Phase 1 Study on the Pharmacokinetics of [14C]-AZ-3102 in Glycosphingolipid Lysosomal Storage Disorders in Healthy Male Subjects
- Trial ID
- 2023-504916-14-00
- Protocol
- AZA-001-31-02
- Sponsor
- Azafaros B.V.
Trial statistics
Objectives
The primary objective of this study is to evaluate the **absorption**, **metabolism**, and **excretion** of [14C]-AZ-3102 in healthy male subjects. This investigation is crucial for understanding the pharmacokinetic profile of the compound, which is essential for determining its potential therapeutic application in treating **glycosphingolipid lysosomal storage disorders**. The study aims to provide insights into how the drug is processed in the body, which can inform dosing regimens and safety assessments in future clinical trials.
Participants
The clinical trial focuses on **glycosphingolipid lysosomal storage disorders** and involves a study population that includes only male participants. The age range of the participants spans from children to adolescents, specifically covering the categories of 2 to 11 years and 12 to 17 years. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants involved in the study. Participants were selected based on specific criteria, although these criteria have not been disclosed. There are no details available regarding the general health status, lifestyle considerations such as diet or physical activity, or any habits of the participants. The trial population was selected to ensure a focus on the specified medical condition, with no additional information on key inclusion or exclusion criteria provided by the sponsor.
Plans and Procedures
The clinical trial is designed as an **open-label**, single-dose, phase 1 study aimed at evaluating the absorption, metabolism, and excretion of [14C]-AZ-3102 in healthy male subjects. The study focuses on **glycosphingolipid lysosomal storage disorders**, a rare disease category. The trial is expected to commence recruitment on July 11, 2023, and conclude by September 6, 2023, with an overall duration of approximately two months. Participants will be involved in a series of study visits, beginning with an inclusion visit to assess eligibility based on predefined criteria. This initial screening will ensure that only suitable candidates are enrolled in the study.
Following the inclusion visit, participants will undergo a baseline assessment, which will include a comprehensive evaluation of their health status and any relevant medical history. The administration of the investigational product will occur during the initial study visit, with subsequent follow-up visits scheduled to monitor the pharmacokinetic parameters and safety profile of the compound. These follow-up visits are critical for collecting data on the absorption, metabolism, and excretion of the drug, as well as for identifying any adverse events or side effects.
The end-of-study visit will mark the conclusion of the participant's involvement, during which final assessments will be conducted to ensure the well-being of the subjects and to gather any remaining data required for the study's objectives. The expected length of participant involvement is approximately two months, aligning with the overall trial duration. Conditions that may lead to early termination from the study include the occurrence of significant adverse events, non-compliance with study protocols, or withdrawal of consent by the participant. The study is structured to ensure the collection of high-quality data while maintaining the safety and rights of the participants throughout the trial period.
Treatment
The clinical trial documentation does not provide specific details regarding the **experimental medication** used in the study. Information such as the name, pharmaceutical form, dosage, route, and frequency of administration is not available. Additionally, there is no data on whether the medication is a **paediatric formulation** or if it is classified as an **orphan drug**. The maximum daily dose, total dose, and treatment period are also unspecified.
Details about any **non-experimental treatments** used in the study, such as standard-of-care therapy, placebo, or comparator treatment, are not provided. There is no information on additional relevant aspects of drug administration, dosing schedules, or participant compliance monitoring. The absence of these details limits the ability to describe the treatment regimen comprehensively.
Efficacy
The clinical trial is designed to assess efficacy in a Phase 3 study. The trial is scheduled to begin recruitment on July 11, 2023, with an estimated end date of September 6, 2023. The efficacy assessment will be conducted using predefined endpoints, although specific primary and secondary endpoints are not detailed in the available data. The trial will follow a structured methodology to ensure the collection and analysis of efficacy data is consistent and reliable. The trial phase indicates a focus on evaluating the effectiveness of the intervention in a larger population, which is typical for Phase 3 studies. The absence of specific endpoints and measurement tools in the provided data suggests that these details will be outlined in the full trial protocol, ensuring adherence to regulatory standards and scientific rigor.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Able and willing to give written informed consent and willing to comply with the requirements and restrictions of the study.
- Healthy male subjects aged between 18 and 65 years (inclusive) at screening.
- A male participant with a female partner of childbearing potential is eligible if he agrees to follow the contraceptive guidance during the study and for up to 14 weeks post discharge from the clinic.
- Willing to refrain from sperm donation during the study and for up to 14 weeks post discharge from the clinic.
- No clinically significant findings on the physical examination at screening.
- Body mass index (BMI) of 18.0 to 30.5 kg/m2 (inclusive) at screening.
- Systolic blood pressure (SBP) 90-140 mmHg, diastolic blood pressure (DBP) 45-90 mmHg, and pulse rate 40-100 beats per minute (bpm) (inclusive), measured at screening.
- 12-lead electrocardiogram (ECG) without clinically relevant abnormalities, measured after at least 5 minutes in the supine or semi-supine position at screening.
- Hematology, coagulation, clinical chemistry, and urinalysis test results not deviating from the normal range to a clinically relevant extent at screening.
- Negative results from urine drug screen at screening and Day -1.
- Ability to communicate well with the investigator and to understand and comply with the requirements of the study.
Exclusion Criteria
- Participation in another mass balance study with a radiation burden. • >0.1 mSv and up to 1.0 mSv in the period of 1 year prior to screening. • from 1.1 and up to 2.0 mSv in the period of 2 years prior to screening. • or 2.1 and up to 3.0 mSv in the period of 3 years prior to screening.
- Exposure to radiation (except dental X-rays and plain X-rays of thorax and bony skeleton [excluding spinal column]), in the period of 1 year prior to screening.
- Known hypersensitivity to the study medication or to drugs of the same class (iminosugars/azasugars).
- History or clinical evidence of any disease and/or existence of any surgical or medical condition which might interfere with the absorption, distribution, metabolism, or excretion of the study treatment (appendectomy and herniotomy allowed, cholecystectomy not allowed).
- Estimated creatinine clearance <90 mL/min at screening.
- Subject has infrequent bowel movements (on average less than once per 2 days) within 2 weeks prior to dosing.
- Recent history of abnormal bowel movements, such as diarrhea, loose stools, within 2 weeks prior to dosing.
- History of fainting, collapse, syncope, orthostatic hypotension, or vasovagal reactions in the past year that generates a risk for participation in the current study as based on investigator judgment.
- History of seizure.
- History of chronic dermatological conditions that required medical follow-up.
- History of corneal erosions, degenerations and active or recurrent keratitis.
- Veins unsuitable for intravenous (i.v.) puncture on either arm (e.g., veins that are difficult to locate, access or puncture, veins with a tendency to rupture during or after puncture).
- Previous exposure to the study medication.
- Treatment with another investigational treatment within 3 months prior to dosing or participation in more than four investigational treatment studies within 1 year prior to dosing.
- History or clinical evidence of alcoholism or drug abuse within the 2-year period prior to screening.
- Excessive caffeine consumption, defined as ≥ 800 mg per day at screening (for reference: 1 soft drink has between 30-40 mg caffeine, 1 cup of coffee 80-100 mg, and 1 energy drink between 40 to 250 mg)1.
- Smoking within 3 months prior to screening and inability to refrain from smoking during the study.
- Previous treatment with any prescribed medications (including vaccines) or over-the-counter (OTC) medications (including homeopathic preparations, herbal medicines such as St John’s Wort, vitamins, and minerals) within 2 weeks or 5 half-lives (whichever is longer) for prescribed- and 7 days for OTC medication prior to study drug administration. An exception is made for paracetamol, which is allowed up to admission to the clinic.
- Blood loss deemed significant by the investigator within 3 months prior to screening, or any amount of plasma in the 7 days prior to screening, or any amount of platelets in the 42 days prior to screening.
- Positive results from the hepatitis serology, except for vaccinated subjects or subjects with past but resolved hepatitis, at screening.
- Positive results from the human immunodeficiency virus (HIV) serology at screening.
- Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol or might confound the results of the study.
- Legal incapacity or limited legal capacity at screening.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 The Netherlands | Not Recruiting | 11 Jul 2023 | — |
| Netherlands | — | — | 7 |