A Bridging Trial Comparing Sugammadex (Org 25969) at Reappearance of T2 in Japanese and Caucasian Participants. Part B: Caucasian Participants (P05971)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 2

Conditions: Anesthesia, General

Treatments: Drug: Placebo; Drug: Vecuronium; Drug: Sugammadex; Drug: Rocuronium

Study type: Interventional

Funder types: Industry

Identifiers

NCT00552617

P05971

19.4.208B (Other Identifier)

2005-001133-15 (EudraCT Number)

MK-8616-035 (Other Identifier)

Details and patient eligibility

About

The objective of the trial was to establish the dose-response relation of sugammadex (Org 25969) given as a reversal agent of rocuronium or vecuronium at reappearance of T2 (the amplitude of the first response of second twitch to train of four (TOF) stimulation, expressed as percentage of control first twitch, T1) during sevoflurane anesthesia for Caucasian participants.

Full description

For most surgical procedures a depth of neuromuscular block of 1-2 twitches after TOF-stimulation is sufficient to avoid unwanted muscular activity. At reappearance of T2, the anesthesiologist might decide to either give (another) maintenance dose of rocuronium or vecuronium when surgery continues, to await spontaneous recovery of neuromuscular block or to reverse the neuromuscular block. Sugammadex has been shown in previous trials to greatly reduce the time to full recovery when administered at reappearance of T2, both after rocuronium- and vecuronium induced neuromuscular blockade. The current trial P05971 was conducted in Europe and set up to establish the dose response relationship of sugammadex given during sevoflurane anesthesia at reappearance of T2 after rocuronium or vecuronium in Caucasian participants. In addition to recovery time, also pharmacokinetics and safety of sugammadex were to be evaluated.

Enrollment: 100 patients

Sex: All

Ages: 20 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Is of American Society of Anesthesiologists (ASA) class 1 - 3;
• Is at least 20 years but under 65 years of age;
• Caucasian participants;
• Is scheduled for elective surgery requiring muscle relaxation in supine position and under sevoflurane anesthesia with an anticipated duration of about 1.5-3 hours;
• Has given written informed consent.

Exclusion criteria

• Participants in whom a difficult intubation because of anatomical malformations was expected;
• Is known or suspected to have neuromuscular disorders impairing neuromuscular blocking (NMB) and/or significant renal dysfunction (for example a creatinine level > 1.6 mg/dl) and/or severe hepatic dysfunction.
• Is known or suspected to have a (family) history of malignant hyperthermia;
• Is known or suspected to have an allergy to narcotics, muscle relaxants or other medication used during general anesthesia;
• Is receiving medication expected to interfere with the rocuronium or vecuronium given in this trial, based on the dose and time of administration;
• Females who were pregnant;
• Females of childbearing potential not using birth control or using only oral contraception as birth control;
• Was breast-feeding;
• Has already participated in P05971, or in another trial with sugammadex;
• Has participated in another clinical trial, not preapproved by the Sponsor, within 6 months of entering into P05971.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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100 participants in 10 patient groups, including a placebo group

Rocuronium + Placebo

Placebo Comparator group

Description:

After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered intravenously (IV), followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of placebo was administered IV.

Treatment:

Drug: Rocuronium

Drug: Placebo

Rocuronium + 0.5 mg/kg Sugammadex

Experimental group

Description:

After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of 0.5 mg/kg sugammadex was administered IV.

Treatment:

Drug: Rocuronium

Drug: Sugammadex

Rocuronium + 1.0 mg/kg Sugammadex

Experimental group

Description:

After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of 1.0 mg/kg sugammadex was administered IV.

Treatment:

Drug: Rocuronium

Drug: Sugammadex

Rocuronium + 2.0 mg/kg Sugammadex

Experimental group

Description:

After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of 2.0 mg/kg sugammadex was administered IV.

Treatment:

Drug: Rocuronium

Drug: Sugammadex

Rocuronium + 4.0 mg/kg Sugammadex

Experimental group

Description:

After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of 4.0 mg/kg sugammadex was administered IV.

Treatment:

Drug: Rocuronium

Drug: Sugammadex

Vecuronium + Placebo

Placebo Comparator group

Description:

After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of placebo was administered IV.

Treatment:

Drug: Placebo

Drug: Vecuronium

Vecuronium + 0.5 mg/kg Sugammadex

Experimental group

Description:

After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of 0.5 mg/kg sugammadex was administered IV.

Treatment:

Drug: Sugammadex

Drug: Vecuronium

Vecuronium + 1.0 mg/kg Sugammadex

Experimental group

Description:

After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of 1.0 mg/kg sugammadex was administered IV.

Treatment:

Drug: Sugammadex

Drug: Vecuronium

Vecuronium + 2.0 mg/kg Sugammadex

Experimental group

Description:

After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of 2.0 mg/kg sugammadex was administered IV.

Treatment:

Drug: Sugammadex

Drug: Vecuronium

Vecuronium + 4.0 mg/kg Sugammadex

Experimental group

Description:

After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.03 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of 4.0 mg/kg sugammadex was administered IV.

Treatment:

Drug: Sugammadex

Drug: Vecuronium