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Safety Study of Long-Acting Local Anesthetic

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Charles Berde, Children's Hospital, Boston
ClinicalTrials.gov Identifier:
NCT01786655
First received: February 6, 2013
Last updated: February 16, 2016
Last verified: February 2016
  Purpose

The primary aim of this Phase 1 study is to evaluate the systemic safety of a novel prolonged-duration local anesthetic, Neosaxitoxin (NeoSTX), given by subcutaneous injection in combination with the commonly used local anesthetic, bupivacaine, and epinephrine.

The investigators hypothesize that a "minimal adverse effect threshold" NeoSTX dose for subcutaneous administration in combination with bupivacaine 0.2% and epinephrine 5mcg/ml respectively, can be defined for awake, young adult healthy volunteer subjects. At the same time, the pharmacokinetics of NeoSTX when delivered subcutaneously will be determined.


Condition Intervention Phase
Safety of Neosaxitoxin in Healthy Volunteers
Drug: Neosaxitoxin in saline
Drug: NeoSTX + bupivacaine 0.2%
Drug: NeoSTX + bupivacaine 0.2% + epinephrine 5mcg/ml
Other: Saline 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)
Official Title: Neosaxitoxin (NeoSTX) Alone and in Combination With Bupivacaine as Prolonged Duration Local Anesthetics: A Phase I Investigator-initiated Dose Escalation Study

Resource links provided by NLM:


Further study details as provided by Boston Children’s Hospital:

Primary Outcome Measures:
  • Presence or absence of Adverse Events as a function of NeoSTX dose [ Time Frame: Within 14 days of injection ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacokinetic parameters characterizing uptake and distribution of NeoSTX (content in serum and urine samples) [ Time Frame: Within 24 hours of injection ] [ Designated as safety issue: Yes ]
  • Cutaneous sensory blockade (numbness) [ Time Frame: Within 14 days of injection ] [ Designated as safety issue: Yes ]
    measured by noninvasive quantitative sensory testing (QST)

  • Local skin reactions (edema, paresthesias and urticaria) [ Time Frame: Within 14 days of injection ] [ Designated as safety issue: Yes ]

Enrollment: 105
Study Start Date: May 2013
Study Completion Date: April 2014
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Neosaxitoxin in saline
Subjects receive only one injection of NeoSTX in saline on the back of one calf (test side). Subjects receive NeoSTX in saline in subsequent dose escalation levels: 5mcg, 10mcg, 15mcg, 20mcg, 30mcg, and 40mcg NeoSTX.
Drug: Neosaxitoxin in saline
NeoSTX will be administered in sequential dose cohorts. Each subject receives one injection with bupivacaine 0.2% alone on one side (control). On the other side they receive NeoSTX in saline (test). Subjects receive NeoSTX in saline in subsequent dose escalation levels: 5 mcg, 10 mcg, 15 mcg, 20 mcg, 30 mcg, and 40 mcg of NeoSTX.
Experimental: Neosaxitoxin + bupivacaine 0.2%
Subjects receive only one injection of NeoSTX in combination with 0.2% bupivacaine on the back of one calf (test side). Subjects receive NeoSTX in bupivacaine in subsequent dose escalation levels: 5 mcg, 10 mcg, 15 mcg, 20 mcg, 30 mcg, and 40 mcg NeoSTX.
Drug: NeoSTX + bupivacaine 0.2%
NeoSTX will be administered in sequential dose cohorts. Each subject receives one injection with bupivacaine 0.2% on one side (control). On the other side they receive NeoSTX with 0.2% bupivacaine. Subjects receive NeoSTX in 0.2% bupivacaine in subsequent dose escalation levels: 5 mcg, 10 mcg, 15 mcg, 20 mcg, 30 mcg, and 40 mcg of NeoSTX.
Experimental: Neosaxitoxin + bupivacaine 0.2% + epinephrine 5mcg/ml
Subjects receive one injection of NeoSTX in bupivacaine 0.2% with epinephrine 5 mcg/ml on the back of one calf (test side). Subjects receive NeoSTX in bupivacaine 0.2% with epinephrine 5 mcg/ml in doses of 10 mcg or 30 mcg of NeoSTX.
Drug: NeoSTX + bupivacaine 0.2% + epinephrine 5mcg/ml
Each subject receives one injection with bupivacaine 0.2% on one side (control). On the other side they receive NeoSTX in 0.2% bupivacaine with epinephrine 5 mcg/ml. Subjects receive NeoSTX in 0.2% bupivacaine with epinephrine 5 mcg/ml in doses of 10 mcg or 30 mcg of NeoSTX.
Placebo Comparator: Saline placebo
Subjects receive one injection of saline on the back of one calf (test side).
Other: Saline placebo
Each subject receives one injection with bupivacaine 0.2% alone on one side. On the other side they receive saline placebo.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 35 Years   (Adult)
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Healthy adult males ages 18-35
  2. ASA physical status 1 or 2
  3. English or Spanish speakers
  4. Must be able to come to Boston Children's Hospital for a 24-hour stay and able and willing to attend 5-10 study visits
  5. Must be able to provide informed consent
  6. Must be able to understand and perform all the procedures of the study including self-reporting of symptom scores

Exclusion Criteria:

  1. ASA physical status 3 or greater
  2. Cognitively challenged or other inability to understand the self-report measures or to give informed consent
  3. Significant cardiovascular, respiratory, neuromuscular disease or other systemic illness(es)
  4. No known or suspected allergies to neosaxitoxin, bupivacaine, or other local anesthetics
  5. Subjects may not be on any pain controlling medications, or any medications that would alter pain tolerance
  6. Subjects may not be on any medication that would alter cognition
  7. Subjects may not have any acute or chronic pain conditions requiring ongoing treatment or limiting daily activities
  8. No alcohol or illicit drug abuse
  9. No current smokers
  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: NCT01786655

Locations
United States, Massachusetts
Boston Children's Hospital
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Charles Berde
Investigators
Principal Investigator: Joseph Cravero, MD Boston Children’s Hospital
  More Information

Responsible Party: Charles Berde, Chief, Division of Pain Medicine (Department of Anesthesiology, Perioperative, and Pain Medicine), Children's Hospital, Boston
ClinicalTrials.gov Identifier: NCT01786655     History of Changes
Other Study ID Numbers: IRB-P00003344 
Study First Received: February 6, 2013
Last Updated: February 16, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Boston Children’s Hospital:
local anesthetic
neosaxitoxin
neoSTX
bupivacaine
safety
phase 1
pharmacokinetic

Additional relevant MeSH terms:
Bupivacaine
Anesthetics, Local
Anesthetics
Epinephrine
Racepinephrine
Epinephryl borate
Neosaxitoxin
Central Nervous System Depressants
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Adrenergic beta-Agonists
Bronchodilator Agents
Autonomic Agents
Anti-Asthmatic Agents
Respiratory System Agents
Mydriatics
Sympathomimetics
Vasoconstrictor Agents
Neuromuscular Blocking Agents
Neuromuscular Agents

ClinicalTrials.gov processed this record on December 06, 2016