Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03519867
Recruitment Status : Completed
First Posted : May 9, 2018
Results First Posted : January 31, 2019
Last Update Posted : January 31, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

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).

Condition or disease Intervention/treatment Phase
Neuromuscular Blockade Drug: MK-8616 Drug: Zemuron® Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multi-center, Randomized, Assessor-blinded, Phase II, Parallel Dose-finding Trial in Subjects of ASA Class 1 - 3 to Assess the Efficacy and Safety of 5 Doses of Org 25969 When Administered at 1-2 PTCs After Administration of Zemuron®
Actual Study Start Date : August 1, 2004
Actual Primary Completion Date : May 26, 2005
Actual Study Completion Date : May 26, 2005

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 1) Zemuron® 0.6 mg/kg + MK-8616 0.5 mg/kg
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.
Drug: MK-8616
MK-8616 will be administered at doses of 0.5, 1.0, 2.0, 4.0 and 8.0 mg/kg iv as a 30-second infusion. Doses are based on actual body weight.
Other Name: Org 25969, sugammadex, Bridion®

Drug: Zemuron®
Zemuron® (0.6 or 1.2 mg/kg, iv) will be administered as a 10-second bolus infusion to achieve 1 to 2 PTCs. If needed, a maintenance dose of 0.15 mg/kg will be given. Doses are based on actual body weight.
Other Name: Rocuronium bromide

Experimental: 2) Zemuron® 1.2 mg/kg + MK-8616 0.5 mg/kg
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.
Drug: MK-8616
MK-8616 will be administered at doses of 0.5, 1.0, 2.0, 4.0 and 8.0 mg/kg iv as a 30-second infusion. Doses are based on actual body weight.
Other Name: Org 25969, sugammadex, Bridion®

Drug: Zemuron®
Zemuron® (0.6 or 1.2 mg/kg, iv) will be administered as a 10-second bolus infusion to achieve 1 to 2 PTCs. If needed, a maintenance dose of 0.15 mg/kg will be given. Doses are based on actual body weight.
Other Name: Rocuronium bromide

Experimental: 3) Zemuron® 0.6 mg/kg + MK-8616 1.0 mg/kg
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.
Drug: MK-8616
MK-8616 will be administered at doses of 0.5, 1.0, 2.0, 4.0 and 8.0 mg/kg iv as a 30-second infusion. Doses are based on actual body weight.
Other Name: Org 25969, sugammadex, Bridion®

Drug: Zemuron®
Zemuron® (0.6 or 1.2 mg/kg, iv) will be administered as a 10-second bolus infusion to achieve 1 to 2 PTCs. If needed, a maintenance dose of 0.15 mg/kg will be given. Doses are based on actual body weight.
Other Name: Rocuronium bromide

Experimental: 4) Zemuron® 1.2 mg/kg + MK-8616 1.0 mg/kg
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.
Drug: MK-8616
MK-8616 will be administered at doses of 0.5, 1.0, 2.0, 4.0 and 8.0 mg/kg iv as a 30-second infusion. Doses are based on actual body weight.
Other Name: Org 25969, sugammadex, Bridion®

Drug: Zemuron®
Zemuron® (0.6 or 1.2 mg/kg, iv) will be administered as a 10-second bolus infusion to achieve 1 to 2 PTCs. If needed, a maintenance dose of 0.15 mg/kg will be given. Doses are based on actual body weight.
Other Name: Rocuronium bromide

Experimental: 5) Zemuron® 0.6 mg/kg + MK-8616 2.0 mg/kg
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.
Drug: MK-8616
MK-8616 will be administered at doses of 0.5, 1.0, 2.0, 4.0 and 8.0 mg/kg iv as a 30-second infusion. Doses are based on actual body weight.
Other Name: Org 25969, sugammadex, Bridion®

Drug: Zemuron®
Zemuron® (0.6 or 1.2 mg/kg, iv) will be administered as a 10-second bolus infusion to achieve 1 to 2 PTCs. If needed, a maintenance dose of 0.15 mg/kg will be given. Doses are based on actual body weight.
Other Name: Rocuronium bromide

Experimental: 6) Zemuron® 1.2 mg/kg + MK-8616 2.0 mg/kg
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.
Drug: MK-8616
MK-8616 will be administered at doses of 0.5, 1.0, 2.0, 4.0 and 8.0 mg/kg iv as a 30-second infusion. Doses are based on actual body weight.
Other Name: Org 25969, sugammadex, Bridion®

Drug: Zemuron®
Zemuron® (0.6 or 1.2 mg/kg, iv) will be administered as a 10-second bolus infusion to achieve 1 to 2 PTCs. If needed, a maintenance dose of 0.15 mg/kg will be given. Doses are based on actual body weight.
Other Name: Rocuronium bromide

Experimental: 7) Zemuron® 0.6 mg/kg + MK-8616 4.0 mg/kg
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.
Drug: MK-8616
MK-8616 will be administered at doses of 0.5, 1.0, 2.0, 4.0 and 8.0 mg/kg iv as a 30-second infusion. Doses are based on actual body weight.
Other Name: Org 25969, sugammadex, Bridion®

Drug: Zemuron®
Zemuron® (0.6 or 1.2 mg/kg, iv) will be administered as a 10-second bolus infusion to achieve 1 to 2 PTCs. If needed, a maintenance dose of 0.15 mg/kg will be given. Doses are based on actual body weight.
Other Name: Rocuronium bromide

Experimental: 8) Zemuron® 1.2 mg/kg + MK-8616 4.0 mg/kg
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.
Drug: MK-8616
MK-8616 will be administered at doses of 0.5, 1.0, 2.0, 4.0 and 8.0 mg/kg iv as a 30-second infusion. Doses are based on actual body weight.
Other Name: Org 25969, sugammadex, Bridion®

Drug: Zemuron®
Zemuron® (0.6 or 1.2 mg/kg, iv) will be administered as a 10-second bolus infusion to achieve 1 to 2 PTCs. If needed, a maintenance dose of 0.15 mg/kg will be given. Doses are based on actual body weight.
Other Name: Rocuronium bromide

Experimental: 9) Zemuron® 0.6 mg/kg + MK-8616 8.0 mg/kg
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.
Drug: MK-8616
MK-8616 will be administered at doses of 0.5, 1.0, 2.0, 4.0 and 8.0 mg/kg iv as a 30-second infusion. Doses are based on actual body weight.
Other Name: Org 25969, sugammadex, Bridion®

Drug: Zemuron®
Zemuron® (0.6 or 1.2 mg/kg, iv) will be administered as a 10-second bolus infusion to achieve 1 to 2 PTCs. If needed, a maintenance dose of 0.15 mg/kg will be given. Doses are based on actual body weight.
Other Name: Rocuronium bromide

Experimental: 10) Zemuron® 1.2 mg/kg + MK-8616 8.0 mg/kg
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.
Drug: MK-8616
MK-8616 will be administered at doses of 0.5, 1.0, 2.0, 4.0 and 8.0 mg/kg iv as a 30-second infusion. Doses are based on actual body weight.
Other Name: Org 25969, sugammadex, Bridion®

Drug: Zemuron®
Zemuron® (0.6 or 1.2 mg/kg, iv) will be administered as a 10-second bolus infusion to achieve 1 to 2 PTCs. If needed, a maintenance dose of 0.15 mg/kg will be given. Doses are based on actual body weight.
Other Name: Rocuronium bromide




Primary Outcome Measures :
  1. Time From Start of Administration of MK-8616 to Recovery T4/T1 Ratio to 0.9 [ Time Frame: 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 :
  1. Percentage of Participants Experiencing ≥1 Adverse Events (AEs) [ Time Frame: 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03519867


Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Layout table for investigator information
Study Director: Medical Director Merck Sharp & Dohme Corp.

Layout table for additonal information
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT03519867     History of Changes
Other Study ID Numbers: P06387
MK-8616-042 ( Other Identifier: Merck Protocol Number )
19.4.204 ( Other Identifier: Organon Protocol Number )
First Posted: May 9, 2018    Key Record Dates
Results First Posted: January 31, 2019
Last Update Posted: January 31, 2019
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

Additional relevant MeSH terms:
Layout table for MeSH terms
Rocuronium
Neuromuscular Nondepolarizing Agents
Neuromuscular Blocking Agents
Neuromuscular Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs