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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 2

Conditions: Neuromuscular Blockade

Treatments: Drug: MK-8616; Drug: Zemuron®

Study type: Interventional

Funder types: Industry

Identifiers

NCT03519867

19.4.204 (Other Identifier)

P06387

MK-8616-042 (Other Identifier)

Details and patient eligibility

About

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).

Enrollment: 50 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

50 participants in 10 patient groups

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

Experimental group

Description:

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.

Treatment:

Drug: Zemuron®

Drug: MK-8616

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

Experimental group

Description:

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.

Treatment:

Drug: Zemuron®

Drug: MK-8616

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

Experimental group

Description:

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.

Treatment:

Drug: Zemuron®

Drug: MK-8616

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

Experimental group

Description:

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.

Treatment:

Drug: Zemuron®

Drug: MK-8616

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

Experimental group

Description:

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.

Treatment:

Drug: Zemuron®

Drug: MK-8616

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

Experimental group

Description:

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.

Treatment:

Drug: Zemuron®

Drug: MK-8616

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

Experimental group

Description:

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.

Treatment:

Drug: Zemuron®

Drug: MK-8616

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

Experimental group

Description:

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.

Treatment:

Drug: Zemuron®

Drug: MK-8616

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

Experimental group

Description:

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.

Treatment:

Drug: Zemuron®

Drug: MK-8616

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

Experimental group

Description:

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.

Treatment:

Drug: Zemuron®

Drug: MK-8616