A Pharmacokinetic Trial of Naproxen Sodium and Diphenhydramine Hydrochloride Soft Capsules Versus Naproxen Sodium and Diphenhydramine Hydrochloride Tablets in Healthy Adult Subjects Under Fed Conditions

NCT03424135 | Completed Phase 1 FDA Drug

• 1 other identifier: 17944
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

To evaluate the relative bioavailability of naproxen sodium/diphenhydramine hydrochloride (DHP HCL) 220/25 mg soft capsules (Test) versus naproxen sodium/DPH HCl 220/25 mg tablets (Reference) after a single oral administration (2 x naproxen sodium 220 mg and DPH HCl 25 mg combination product) under fed conditions in healthy adult subjects. To assess the safety and tolerability of the investigational products in terms of adverse events (AEs) and clinical parameters (systolic/diastolic blood pressure, pulse rate, physical examination, clinical and laboratory testing).

Conditions

Clinical Pharmacology

Outcome Measures

Primary Outcomes (3)

• AUC

  Area under the concentration vs. time curve from zero to infinity after single (first) dose

  Within 30 minutes prior to dosing (baseline) 20, 40, 60 minutes and 1 h 30 min, 2 h, 2 h 20 min, 2 h 40 min, 3, 3 h 20 min, 3 h 40 min, 4 h, 4 h 30 min, 5, 6, 8, 12, 16, 24, 36, 48 and 72 hours post-dose.

• AUC(0-tlast)

  Area under plasma concentration vs. time curve from zero to last data point \>LLOQ (lower limit of quantitation), calculated up by linear trapezoidal rule, down by logarithmic trapezoidal rule

  Within 30 minutes prior to dosing (baseline) 20, 40, 60 minutes and 1 h 30 min, 2 h, 2 h 20 min, 2 h 40 min, 3, 3 h 20 min, 3 h 40 min, 4 h, 4 h 30 min, 5, 6, 8, 12, 16, 24, 36, 48 and 72 hours post-dose.

• Cmax

  Maximum observed drug concentration, directly observed from analytical data

  Within 30 minutes prior to dosing (baseline) 20, 40, 60 minutes and 1 h 30 min, 2 h, 2 h 20 min, 2 h 40 min, 3, 3 h 20 min, 3 h 40 min, 4 h, 4 h 30 min, 5, 6, 8, 12, 16, 24, 36, 48 and 72 hours post-dose.

Secondary Outcomes (1)

• Number of adverse events as a measure of safety and tolerability

  Up to 5 weeks

Study Arms (2)

Test product + Reference product

EXPERIMENTAL

Each treatment sequence consists of two treatment periods (Dosing Periods 1 and 2) with each period consisting of 4 days starting with an overnight fast of at least 10 hours. Subjects will consume a standardized high calorie, high fat breakfast approximately 30 minutes prior to dosing followed by a single dose of study drug administration the morning of Day 1, then a 72-hour PK blood sampling period. The two study drug administrations are separated by a 7 calendar days washout phase.

Drug: Naproxen sodium and diphenhydramine hydrochloride soft capsules; Drug: Naproxen sodium and diphenhydramine hydrochloride coated tablets (Aleve PM, BAY98-7111)

Reference product + Test product

EXPERIMENTAL

Each treatment sequence consists of two treatment periods (Dosing Periods 1 and 2) with each period consisting of 4 days starting with an overnight fast of at least 10 hours. Subjects will consume a standardized high calorie, high fat breakfast approximately 30 minutes prior to dosing followed by a single dose of study drug administration the morning of Day 1, then a 72-hour PK blood sampling period. The two study drug administrations are separated by a 7 calendar days washout phase.

Drug: Naproxen sodium and diphenhydramine hydrochloride soft capsules; Drug: Naproxen sodium and diphenhydramine hydrochloride coated tablets (Aleve PM, BAY98-7111)

Interventions

Naproxen sodium and diphenhydramine hydrochloride soft capsules DRUG

Single oral administration of Naproxen sodium 220 mg/DPH HCl 25mg (2 capsules)

Reference product + Test product; Test product + Reference product

Naproxen sodium and diphenhydramine hydrochloride coated tablets (Aleve PM, BAY98-7111) DRUG

Single administration of Naproxen sodium 220 mg/DPH HCl 25mg (2 tablets)

Reference product + Test product; Test product + Reference product

Eligibility Criteria

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

You may qualify if:

• Healthy, ambulatory male and female subjects between 18 to 55 years of age inclusive;
• Body Mass Index (BMI) in the range of 18 to 30 kg/m2 inclusive; 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 and 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) \[e.g., hormonal contraceptives (oral, patch, injectable or vaginal ring), implantable device (implantable rod or intrauterine device), or a double barrier\] and have a negative pregnancy test at Screening and prior to study drug administration on Day -1 of Dosing Periods 1 and 2. Female subjects of non-childbearing potential must be amenorrheic for at least two years or have had a hysterectomy and/or bilateral oophorectomy;

You may not qualify if:

• History of hypersensitivity symptoms with the use of naproxen/naproxen sodium, diphenhydramine hydrochloride/citrate, acetylsalicylic acid (ASA), other Nonsteroidal anti-inflammatory drugs (NSAIDs) or similar pharmacological agents or components of the products;
• Females who are pregnant or lactating;
• Vegetarian or restricted diet (e.g., gluten-free);
• Any active disease, acute or chronic;
• Have taken naproxen/naproxen sodium, DPH HCl or diphenhydramine citrate, DPH HCl or diphenhydramine citrate-containing products, acetylsalicylic acid, ASA-containing products, acetaminophen, ibuprofen, any other NSAIDs (Over-the-Counter \[OTC\] or prescription) or NSAID containing products, xanthines, antihistamines or caffeine-containing products (e.g., coffee, tea and chocolate) 7 days prior to dosing or during the Dosing Periods, other than trial treatment;
• Use of any over-the-counter or prescription medications, vitamins or herbal supplements (except acceptable forms of birth control) within 7 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;
• Positive test for Human immunodeficiency virus (HIV) antibodies and antigens;
• Positive test for hepatitis B surface antigen (HBsAg) test;
• Positive test for anti-hepatitis C virus (Anti-HCV) antibodies;
• In the judgment of the investigator, any need of other medication during the trial besides the test and reference study medication;
• Recently had (past 30 days) or plan to have surgery, an invasive procedure, tattoos or piercings during the trial or within 2 weeks after treatment;
• More than moderate alcohol consumption (\>40 g of alcohol regularly per day);
• Positive alcohol or drug screen at Screening or on Day -1 of each dosing period.
• Any history or suspicion of barbiturate, amphetamine, benzodiazepine, cocaine, opiates, methamphetamine or cannabis abuse;
• Loss of blood in excess of 50 mL to 499 mL within 30 days or 500 ml or greater within 56 days of the first dose of trial treatment (e.g., donation, plasmapheresis or injury);

Sponsors & Collaborators

• Bayer: lead

Study Sites (1)

ICON Development Solutions, LLC

San Antonio, Texas, 78219, United States

Location

Related Links

• Click here to find results for studies related to Bayer products.

MeSH Terms

Interventions

Naproxen

Intervention Hierarchy (Ancestors)

Naphthaleneacetic Acids; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2018
• First Posted: February 6, 2018
• Study Start: March 2, 2018
• Primary Completion: April 4, 2018
• Study Completion: April 4, 2018
• Last Updated: March 20, 2019

Record last verified: 2019-03

Locations

US (1)