| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Reversal of neuromuscular blockade |
|
| E.1.1.1 | Medical condition in easily understood language |
| Reversal of paralysis induced by the steroidal neuromuscular blocking agents (NMBAs), rocuronium and vecuronium, during surgery |
|
| E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10018061 |
| E.1.2 | Term | General anesthesia |
| E.1.2 | System Organ Class | 100000004865 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
1.To characterize the incidence of treatment emergent sinus bradycardia, treatment emergent sinus tachycardia, or other treatment emergent cardiac arrhythmias after administration of sugammadex in a population of ASA Class 3 and 4 subjects in a surgical setting.
2.To evaluate the general safety of sugammadex in a population of ASA Class 3 and 4 subjects in a surgical setting.
|
|
| E.2.2 | Secondary objectives of the trial |
| There are no secondary objectives (or hypotheses) for this trial. |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
| Merck will conduct Future Biomedical Research on DNA (blood) specimens collected during this clinical trial. Such research is for biomarker testing to address emergent questions not described elsewhere in the protocol (as part of the main trial) and will only be conducted on specimens from appropriately consented subjects. The objective of collecting specimens for Future Biomedical Research is to explore and identify biomarkers that inform the scientific understanding of diseases and/or their therapeutic treatments. The overarching goal is to use such information to develop safer, more effective drugs, and/or to ensure that subjects receive the correct dose of the correct drug at the correct time. |
|
| E.3 | Principal inclusion criteria |
1. Have a body mass index (BMI) < 40 kg/m2.
2. Be categorized as ASA Physical Status Class 3 or 4, as determined by the Investigator. Note that subject should meet criteria for ASA Class 3 or 4, independent of the BMI > or = 40 kg/m2 criterion.
3. Have a planned surgical procedure that requires neuromuscular block with either rocuronium or vecuronium.
4. Have a planned surgical procedure (e.g., gastrointestinal [GI], urologic, or laparoscopic procedures) that in the opinion of the investigator does not preclude maintenance of moderate or deep depth of NMB throughout the case (maintained by re-dosing or continuous infusion).
5. If female, who is not of reproductive potential be one of the following: (1) postmenopausal (defined as at least 12 months with no menses in women ≥45 years of age); (2) has had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy, or bilateral tubal ligation/occlusion at least 6 weeks prior to screening; (3) has a congenital or acquired condition that prevents childbearing; or (4) is undergoing surgical sterilization as the planned surgical procedure associated with participation in this study (e.g., hysterectomy or tubal ligation).
6. If female, who is sexually active and of child-bearing potential, agrees to use a medically accepted method of contraception through seven days after receiving protocol-specified medication. Medically accepted methods of contraception include condoms (male or female) with a spermicidal agent, diaphragm, or cervical cap with spermicide, medically prescribed intrauterine device (IUD), inert or copper - containing IUD, surgical sterilization (e.g., hysterectomy or tubal ligation). Abstinence (relative to heterosexual activity) can be used as the sole method of contraception if it is consistently employed as the subject’s preferred and usual lifestyle and if considered acceptable by local regulatory agencies and ERCs/IRBs. Periodic abstinence (e.g., calendar, ovulation, sympto- thermal, post-ovulation methods, etc.) and withdrawal are not acceptable methods of contraception.
If a contraceptive method listed above is restricted by local regulations/guidelines, then it does not qualify as an acceptable method of contraception for subjects participating at sites in this country/region.
7. Be able to provide (or the subject’s legally authorized representative, in accordance with local requirements), written informed consent for the trial. The subject or legally authorized representative may also provide consent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research. |
|
| E.4 | Principal exclusion criteria |
1. Has a pacemaker or automatic implantable cardioverter-defibrillator (AICD) that precludes the assessment of bradycardia or arrhythmias.
2. Has a medical condition or surgical procedure that precludes reversal of neuromuscular block at the end of surgery.
3. Has a neuromuscular disorder(s) that may affect neuromuscular block and/or trial assessments.
4. Is dialysis-dependent or has severe renal insufficiency (defined as estimated creatinine clearance of <30 mL/min based on results from local labs within the past 2 weeks prior to Visit 1 or labs performed between V1 and V2).
5. Has or is suspected of having a personal history or family history (parents, grandparents, or siblings) of malignant hyperthermia.
6. Has or is suspected of having an allergy (e.g., hypersensitivity and/or anaphylactic reaction) to study treatments or its/their excipients, to opioids/opiates, muscle relaxants or their excipients, or other medication(s) used during general anesthesia.
7. Has received or is planned to receive toremifene within 24 hours before or within 24 hours after study medication administration.
8. Has any condition that would contraindicate the administration of study medication.
9. Is pregnant, is attempting to become pregnant, or is lactating.
10. Has any clinically significant condition or situation (e.g., anatomical malformation that complicates intubation) other than the condition being studied that, in the opinion of the investigator, would interfere with the trial evaluations or optimal participation in the trial.
11. Is currently participating in or has participated in an interventional clinical trial (including any other current or ongoing trial with a sugammadex treatment arm) with an investigational compound or device within 30 days of signing the informed consent form of this current trial.
12. Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or child) who is investigational site or sponsor staff directly involved with this trial. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
1.The proportion of subjects with treatment emergent sinus bradycardia
2.The proportion of subjects with treatment emergent sinus tachycardia
3.The proportion of subjects with other treatment emergent cardiac arrhythmias |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Continuous ECG monitoring will be performed, beginning at least 5 minutes before, during, and for at least 30 minutes after administration of study medication to facilitate arrhythmia assessment. Other safety events and tolerability of sugammadex will be continuously assessed throughout the trial via standard AE reporting. |
|
| E.5.2 | Secondary end point(s) |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | No |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 10 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Austria |
| Denmark |
| Germany |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
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