Safety Study of Long-Acting Local Anesthetic

NCT01786655 | Completed Phase 1 DMC

• 1 other identifier: IRB-P00003344
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Safety of Neosaxitoxin in Healthy Volunteers

Keywords

local anesthetic; neosaxitoxin; neoSTX; bupivacaine; safety; phase 1; pharmacokinetic

Outcome Measures

Primary Outcomes (1)

• Presence or absence of Adverse Events as a function of NeoSTX dose

  Within 14 days of injection

Secondary Outcomes (3)

• Pharmacokinetic parameters characterizing uptake and distribution of NeoSTX (content in serum and urine samples)

  Within 24 hours of injection

• Cutaneous sensory blockade (numbness)

  Within 14 days of injection

• Local skin reactions (edema, paresthesias and urticaria)

  Within 14 days of injection

Study Arms (4)

Neosaxitoxin in saline

EXPERIMENTAL

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

Neosaxitoxin + bupivacaine 0.2%

EXPERIMENTAL

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%

Neosaxitoxin + bupivacaine 0.2% + epinephrine 5mcg/ml

EXPERIMENTAL

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

Saline placebo

PLACEBO COMPARATOR

Subjects receive one injection of saline on the back of one calf (test side).

Other: Saline placebo

Interventions

Neosaxitoxin in saline DRUG

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.

Neosaxitoxin in saline

NeoSTX + bupivacaine 0.2% DRUG

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.

Neosaxitoxin + bupivacaine 0.2%

NeoSTX + bupivacaine 0.2% + epinephrine 5mcg/ml DRUG

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.

Neosaxitoxin + bupivacaine 0.2% + epinephrine 5mcg/ml

Saline placebo OTHER

Each subject receives one injection with bupivacaine 0.2% alone on one side. On the other side they receive saline placebo.

Saline placebo

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy adult males ages 18-35
• ASA physical status 1 or 2
• English or Spanish speakers
• 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
• Must be able to provide informed consent
• Must be able to understand and perform all the procedures of the study including self-reporting of symptom scores

You may not qualify if:

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

Sponsors & Collaborators

• Charles Berde: lead

Study Sites (1)

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Interventions

neosaxitoxin; Sodium Chloride; Bupivacaine; Epinephrine

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Ethanolamines; Amino Alcohols; Alcohols; Biogenic Monoamines; Biogenic Amines; Catecholamines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Joseph Cravero, MD

  Boston Children's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief, Division of Pain Medicine (Department of Anesthesiology, Perioperative, and Pain Medicine)

Study Record Dates

• First Submitted: February 6, 2013
• First Posted: February 8, 2013
• Study Start: May 1, 2013
• Primary Completion: March 1, 2014
• Study Completion: April 1, 2014
• Last Updated: February 17, 2016

Record last verified: 2016-02

Locations

US (1)