Dose-Finding Trial With Sugammadex at 3 and 15 Minutes After 1.0 and 1.2 mg/kg Rocuronium Bromide in Subjects of ASA Class 1-3 (19.4.206)(P05944)

Condition(s) targeted: Anesthesia, General

Intervention: sugammadex (Org 25969) (Drug); Placebo (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: Merck Sharp & Dohme Corp.

The objective of the trial was to explore the dose-response relation of Org 25969 given as a reversal agent at 3 and 15 minutes following administration of 1. 0 and 1. 2 mg/kg of Esmeron® (rocuronium) in subjects of ASA 1 to 3, and to evaluate the safety of single doses of Org 25969 administered to subjects of ASA 1 to 3.

Official title: A Multi-Center, Randomized, Safety Assessor-Blinded, Placebo- Controlled, Phase II, Parallel Dose-Finding Trial in Subjects of ASA 1-3 to Assess the Efficacy and Safety of 5 Doses of Sugammadex Administered at 3 and 15 Minutes After Administration of 1.0 and 1.2 mg/kg Rocuronium Bromide

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Time from start of administration of Org 25969 / placebo to recovery of the T4/T1 ratio to 0.9

Secondary outcome: Time from start of administration of Org 25969 / placebo to recovery of the T4/T1 ratio to 0.7; Time from start of administration of Org 25969 / placebo to recovery of the T4/T1 ratio to 0.8.

Detailed description: In the US the highest dose recommended in the package insert of Zemuron® (i. e. the trade name for Esmeron® in the US) is 1. 2 mg/kg whereas in Europe it is 1. 0 mg/kg. For both doses, dose recommendations for reversal with Org 25969 were to be found. Hence, the present trial was set up to explore the dose-response relation of Org 25969 given as a reversal agent at 3 and 15 minutes following administration of 1. 0 and 1. 2 mg/kg of Esmeron® in subjects of ASA 1 to 3. The sub-investigator who performed any subjective safety assessments after anesthesia was to be remained blinded.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Subjects of ASA class 1 - 3, above or equal to the age of 18 years;

- Subjects scheduled for surgical procedures with an anticipated duration of anesthesia

of at least 120 minutes, without further need for muscle relaxation other than for intubation;

- Subjects scheduled for surgical procedures in supine position;

- Subjects who had given written informed consent.

Exclusion Criteria:

- Subjects in whom a difficult intubation because of anatomical malformations was

expected;

- Subjects known or suspected to have neuromuscular disorders impairing neuromuscular

blocking and/or significant renal dysfunction;

- Subjects known or suspected to have a (family) history of malignant hyperthermia;

- Subjects known or suspected to have an allergy to narcotics, muscle relaxants or

other medication used during general anesthesia;

- Subjects receiving medication known to interfere with neuromuscular blocking agents,

such as anticonvulsants and Mg2+;

- Subjects who had already participated in CT 19. 4.206;

- Subjects who had participated in another clinical trial, not pre-approved by NV

Organon, within 30 days of entering into CT 19. 4.206;

- Female subjects who were pregnant: in females pregnancy was to be excluded both from

medical history and by an hCG test within 24 hours before surgery except in females who were not of childbearing potential, i. e. at least 2 years menopausal or who had undergone tubal ligation or an hysterectomy;

- Female subjects of childbearing potential not using any of the following methods of

birth control (for one month): condom or diaphragm with spermicide, vasectomized partner (>6 months), IUD, abstinence;

- Female subjects who were breast-feeding.

Starting date: March 2004
Last updated: January 5, 2015