To Evaluate the Safety, Tolerability and Pharmacokinetics of Oral NNZ-2591 in Healthy Volunteers

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety, tolerability and pharmacokinetics of NNZ-2591 when administered to healthy volunteers.

Detailed Description
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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.

Official Title
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A Combined Single Dose and Multiple Ascending Dose Study to Assess the Safety, Tolerability and Pharmacokinetic Profile of NNZ-2591 in Healthy Volunteers

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: NNZ-2591
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NNZ-2591 Single dose Cohort 1<br>Single dose of oral NNZ-2591 in healthy volunteers | Drug: NNZ-2591<br>* Single dose of NNZ-2591<br>|
| Experimental: NNZ-2591 Single dose Cohort 2<br>Single dose of oral NNZ-2591 in healthy volunteers | Drug: NNZ-2591<br>* Single dose of NNZ-2591<br>|
| Experimental: NNZ-2591 MAD Cohort 1<br>Multiple Ascending Dose (MAD) of oral NNZ-2591 in healthy volunteers | Drug: NNZ-2591<br>* Single dose of NNZ-2591<br>Drug: Placebo<br>* Comparator for double-blind MAD<br>|
| Experimental: NNZ-2591 MAD Cohort 2<br>Multiple Ascending Dose (MAD) of oral NNZ-2591 in healthy volunteers | Drug: NNZ-2591<br>* Single dose of NNZ-2591<br>Drug: Placebo<br>* Comparator for double-blind MAD<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability measured through Adverse Events /Serious Adverse Events | The frequency and severity of Adverse Events in healthy volunteers administered single and repeated oral doses of NNZ-2591 | 25 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic - Cmax | Maximum observed plasma concentration (Cmax) of NNZ-2591 | 17 days | 
| Pharmacokinetic - AUC∞ | Area under the concentration-time curve from time 0 to infinity of NNZ-2591 | 17 days | 
| Pharmacokinetic - Tmax | Time to Cmax of NNZ-2591 | 17 days | 
| Pharmacokinetic - t1/2 | Terminal elimination half-life | 17 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy Volunteers