A Bridging Trial Comparing Sugammadex (Org 25969) at Reappearance of T2 in Japanese and Caucasian Participants. Part A: Japanese Participants (P05956)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 2

Conditions: Anesthesia, General

Treatments: Drug: Placebo; Drug: sugammadex

Study type: Interventional

Funder types: Industry

Identifiers

NCT00591409

19.4.208A (Other Identifier)

MK-8616-030 (Other Identifier)

P05956

Details and patient eligibility

About

The objective of this trial was to establish the dose-response 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) in Japanese and Caucasian participants. Part A: Japanese 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 (Org 25969) 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 P05956 was conducted in Japan and set up to establish the dose-response relationship of sugammadex given during sevoflurane anesthesia at reappearance of T2 after rocuronium or vecuronium in Japanese participants. In addition to recovery time, also pharmacokinetics and safety of sugammadex were 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;
• Japanese participants;
• Is scheduled for elective surgery in supine position and under sevoflurane anesthesia, in need of administration of neuromuscular blocking agents (NMBAs), 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 the effect of NMBAs 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 not using birth control or using only oral contraception as birth control continuously;
• Were breast-feeding;
• Has already participated in P05956, or in another trial with sugammadex;
• Has participated in another clinical trial within 6 months of entering into P05956

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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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: 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: 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: 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: 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: 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 0.02-0.04 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of placebo was administered IV.

Treatment:

Drug: Placebo

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 0.02-0.04 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

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 0.02-0.04 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

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 0.02-0.04 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

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 0.02-0.04 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