Compare Pharmacokinetic (PK) Profiles of Naproxen Sodium, Diphenhydramine Hydrochloride, and Naproxen Sodium and Diphenhydramine Hydrochloride Combination (Morpheus PK)

A Bioavailability Study of Naproxen Sodium and Diphenhydramine Hydrochloride Under Fasting Conditions and Naproxen Sodium and Diphenhydramine Hydrochloride Combination Under Fasting and Fed Conditions

The purpose of the current trial is to evaluate the bioavailability of a single oral dose of naproxen sodium 440 mg and DPH HCL 50 mg under fasting and fed conditions and currently marketed single ingredient products containing naproxen sodium (2 x Aleve® 220 mg tablets) or DPH HCL (2 Allergy Relief x 25 mg tablets) under fasting conditions.

Study Overview

• Status: Completed
• Conditions: Therapeutic Equivalence
• Intervention / Treatment: Drug: BAY98-7111; Drug: BAY98-7111; Drug: Naproxen Sodium (Aleve, BAYH6689); Drug: Diphenhydramine HCl

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Hackensack, New Jersey, United States, 07601

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 53 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Health, ambulatory male and female subjects between 18 to 55 years of age inclusive
• Body Mass Index (BMI) of approximately 18 to 30 kg/m2; and a total body weight >50 kg (110 lbs)
• Results of screening and clinical laboratory tests are within normal range or considered not clinically significant by the Principal Investigator or Sponsor
• Female subjects of childbearing potential must be using a medically acceptable form of birth control for at least 1 month prior to screening (3 months on oral contraceptives), e.g., oral or patch contraceptives, intrauterine device, Depo-Provera, or a double barrier and have a negative pregnancy test at Screening and Day 0 for each Dosing Period. Female subjects of non childbearing potential must be amenorrheic for at least 2 years or had a hysterectomy and/or bilateral oophorectomy

Exclusion Criteria:

• History of hypersensitivity to aspirin (ASA), naproxen sodium, NSAIDs, acetaminophen, DPH HCL, and similar pharmacological agents or components of the products
• History of hypersensitivity to any of the food products in the standardized breakfast or cannot consume all food/beverage items contained in the standardized breakfast
• Have taken ASA, ASA-containing products, acetaminophen or any other NSAID (OTC or prescription) 7 days prior to dosing or during the Dosing Periods, other than trial treatment
• Use of any over-the-counter or prescription medications (except acceptable forms of birth control) within 10 days prior to dosing or throughout the trial, unless in the opinion of the Investigator, the medication will not interfere with the trial procedures, data integrity, or compromise the safety of the subject
• Recently had (past 30 days) or plan to have surgery, an invasive procedure, tattoos or piercings during the trial or 1-2 weeks after treatment
• Loss of blood in excess of 500 ml within 56 days of the first dose of trial treatment (e.g., donation, plasmapheresis or injury)
• History of gastrointestinal bleeding or perforation, related to previous NSAID therapy or active or history of recurrent peptic ulcer/hemorrhage (two or more distinct episodes of proven ulceration or bleeding)
• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic diseases or malignancies
• Smokers or currently consuming any type of tobacco product(s) including any smoking cessation nicotine-containing product (e.g., nicotine patch, nicotine gum)
• Have taken any vitamin or herbal supplement within 7 days prior to dosing or refuse to refrain from use during the trial

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm 2	Drug: Naproxen Sodium (Aleve, BAYH6689); 2 x Naproxen Sodium 220 mg under fasting conditions
Experimental: Arm 1	Drug: BAY98-7111; 2 x Naproxen Sodium 220 mg / Diphenhydramine HCl 25 mg combination under fasting conditions; Drug: BAY98-7111; 2 x Naproxen Sodium 220 mg / Diphenhydramine HCl 25 mg combination under fed conditions
Experimental: Arm 4	Drug: BAY98-7111; 2 x Naproxen Sodium 220 mg / Diphenhydramine HCl 25 mg combination under fasting conditions; Drug: BAY98-7111; 2 x Naproxen Sodium 220 mg / Diphenhydramine HCl 25 mg combination under fed conditions
Active Comparator: Arm 3	Drug: Diphenhydramine HCl; 2 x Diphenhydramine HCl 25 mg under fasting conditions

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
AUC(0-tn) (area under the measurement versus time curve from time 0 to the last data point) of naproxen sodium	within 30 minutes prior to dosing (baseline) and 10, 20, 30, 45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, 24, and 36 hours post dosing
AUC(0-tn) (area under the measurement versus time curve from time 0 to the last data point) of DPH HCL(Diphenhydramine Hydrochloride)	within 30 minutes prior to dosing (baseline) and 10, 20, 30, 45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, 24, and 36 hours post dosing
Cmax(Maximum drug concentration) in plasma of naproxen sodium	within 30 minutes prior to dosing (baseline) and 10, 20, 30, 45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, 24, and 36 hours post dosing
Cmax(Maximum drug concentration) in plasma of DPH HCL(Diphenhydramine Hydrochloride)	within 30 minutes prior to dosing (baseline) and 10, 20, 30, 45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, 24, and 36 hours post dosing

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of participants with adverse events as a measure of safety and tolerability	up to 6 weeks

Collaborators and Investigators

• Sponsor: Bayer

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Actual): February 1, 2012
• Study Completion (Actual): March 1, 2012

Study Registration Dates

• First Submitted: August 14, 2012
• First Submitted That Met QC Criteria: August 14, 2012
• First Posted (Estimate): August 16, 2012

Study Record Updates

• Last Update Posted (Estimate): August 21, 2014
• Last Update Submitted That Met QC Criteria: August 20, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Keywords: Bioequivalence
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anesthetics; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antiemetics; Gastrointestinal Agents; Dermatologic Agents; Hypnotics and Sedatives; Anesthetics, Local; Anti-Allergic Agents; Sleep Aids, Pharmaceutical; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Antipruritics; Gout Suppressants; Diphenhydramine; Promethazine; Naproxen
• Other Study ID Numbers: 16135