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

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

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

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: NNZ-2591; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2031
      • Scientia Clinical Research
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Linear Clinical Research, The Queen Elizabeth II Medical Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 51 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Neuren Pharmaceuticals Limited
• Investigators: Study Director: James Shaw, Neuren Pharmaceuticals; Principal Investigator: Jasmine Williams, Linear Clinical Research

Study record dates

Study Major Dates

• Study Start (Actual): May 29, 2020
• Primary Completion (Actual): February 11, 2021
• Study Completion (Actual): February 11, 2021

Study Registration Dates

• First Submitted: April 30, 2020
• First Submitted That Met QC Criteria: May 4, 2020
• First Posted (Actual): May 8, 2020

Study Record Updates

• Last Update Posted (Actual): July 9, 2021
• Last Update Submitted That Met QC Criteria: July 5, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Healthy Volunteers
• Other Study ID Numbers: NEU-2591-HV-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No