Cmax
timeFrame: Cohorts 1 and 2 - Days 1 and 4: Pre-dose and up to 24 hours post-dose; Cohort 3 - Day 1: Pre-dose and up to 24 hours post-dose
measure: Dose Proportionality of AUC0-t
timeFrame: Cohorts 1 and 2 - Days 1 and 4: Pre-dose and up to 24 hours post-dose; Cohort 3 - Day 1: Pre-dose and up to 24 hours post-dose
measure: Dose Proportionality of AUC0-inf
timeFrame: Cohorts 1 and 2 - Days 1 and 4: Pre-dose and up to 24 hours post-dose; Cohort 3 - Day 1: Pre-dose and up to 24 hours post-dose
Other outcomes:
Locations:
city: Randwick
country: Australia
facility: Scientia Clinical Research Ltd
state: New South Wales
Study officials:
affiliation: Asieris Pharmaceuticals (AUS) Pty Ltd.
name: Dr Christopher Argent
role: PRINCIPAL_INVESTIGATOR
References: