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

NCT03519867 | Completed Phase 2 Results

• 3 other identifiers: P06387MK-8616-04219.4.204
• Study Type: interventional
• Target: 50
• Locations: 0 countries
• Sites: N/A

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).

Conditions

Neuromuscular Blockade

Outcome Measures

Primary Outcomes (1)

• Time From Start of Administration of MK-8616 to Recovery T4/T1 Ratio to 0.9

  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.

  Up to 90 minutes

Secondary Outcomes (1)

• Percentage of Participants Experiencing ≥1 Adverse Events (AEs)

  Up to 7 days following MK-8616 administration

Study Arms (10)

1) Zemuron® 0.6 mg/kg + MK-8616 0.5 mg/kg

EXPERIMENTAL

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; Drug: Zemuron®

2) Zemuron® 1.2 mg/kg + MK-8616 0.5 mg/kg

EXPERIMENTAL

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; Drug: Zemuron®

3) Zemuron® 0.6 mg/kg + MK-8616 1.0 mg/kg

EXPERIMENTAL

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; Drug: Zemuron®

4) Zemuron® 1.2 mg/kg + MK-8616 1.0 mg/kg

EXPERIMENTAL

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; Drug: Zemuron®

5) Zemuron® 0.6 mg/kg + MK-8616 2.0 mg/kg

EXPERIMENTAL

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; Drug: Zemuron®

6) Zemuron® 1.2 mg/kg + MK-8616 2.0 mg/kg

EXPERIMENTAL

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; Drug: Zemuron®

7) Zemuron® 0.6 mg/kg + MK-8616 4.0 mg/kg

EXPERIMENTAL

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; Drug: Zemuron®

8) Zemuron® 1.2 mg/kg + MK-8616 4.0 mg/kg

EXPERIMENTAL

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; Drug: Zemuron®

9) Zemuron® 0.6 mg/kg + MK-8616 8.0 mg/kg

EXPERIMENTAL

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; Drug: Zemuron®

10) Zemuron® 1.2 mg/kg + MK-8616 8.0 mg/kg

EXPERIMENTAL

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; Drug: Zemuron®

Interventions

MK-8616 DRUG

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.

Also known as: Org 25969, sugammadex, Bridion®

1) Zemuron® 0.6 mg/kg + MK-8616 0.5 mg/kg; 10) Zemuron® 1.2 mg/kg + MK-8616 8.0 mg/kg; 2) Zemuron® 1.2 mg/kg + MK-8616 0.5 mg/kg; 3) Zemuron® 0.6 mg/kg + MK-8616 1.0 mg/kg; 4) Zemuron® 1.2 mg/kg + MK-8616 1.0 mg/kg; 5) Zemuron® 0.6 mg/kg + MK-8616 2.0 mg/kg; 6) Zemuron® 1.2 mg/kg + MK-8616 2.0 mg/kg; 7) Zemuron® 0.6 mg/kg + MK-8616 4.0 mg/kg; 8) Zemuron® 1.2 mg/kg + MK-8616 4.0 mg/kg; 9) Zemuron® 0.6 mg/kg + MK-8616 8.0 mg/kg

Zemuron® DRUG

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.

Also known as: Rocuronium bromide

1) Zemuron® 0.6 mg/kg + MK-8616 0.5 mg/kg; 10) Zemuron® 1.2 mg/kg + MK-8616 8.0 mg/kg; 2) Zemuron® 1.2 mg/kg + MK-8616 0.5 mg/kg; 3) Zemuron® 0.6 mg/kg + MK-8616 1.0 mg/kg; 4) Zemuron® 1.2 mg/kg + MK-8616 1.0 mg/kg; 5) Zemuron® 0.6 mg/kg + MK-8616 2.0 mg/kg; 6) Zemuron® 1.2 mg/kg + MK-8616 2.0 mg/kg; 7) Zemuron® 0.6 mg/kg + MK-8616 4.0 mg/kg; 8) Zemuron® 1.2 mg/kg + MK-8616 4.0 mg/kg; 9) Zemuron® 0.6 mg/kg + MK-8616 8.0 mg/kg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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®

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

MeSH Terms

Interventions

Sugammadex; Rocuronium

Intervention Hierarchy (Ancestors)

gamma-Cyclodextrins; Cyclodextrins; Macrocyclic Compounds; Polycyclic Compounds; Dextrins; Starch; Glucans; Polysaccharides; Carbohydrates; Androstanols; Androstanes; Steroids; Fused-Ring Compounds

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2018
• First Posted: May 9, 2018
• Study Start: August 1, 2004
• Primary Completion: May 26, 2005
• Study Completion: May 26, 2005
• Last Updated: January 31, 2019
• Results First Posted: January 31, 2019

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will share