Alzheimer’s disease (AD), frontotemporal dementia (FTD) Nervous System Diseases
Conditions
Interventions
This is a Phase I, single-centre, single-part, open-label study. This healthy volunteer study will try to assess what the body does to the test medicine (pharmacokinetics) and how the body takes up th
MR) tablet versus an immediate release (IR) capsule (relative bioavailability). This study will take place at a single non-NHS site, enrolling up to 12 male and female volunteers of non-childbearing p
Sponsors
Anavex Germany GmbH
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Inclusion criteria
Inclusion criteria: 1. Must provide written informed consent 2. Must be willing and able to communicate and participate in the whole study 3. Aged 18 to 55 years inclusive at the time of signing informed consent 4. Must agree to adhere to the contraception requirements defined in the Clinical Protocol 5. Must be vaccinated for COVID-19 in accordance with current UK government guidance or have had a previous COVID-19 infection in the past 6 months. One of the following options must apply in order for a subject to be eligible: 5.1. An approved COVID-19 vaccine primary series (Moderna, Pfizer/BioNTech, Nuvaxovid vaccine (Novavax), Oxford/AstraZeneca vaccine, Janssen vaccine) 5.2. An approved COVID-19 vaccine primary series and a COVID-19 infection in the last 6 months prior to screening 5.3. A COVID-19 infection in the last 6 months prior to screening 6. Healthy males or non-pregnant, non-lactating healthy females of non-childbearing potential. Participants who are healthy as determined by medical evaluation including medical history, physical and neurological examination, vital signs, single 12-lead ECG, clinical laboratory profiles (haematology, clinical chemistry, coagulation and urinalysis), as deemed by the investigator or designee at screening 7. Body mass index (BMI) of 18.0 to 30.0 kg/m2 as measured at screening 8. Minimum weight =50.0 kg and maximum weight 120.0 kg at screening 9. Adequate peripheral venous access at screening
Exclusion criteria
Exclusion criteria: 1. Serious adverse reaction or serious hypersensitivity to any drug or formulation excipients 2. Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hay fever is allowed unless it is active 3. History of clinically significant cardiovascular, renal, hepatic, dermatological, chronic respiratory or GI disease, or neurological, as judged by the investigator 4. History of psychiatric disease needing treatment in the last 5 years 5. History of postural hypotension or unexplained syncope, or seizures 6. Participants with a history of cholecystectomy or gallstones 7. Evidence of current SARS-CoV-2 infection or reports to have had COVID-19 within 2 weeks of first IMP administration 8. Clinically significant abnormal clinical chemistry, haematology, coagulation or urinalysis as judged by the investigator. - Participants with renal (urea or creatinine) and hepatic function test (total bilirubin, alanine aminotransferase [ALT], alkaline phosphatase, gamma glutamyl transferase [GGT]) results greater than the normal reference values at screening. Participants with Gilbert’s Syndrome are not allowed 9. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) 1 and 2 antibody results 10. Females of childbearing potential including those who are pregnant or lactating (all female participants must have a negative highly sensitive serum pregnancy test). A woman is considered of childbearing potential unless she is permanently sterile (hysterectomy, bilateral salpingectomy, and bilateral oophorectomy) or is postmenopausal (had no menses for 12 months without an alternative medical cause and a serum follicle-stimulating hormone [FSH] concentration =40 IU/L) 11. Heart rate on ECG or vital signs 100 bpm; PR >220 msec; Corrected QT interval by Fridericia’s formula (QTcF) =350 msec or =450 msec for males or QTcF =360 msec or =460 msec for females; second degree or higher heart block at screening or pre-dose Period 1, Day 1 12. Participants who have received any IMP in a clinical research study within the 90 days prior to Period 1, Day 1, or less than 5 elimination half-lives prior to Period 1, Day 1, whichever is longer 13. Donation of blood or plasma within the previous 3 months or loss of greater than 400 ml of blood 14. Participants who are taking, or have taken, any prescribed or over-the-counter drug or herbal remedies (other than up to 4 g of paracetamol per day and HRT) in the 14 days before IMP administration. COVID-19 vaccines are accepted concomitant medications. Exceptions may apply, as determined by the investigator and agreed to by the sponsor’s medical monitor, if each of the following criteria are met: medication with a short half life if the washout is such that no PD activity is expected by the time of dosing with IMP; and if the use of medication does not jeopardise the safety of the trial participant; and if the use of medication is not considered to interfere with the objectives of the study 15. History of any drug or alcohol abuse in the past 2 years 16. Regular alcohol consumption in males >21 units per week and females >14 units per week (1 unit = ½ pint beer, or a 25 mL shot of 40% spirit, 1.5 to 2 units = 125 mL glass of wine, depending on type) 17. A confirmed positive alcohol breath test at screening or admission 18. Current smokers and those who have smoked within the last 6 months. A confirmed breath carb
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. The appropriate ANAVEX3-71 and M8 plasma PK parameters of ANAVEX3-71 MR Prototype Tablets and IR oral capsules (reference formulation), measured using blood samples collected from Day 1 to 96 hours post-dose on Day 5 in Periods 1-5. 2. Calculation of the relative bioavailability (Frel) for ANAVEX3-71 Cmax, C8 (IR reference only), C24 (MR prototype tablets only), AUC(0-24) and AUC(0-inf) for the ANAVEX3-71 MR Prototype Tablets in comparison with an ANAVEX3-71 IR Oral Capsules (reference formulation), measured using blood samples collected from Day 1 to 96 hours post-dose on Day 5 in Periods 1-5. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Safety and tolerability measured using assessment of physical examinations, safety laboratory tests, vital signs, electrocardiograms (ECGs), adverse events (AEs) and C-SSRS from screening until discharge from the study. 2. The appropriate plasma PK parameters of ANAVEX3-71 following administration of a selected ANAVEX3-71 MR Prototype Tablet, measured using blood samples collected from Day 1 to 96 hours post-dose on Day 5 in Periods 1-5. 3. The appropriate urine PK parameters for the ANAVEX3-71 IR Oral Capsules for ANAVEX3-71 and its metabolite M8, measured using blood samples collected from Day 1 to 48 hours post-dose on Day 3 in Period 1. | — |
Countries
England, United Kingdom
Contacts
Public ContactJames Tran
Outcome results
None listed