Healthy volunteers Other
Conditions
Interventions
In this study, all healthy participants are enrolled to receive same treatment.
Treatment details: Day 1: single dose midazolam 2.5 mg
Days 2 – 15: ASN51 QD
Day 3: midazolam 2.5 mg (in addition to AS
Sponsors
Asceneuron (Switzerland)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male healthy volunteers or healthy female volunteers of non-childbearing potential. A woman is considered to be of non-childbearing potential if she meets one of the following criteria: 2. Post-menopausal (amenorrhea for at least 12 months, and follicle-stimulating hormone (FSH) at screening confirms post-menopausal status) 3. Has no uterus, ovaries or fallopian tubes 4. Aged 18–55 years. 5. Deemed healthy based on medical history, physical examination, ECG, vital signs, neurological examination, and laboratory tests of blood and urine. 6. Body weight = 50.0 kg (men) or = 45.0 kg (women). 7. Body mass index (BMI; Quetelet index) in the range 18.0–30.9 kg/m2 (inclusive). 8. Sufficient intelligence to understand the nature of the trial and any hazards of participating in it. Ability to communicate satisfactorily with the investigator and to participate in, and comply with the requirements of, the entire trial (ie be fluent in the local language). 9. Willingness to give written consent to participate after reading the ICF, and after having the opportunity to discuss the trial with the investigator or their delegate. 10. Agree not to donate blood or blood products during the study and for up to 3 months after the final visit. 11. Willingness to give written consent to have data entered into The Overvolunteering Prevention System (TOPS).
Exclusion criteria
Exclusion criteria: 1. Clinically relevant abnormal medical history, physical or neurological findings, ECG, or laboratory values at screening, or before the first dose of trial medication, that could interfere with the objectives of the trial or the safety of the volunteer. 2. History or presence of acute or chronic illness, or clinically-significant medical abnormality, sufficient to invalidate the volunteer’s participation in the trial or make it unnecessarily hazardous. 3. History or presence of any disease, medical condition, or surgery (eg stomach bypass), likely to affect the absorption, distribution, metabolism, or excretion of medicines. Subjects with a history of cholecystectomy should be excluded. 4. Impaired endocrine, thyroid, hepatic, respiratory or renal function, diabetes mellitus, coronary heart disease, or history of any psychotic mental illness. 5. Presence or history of severe or clinically significant adverse reaction to any drug; or a history of sensitivity to ASN51 or midazolam, or any components of those medications. 6. History of psychiatric disorders, including substance use disorders, according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria. 7. Any diagnosis of intellectual disability (intellectual developmental disorder) or mental retardation. 8. History of epilepsy or seizures, other than a single instance of benign febrile convulsion in childhood. 9. History of clinically significant head trauma, including closed head injury with loss of consciousness. 10. History of clinically significant orthostatic hypotension (ie postural syncope). 11. History of neuroleptic malignant syndrome. 12. History of chronic urinary tract infections. 13. Suicidal ideation, as determined by the C-SSRS, during the previous 6 months. 14. Blood pressure and pulse rate in supine position at the screening examination or Day -1 outside the following ranges: blood pressure 90–140 mm Hg systolic, 40–90 mm Hg diastolic; pulse rate 40_100 beats/min. The median of triplicate measurements (each 5 min apart) will be used to assess eligibility. Repeat measurements are permitted if values are borderline (ie values that are within 5 mm Hg for blood pressure or 5 beats/min for pulse rate) or if requested by the investigator. Subjects can be included if the repeat value is within range. 15. Significant (> 10%) weight loss or gain within 30 days before the (first) screening visit or before the first dose of trial medication. 16. Unsatisfactory venous access. 17. Subjects with a COVID-19 vaccination within 2 weeks of screening, or who are due to receive a dose of a COVID-19 vaccine while participating in the study. 18. Positive test for hepatitis B, hepatitis C or human immunodeficiency virus (HIV).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Maximum Plasma Concentration (Cmax) of Midazolam and 1-hydroxymidazolam with and without the co-administration of ASN51 2. Dose-normalised Cmax (Cmax/Dose) of Midazolam with and without the co-administration of ASN51 3. Time to Reach Maximum Plasma Concentration (Tmax) of Midazolam and 1-hydroxymidazolam with and without the co-administration of ASN51 4. Terminal Half-life (T1/2) of Midazolam and 1-hydroxymidazolam with and without the co-administration of ASN51 5. Terminal Rate Constant (Lambda z) of Midazolam and 1-hydroxymidazolam with and without the co-administration of ASN51 6. Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last (AUClast) measurable concentration of Midazolam and 1-hydroxymidazolam with and without the co-administration of ASN51 7. Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUCinf) measurable concentration of Midazolam and 1-hydroxymidazolam with and without the co-administration of ASN51 8. Dose-normalised AUC to Infinity (AUCinf/Dose) of Midazolam with and without the co-administration of ASN51 9. Apparent Total Clearance (CL/F) from plasma after non-intravenous administration of Midazolam with and without the co-administration of ASN51 10. Apparent Volume of Distribution (Vz/F) after non-intravenous administration of Midazolam with and without the co-administration of ASN51 | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Number of Participants With Clinically Significant Abnormalities in Clinical Laboratory Parameters 2. Number of Participants With Clinically Significant Abnormalities in Vital Signs 3. Number of Participants With Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Parameters 4. Number of Participants With Clinically Significant Abnormalities in Physical and Neurological Examination 5. Number of Participants With Positive Columbia-Suicide Severity Rating Scale (C-SSRS) Results 6. Number of Participants With at Least One Treatment Emergent Adverse Events (TEAEs) | — |
Countries
England, United Kingdom
Contacts
Public ContactRyan Schubert
Outcome results
None listed