Neuromuscular BlockadePhase 2NCT03519867
Efficacy and Safety of Org 25969 Administered After Zemuron® (MK-8616-042)
A Phase 2 study testing MK-8616 and Zemuron® in people with Neuromuscular Blockade, run by Merck Sharp & Dohme LLC.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neuromuscular Blockade
- What is being tested?
- MK-8616 and Zemuron®
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- No sites listed yet
- Study dates
- 1 Aug 2004to 26 May 2005
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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®
Who cannot join
- 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
Show all 10Show fewer
- 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
About this study
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®
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
- Being tested
- MK-8616, Zemuron®
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MK-8616Drug
Also called Org 25969, sugammadex, Bridion®
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.
Zemuron®Drug
Also called Rocuronium bromide
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: MK-8616; Drug: Zemuron® |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 90 minutes
Secondary outcomes (1)
Percentage of Participants Experiencing ≥1 Adverse Events (AEs)
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.
Measured: Up to 7 days following MK-8616 administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2018
- Study start1 Aug 2004
- Primary completion26 May 2005
- Study completion26 May 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Neuromuscular BlockadeStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03519867
- Sponsor's protocol ID
- P06387
- Other IDs
- MK-8616-042, 19.4.204
- Status last verified
- Aug 2018
- First submitted
- 8 May 2018
- Last updated
- 31 Jan 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
Study at a glance
From the registry record, last updated by the sponsor on 31 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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®
- ClinicalTrials.gov ID
- NCT03519867
- Acronym / sponsor ID
- P06387
- Conditions
- Neuromuscular Blockade
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 1 Aug 2004 (actual)
- Primary completion
- 26 May 2005 (actual)
- Study completion
- 26 May 2005 (actual)
- First posted
- 9 May 2018 (actual)
- Results
- Posted 31 Jan 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 10
| Arm | Type | Receives |
|---|---|---|
| 1) Zemuron® 0.6 mg/kg + MK-8616 0.5 mg/kg | Experimental | Drug: MK-8616, Drug: 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. |
| 2) Zemuron® 1.2 mg/kg + MK-8616 0.5 mg/kg | Experimental | Drug: MK-8616, Drug: 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. |
| 3) Zemuron® 0.6 mg/kg + MK-8616 1.0 mg/kg | Experimental | Drug: MK-8616, Drug: 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. |
| 4) Zemuron® 1.2 mg/kg + MK-8616 1.0 mg/kg | Experimental | Drug: MK-8616, Drug: 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. |
| 5) Zemuron® 0.6 mg/kg + MK-8616 2.0 mg/kg | Experimental | Drug: MK-8616, Drug: 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. |
| 6) Zemuron® 1.2 mg/kg + MK-8616 2.0 mg/kg | Experimental | Drug: MK-8616, Drug: 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 | Experimental | Drug: MK-8616, Drug: 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. |
| 8) Zemuron® 1.2 mg/kg + MK-8616 4.0 mg/kg | Experimental | Drug: MK-8616, Drug: 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. |
| 9) Zemuron® 0.6 mg/kg + MK-8616 8.0 mg/kg | Experimental | Drug: MK-8616, Drug: 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. |
| 10) Zemuron® 1.2 mg/kg + MK-8616 8.0 mg/kg | Experimental | Drug: MK-8616, Drug: 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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®
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MK-8616Also: Org 25969, sugammadex, Bridion®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. | Drug | 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®Also: Rocuronium bromideZemuron® (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. | Drug | 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 |
Primary outcome
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.
1 secondary outcome
Percentage of Participants Experiencing ≥1 Adverse Events (AEs)
Time frame: Up to 7 days following MK-8616 administration
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jan 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
Related trials for Neuromuscular Blockade
Active, not recruiting
Efficacy of Laparoscopic-Assisted TAP Block in Laparoscopic Appendectomy
Appendectomy, Laparoscopic, Blockades Neuromuscular
Not yet recruitingObservational study
Diaphragm Ultrasound and Neuromuscular Monitoring for Predicting Early Respiratory Events After Extubation
Residual Neuromuscular Blockade, Diaphragm Dysfunction
Recruiting
Inspiratory Muscle Training and Diaphragmatic Breathing in GAD
Generalized Anxiety Disorder (GAD)
Not yet recruiting
Comparative Effects Of Exercises Targeting Upper Trapezius In Patients With Non Specific Neck Pain
Non Specific Neck Pain
RecruitingObservational study
The Association Between Residual Neuromuscular Block Risk Prediction Score and the Train-of-Four Ratio
Muscle Relaxants
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Merck Sharp & Dohme LLC
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing MK-8616 and Zemuron® in people with Neuromuscular Blockade, run by Merck Sharp & Dohme LLC.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time From Start of Administration of MK-8616 to Recovery T4/T1 Ratio to 0.9 (time frame: Up to 90 minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jan 2019.