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NCT Number: NCT02848729

Drug Interactions Between Morphine and Orally or IV Administered Acetaminophen

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.

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Key information

Conditions

Pain Neurologic Manifestations Pain, Postoperative Pathologic Processes Pathological Conditions, Signs and Symptoms Postoperative Complications Signs and Symptoms

Age range

18 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

University of Arizona College of Pharmacy, Tucson, Arizona, United States

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About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.
  • 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

  • Subject has a positive test result for human immunodeficiency virus (HIV), hepatitis B (surface antigen), or hepatitis C virus antibody at screening.
  • 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.
  • Subject has an oxygen saturation of less than 95% while awake at screening and check-in.
  • 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.
  • 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.
  • Subject has any other medical, psychiatric and/or social reason for exclusion as determined by the investigator.

Treatment and study plan

Oral acetaminophen

Drug

Acetaminophen for oral administration (2 tablets, 500 mg/tablet)

Other names: APAP Oral

IV acetaminophen

Drug

Acetaminophen for intravenous (IV) administration (1,000 mg/100 mL)

Other names: APAP IV

IV morphine

Drug

Morphine for IV administration (0.125 mg/kg)

Placebo tablets

Drug

Placebo tablets matching oral acetaminophen

Saline

Drug

Saline placebo matching IV acetaminophen

Primary outcomes

  1. Area Under the Plasma Concentration-time Curve Over 6 Hours (AUC6) for Acetaminophen

    Time frame: hours -6 to 0, 0-6, 6-12, and 12-18 during treatment with each mode of acetaminophen administration

    The area under the plasma drug concentration-time curve (AUC) is an estimate of how much drug remains available for the body to use, within a certain amount of time after the drug is administered. AUC6 is reported for each of the 6-hour dosing periods of acetaminophen before (hours -6 to 0), during (hours 0-6 and 6-12) and after (hours 12-18) morphine co-administration for each route of acetaminophen administration

  2. Area Under the Plasma Concentration-time Curve Over 18 Hours (AUC18) for Acetaminophen After First Morphine Co-administration

    Time frame: hours 0-18 during treatment with each mode of acetaminophen administration

    AUC18 is reported for the 18-hour treatment period after first morphine co-administration, for each route of acetaminophen administration

  3. Maximum Concentration (Cmax) of Acetaminophen

    Time frame: hours -6 to 0, 0-6, 6-12, and 12-18 during treatment with each mode of acetaminophen administration

    Following the administration of drugs, the plasma concentration generally reaches a single, well-defined peak which is the most drug that is available for the body to use (Cmax). Cmax is reported for the 6-hour dosing periods before (hours -6 to 0), during (hours 0-6 and 6-12), and after (hours 12-18) morphine co-administration for each route of acetaminophen administration.

  4. Time to Maximum Concentration (Tmax) of Acetaminophen

    Time frame: hours -6 to 0, 0-6, 6-12 and 12-18 during treatment with each mode of acetaminophen administration

    Following the administration of drugs, the time at which the plasma concentration reaches Cmax is called Tmax. Tmax is reported for the 6-hour dosing periods before (hours -6 to 0), during (hours 0-6 and 6-12) and after (hours 12-18) morphine co-administration for each route of acetaminophen administration.

Sponsors and collaborators

Lead sponsor

Mallinckrodt

Industry

Registry information

Official study 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

Important dates

Study start
2016
Primary completion
2016
Study completion
2016
First posted
Jul 28, 2016
Registry last updated
Feb 5, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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