Drug-Drug Interaction Study With AGMB-129 and Midazolam in Healthy Participants

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Agomab Spain S.L.

Participant type

Healthy volunteers

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

26 Jun 2023 → 29 Aug 2023

Decision date (initial)

2023-06-26

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Others

To determine the effect of AGMB-129 on the PK of Midazolam and its metabolite.

Secondary objectives 2

1. To evaluate the PK of AGMB-129
2. To evaluate the safety and tolerability of multiple oral doses of AGMB-129

Conditions and MedDRA coding

Fibrostenotic Crohn’s disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Informed Consent Form (ICF) signed voluntarily before any study-related procedure is performed, indicating that the participant understands the purpose of and procedures required for the study and is willing to participate in the study.
2. Male or female, between 18 and 55 years old (extremes included) on the date of signing the ICF
3. Body weight of at least 50.0 kg for men and 45.0 kg for women, and a body mass index (BMI) between 19.0 and 30.0 kg/m2 (extremes included) at screening
4. a) Male participant is eligible to participate if: o He is vasectomized, OR o He agrees to the following during the intervention period and for at least 4 weeks after the last administration of IP:  Refrain from donating fresh unwashed semen, Plus either:  Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent, OR  Must agree to use a male condom when:  Having sexual intercourse with a woman of childbearing potential who is not currently pregnant.  Engaging in any activity that allows for passage of ejaculate to another person. b) Female participant Is eligible to participate if she is not pregnant or breastfeeding, or intending to become pregnant or breastfeed during the study, and at least one of the following conditions applies: - Is a woman of nonchildbearing potential (WONCBP). OR - Is a woman of childbearing potential (WOCBP) and agrees to use a highly effective contraceptive method (with a failure rate of <1% per year) OR be abstinent from heterosexual intercourse as their preferred method and usual lifestyle, during the intervention period and for at least 4 weeks after the last administration of IP. The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first administration of IP. Must agree not to donate eggs during the study and for at least 4 weeks after last administration of IP
5. Female participants must have a negative highly sensitive serum (beta human chorionic gonadotropin [β-hCG]) pregnancy test at screening and a negative urine pregnancy test on Day -1
6. Must be in good health based on medical history, physical examination, vital signs, and 12-lead ECG in the opinion of the investigator at screening.
7. Total bilirubin, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) must be ≤1.5x upper limit of normal (ULN) at screening. Other clinical laboratory safety test results must be within the reference ranges or test results that are outside the reference ranges need to be considered not clinically significant in the opinion of the investigator.
8. Negative urine test for selected drugs of abuse (amphetamines, barbiturates, benzodiazepines, tetrahydrocannabinol (THC), cocaine, opiates, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine [EDDP], tricyclic antidepressants) and alcohol breath test at screening or Day -1
9. Negative COVID 19 test (polymerase chain reaction [PCR]) and no clinical symptoms of corona on Day -1
10. Willing to adhere to the lifestyle considerations specified in this protocol

Exclusion criteria 20

1. Known hypersensitivity to AGMB-129 ingredients or history of a significant allergic reaction to AGMB-129 ingredients as determined by the investigator.
2. Positive serology for hepatitis B virus surface antigen (HBsAg) or anti-hepatitis C virus [HCV] antibodies at screening, or history of hepatitis from any cause except for hepatitis A that was resolved at least 3 months prior to the first IP administration.
3. History of or a current immunosuppressive condition, including positive human immunodeficiency virus types 1 or 2 (HIV-1 [2]) antibodies at screening.
4. Current or history of vasculitis, valvular heart disease, or large vessel vascular disease (such as aneurism or dissection) at screening.
5. Any illness, judged by the investigator as clinically significant, in the 3 months prior to the first IP administration.
6. Presence or sequelae of gastrointestinal, liver, kidney (estimated glomerular filtration rate [eGFR] ≤80 mL/min/1.73 m² using the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula) or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs at screening.
7. History of malignancy within the past 5 years prior to screening, except for excised and curatively treated non-metastatic basal cell carcinoma, squamous cell carcinoma of the skin, or carcinoma in situ of cervix which is considered cured with minimal risk of recurrence.
8. History or presence of clinically significant abnormalities detected on 12-lead ECG of either rhythm or conduction, e.g., known long QT syndrome or a QT interval corrected for heart rate according to Fridericia’s formula (QTcF) >450 ms detected on the 12-lead ECG at screening or Day -1. A first-degree atrioventricular block will not be considered as a clinically significant abnormality.
9. Significant blood loss (including blood donation [>450 mL]), or transfusion of any blood product within 3 months prior to screening.
10. Treatment with any drug known to have a potential for major organ toxicity in the last 3 months before the first IP administration.
11. Treatment with any medication (including over-the-counter and/or prescription medication, dietary supplements, nutraceuticals, vitamins and/or herbal supplements), except for occasional use of paracetamol (maximum dose of 2 g/day and maximum of 10 g/2 weeks) in the last 14 days or 5 half-lives of the drug, whichever is longer, prior to the first IP administration, and the use of hormonal contraceptives in women of childbearing potential and hormonal replacement therapy (HRT) in postmenopausal women.
12. Has received or plans to receive any authorized or investigational live vaccine within 4 weeks before the first IP administration. Receipt of vaccines authorized for emergency use (e.g., COVID-19) within the aforementioned timeframe is allowed.
13. Concurrent participation or participation in a: - Drug or drug/device study within 30 days or 5 half-lives of the drug (if known by the participant or investigator), whichever is longer, prior to the first IP administration, or - Biologic investigational research study within 3 months or 5 half-lives of the biologic (if known by the participant or investigator), whichever is longer, prior to the first IP administration
14. Active drug abuse or alcohol abuse (alcohol abuse defined as regular weekly intake of more than 14 units) within 2 years prior to the first IP administration
15. Active smoker and/or has used e-cigarettes, nicotine, or nicotine-containing products (including e-cigarettes or the equivalent of e-cigarettes) within 6 months prior to the first IP administration.
16. Regular consumption of a large quantity of any alcohol- or xanthine-containing foods or beverages (caffeine or coffee [>6 cups per day], theine or tea [>6 cups per day], cocoa or chocolate, cola, or energy drinks such as Red Bull etc.) at screening or Day 1
17. Investigator or other study staff or relative thereof who is directly involved in the conduct of the study.
18. Any condition or circumstances at screening that in the opinion of the investigator could compromise the well being of the participant, may make the participant unlikely or unable to complete the study or comply with study procedures and requirements.
19. Have poor venous access that limits blood sampling at screening.
20. Any condition that in the opinion of the investigator can be considered as contraindication for MDZ (refer to the SmPC), including but not limited to respiratory conditions and diseases, and acute narrow-angle glaucoma at screening or Day 1.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Pharmacokinetic parameters of Midazolam (and its metabolite 1-OH-midazolam) in plasma: Cmax and AUC0-∞.

Secondary endpoints 2

1. Pharmacokinetic parameters of AGMB-129 and its metabolites MET-158 and MET-154 in plasma
2. Evaluation throughout the study of: - Frequency and severity of TEAEs and SAEs, and TEAEs leading to IP discontinuation. - Clinical laboratory tests. - Vital signs. - Physical examination.

Investigational products

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

Test 1

Auxiliary 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Agomab Spain S.L.

Sponsor organisation

Agomab Spain S.L.

Address

Poligono Parque Empresarial Parcelas 26-27, Fonte Diaz Fonte Diaz

City

Touro

Postcode

15822

Country

Spain

Scientific contact point

Organisation

Agomab Spain S.L.

Contact name

Tim Van Kaem

Public contact point

Organisation

Agomab Spain S.L.

Contact name

Clinical Operations

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

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