Safety Study of NNZ-2566 in Healthy Subjects, Following Oral Administration

A Phase I, Double-Blind, Randomized, Dose Escalation Study to Assess the Safety, Tolerability, and Pharmacokinetics of NNZ-2566 in Healthy Subjects, Following Oral Administration

The purpose of this study is to obtain evidence of safety and determine the pharmacokinetics (PK) of NNZ-2566 in healthy volunteers, when administered orally.

Study Overview

• Status: Completed
• Conditions: Brain Injuries, Traumatic
• Intervention / Treatment: Drug: Placebo; Drug: NNZ-2566

Detailed Description

Double-blind, placebo-controlled, randomized (with a 6:2 randomization for active versus placebo) safety, dose-escalation, and pharmacokinetic study of NNZ-2566.

Three cohorts will be sequentially dosed, starting with two cohorts receiving a single dose (6mg/kg followed by 30mg/kg). The third cohort will receive two 100mg/kg doses over the course of one day and following a formal safety review the same subjects will then receive two 100mg/kg doses each day for five days.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia
      • Nucleus Network

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males: 60.0-100.0 kg, Females: 50.0-100.0 kg (inclusive).
• Males: Body mass index (BMI) of 20-30.0, Females: BMI of 18.5-30.0 kg/m2 (inclusive).

• Healthy, determined by a medical history with particular attention to:

  • drug history identifying any known drug allergies and the presence of drug abuse;
  • any chronic use of medication
  • thorough review of body systems: no clinically significant abnormal findings on physical examination and electrocardiogram (ECG),
• Adequate venous access in arms to allow collection of blood samples.
• Fluent in the English language.
• Have voluntarily given written informed consent.

Exclusion Criteria:

• Pregnant and lactating females.
• History of allergy/hypersensitivity to any of the ingredients of the formulations
• History of clinically significant gastrointestinal, hepatic, renal, cardiovascular, dermatological, immunological, respiratory, endocrine, oncological, neurological, metabolic, gynecological, ENT or musculoskeletal disorders, psychiatric disease or hematological disorders.
• Any history of asthma during the last 10 years.
• Creatinine clearance <65 mL/min.
• Any predisposing condition that might interfere with the absorption, distribution, metabolism, and/or excretion of the investigational product.
• History of abnormal bleeding tendencies or thrombophlebitis unrelated to venepuncture.
• History of hepatitis B, a positive test for hepatitis B surface antigen, a history of hepatitis C, a positive test for hepatitis C antibody, a history of HIV infection or demonstration of HIV antibodies.
• Any evidence of organ dysfunction, or any clinically significant clinical laboratory value which, in the opinion of the Investigator would jeopardize the safety of the subject or impact on the validity of the study results, including a liver function test (LFT) >1.5 x upper limit of normal (ULN).
• Those who may have difficulty abstaining from alcohol during the 48 hr prior to dose administration and until completion of the Study Exit visit.
• History of, or current evidence of, abuse of alcohol or any drug substance, licit or illicit, or positive urine drug screen for drugs of abuse.
• Difficulty in abstaining from any prescription medications for 14 days prior to dose administration and for the duration of the study.
• Difficulty in abstaining from over-the-counter (OTC) medications or herbal supplements for 14 days prior to dose administration and for the duration of the study, (with the exception of occasional analgesia, vitamin and other nutrient supplement use, at the discretion of the Investigator).
• Difficulty in abstaining from food and/or beverages that contain caffeine or other xanthines, (e.g. coffee, tea, cola and chocolate) during the 48 hrs prior to dose administration and for the duration of the study.
• History of any psychiatric illness which may impair the ability to provide written informed consent.
• Poor compliers or those unlikely to attend.
• Receipt of any drug as part of a research study within 30 days of initial dose administration in this study.
• Standard blood donation (usually 550 mL) within the 12-week period before dose administration.
• Unusual dietary habits and excessive or unusual vitamin intakes.
• Vaccination or immunizations within 30 days of initial dose administration.

• Whilst there were no QT/QTc effects seen in the human volunteers at a dose of 20 mg/kg administered intravenously as a 10 min infusion, until the effects of the drug on QT/QTc interval have been formally characterized, the study will use the exclusion criteria defined in International Conference on Harmonisation (ICH) Guideline E14 to exclude subjects with a risk of QT/QTc prolongation, namely:

  • A marked baseline prolongation of corrected QT interval >450 ms in two ECGs, or
  • A history of risk factors for Torsade de Pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo (lemon flavoured cordial); NNZ-2566 reconstituted in Lemon flavoured cordial and Water for Injection. 6/8 subjects in each cohort (3 cohorts in total) to receive NNZ-2566 experimental treatment.	Drug: Placebo; Lemon flavoured cordial and Water for Injection; Other Names: Bickford's Bitter Lemon Cordial, 1:1 in Water for Injection
EXPERIMENTAL: NNZ-2566	Drug: NNZ-2566; Glycyl-L-2-Methylprolyl-L-Glutamic Acid (NNZ-2566) supplied as a lyophilized powder (2g in 50mL vials) for reconstitution with lemon flavoured cordial and Water for Injection.; Other Names: NNZ-2566 Lot NNZP25

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of adverse events (AE) and serious adverse events (SAE)	Through to Day 7 post end of study drug administration or until resolved

Collaborators and Investigators

• Sponsor: Neuren Pharmaceuticals Limited
• Investigators: Principal Investigator: Maggie Scott, Neuren Pharmaceuticals Ltd

Study record dates

Study Major Dates

• Study Start: February 1, 2012
• Primary Completion (ACTUAL): August 1, 2012
• Study Completion (ACTUAL): September 1, 2012

Study Registration Dates

• First Submitted: August 17, 2011
• First Submitted That Met QC Criteria: August 17, 2011
• First Posted (ESTIMATE): August 19, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): November 22, 2012
• Last Update Submitted That Met QC Criteria: November 20, 2012
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Brain Injuries, Traumatic
• Other Study ID Numbers: Neu-2566-HV-005