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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Neuren Pharmaceuticals Limited
ClinicalTrials.gov Identifier:
NCT01420042
First received: August 17, 2011
Last updated: November 20, 2012
Last verified: November 2012
  Purpose

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.


Condition Intervention Phase
Brain Injuries, Traumatic
Drug: NNZ-2566
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Neuren Pharmaceuticals Limited:

Primary Outcome Measures:
  • Incidence of adverse events (AE) and serious adverse events (SAE) [ Time Frame: Through to Day 7 post end of study drug administration or until resolved ] [ Designated as safety issue: Yes ]

Enrollment: 24
Study Start Date: February 2012
Study Completion Date: September 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: NNZ-2566 Lot NNZP25

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.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01420042

Locations
Australia, Victoria
Nucleus Network
Melbourne, Victoria, Australia
Sponsors and Collaborators
Neuren Pharmaceuticals Limited
Investigators
Principal Investigator: Maggie Scott Neuren Pharmaceuticals Ltd
  More Information

No publications provided

Responsible Party: Neuren Pharmaceuticals Limited
ClinicalTrials.gov Identifier: NCT01420042     History of Changes
Other Study ID Numbers: Neu-2566-HV-005
Study First Received: August 17, 2011
Last Updated: November 20, 2012
Health Authority: United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration

Additional relevant MeSH terms:
Brain Injuries
Wounds and Injuries
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System

ClinicalTrials.gov processed this record on August 28, 2014