Safety Study of NNZ-2566 in Healthy Female Subjects

A Phase I, Double-Blind, Randomized, Dose Escalation Study to Assess the Safety, Tolerability and PK of NNZ-2566 in Healthy Females, When Administered as a Loading Dose (10-Min), and as a Loading Dose Followed by a Maintenance Dose (72-Hr).

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

Study Overview

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

Detailed Description

To obtain evidence of the safety of NNZ-2566 in healthy female volunteers, compared to placebo when administered as a 10 minute intravenous (i.v.) bolus infusion, and when administered as a 10-minute bolus infusion immediately followed by a continuous 72-hour maintenance infusion.

To determine the blood pharmacokinetics (PK) of an intravenous dose of NNZ-2566 in healthy female volunteers when administered as a 10-minute bolus infusion, and when administered as a 10-minute bolus followed by a continuous 72-hour maintenance infusion.

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Nucleus Network

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Aged between 18 years and 50 years (inclusive).
• Females only.
• Weight 50 to 105 kg
• BMI of 18 to 30 kg/m2.

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

  • a drug history identifying any known drug allergies and the presence of drug abuse;
  • any chronic use of medication; and
  • a thorough review of body systems. This will also be determined by having no clinically significant abnormal findings on physical examination, which includes an electrocardiogram (ECG), which in the opinion of the Investigator would jeopardize the safety of the subject or impact on the validity of the study results.
• Venous Access: Volunteers with adequate venous access in their left and right arm to allow collection of blood samples and drug administration.
• Language: Fluent in the English language.
• Informed Consent: Have voluntarily given written informed consent to participate in this study.

Exclusion Criteria:

• Pregnant and lactating females are excluded from participating in the study.
• History of allergy and/or hypersensitivity to any of the stated ingredients of the formulations.
• History of clinically significant gastrointestinal, hepatic, renal, cardiovascular, dermatological, immunological, respiratory, endocrine, oncological, neurological, metabolic, psychiatric disease or hematological disorders.
• Any history of asthma during the last 10 years.
• A creatinine clearance of less than 75 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 or intravenous cannulation.
• 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.
• Pregnancy.
• Any evidence of organ dysfunction, or any clinically significant clinical laboratory value, including a liver function test (LFT) > 1.5 x upper limit of normal (ULN).
• Difficulty abstaining from alcohol during the 48 hours prior to dose administration and until completion of blood sampling at exit assessment.
• 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 24 hours prior to dose administration and whilst confined at the clinical study facility.
• History of any psychiatric illness which may impair the ability to provide written informed consent.
• Poor protocol 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.
• QT/QTc Exclusions i.e., 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 Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo (Normal saline infusion)	Drug: Placebo; Normal saline infusion; Other Names: Sodium Chloride 0.9% Injection
Experimental: NNZ-2566; NNZ-2566 reconstituted in bicarbonate buffer and normal saline. 6/8 subjects in each cohort (5 cohort in total) to receive NNZ-2566 experimental treatment.	Drug: NNZ-2566; Glycyl-L-2-Methylprolyl-L-Glutamic Acid (NNZ-2566) supplied as a lyophilized powder (2g in 50mL vials) for reconstitution with bicarbonate buffer and normal saline.; Other Names: Experimental name: NNZ-2566

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of AEs and SAEs	Through to Day 7 post end of study drug infusion or until resolved

Collaborators and Investigators

• Sponsor: Neuren Pharmaceuticals Limited
• Investigators: Study Director: Douglas J Wilson, MB ChB, PhD, Neuren Pharmaceuticals Ltd

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Actual): August 1, 2010
• Study Completion (Actual): September 1, 2010

Study Registration Dates

• First Submitted: August 17, 2009
• First Submitted That Met QC Criteria: August 18, 2009
• First Posted (Estimate): August 19, 2009

Study Record Updates

• Last Update Posted (Estimate): October 7, 2014
• Last Update Submitted That Met QC Criteria: October 3, 2014
• Last Verified: October 1, 2014

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-004

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No