Drug Interactions Between Morphine and Orally or IV Administered Acetaminophen

NCT02848729 | Completed Phase 4 Results

• 1 other identifier: MNK14564059
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 3

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.

Conditions

Pain

Keywords

Post-surgical pain; Pharmacokinetics

Outcome Measures

Primary Outcomes (4)

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

  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

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

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

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

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

• Maximum Concentration (Cmax) of Acetaminophen

  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.

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

• Time to Maximum Concentration (Tmax) of Acetaminophen

  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.

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

Study Arms (2)

Treatment A: Oral Acetaminophen

EXPERIMENTAL

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

Drug: Oral Acetaminophen; Drug: IV Morphine; Drug: Saline

Treatment B: IV Acetaminophen

EXPERIMENTAL

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.

Drug: IV Acetaminophen; Drug: IV Morphine; Drug: Placebo Tablets

Interventions

Oral Acetaminophen DRUG

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

Also known as: APAP Oral

Treatment A: Oral Acetaminophen

IV Acetaminophen DRUG

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

Also known as: APAP IV

Treatment B: IV Acetaminophen

IV Morphine DRUG

Morphine for IV administration (0.125 mg/kg)

Treatment A: Oral Acetaminophen; Treatment B: IV Acetaminophen

Placebo Tablets DRUG

Placebo tablets matching oral acetaminophen

Treatment B: IV Acetaminophen

Saline DRUG

Saline placebo matching IV acetaminophen

Treatment A: Oral Acetaminophen

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mallinckrodt: lead

Study Sites (3)

University of Arizona College of Pharmacy

Tucson, Arizona, 85718, United States

Location

NEMA Research, Inc.

Naples, Florida, 34108, United States

Location

The University of Rhode Island College of Pharmacy

Kingston, Rhode Island, 02881, United States

Location

Related Publications (1)

• 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.

  PMID: 29214506 DERIVED

MeSH Terms

Conditions

Pain; Pain, Postoperative

Interventions

Acetaminophen; Morphine; Sodium Chloride

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Medical Information Call Center
• Organization: Mallinckrodt Pharmaceuticals

clinicaltrials@mnk.com

800-556-3314

Study Officials

• Global Clinical Leader

  Mallinckrodt

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2016
• First Posted: July 28, 2016
• Study Start: February 1, 2016
• Primary Completion: March 1, 2016
• Study Completion: March 1, 2016
• Last Updated: February 5, 2020
• Results First Posted: January 29, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)