An open-label, single-dose phase 1 study to evaluate the Absorption, Metabolism, and Excretion of [14C]-AZ-3102 in Healthy Male Subjects

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Azafaros B.V.

Participant type

Healthy volunteers

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

13 Jul 2023 → 25 Aug 2023

Decision date (initial)

2023-06-21

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

AZAFAROS B.V.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic

To determine the routes and rates of elimination of drug-related materials by assessing the mass balance (i.e., cumulative excretion of total radioactivity in urine and feces) following a single oral administration of 9 mg (~3.7 MBq [100 μCi]) [14C]-AZ-3102.

To assess the metabolic profile of AZ-3102 in plasma, urine, and feces following a single oral administration of 9 mg (~3.7 MBq [100 μCi]) [14C]-AZ-3102.

To characterize the pharmacokinetic (PK) of total radioactivity in applicable matrices following a single oral solution dose of 9 mg (~3.7 MBq [100 μCi]) [14C]- AZ-3102.

Secondary objectives 2

1. To explore the PK of AZ-3102 and its metabolites (when applicable) in applicable matrices following a single oral dose of 9 mg (~3.7 MBq [100 μCi]) [14C]-AZ-3102.
2. To determine the safety and tolerability of a single oral dose of 9 mg (~3.7 MBq [100 μCi]) [14C]-AZ-3102.

Conditions and MedDRA coding

Glycosphingolipid lysosomal storage disorders

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Able and willing to give written informed consent and willing to comply with the requirements and restrictions of the study.
2. Healthy male subjects aged between 18 and 65 years (inclusive) at screening.
3. 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.
4. Willing to refrain from sperm donation during the study and for up to 14 weeks post discharge from the clinic.
5. No clinically significant findings on the physical examination at screening.
6. Body mass index (BMI) of 18.0 to 30.5 kg/m2 (inclusive) at screening.
7. 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.
8. 12-lead electrocardiogram (ECG) without clinically relevant abnormalities, measured after at least 5 minutes in the supine or semi-supine position at screening.
9. Hematology, coagulation, clinical chemistry, and urinalysis test results not deviating from the normal range to a clinically relevant extent at screening.
10. Negative results from urine drug screen at screening and Day -1.
11. Ability to communicate well with the investigator and to understand and comply with the requirements of the study.

Exclusion criteria 23

1. 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.
2. 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.
3. Known hypersensitivity to the study medication or to drugs of the same class (iminosugars/azasugars).
4. 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).
5. Estimated creatinine clearance <90 mL/min at screening.
6. Subject has infrequent bowel movements (on average less than once per 2 days) within 2 weeks prior to dosing.
7. Recent history of abnormal bowel movements, such as diarrhea, loose stools, within 2 weeks prior to dosing.
8. 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.
9. History of seizure.
10. History of chronic dermatological conditions that required medical follow-up.
11. History of corneal erosions, degenerations and active or recurrent keratitis.
12. 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).
13. Previous exposure to the study medication.
14. 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.
15. History or clinical evidence of alcoholism or drug abuse within the 2-year period prior to screening.
16. 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.
17. Smoking within 3 months prior to screening and inability to refrain from smoking during the study.
18. 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.
19. 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.
20. Positive results from the hepatitis serology, except for vaccinated subjects or subjects with past but resolved hepatitis, at screening.
21. Positive results from the human immunodeficiency virus (HIV) serology at screening.
22. 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.
23. Legal incapacity or limited legal capacity at screening.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. TOLERABILITY/SAFETY ENDPOINTS • Treatment-emergent AEs from study treatment administration until EOS.
2. TOLERABILITY/SAFETY ENDPOINTS • Treatment-emergent serious adverse events (SAEs) from study treatment administration until EOS.
3. TOLERABILITY/SAFETY ENDPOINTS • Abnormal safety laboratory findings, abnormal vital signs, and abnormal ECG parameters from study treatment administration until EOS.
4. Pharmacokinetic endpoints: See protocol

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Azafaros B.V.

Sponsor organisation

Azafaros B.V.

Address

J.h. Oortweg 21

City

Leiden

Postcode

2333 CH

Country

Netherlands

Scientific contact point

Organisation

Azafaros B.V.

Contact name

Christian Freitag

Public contact point

Organisation

Azafaros B.V.

Contact name

Christian Freitag

Third parties 3

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 3 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications