ANX-042 Healthy Volunteer Dose Escalation Study

NCT01638104 | Completed Phase 1 FDA Drug

• 1 other identifier: ANX-042-C100
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (1)

• Number of participants with one or more drug-related adverse events (AEs) or any serious AEs

  0 to 4 weeks

Secondary Outcomes (2)

• Pharmacokinetics: Area under the plasma concentration-time curve (AUC) of ANX-042

  0 to 24 hours post dose

• Pharmacokinetics: Steady state plasma concentration of ANX-042

  12 hours post dose

Study Arms (12)

ANX-042: 0.001 mcg/kg/min (with low sodium diet)

EXPERIMENTAL

0.001 dose unit equal to 1 millionth of a gram of an ANX-042 preparation / 1 kilogram of body mass administered / unit of time equal to 1 minute(mcg/kg/min), w/ diet restricted to 2.5 grams (gm) per day sodium (Na+) and 2.1 liters (L) fluid total daily intake

Drug: ANX-042

ANX-042: 0.001 mcg/kg/min

EXPERIMENTAL

0.001 mcg/kg/min ANX-042 with diet restricted to 4 gm per day Na+ and 3.6 L fluid total daily intake

Drug: ANX-042

ANX-042: 0.003 mcg/kg/min (low sodium diet)

EXPERIMENTAL

0.003 mcg/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

ANX-042: 0.003 mcg/kg/min

EXPERIMENTAL

0.003 mcg/kg/min ANX-042 with diet restricted to 4 gm per day Na+ and 3.6 L fluid total daily intake

Drug: ANX-042

ANX-042: 0.0065 mcg/kg/min (low sodium diet)

EXPERIMENTAL

0.0065 mcg/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

ANX-042: 0.01 mcg/kg/min (low sodium diet)

EXPERIMENTAL

0.01 mcg/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

ANX-042: 0.01 mcg/kg/min

EXPERIMENTAL

0.01 mcg/kg/min ANX-042 with diet restricted to 4 gm per day Na+ and 3.6 L fluid total daily intake

Drug: ANX-042

ANX-042: 0.03 mcg/kg/min

EXPERIMENTAL

0.03 mcg/kg/min ANX-042 with diet restricted to 4 gm per day Na+ and 3.6 L fluid total daily intake

Drug: ANX-042

ANX-042: 0.1 mcg/kg/min

EXPERIMENTAL

0.1 mcg/kg/min ANX-042 with diet restricted to 4 gm per day Na+ and 3.6 L fluid total daily intake

Drug: ANX-042

ANX-042: 0.3 mcg/kg/min

EXPERIMENTAL

0.3 mcg/kg/min ANX-042 with diet restricted to 4 gm per day Na+ and 3.6 L fluid total daily intake

Drug: ANX-042

Placebo (low sodium diet)

PLACEBO COMPARATOR

Placebo and diet restricted to 2.5 gm per day Na+ and 2.1 L fluid total daily intake

Drug: Placebo

Placebo

PLACEBO COMPARATOR

Placebo and diet restricted to 4 gm per day Na+ and 3.6 L fluid total daily intake

Drug: Placebo

Interventions

ANX-042 DRUG

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)

ANX-042: 0.001 mcg/kg/min; ANX-042: 0.001 mcg/kg/min (with low sodium diet); ANX-042: 0.003 mcg/kg/min; ANX-042: 0.003 mcg/kg/min (low sodium diet); ANX-042: 0.0065 mcg/kg/min (low sodium diet); ANX-042: 0.01 mcg/kg/min; ANX-042: 0.01 mcg/kg/min (low sodium diet); ANX-042: 0.03 mcg/kg/min; ANX-042: 0.1 mcg/kg/min; ANX-042: 0.3 mcg/kg/min

Placebo DRUG

Administered once by 12 hour continuous intravenous infusion with D5W (USP)

Placebo; Placebo (low sodium diet)

Eligibility Criteria

• Age: 19 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 international unit/liter (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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Mayo Clinic: lead
• Anexon, Incorporated: collaborator
• Celerion: collaborator

Study Sites (1)

Celerion

Lincoln, Nebraska, 68502, United States

Location

Study Officials

• Email: Anexon@Choruspharma.com

  Anexon, Incorporated

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: July 9, 2012
• First Posted: July 11, 2012
• Study Start: August 1, 2012
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: October 13, 2017

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)