Efficacy and Safety of Org 25969 Administered After Zemuron® (MK-8616-042)

Phase 2

Completed

• Conditions: Neuromuscular Blockade
• Interventions: Drug: MK-8616; Drug: Zemuron®

• Registration Number: NCT03519867
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

The primary objective of this study is to explore the dose-response relation of MK-8616 (Org 25969) given as a reversal agent of Zemuron® at 1 to 2 post tetanic counts (PTCs); both Zemuron® and MK-8616 are administered by intravenous (iv) infusion. Another goal of the study is to evaluate the safety of single doses of MK-8616 administered to participants of American Society of Anesthesiologists (ASA) Physical Status Class 1 (otherwise normal, healthy participant); Class 2 (participant with a mild systemic disease); or Class 3 (participant with a severe systemic disease that limits activity, but is not incapacitating).

Detailed Description

Not available

Study Timeline

• Study Start: 2004-08-01
• Primary Completion: 2005-05-26
• Study Completion: 2005-05-26
• Study First Submitted: 2018-05-08
• Study First Submitted QC: 2018-05-08
• Study First Posted: 2018-05-09
• Status Verified: 2018-08
• Results First Submitted: 2018-08-30
• Results First Submitted QC: 2018-08-30
• Last Update Submitted: 2018-08-30
• Results First Posted: 2019-01-31
• Last Update Posted: 2019-01-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

• Has an ASA Class of 1 to 3
• Is scheduled for surgical procedures (excluding dental and neck surgeries) with an anticipated duration of anesthesia of ≥45 minutes with the use of Zemuron®

Exclusion Criteria

• Is undergoing dental or neck surgery
• Has anatomical malformation that would impede intubation
• Has or is suspected to have neuromuscular disorders impairing neuromuscular block and/or significant renal 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 medications used during general anesthesia
• Is pregnant
• Is a female of childbearing potential not using 1 of the following methods of birth control: condom or diaphragm with spermicide, vasectomized partner (<6 months), intrauterine device (IUD), or abstinence
• Is breast-feeding
• Has already participated in the study
• Has participated in another clinical trial, not pre-approved by Organon Pharmaceuticals USA within 30 days of entering this study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
6) Zemuron® 1.2 mg/kg + MK-8616 2.0 mg/kg	Zemuron®	Participants (ASA Class 1 to 3) will receive an iv bolus of Zemuron® 1.2 mg/kg followed by MK-8616 2.0 mg/kg iv during a single study session. MK-8616 will be administered once Zemuron®-induced NMB reaches 1 to 2 PTCs.
7) Zemuron® 0.6 mg/kg + MK-8616 4.0 mg/kg	Zemuron®	Participants (ASA Class 1 to 3) will receive an iv bolus of Zemuron® 0.6 mg/kg followed by MK-8616 4.0 mg/kg iv during a single study session. MK-8616 will be administered once Zemuron®-induced NMB reaches 1 to 2 PTCs.
2) Zemuron® 1.2 mg/kg + MK-8616 0.5 mg/kg	Zemuron®	Participants (ASA Class 1 to 3) will receive an iv bolus of Zemuron® 1.2 mg/kg followed by MK-8616 0.5 mg/kg iv during a single study session. MK-8616 will be administered once Zemuron®-induced NMB reaches 1 to 2 PTCs.
1) Zemuron® 0.6 mg/kg + MK-8616 0.5 mg/kg	Zemuron®	Participants (ASA Class 1 to 3) will receive an iv bolus of Zemuron® 0.6 mg/kg followed by MK-8616 0.5 mg/kg iv during a single study session. MK-8616 will be administered once Zemuron®-induced neuromuscular blockade (NMB) reaches 1 to 2 PTCs.
4) Zemuron® 1.2 mg/kg + MK-8616 1.0 mg/kg	Zemuron®	Participants (ASA Class 1 to 3) will receive an iv bolus of Zemuron® 1.2 mg/kg followed by MK-8616 1.0 mg/kg iv during a single study session. MK-8616 will be administered once Zemuron®-induced NMB reaches 1 to 2 PTCs.
8) Zemuron® 1.2 mg/kg + MK-8616 4.0 mg/kg	Zemuron®	Participants (ASA Class 1 to 3) will receive an iv bolus of Zemuron® 1.2 mg/kg followed by MK-8616 4.0 mg/kg iv during a single study session. MK-8616 will be administered once Zemuron®-induced NMB reaches 1 to 2 PTCs.
1) Zemuron® 0.6 mg/kg + MK-8616 0.5 mg/kg	MK-8616	Participants (ASA Class 1 to 3) will receive an iv bolus of Zemuron® 0.6 mg/kg followed by MK-8616 0.5 mg/kg iv during a single study session. MK-8616 will be administered once Zemuron®-induced neuromuscular blockade (NMB) reaches 1 to 2 PTCs.
7) Zemuron® 0.6 mg/kg + MK-8616 4.0 mg/kg	MK-8616	Participants (ASA Class 1 to 3) will receive an iv bolus of Zemuron® 0.6 mg/kg followed by MK-8616 4.0 mg/kg iv during a single study session. MK-8616 will be administered once Zemuron®-induced NMB reaches 1 to 2 PTCs.
9) Zemuron® 0.6 mg/kg + MK-8616 8.0 mg/kg	Zemuron®	Participants (ASA Class 1 to 3) will receive an iv bolus of Zemuron® 0.6 mg/kg followed by MK-8616 8.0 mg/kg iv during a single study session. MK-8616 will be administered once Zemuron®-induced NMB reaches 1 to 2 PTCs.
2) Zemuron® 1.2 mg/kg + MK-8616 0.5 mg/kg	MK-8616	Participants (ASA Class 1 to 3) will receive an iv bolus of Zemuron® 1.2 mg/kg followed by MK-8616 0.5 mg/kg iv during a single study session. MK-8616 will be administered once Zemuron®-induced NMB reaches 1 to 2 PTCs.
5) Zemuron® 0.6 mg/kg + MK-8616 2.0 mg/kg	MK-8616	Participants (ASA Class 1 to 3) will receive an iv bolus of Zemuron® 0.6 mg/kg followed by MK-8616 2.0 mg/kg iv during a single study session. MK-8616 will be administered once Zemuron®-induced NMB reaches 1 to 2 PTCs.
4) Zemuron® 1.2 mg/kg + MK-8616 1.0 mg/kg	MK-8616	Participants (ASA Class 1 to 3) will receive an iv bolus of Zemuron® 1.2 mg/kg followed by MK-8616 1.0 mg/kg iv during a single study session. MK-8616 will be administered once Zemuron®-induced NMB reaches 1 to 2 PTCs.
3) Zemuron® 0.6 mg/kg + MK-8616 1.0 mg/kg	MK-8616	Participants (ASA Class 1 to 3) will receive an iv bolus of Zemuron® 0.6 mg/kg followed by MK-8616 1.0 mg/kg iv during a single study session. MK-8616 will be administered once Zemuron®-induced NMB reaches 1 to 2 PTCs.
3) Zemuron® 0.6 mg/kg + MK-8616 1.0 mg/kg	Zemuron®	Participants (ASA Class 1 to 3) will receive an iv bolus of Zemuron® 0.6 mg/kg followed by MK-8616 1.0 mg/kg iv during a single study session. MK-8616 will be administered once Zemuron®-induced NMB reaches 1 to 2 PTCs.
5) Zemuron® 0.6 mg/kg + MK-8616 2.0 mg/kg	Zemuron®	Participants (ASA Class 1 to 3) will receive an iv bolus of Zemuron® 0.6 mg/kg followed by MK-8616 2.0 mg/kg iv during a single study session. MK-8616 will be administered once Zemuron®-induced NMB reaches 1 to 2 PTCs.
8) Zemuron® 1.2 mg/kg + MK-8616 4.0 mg/kg	MK-8616	Participants (ASA Class 1 to 3) will receive an iv bolus of Zemuron® 1.2 mg/kg followed by MK-8616 4.0 mg/kg iv during a single study session. MK-8616 will be administered once Zemuron®-induced NMB reaches 1 to 2 PTCs.
6) Zemuron® 1.2 mg/kg + MK-8616 2.0 mg/kg	MK-8616	Participants (ASA Class 1 to 3) will receive an iv bolus of Zemuron® 1.2 mg/kg followed by MK-8616 2.0 mg/kg iv during a single study session. MK-8616 will be administered once Zemuron®-induced NMB reaches 1 to 2 PTCs.
10) Zemuron® 1.2 mg/kg + MK-8616 8.0 mg/kg	MK-8616	Participants (ASA Class 1 to 3) will receive an iv bolus of Zemuron® 1.2 mg/kg followed by MK-8616 8.0 mg/kg iv during a single study session. MK-8616 will be administered once Zemuron®-induced NMB reaches 1 to 2 PTCs.
10) Zemuron® 1.2 mg/kg + MK-8616 8.0 mg/kg	Zemuron®	Participants (ASA Class 1 to 3) will receive an iv bolus of Zemuron® 1.2 mg/kg followed by MK-8616 8.0 mg/kg iv during a single study session. MK-8616 will be administered once Zemuron®-induced NMB reaches 1 to 2 PTCs.
9) Zemuron® 0.6 mg/kg + MK-8616 8.0 mg/kg	MK-8616	Participants (ASA Class 1 to 3) will receive an iv bolus of Zemuron® 0.6 mg/kg followed by MK-8616 8.0 mg/kg iv during a single study session. MK-8616 will be administered once Zemuron®-induced NMB reaches 1 to 2 PTCs.

Primary Outcome Measures

Name	Time	Method
Time From Start of Administration of MK-8616 to Recovery T4/T1 Ratio to 0.9	Up to 90 minutes	The mean time from the start of MK-8616 administration to recovery T4/T1 ratio of 0.9 was determined. Less time indicates faster recovery from NMB. The ratio of T4 (fourth twitch; amplitude of fourth response to train of four \[TOF\] stimulation is expressed as percent of control T4) over T1 (first twitch; amplitude of first response to TOF stimulation is expressed as percent of control T1) ranges from 0 (complete loss of T4 twitch response) to 1.0 (complete recovery of T4 twitch response). For TOF stimulation, 4 consecutive square wave supra-maximal stimuli of 0.2 msec duration were delivered at 2 Hz every 15 seconds. Neuromuscular monitoring was performed with the TOF-Watch® SX.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Experiencing ≥1 Adverse Events (AEs)	Up to 7 days following MK-8616 administration	The percentage of participants experiencing ≥1 AEs was determined. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment.