Drug Interactions Between Morphine and Orally or IV Administered Acetaminophen

Mallinckrodt

Status and phase: Completed; Phase 4

Conditions: Pain

Treatments: Drug: IV Acetaminophen; Drug: IV Morphine; Drug: Saline; Drug: Placebo Tablets; Drug: Oral Acetaminophen

Study type: Interventional

Funder types: Industry

Identifiers

NCT02848729

MNK14564059

Details and patient eligibility

About

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.

Full 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.

Enrollment: 50 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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50 participants in 2 patient groups

Treatment A: Oral Acetaminophen

Experimental group

Description:

Treatment A = 4 repeat doses of 1,000 mg oral acetaminophen (2 x 500 mg tablets) and an IV infusion of saline every 6 hours (Hours -6, 0, 6, and 12), and 2 infusions of intravenous (IV) morphine (0.125 mg/kg) at Hours 0 and 6

Treatment:

Drug: IV Morphine

Drug: Oral Acetaminophen

Drug: Saline

Treatment B: IV Acetaminophen

Experimental group

Description:

Treatment B = 4 repeat doses of IV acetaminophen (1,000 mg/100 mL) and 2 placebo tablets every 6 hours (Hours -6, 0, 6, and 12), and 2 infusions of IV morphine (0.125 mg/kg) at Hours 0 and 6.

Treatment:

Drug: Placebo Tablets

Drug: IV Morphine

Drug: IV Acetaminophen