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

Healthy Volunteers Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04379869
• Other study ID #: NEU-2591-HV-001
• Status: Completed
• Phase: Phase 1
• Start date: May 29, 2020
• Est. completion date: February 11, 2021

Study information

• Verified date: July 2021
• Source: Neuren Pharmaceuticals Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: February 11, 2021
• Est. primary completion date: February 11, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• NNZ-2591
Single dose of NNZ-2591
• Placebo
Comparator for double-blind MAD

Locations

Country	Name	City	State
Australia	Linear Clinical Research, The Queen Elizabeth II Medical Centre	Nedlands	Western Australia
Australia	Scientia Clinical Research	Sydney	New South Wales

Sponsors (1)

Lead Sponsor	Collaborator
Neuren Pharmaceuticals Limited

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Pharmacokinetic - Cmax	Maximum observed plasma concentration (Cmax) of NNZ-2591	17 days
Secondary	Pharmacokinetic - AUC8	Area under the concentration-time curve from time 0 to infinity of NNZ-2591	17 days
Secondary	Pharmacokinetic - Tmax	Time to Cmax of NNZ-2591	17 days
Secondary	Pharmacokinetic - t1/2	Terminal elimination half-life	17 days