A Multi-Center Study of the Efficacy, Pharmacokinetics (PK) and Pharmacodynamics (PD) of IV Acetaminophen for the Treatment of Acute Pain in Pediatric Patients

A Randomized, Placebo Controlled, Multi-Center Study of the Efficacy, Pharmacokinetics (PK) and Pharmacodynamics (PD) of IV Acetaminophen for the Treatment of Acute Pain in Pediatric Patients

The purpose of this study is to demonstrate the efficacy and safety of Intravenous (IV) acetaminophen plus rescue opioids for the relief of moderate to severe acute pain in neonates and infants (age < 2 years) compared to placebo plus standard of care rescue opioids as well as characterize the concentration-effect relationship (PK/PD) of the intravenous acetaminophen as compared to the control group.

Inclusion Criteria:

• Subject is ≥ 28 weeks gestational age and < 2 years old at study enrollment
• Subject will undergo surgery or had a traumatic injury expected to produce moderate to severe pain and patient is expected to require analgesic treatment for acute pain for 24 hours
• Subject has a medically reasonable need for IV treatment due to their underlying procedure(s) or medical condition(s) for the duration of the study
• Subject has reliable vascular access for administration of study medication and PK sampling
• Subject has a bodyweight which, in the opinion of the Investigator does not preclude participation in the study.
• Subject is free of other physical, mental, or medical conditions which, in the opinion of the Investigator, make study participation inadvisable or make it impossible to accurately assess efficacy or safety endpoints
• Subject's parent or guardian must provide written informed consent prior to participation in the study
• Subject's parent or guardian must have the ability to read and understand the study procedures and have the ability to communicate meaningfully with the study investigator and staff

Exclusion Criteria:

• Subject is not able to comply with the sampling requirements of the study
• Subject has known or suspected hypersensitivity to acetaminophen or the excipients of IV acetaminophen
• Subject has any significant medical condition that in the opinion of the Investigator contraindicates participation in the study or impairs the assessment of efficacy or safety
• Subject has participated in another interventional clinical study within 30 days of the planned study randomization date

Pre-Randomization (Qualification) Inclusion Criteria

Subject has not been administered any of the following:

• any acetaminophen-containing product, nonsteroidal anti-inflammatory agent, central alpha-adrenergic agents (e.g., clonidine, dexmedetomidine) or ketamine within 6 hours of baseline (T0)
• received a regional or neuraxial (caudal, epidural or spinal) anesthetic with local anesthetics within 6 hours of T0
• Subject does not have abnormal liver function tests from a sample obtained post-operatively/post-trauma and prior to randomization above protocol-specified limits
• Subject does not have significantly impaired renal function or known significant renal disease which in the opinion of the Investigator would contraindicate study participation.
• Subject had a nursing assessment documenting moderate to severe pain within 6 hours prior to randomization
• Subject required at least one dose of parenteral opioid medication for pain management (i.e., not pre-emptive therapy) during the 6-hour pre-randomization period, and is anticipated to require at least one dose of parenteral opioid medication during the 24 hour treatment period
• If subject is breast feeding, mother has not been administered any acetaminophen containing product in the previous 6 hours to T0 and throughout the treatment period