A Study of APL-1501 Extended Release Capsules Compared to APL-1202 Immediate Release Tablets in Healthy Volunteers

Healthy Volunteers Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06435039
• Other study ID #: YHGT-APL1501-NHS-103
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: June 26, 2024
• Est. completion date: October 22, 2024

Study information

• Verified date: May 2024
• Source: Syneos Health
• Contact: Dr Christopher Argent
• Phone: +61 2 9382 5800
• Email: christopher.argent[@]scientiaclinicalresearch.com.au
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 32
• Est. completion date: October 22, 2024
• Est. primary completion date: August 21, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• APL-1202
APL-1202 IR tablets.
• APL-1501
APL-1501 ER capsules.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Syneos Health	Asieris Pharmaceuticals (AUS) Pty Ltd.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Adverse Events (AEs)		From Baseline up to Day 9
Primary	Number of Participants With Abnormal Vital Sign Measurements		From Baseline up to Day 9
Primary	Number of Participants With Abnormal 12-Lead Electrocardiogram (ECGs) Recordings		From Baseline up to Day 9
Primary	Number of Participants With Abnormal Physical Examinations		From Baseline up to Day 9
Primary	Number of Participants With Abnormal Clinical Laboratory Values		From Baseline up to Day 9
Secondary	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		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
Secondary	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		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
Secondary	Cmax: Maximal Observed Concentration of APL-1202, and ASN-1651 (Metabolite) Following APL-1501 ER Capsules		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
Secondary	Tlast: Time When the Last Concentration is Observed of APL-1202, and ASN-1651 (Metabolite) Following APL-1501 ER Capsules		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
Secondary	Tmax: Time When the Cmax is Observed of APL-1202, and ASN-1651 (Metabolite) Following APL-1501 ER Capsules		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
Secondary	Residual Area of APL-1202, and ASN-1651 (Metabolite) Following APL-1501 ER Capsules	Residual area is defined as percentage of AUC0-inf due to extrapolation from the time of the last observed concentration to infinity and is calculated as, [1-(AUC0-t/AUC0-inf)]*100.	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
Secondary	T½ el: Terminal Elimination Half-life of APL-1202, and ASN-1651 (Metabolite) Following APL-1501 ER Capsules		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
Secondary	Kel: Terminal Elimination Rate Constant of APL-1202, and ASN-1651 (Metabolite) Following APL-1501 ER Capsules		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
Secondary	Cl/F: Apparent Clearance of APL-1202, and ASN-1651 (Metabolite) Following APL-1501 ER Capsules		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
Secondary	Vz/F: Apparent Volume of Distribution of APL-1202, and ASN-1651 (Metabolite) Following APL-1501 ER Capsules		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
Secondary	DNAUC0-inf: Dose Normalized AUC0-inf of APL-1202, and ASN-1651 (Metabolite) Following APL-1501 ER Capsules		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
Secondary	DNCmax: Dose Normalized Cmax of APL-1202, and ASN-1651 (Metabolite) Following APL-1501 ER Capsules		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
Secondary	Geometric Mean Ratio of Cmax of APL-1501 ER Capsules in Reference to APL-1202 IR Tablets		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
Secondary	Geometric Mean Ratio of AUC0-t of APL-1501 ER Capsules in Reference to APL-1202 IR Tablets		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
Secondary	Geometric Mean Ratio of AUC0-inf of APL-1501 ER Capsules in Reference to APL-1202 IR Tablets		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
Secondary	Frel: Relative Bioavailability of APL-1501 ER Capsules and APL-1202 IR Tablets	The relative bioavailability of APL-1501 versus APL-1202 will be assessed through linear mixed modelling.	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
Secondary	Dose Proportionality of Cmax	Dose proportionality will be assessed by visual inspection of dose normalised Cmax values versus dose.	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
Secondary	Dose Proportionality of AUC0-t	Dose proportionality will be assessed by visual inspection of dose normalised AUC0-t values versus dose.	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
Secondary	Dose Proportionality of AUC0-inf	Dose proportionality will be assessed by visual inspection of dose normalised AUC0-inf values versus dose.	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