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

• ClinicalTrials.gov Identifier: NCT04379869
• Recruitment Status: Completed
• First Posted: May 8, 2020
• Last Update Posted: July 9, 2021
• Sponsor: Neuren Pharmaceuticals Limited
• Information provided by (Responsible Party): Neuren Pharmaceuticals Limited

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
Healthy Volunteers	Drug: NNZ-2591; Drug: Placebo	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

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 28 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• 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
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Stage 1: None Stage 2: Double-blind
• Primary Purpose: Treatment
• Official Title: A Combined Single Dose and Multiple Ascending Dose Study to Assess the Safety, Tolerability and Pharmacokinetic Profile of NNZ-2591 in Healthy Volunteers
• Actual Study Start Date: May 29, 2020
• Actual Primary Completion Date: February 11, 2021
• Actual Study Completion Date: February 11, 2021

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 :

1. Safety and Tolerability measured through Adverse Events /Serious Adverse Events [ Time Frame: 25 days ]
   The frequency and severity of Adverse Events in healthy volunteers administered single and repeated oral doses of NNZ-2591

Secondary Outcome Measures :

1. Pharmacokinetic - Cmax [ Time Frame: 17 days ]
   Maximum observed plasma concentration (Cmax) of NNZ-2591
2. Pharmacokinetic - AUC∞ [ Time Frame: 17 days ]
   Area under the concentration-time curve from time 0 to infinity of NNZ-2591
3. Pharmacokinetic - Tmax [ Time Frame: 17 days ]
   Time to Cmax of NNZ-2591
4. Pharmacokinetic - t1/2 [ Time Frame: 17 days ]
   Terminal elimination half-life

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Locations

Australia, New South Wales

Scientia Clinical Research

Sydney, New South Wales, Australia, 2031

Australia, Western Australia

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

More Information

• Responsible Party: Neuren Pharmaceuticals Limited
• ClinicalTrials.gov Identifier: NCT04379869
• Other Study ID Numbers: NEU-2591-HV-001
• First Posted: May 8, 2020
• Last Update Posted: July 9, 2021
• Last Verified: July 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Neuren Pharmaceuticals Limited:

Healthy Volunteers