ANX-042 Healthy Volunteer Dose Escalation Study

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Anexon, Incorporated
ClinicalTrials.gov Identifier:
NCT01638104
First received: July 9, 2012
Last updated: July 17, 2013
Last verified: July 2013
  Purpose

The purpose of this study is to investigate the safety and tolerability of ANX-042 when administered by continuous intravenous (IV) infusion in healthy volunteers.


Condition Intervention Phase
Healthy Volunteers
Drug: ANX-042
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: ANX-042 Healthy Volunteer Dose Escalation Study

Further study details as provided by Anexon, Incorporated:

Primary Outcome Measures:
  • Number of participants with one or more drug-related adverse events (AEs) or any serious AEs [ Time Frame: 0 to 4 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacokinetics: Area under the plasma concentration-time curve (AUC) of ANX-042 [ Time Frame: 0 to 24 hours post dose ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Steady state plasma concentration of ANX-042 [ Time Frame: 12 hours post dose ] [ Designated as safety issue: No ]

Enrollment: 30
Study Start Date: August 2012
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ANX-042: 0.001 μg/kg/min (with low sodium diet)
0.001 dose unit equal to one millionth of a gram of an ANX-042 preparation per one kilogram of body mass administered per unit of time equal to one minute(μg/kg/min), with diet restricted to 2.5 grams (gm) per day sodium (Na+) and 2.1 liters (L) fluid total daily intake
Drug: ANX-042
Reconstituted in Sterile Water for Injection, United States Pharmacopeia (USP) and administered by 12 hour continuous intravenous infusion with 5% dextrose in water (D5W), United States Pharmacopeia (USP)
Experimental: ANX-042: 0.001 μg/kg/min
0.001 μg/kg/min ANX-042 with diet restricted to 4 gm per day Na+ and 3.6 L fluid total daily intake
Drug: ANX-042
Reconstituted in Sterile Water for Injection, United States Pharmacopeia (USP) and administered by 12 hour continuous intravenous infusion with 5% dextrose in water (D5W), United States Pharmacopeia (USP)
Experimental: ANX-042: 0.003 μg/kg/min (low sodium diet)
0.003 μg/kg/min ANX-042 with diet restricted to 2.5 gm per day Na+ and 2.1 L fluid total daily intake
Drug: ANX-042
Reconstituted in Sterile Water for Injection, United States Pharmacopeia (USP) and administered by 12 hour continuous intravenous infusion with 5% dextrose in water (D5W), United States Pharmacopeia (USP)
Experimental: ANX-042: 0.003 μg/kg/min
0.003 μg/kg/min ANX-042 with diet restricted to 4 gm per day Na+ and 3.6 L fluid total daily intake
Drug: ANX-042
Reconstituted in Sterile Water for Injection, United States Pharmacopeia (USP) and administered by 12 hour continuous intravenous infusion with 5% dextrose in water (D5W), United States Pharmacopeia (USP)
Experimental: ANX-042: 0.0065 μg/kg/min (low sodium diet)
0.0065 μg/kg/min ANX-042 with diet restricted to 2.5 gm per day Na+ and 2.1 L fluid total daily intake
Drug: ANX-042
Reconstituted in Sterile Water for Injection, United States Pharmacopeia (USP) and administered by 12 hour continuous intravenous infusion with 5% dextrose in water (D5W), United States Pharmacopeia (USP)
Experimental: ANX-042: 0.01 μg/kg/min (low sodium diet)
0.01 μg/kg/min ANX-042 with diet restricted to 2.5 gm per day Na+ and 2.1 L fluid total daily intake
Drug: ANX-042
Reconstituted in Sterile Water for Injection, United States Pharmacopeia (USP) and administered by 12 hour continuous intravenous infusion with 5% dextrose in water (D5W), United States Pharmacopeia (USP)
Experimental: ANX-042: 0.01 μg/kg/min
0.01 μg/kg/min ANX-042 with diet restricted to 4 gm per day Na+ and 3.6 L fluid total daily intake
Drug: ANX-042
Reconstituted in Sterile Water for Injection, United States Pharmacopeia (USP) and administered by 12 hour continuous intravenous infusion with 5% dextrose in water (D5W), United States Pharmacopeia (USP)
Experimental: ANX-042: 0.03 μg/kg/min
0.03 μg/kg/min ANX-042 with diet restricted to 4 gm per day Na+ and 3.6 L fluid total daily intake
Drug: ANX-042
Reconstituted in Sterile Water for Injection, United States Pharmacopeia (USP) and administered by 12 hour continuous intravenous infusion with 5% dextrose in water (D5W), United States Pharmacopeia (USP)
Experimental: ANX-042: 0.1 μg/kg/min
0.1 μg/kg/min ANX-042 with diet restricted to 4 gm per day Na+ and 3.6 L fluid total daily intake
Drug: ANX-042
Reconstituted in Sterile Water for Injection, United States Pharmacopeia (USP) and administered by 12 hour continuous intravenous infusion with 5% dextrose in water (D5W), United States Pharmacopeia (USP)
Experimental: ANX-042: 0.3 μg/kg/min
0.3 μg/kg/min ANX-042 with diet restricted to 4 gm per day Na+ and 3.6 L fluid total daily intake
Drug: ANX-042
Reconstituted in Sterile Water for Injection, United States Pharmacopeia (USP) and administered by 12 hour continuous intravenous infusion with 5% dextrose in water (D5W), United States Pharmacopeia (USP)
Placebo Comparator: Placebo (low sodium diet)
Placebo and diet restricted to 2.5 gm per day Na+ and 2.1 L fluid total daily intake
Drug: Placebo
Administered once by 12 hour continuous intravenous infusion with D5W (USP)
Placebo Comparator: Placebo
Placebo and diet restricted to 4 gm per day Na+ and 3.6 L fluid total daily intake
Drug: Placebo
Administered once by 12 hour continuous intravenous infusion with D5W (USP)

Detailed Description:

Each subject will receive a total of two, approximately 12-hour continuous infusions of ANX-042,and one 12-hour continuous infusion of placebo, with a 36-hour washout period between treatments.

  Eligibility

Ages Eligible for Study:   19 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Men or women of non-reproductive potential (WNRP)

    • Men must be willing to use effective contraception and not donate sperm for up to 90 days after the final dose of study drug
    • Women must be of non-reproductive potential defined as a history of surgical sterilization or postmenopausal status (that is, greater than ( >) 50 years of age with >12 months amenorrhea while not using hormonal contraceptives or >50 years of age with 6-12 months of amenorrhea and follicle stimulating hormone (FSH) level >40 IU/L)
  • Good health status, physically active without cardio-respiratory limitations and minimal concomitant medications as determined by medical history and physical examination
  • Able and willing to comply with study procedures, including controlled sodium (Na) intake and restriction of caffeine and tobacco product
  • Have given written informed consent prior to the initiation of any study procedures

Exclusion Criteria:

  • History of cardiovascular disease, unexplained syncope, postural tachycardia syndrome or frequent postural hypotension
  • History or current evidence of respiratory, hepatic, renal, gastrointestinal, endocrine, hematological or neurological disorders that would constitute a risk when taking the study medication or interfere with the interpretation of data
  • Clinically significantly abnormal clinical laboratory results (including Hepatitis B, Hepatitis C and Human Immunodeficiency Virus (HIV) serology) or physical examination results (confirmed by repeat measurement, if appropriate) that, in the opinion of the Investigator, would constitute a risk when taking the study medication or interfere with the interpretation of data
  • Abnormal orthostatic Blood Pressure/Heart Rate (BP/HR) response at screening as defined by:

    • Systolic Blood Pressure (BP) decrease >20 millimeters of mercury mmHg
    • Diastolic BP decrease >10 mmHg, or
    • HR increase >25 beats per minute (bpm) and to a level above 100 bpm
  • One or two supine values must be obtained between 8 and 10 minutes of supine rest. One or two upright values must be obtained between 3 and 5 minutes upright with the arm passively supported to maintain the brachial artery at heart level
  • Abnormal 12-lead electrocardiogram (ECG) that interferes with proper measurement of QT-interval or, in the opinion of the Investigator, increases the risk of participating in the study
  • Elevated BP (>140/90 mmHg) in any posture, confirmed by repeat measurement
  • Current use (within 7 days of first dosing) or expected need for concomitant medications with hemodynamic effects including: non-steroidal anti-inflammatory drugs (NSAIDS), decongestants, BP medications, diuretics, monoamine oxidase inhibitors, norepinephrine uptake inhibitors (for example, attention-deficit disorder medications, anti-depressants) and erectile dysfunction medications. Medications with low likelihood of hemodynamic or renal effects are permitted (for example, acetaminophen, vitamins, stable thyroid hormone, gastritis therapies, antihistamines, topical medications, et cetera) after approval by the Investigator
  • Evidence of current or recent use of known drugs of abuse and/or positive findings on urinary drug screening
  • History of an average weekly alcohol intake that exceeds 21 units per week (1 unit equal to (=) 12 ounces (oz) or 360 milliliters (mL) of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits), or are unwilling to stop alcohol consumption for the duration of the study
  • History of regular smoking of >5 cigarettes, cigars and/or pipe bowls of tobacco per day
  • Known allergies to nesiritide (Natrecor)
  • History of blood donation of >500 mL within one month, or plasma donation within 14 days, of first dosing
  • Are currently enrolled in, or have completed or discontinued within the last 30 days from, a clinical trial involving an investigational product or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
  • Are investigator site personnel directly affiliated with this study or their immediate family members. Immediate family is defined as a spouse, parent, child or sibling, whether biological or legally adopted
  • Are Lilly or Anexon employees or employees of any third-party organization (TPO) involved with the study that require exclusion of their employees
  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: NCT01638104

Locations
United States, Nebraska
Celerion
Lincoln, Nebraska, United States, 68502
Sponsors and Collaborators
Anexon, Incorporated
Investigators
Study Director: Email: Anexon@Choruspharma.com Anexon, Incorporated
  More Information

No publications provided

Responsible Party: Anexon, Incorporated
ClinicalTrials.gov Identifier: NCT01638104     History of Changes
Other Study ID Numbers: ANX-042-C100
Study First Received: July 9, 2012
Last Updated: July 17, 2013
Health Authority: United States: Food and Drug Administration

ClinicalTrials.gov processed this record on August 21, 2014