What are the benefits of this drug (results of trials used to assess efficacy)?

The two figures below depict efficacy results from Trial 1 (moderate blockade).

Figure 4. Time (Minutes) from Administration of BRIDION or Neostigmine at the Reappearance of T2 after Rocuronium to Recovery of the T4/T1 Ratio to 0.9

BRIDION Prescribing Information

Figure 5. Time (Minutes) from Administration of BRIDION or Neostigmine at the Reappearance of T2 after Vecuronium to Recovery of the T4/T1 Ratio to 0.9

 BRIDION Prescribing Information

Efficacy results from Trial 2 (deep blockade) are summarized below:

Return of the T4/T1 ratio to 0.9 in patients with 1 to 2 PTCs with BRIDION 4 mg/kg had a wider range of recovery times but the median time to recovery was comparable to the study of reversal at T2 (2.7 minutes with 25th and 75th percentiles of 2.1 and 4.3 minutes for rocuronium [N=37], and 3.3 minutes with 25th and 75th percentiles of 2.3 and 6.6 minutes for vecuronium [N=47]). There were 7 and 6 censored observations in the rocuronium and vecuronium groups, respectively.

BRIDION Prescribing Information

The table below summarizes results of Trial 3 that compared to succinylcholine to rocuronium plus BRIDION.

Table 2. Time (minutes) from Start of Administration of Rocuronium or Succinylcholine to Recovery of T1 to 10% of Baseline

Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?

The table below summarizes the efficacy subgroup analysis for Trials 1, 2, and the dedicated trial in older adults.

Table 3. Primary Efficacy Endpoint Results, by Subgroup--Pooled Data for Trial 1, Trial 2, and dedicated trial in older adults.

Note: Values are geometric mean times (mm:ss) from treatment administration to recovery of TOF >=0.9 (95% CI); Protocol 305 was a dedicated geriatric trial
Clinical Trial Data

The table below separately summarizes the subgroup efficacy analysis for the trial that compared BRIDION to spontaneous reversal after succinylcholine.

Table 4. Primary Efficacy Endpoint Results, by Subgroup for Trial 3

What are the possible side effects (results of trials used to assess safety)?

The table below summarizes adverse reactions in the Phase 1 to 3 trials that supported the side effect profile of BRIDION.

Table 5. Percent of Subject Exposures in Pooled Phase 1 to 3 Studies with Adverse Reactions Incidence ≥ 2%

Were there any differences in side effects of the clinical trials among sex, race, and age groups?

The table below summarizes the subgroup analysis for overall treatment-emergent adverse events (TEAEs) in the pooled Phase 1 through Phase 3 trials.

Table 6. Subgroup Analysis for Safety--Overall TEAEs by Subgroup in Pooled Phase 1-3 Clinical Trials

Who participated in the trials?

The table below summarizes the demographics for patients in the pooled Safety population.

Table 7. Baseline Demographics for the Clinical Trials (Safety Population)

Clinical Trial Data

The table below summarizes demographic information from the pooled efficacy trials (Trial 1, Trial 2, and the dedicated trial in older adults). Because of a different clinical trial design, the table excludes patients from the third clinical trial (comparing succinylcholine to rocuronium plus BRIDION) and demographics of that trial are presented separately.

Table 8. Baseline Demographics for Efficacy Trials (Trial 1, Trial 2, and dedicated trial in older adults)

Clinical Trial Data

Table 9. Baseline Demographics for the Third Efficacy Trial (Comparing BRIDION/Rocuronium versus Succinylcholine)

How were the trials designed?

Trial 1 was a multicenter, randomized, parallel-group, active-controlled, safety-assessor blinded study comparing BRIDION and neostigmine. Patients were randomly assigned to the rocuronium or vecuronium group and underwent elective surgical procedures under general anesthesia that required endotracheal intubation and maintenance of neuromuscular blockade. The surgical procedures were mainly endocrine, ocular, ENT, abdominal (gynecological, colorectal, urological), orthopedic, vascular, or dermatological. At the reappearance of T2, after the last dose of rocuronium or vecuronium, 2 mg/kg BRIDION or 50 mcg/kg neostigmine was administered in a randomized order as a single bolus injection. The time from start of administration of BRIDION or neostigmine to recovery of the TOF (T4/T1) ratio to 0.9 was assessed. Generally, a T4/T1 ratio 0.9 correlates with recovery from neuromuscular blockade.

Trial 2 was a multicenter, randomized, parallel-group, active-controlled, safety-assessor blinded study comparing BRIDION and neostigmine. Patients were randomly assigned to the rocuronium or vecuronium group and underwent elective surgical procedures under general anesthesia that required endotracheal intubation and maintenance of neuromuscular blockade. The surgical procedures were mainly abdominal (gynecological, colorectal, urological), orthopedic, reconstructive, or neurological. At 1 to 2 PTCs, after the last dose of rocuronium or vecuronium, 4 mg/kg BRIDION or 70 mcg/kg neostigmine was administered in a randomized order as a single bolus injection. The time from start of administration of BRIDION or neostigmine to recovery of the TOF (T4/T1) ratio to 0.9 was assessed, although neostigmine was not expected to reverse neuromuscular blockade at a depth of 1 to 2 PTCs. Generally, a T4/T1 ratio 0.9 correlates with recovery from neuromuscular blockade.

Trial 3 was a multicenter, randomized, parallel-group, active-controlled, safety-assessor blinded study in which time to recovery from neuromuscular blockade induced by succinylcholine compared with recovery from neuromuscular blockade induced by rocuronium followed 3 minutes later with BRIDION was assessed. Patients underwent elective surgical procedures under general anesthesia that required endotracheal intubation and a short duration of neuromuscular relaxation. The laparoscopic or open surgical procedures were mainly gynecological, orthopedic, or reconstructive. Return of the first twitch in a TOF (T1) to 10% of baseline was compared between BRIDION 16 mg/kg for reversal of rocuronium 1.2 mg/kg versus spontaneous recovery from succinylcholine 1 mg/kg.