Protective Effects of Propylene Glycol in Daily Acetaminophen Dosing

NCT02322879 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: 2013P000070
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

A purpose of this protocol is to is to compare the metabolites of the toxic bioactivating pathway after acetaminophen alone or acetaminophen followed by Propylene Glycol (PG) and to determine if it prevents the formation of the toxic metabolites of acetaminophen.

Conditions

Acetaminophen Toxicity

Keywords

Acetaminophen; Propylene glycol

Outcome Measures

Primary Outcomes (1)

• Rise in Plasma Transaminases: Proportion of Responders.

  Blood tests to monitor Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) were obtained on every visit prior dosing. ALT and AST were analyzed on a Roche Cobas c501 chemistry module at BIDMC. Responders was defined as peak ALT increased 2x baseline (average of first 3 days)

  Daily during the treatment periods (D1-D14 and D29 to 42)

Study Arms (2)

Acetaminophen first, then Acetaminophen + Propylene Glycol

EXPERIMENTAL

Subjects in this arm will receive 4 grams of solid acetaminophen formulation for two weeks, followed by a two week wash out period. Then, subjects will receive 4 grams of solid acetaminophen formulation in addition to 70 mg/kg/day of liquid propylene glycol for two weeks. The total study time is 6 weeks.

Drug: First Treatment Period; Other: Washout; Drug: Second Treatment Period

Acetaminophen + Propylene Glycol first, then Acetaminophen

EXPERIMENTAL

Subjects in this arm will receive 4 grams of solid acetaminophen formulation in addition to 70 mg/kg/day of liquid propylene glycol for two weeks, followed by a two week wash out period. Then, subjects will receive 4 grams of solid acetaminophen formulation for two weeks. The total study time is 6 weeks.

Drug: First Treatment Period; Other: Washout; Drug: Second Treatment Period

Interventions

First Treatment Period DRUG

(duration: 14 days) Subjects will be randomized to receive either of the 2 interventions (4 grams of solid acetaminophen formulation for two weeks vs. 4 grams of solid acetaminophen formulation + 70 mg/kg/day of liquid propylene glycol)

Acetaminophen + Propylene Glycol first, then Acetaminophen; Acetaminophen first, then Acetaminophen + Propylene Glycol

Washout OTHER

(duration: 14 days) At the end of the First intervention period all participants will enter a washout period.

Acetaminophen + Propylene Glycol first, then Acetaminophen; Acetaminophen first, then Acetaminophen + Propylene Glycol

Second Treatment Period DRUG

(duration: 14 days) At the end of the washout period, participants will receive the alternative intervention.

Acetaminophen + Propylene Glycol first, then Acetaminophen; Acetaminophen first, then Acetaminophen + Propylene Glycol

Eligibility Criteria

• Age: 20 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy volunteers ages 20-40
• Patients not taking any chronic medications

You may not qualify if:

• Any history of liver disease
• Frequent alcohol use (2 or more drinks more than 4 times per week)
• Pregnant women
• Chronic medical condition requiring daily pharmacotherapy or the use of any daily prescription medications.
• Unable to provide informed consent

Sponsors & Collaborators

• Beth Israel Deaconess Medical Center: lead
• Harvard University: collaborator

Study Sites (1)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Interventions

WASH protein, Drosophila

Results Point of Contact

• Title: Michael Ganetsky, MD
• Organization: BIDMC

mganetsk@bidmc.harvard.edu

617-754-2323

Study Officials

• Steven Salhanick, MD

  Beth Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Emergency Medicine

Model Details: Eligible subjects will then be randomized at a 1:1 ratio to receive either acetaminophen (APAP) or APAP + propylene glycol for 2 weeks (Treatment Period 1). At the end of the Treatment Period 1 subjects will enter the Wash-Out period for 2 weeks. Study subjects will then receive the alternative treatment for 2 weeks (Treatment Period 2). Overall, the maximum duration of treatment is approximately 6 weeks. RESPONDERS: Subjects whose transaminase levels rise to 3 times normal or greater during either of the Treatment Periods will be deemed responders and the intervention will cease. * If subjects are in the Treatment Period 1, they will enter the washout period and continue to return daily to ensure that liver function tests decline. After the 2 week washout-period, responders will cross over to Treatment Period 2. * If subjects are in the Treatment Period 2 phase, they will continue to return to the CRC and have their transaminases checked until they return to normal.

Study Record Dates

• First Submitted: October 22, 2014
• First Posted: December 23, 2014
• Study Start: May 1, 2013
• Primary Completion: August 1, 2016
• Study Completion: December 1, 2016
• Last Updated: September 1, 2017
• Results First Posted: September 1, 2017

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)