Healthy Volunteers
Conditions
Keywords
Healthy Volunteers
Brief summary
The purpose of this study is to assess the safety, tolerability and pharmacokinetics of NNZ-2591 when administered to healthy volunteers.
Detailed description
This study is in two stages: Stage 1: A First-in-Human (FIH), single dose escalation study of oral NNZ-2591 in healthy volunteers to establish safety, tolerability and pharmacokinetic parameters. Stage 2: A First-in-Human (FIH), randomised, double-blind, placebo-controlled, Multiple Ascending Dose study (MAD) in healthy volunteers to establish safety, tolerability and pharmacokinetic parameters.
Interventions
DRUGNNZ-2591
Single dose of NNZ-2591
DRUGPlacebo
Comparator for double-blind MAD
Sponsors
Neuren Pharmaceuticals Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Stage 1: None Stage 2: Double-blind
Intervention model description
Stage 1: Open-label, single dose with 2 dose cohorts. Stage 2: Randomised, Double-blind, Placebo-controlled, Multiple Ascending Dose (MAD) with 2 dose cohorts
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Male or female subjects aged 18 to 55 years, inclusive; 2. Weight at screening and admission between 45 kg and 100 kg; 3. Body mass index (BMI) between 18.0 and 32.0 kg/m2 inclusive; 4. Healthy as determined by the Investigator based on pre-study medical history, physical examination, vital signs, complete neurological examination and 12-lead electrocardiogram (ECG); 5. Negative tests for Hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (anti-HCV) and human immunodeficiency virus (HIV)-1 and HIV-2 antibody at screening; 6. Clinical laboratory test results up to \>1.5 x Lower Limit of Normal (LLN) or \<1.5 x Upper Limit of Normal (ULN) at screening and admission and deemed not clinically significant by the Investigator; 7. Negative screen for alcohol and drugs of abuse at screening and admission; 8. Non-smokers or ex-smokers (must have ceased smoking \>3 months prior to screening visit); If female: 9. Woman with no childbearing potential by reason of surgery or at least 1year post- menopause (i.e., 12 months post last menstrual period), and menopause confirmed by follicle-stimulating hormone (FSH) testing; 10. If of childbearing potential, using an effective nonhormonal method of contraception (intrauterine device; condom or occlusive cap \[diaphragm or cervical or vault caps\]; true abstinence; or vasectomized male partner (provided that he is the sole partner of that subject and had a vasectomy ≥30 days prior to screening) for the duration of the study and up to one month after the last investigational medicinal product (IMP) administration; 11. Negative serum pregnancy test at screening and negative urine pregnancy test on admission (women of childbearing potential only); If male: 12. Using an effective method of contraception (condom) if sexually active with a female partner of child-bearing potential; true abstinence; or vasectomy ≥30 days prior to screening) throughout the study and for one month after the last IMP administration.
Exclusion criteria
1. Subjects who have a clinically relevant history as determined by the Investigator, or presence of respiratory, gastrointestinal, renal, hepatic, haematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, endocrine, connective tissue diseases or disorders; 2. Fridericia's correction factor for QT (QTcF) \> 450 ms for male participants and \>470ms for female participants or history of QT interval prolongation. 3. Have a clinically relevant surgical history, as determined by the Investigator; 4. Have a history of relevant atopy or drug hypersensitivity; 5. Have a history of alcoholism or drug abuse; 6. Consume more than 21 standard drinks a week for males and more than 14 standard drink if female \[1 standard drink is any drink containing 10g of alcohol, regardless of container size or alcohol type\]. 7. Have a significant infection or known inflammatory process on screening or admission; 8. Have acute gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea, heartburn) at the time of screening or admission; 9. Have used any prescription or non-prescription medicines within 2 weeks of admission, unless in the investigator's opinion will not affect determination of safety or other study assessments. Occasional paracetamol use (up to 2g/day is permitted); 10. Have received any investigational drug within 30 days prior to screening; 11. Have used tobacco or nicotine products within 3 months of screening 12. Have donated or received any blood or blood products within the 3 months prior to screening; 13. Cannot communicate reliably with the investigator; 14. Are unlikely to co-operate with the requirements of the study; 15. Are unwilling or unable to give written informed consent. If female: 16. Pregnancy or breast-feeding; 17. Woman of childbearing potential not willing to use an accepted effective contraceptive method or using hormonal contraceptives; If male: 18. Not willing to use an accepted effective method of contraception.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability measured through Adverse Events /Serious Adverse Events | 25 days | The frequency and severity of Adverse Events in healthy volunteers administered single and repeated oral doses of NNZ-2591 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic - Cmax | 17 days | Maximum observed plasma concentration (Cmax) of NNZ-2591 |
| Pharmacokinetic - AUC∞ | 17 days | Area under the concentration-time curve from time 0 to infinity of NNZ-2591 |
| Pharmacokinetic - Tmax | 17 days | Time to Cmax of NNZ-2591 |
| Pharmacokinetic - t1/2 | 17 days | Terminal elimination half-life |
Countries
Australia
Outcome results
None listed