To Evaluate the Safety, Tolerability and Pharmacokinetics of Oral NNZ-2591 in Healthy Volunteers
Study Details
Study Description
Brief Summary
The purpose of this study is to assess the safety, tolerability and pharmacokinetics of NNZ-2591 when administered to healthy volunteers.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: NNZ-2591 Single dose Cohort 1 Single dose of oral NNZ-2591 in healthy volunteers |
Drug: NNZ-2591
Single dose of NNZ-2591
|
| Experimental: NNZ-2591 Single dose Cohort 2 Single dose of oral NNZ-2591 in healthy volunteers |
Drug: NNZ-2591
Single dose of NNZ-2591
|
| Experimental: NNZ-2591 MAD Cohort 1 Multiple Ascending Dose (MAD) of oral NNZ-2591 in healthy volunteers |
Drug: NNZ-2591
Single dose of NNZ-2591
Drug: Placebo
Comparator for double-blind MAD
|
| Experimental: NNZ-2591 MAD Cohort 2 Multiple Ascending Dose (MAD) of oral NNZ-2591 in healthy volunteers |
Drug: NNZ-2591
Single dose of NNZ-2591
Drug: Placebo
Comparator for double-blind MAD
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Male or female subjects aged 18 to 55 years, inclusive;
-
Weight at screening and admission between 45 kg and 100 kg;
-
Body mass index (BMI) between 18.0 and 32.0 kg/m2 inclusive;
-
Healthy as determined by the Investigator based on pre-study medical history, physical examination, vital signs, complete neurological examination and 12-lead electrocardiogram (ECG);
-
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;
-
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;
-
Negative screen for alcohol and drugs of abuse at screening and admission;
-
Non-smokers or ex-smokers (must have ceased smoking >3 months prior to screening visit);
If female:
-
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;
-
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;
-
Negative serum pregnancy test at screening and negative urine pregnancy test on admission (women of childbearing potential only);
If male:
- 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:
-
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;
-
Fridericia's correction factor for QT (QTcF) > 450 ms for male participants and >470ms for female participants or history of QT interval prolongation.
-
Have a clinically relevant surgical history, as determined by the Investigator;
-
Have a history of relevant atopy or drug hypersensitivity;
-
Have a history of alcoholism or drug abuse;
-
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].
-
Have a significant infection or known inflammatory process on screening or admission;
-
Have acute gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea, heartburn) at the time of screening or admission;
-
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);
-
Have received any investigational drug within 30 days prior to screening;
-
Have used tobacco or nicotine products within 3 months of screening
-
Have donated or received any blood or blood products within the 3 months prior to screening;
-
Cannot communicate reliably with the investigator;
-
Are unlikely to co-operate with the requirements of the study;
-
Are unwilling or unable to give written informed consent.
If female:
-
Pregnancy or breast-feeding;
-
Woman of childbearing potential not willing to use an accepted effective contraceptive method or using hormonal contraceptives;
If male:
- Not willing to use an accepted effective method of contraception.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Scientia Clinical Research | Sydney | New South Wales | Australia | 2031 |
| 2 | Linear Clinical Research, The Queen Elizabeth II Medical Centre | Nedlands | Western Australia | Australia | 6009 |
Sponsors and Collaborators
- Neuren Pharmaceuticals Limited
Investigators
- Study Director: James Shaw, Neuren Pharmaceuticals
- Principal Investigator: Jasmine Williams, Linear Clinical Research
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NEU-2591-HV-001