The purpose of this study is to test the safety and efficacy of an investigational neuromuscular blocking agent called CW002 and to document its effects on healthy adult volunteers. A neuromuscular blocking agent is a drug that temporarily prevents muscles from moving. CW002 has not yet been approved by the Food and Drug Administration (FDA). Usually, neuromuscular blocking agents are used together with other drugs that put people completely "asleep". These drugs allow doctors to place a breathing tube in the airway, stop muscles from moving during surgical operations, and allow ventilation (movement of air). This research is being done because CW002 is expected to act quickly and to provide a muscle block of intermediate (not too long, not too short) duration. The researchers would like to test increasing doses of CW002 that can be given without causing severe side effects. If shown to be both safe and effective, such a compound would be useful in surgical procedures and could improve future anesthetic care.
Neuromuscular blocking agents are especially important in intubation (insertion of breathing tube into the windpipe) because a quick and effective muscle block is needed to promptly complete the process and secure the airway. In addition, being able to rapidly reverse a blocking agent is desirable so that the patient can breathe on his/her own as soon as possible.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Masking
NONE
Enrollment
136
For Cohort 1, subjects receive a single bolus of 0.02 mg/kg CW 002 (i.v.) and neuromuscular function will be allowed to recover spontaneously for at least 5 half-lives. For Cohort 2, an estimated ED50 bolus dose of CW 002 (approximately 0.03 mg/kg) will be given i.v. followed by a second bolus of the same dosage\*. For Cohort 3, an estimated ED 75 bolus dose of CW 002 (approximately 0.04 mg/kg) will be given i.v. followed by a second bolus of the same dosage \*. For Cohort IV, an estimated ED 90 bolus dose of CW 002 (approximately 0.06 mg/kg) will be given i.v. followed by a second bolus of the same dosage\*. \*For Cohorts 2-4, a second bolus dose will be administered following a minimum of 5 half-lives of CW002 (based on PK data from Cohort 1).
Subjects receive an initial ascending bolus dose of CW 002 injection, and a second bolus followed by a continuous infusion initiated at the point of 25% recovery of twitch response. Infusion rate will be adjusted to maintain 97%- 99% suppression of twitch, but to avoid complete neuromuscular block. For the first 3 subjects of each cohort, CW 002 will be allowed to recover spontaneously. For the second 3 subjects, reversal will be performed at the appearance of 1st twitch using 0.05 mg/kg neostigmine and 0.01 mg/kg glycopyrrolate. Cohort 5- subject receives 2.0x ED95 dose of CW 002, followed by 1.5x ED95 dose and 30 min infusion of 2-10 mcg/kg/min of CW 002 Cohort 6 - subject receives 3.0x ED95 dose of CW 002, followed by 1.5x ED95 dose and 60 min infusion of 2-10 mcg/kg/min of CW 002 Cohort 7 - subject receives 4.0x ED95 dose of CW 002, followed by 1.5x ED95 dose and 90 min infusion of 2-10 mcg/kg/min of CW 002 Bolus doses of ED95 are determined in Part I of the study.
In Part III, safety, intubation efficacy, and PK will be evaluated in 2 cohorts (Cohorts 8 and 9) of 6 subjects each, who will undergo endotracheal intubation at 60 or 90 seconds after a bolus dose of CW002 injection at 3 to 4 times the ED95. For the first 3 subjects of each cohort, CW 002 will be allowed to recover spontaneously. For the second 3 subjects, reversal will be performed at the appearance of 1st twitch using 0.05 mg/kg neostigmine and 0.01 mg/kg glycopyrrolate. Cohort 8 - subject receives 3.0x ED95 dose of CW 002, and intubation attempt is made 90 seconds post-bolus. Cohort 9 - subject receives 4.0x ED95 dose of CW 002, and intubation attempt is made 60 seconds post-bolus.
Weill Cornell Medical College
New York, New York, United States
To evaluate the safety of the use of CW002 in healthy human volunteers by monitoring changes in ECG, heart rate (HR), mean arterial pressure, plasma histamine levels, clinical laboratory values, and noting the occurrence of adverse events.
Time frame: 4 weeks
To estimate the ED95 (dose required to produce 95% suppression of neuromuscular activity
Neuromuscular activity is measured by the mechanomyographic response of the adductor pollicis (a muscle in the hand that functions to move the thumb muscle) to indirect stimulation.
Time frame: 24 hours
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