Clinical trial NCT02848729: Drug Interactions Between Morphine and Orally or IV Administered Acetaminophen
Official title: A Randomized, 2-Way, Parallel, Single-Blind Pharmacokinetic Study to Evaluate the Interaction Between Intravenous Morphine and Orally or Intravenously Administered Acetaminophen in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pain
Keywords: Post-surgical pain
Pharmacokinetics
Lead sponsor: Mallinckrodt
Sponsor class: INDUSTRY
First posted: 2016-07-28
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Morphine is the opioid used to treat pain after surgery. Acetaminophen (called APAP) can reduce the amount of opioids needed for this.

The problem is that morphine slows down digestion. That can delay pain relief from APAP pills. It can even change what the body does to the drug \[pharmacokinetics (PK)\].

Some doctors have started using intravenous (IV) APAP with morphine, instead of the pills.

This study will measure the PK of APAP pills and IV when used with morphine in healthy volunteers.

IV APAP will likely be more effective and cause fewer side effects when used with morphine to treat pain after surgery.

Detailed description: Acetaminophen can significantly reduce the use of opioid analgesics when both are used concomitantly for treating moderate to severe pain. The use of IV acetaminophen used concomitantly with opioids has increased in practice for postsurgical pain relief over orally administered acetaminophen because it provides an immediate peak plasma concentration and is believed to provide a faster analgesic effect. Opioids used to treat pain inhibit gastrointestinal motility, including delaying gastric emptying. In patients receiving opioids the absorption of orally administered acetaminophen may be delayed and could result in gastric accumulation of acetaminophen thereby markedly changing the pharmacokinetic profile. The opioid-induced inhibition of gastrointestinal motility would not be expected to affect IV acetaminophen pharmacokinetics. Thus coadministered IV acetaminophen with opioid would yield better outcome in efficacy and reduced risk of side effects comparing with coadministration of oral acetaminophen and opioids.

Eligibility criteria: Inclusion Criteria:

1. Subject must have a health status of "healthy" assessed by the investigator and defined as no clinically significant deviation from normal medical history, physical examination, vital signs, and clinical laboratory determinations.
2. Subject must have a body mass index ≥ 19.0 and ≤ 32.0 kg/m² with a minimum weight of 110 pounds (50 kg) at Screening.

Exclusion Criteria:

1. Subject has a positive test result for human immunodeficiency virus (HIV), hepatitis B (surface antigen), or hepatitis C virus antibody at screening.
2. Subject has a history of any drug allergy, hypersensitivity, or intolerance to acetaminophen or morphine/opioids or to any of the excipients in the IV or oral formulations used.
3. Subject has an oxygen saturation of less than 95% while awake at screening and check-in.
4. Subject has a positive test result for drugs of abuse (minimum: opioids, barbiturates, cannabinoids, benzodiazepines, cocaine, amphetamine) or alcohol at the screening and check-in.
5. Subject has donated or had significant loss of whole blood (480 mL or more) within 30 days, or plasma within 14 days prior to dosing.
6. Subject has any other medical, psychiatric and/or social reason for exclusion as determined by the investigator.

Primary outcomes:
measure: Area Under the Plasma Concentration-time Curve Over 6 Hours (AUC6) for Acetaminophen
timeFrame: hours -6 to 0, 0-6, 6-12, and 12-18 during treatment with each mode of acetaminophen administration
measure: Area Under the Plasma Concentration-time Curve Over 18 Hours (AUC18) for Acetaminophen After First Morphine Co-administration
timeFrame: hours 0-18 during treatment with each mode of acetaminophen administration
measure: Maximum Concentration (Cmax) of Acetaminophen
timeFrame: hours -6 to 0, 0-6, 6-12, and 12-18 during treatment with each mode of acetaminophen administration
measure: Time to Maximum Concentration (Tmax) of Acetaminophen
timeFrame: hours -6 to 0, 0-6, 6-12 and 12-18 during treatment with each mode of acetaminophen administration
Secondary outcomes:
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona College of Pharmacy
state: Arizona
city: Naples
country: United States
facility: NEMA Research, Inc.
state: Florida
city: Kingston
country: United States
facility: The University of Rhode Island College of Pharmacy
state: Rhode Island
Study officials:
affiliation: Mallinckrodt
name: Global Clinical Leader
role: STUDY_DIRECTOR
References:
citation: Raffa RB, Pawasauskas J, Pergolizzi JV Jr, Lu L, Chen Y, Wu S, Jarrett B, Fain R, Hill L, Devarakonda K. Pharmacokinetics of Oral and Intravenous Paracetamol (Acetaminophen) When Co-Administered with Intravenous Morphine in Healthy Adult Subjects. Clin Drug Investig. 2018 Mar;38(3):259-268. doi: 10.1007/s40261-017-0610-4.