TABLE 4

Summary of adverse eventsa

ParameterSubjects with AE by treatment group, n (%)REL vs placebo comparison, % difference (95% CI)b
250 mg REL + IMI (n = 117)125 mg REL + IMI (n = 116)Placebo + IMI (n = 114)250 mg REL + IMI125 mg REL + IMI
At least 1 AE57 (48.7)55 (47.4)47 (41.2)7.5 (−5.4 to 20.1)6.2 (−6.7 to 18.8)
Drug-related AE16 (13.7)16 (13.8)11 (9.6)4.0 (−4.5 to 12.7)4.1 (−4.4 to 12.8)
Serious AE4 (3.4)11 (9.5)8 (7.0)−3.6 (−10.3 to 2.4)2.5 (−5.0 to 10.1)
Serious and drug-related AE1 (0.9)c01 (0.9)−0.0 (−4.0 to 3.9)−0.9 (−4.8 to 2.4)
Death03 (2.6)00.0 (−3.3 to 3.2)2.6 (−0.7 to 7.3)
Discontinued due to AE1 (0.9)5 (4.3)3 (2.6)−1.8 (−6.7 to 2.3)1.7 (−3.7 to 7.4)
    Drug-related AE01 (0.9)3 (2.6)−2.6 (−7.5 to 0.6)−1.8 (−6.7 to 2.4)
    Serious AE03 (2.6)1 (0.9)−0.9 (−4.8 to 2.3)1.7 (−2.5 to 6.6)
    Drug-related serious AE001 (0.9)−0.9 (−4.8 to 2.3)−0.9 (−4.8 to 2.4)
Most common AEs
    Diarrhea7 (6.0)7 (6.0)5 (4.4)1.6 (−4.7 to 8.1)1.6 (−4.6 to 8.2)
    Nausea8 (6.8)9 (7.8)8 (7.0)−0.2 (−7.3 to 6.9)0.7 (−6.5 to 8.0)
    Vomiting7 (6.0)9 (7.8)3 (2.6)3.4 (−2.3 to 9.6)5.1 (−0.7 to 11.8)
Events of clinical interest
    AST or ALT of ≥5× ULN2 (1.7)02 (1.8)−0.0 (−4.7 to 4.5)−1.8 (−6.2 to 1.5)
    AST or ALT of ≥3× ULN, total bilirubin level of ≥2× ULN, and alkaline phosphatase level of <2× ULN1 (0.9)000.9 (−2.4 to 4.7)0.0 (−3.3 to 3.2)
  • a AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CI, confidence interval; IMI, imipenem-cilastatin; ULN, upper limit of normal.

  • b The difference in percentage and 95% CI are based on the unconditional and asymptotic Miettinen and Nurminen method without stratification.

  • c Although subsequently determined by the investigator not to be drug related, this event appears in the table because the change in causality was not corrected in the clinical database prior to database lock.