Clinical trial NCT04379869: To Evaluate the Safety, Tolerability and Pharmacokinetics of Oral NNZ-2591 in Healthy Volunteers
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Healthy Volunteers
Lead sponsor: Neuren Pharmaceuticals Limited
Sponsor class: INDUSTRY
First posted: 2020-05-08
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
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
Primary purpose: TREATMENT

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

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.

Eligibility 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.

Primary outcomes:
measure: Safety and Tolerability measured through Adverse Events /Serious Adverse Events
timeFrame: 25 days
Secondary outcomes:
measure: Pharmacokinetic - Cmax
timeFrame: 17 days
measure: Pharmacokinetic - AUC∞
timeFrame: 17 days
measure: Pharmacokinetic - Tmax
timeFrame: 17 days
measure: Pharmacokinetic - t1/2
timeFrame: 17 days
Other outcomes:
Locations:
city: Sydney
country: Australia
facility: Scientia Clinical Research
state: New South Wales
city: Nedlands
country: Australia
facility: Linear Clinical Research, The Queen Elizabeth II Medical Centre
state: Western Australia
Study officials:
affiliation: Neuren Pharmaceuticals
name: James Shaw
role: STUDY_DIRECTOR
affiliation: Linear Clinical Research
name: Jasmine Williams
role: PRINCIPAL_INVESTIGATOR
References: