CLINICAL TRIALS PROFILE FOR DIPHENHYDRAMINE HYDROCHLORIDE; NAPROXEN SODIUM

505(b)(2) Clinical Trials for Diphenhydramine Hydrochloride; Naproxen Sodium

This table shows clinical trials for potential 505(b)(2) applications. See the next table for all clinical trials

Trial Type	Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
OTC	NCT01365052 ↗	Safety Trial of Naproxen Sodium/ Diphenhydramine	Completed	Bayer	Phase 3	2011-05-01	The purpose of this trial is to see how safe the combination of naproxen sodium 440 mg and diphenhydramine hydrochloride (DPH) 50 mg (the investigational product) is compared to placebo (capsules containing no drug) when taken for 10 days.

All Clinical Trials for Diphenhydramine Hydrochloride; Naproxen Sodium

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT01118273 ↗	Evaluate Analgesic/Sedative Efficacy of Naproxen Sodium and Diphenhydramine	Completed	Bayer	Phase 4	2008-01-01	The objectives of the study are to evaluate the analgesic and hypnotic efficacy of naproxen sodium and diphenhydramine combination when compared to naproxen sodium, diphenhydramine, and an ibuprofen and diphenhydramine combination
NCT01280591 ↗	Evaluate Analgesic/Sedative Efficacy of Naproxen Sodium and Diphenhydramine in Patients With Postsurgical Dental Pain	Completed	Bayer	Phase 3	2010-10-01	The objective of the study is to evaluate the efficacy and safety of a single oral dose of two dose combinations of naproxen sodium and diphenhydramine (DPH) to demonstrate that naproxen sodium/DPH combination provides added clinical benefit to sleep improvement than either single ingredient alone in subjects with post-surgical dental pain and phase advanced sleep.
NCT01365052 ↗	Safety Trial of Naproxen Sodium/ Diphenhydramine	Completed	Bayer	Phase 3	2011-05-01	The purpose of this trial is to see how safe the combination of naproxen sodium 440 mg and diphenhydramine hydrochloride (DPH) 50 mg (the investigational product) is compared to placebo (capsules containing no drug) when taken for 10 days.
NCT01495858 ↗	Evaluate Analgesic / Sedative Efficacy of Naproxen Sodium and Diphenhydramine in Patients With Postsurgical Dental Pain	Completed	Bayer	Phase 3	2011-12-01	The objective of the study is to evaluate the efficacy and safety of a single oral dose of naproxen sodium 440 mg in combination with DPH (diphenhydramine) 25 mg in subjects with postsurgical dental pain and phase advanced sleep.
NCT01666678 ↗	Compare Pharmacokinetic (PK) Profiles of Naproxen Sodium, Diphenhydramine Hydrochloride, and Naproxen Sodium and Diphenhydramine Hydrochloride Combination	Completed	Bayer	Phase 1	2012-01-01	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.
NCT03299452 ↗	Clinical Studies by Using Alphacait to Screen Drugs for Advanced Solid Tumor	Unknown status	Alphacait, LLC	Phase 2	2017-01-01	This is a single-center, open-label, single-arm, non-randomized study designed to evaluate PFS, safety, overall survival (OS), objective response rate (OPR), disease control rate (DCR) and biomarkers of cancer therapy based on Alphacait screening system in subjects with advanced malignant tumor.
NCT03299452 ↗	Clinical Studies by Using Alphacait to Screen Drugs for Advanced Solid Tumor	Unknown status	Haining Health-Coming Biotech Co., Ltd.	Phase 2	2017-01-01	This is a single-center, open-label, single-arm, non-randomized study designed to evaluate PFS, safety, overall survival (OS), objective response rate (OPR), disease control rate (DCR) and biomarkers of cancer therapy based on Alphacait screening system in subjects with advanced malignant tumor.

Clinical Trial Conditions for Diphenhydramine Hydrochloride; Naproxen Sodium

Condition Name

Condition Name for Diphenhydramine Hydrochloride; Naproxen Sodium
Intervention	Trials
Pain	3
Pain, Postoperative	2
Therapeutic Equivalence	1
Anesthesia	1

Condition MeSH

Condition MeSH for Diphenhydramine Hydrochloride; Naproxen Sodium
Intervention	Trials
Pain, Postoperative	3
Toothache	2
Malnutrition	1
Neoplasm Metastasis	1

Clinical Trial Locations for Diphenhydramine Hydrochloride; Naproxen Sodium

Trials by Country

Trials by Country for Diphenhydramine Hydrochloride; Naproxen Sodium
Location	Trials
United States	19
China	1
Canada	1

Trials by US State

Trials by US State for Diphenhydramine Hydrochloride; Naproxen Sodium
Location	Trials
Texas	5
Utah	4
New Jersey	1
South Carolina	1
Rhode Island	1

Clinical Trial Progress for Diphenhydramine Hydrochloride; Naproxen Sodium

Clinical Trial Phase

Clinical Trial Phase for Diphenhydramine Hydrochloride; Naproxen Sodium
Clinical Trial Phase	Trials
Phase 4	1
Phase 3	3
Phase 2	1

Clinical Trial Status

Clinical Trial Status for Diphenhydramine Hydrochloride; Naproxen Sodium
Clinical Trial Phase	Trials
Completed	7
Not yet recruiting	1
Unknown status	1

Clinical Trial Sponsors for Diphenhydramine Hydrochloride; Naproxen Sodium

Sponsor Name

Sponsor Name for Diphenhydramine Hydrochloride; Naproxen Sodium
Sponsor	Trials
Bayer	7
Alphacait, LLC	1
Haining Health-Coming Biotech Co., Ltd.	1

Sponsor Type

Sponsor Type for Diphenhydramine Hydrochloride; Naproxen Sodium
Sponsor	Trials
Industry	7
Other	3

Clinical Trials, Market Analysis, and Projections for the Drug: Diphenhydramine Hydrochloride and Naproxen Sodium

Introduction

The combination of diphenhydramine hydrochloride and naproxen sodium, commonly known as Aleve PM, has been a subject of extensive clinical trials and market analysis. This article will delve into the clinical trials, safety and efficacy data, market analysis, and future projections for this drug combination.

Clinical Trials Overview

Purpose and Design

The clinical trials for the combination of naproxen sodium 440 mg and diphenhydramine hydrochloride 50 mg were designed to assess the safety, tolerability, and efficacy of this combination. These trials were multicenter, randomized, double-blind, and placebo-controlled, involving parallel group assignments[1][2][4].

Key Studies

• Study 15560: This trial focused on the safety and tolerability of the combination product compared to a placebo over a 10-day period. It was conducted in an over-the-counter (OTC) population[1].
• Pilot Efficacy Study: A double-blind, randomized pilot study evaluated the analgesic and hypnotic effects of the combination in patients with dental pain. This study showed significant improvements in sleep latency and wake after sleep onset (WASO) compared to either component alone[4].
• Phase 3 Study: A single-dose, double-blind, parallel-group study (Study #14837) demonstrated the efficacy of the combination in reducing WASO and sleep latency. The results indicated that the analgesic effect of naproxen and the sleep aid effect of diphenhydramine were synergistic[4].

Safety and Efficacy

Safety Profile

The combination of naproxen sodium and diphenhydramine hydrochloride did not reveal any new or unexpected adverse events compared to the individual components. However, common adverse events included nausea, headache, dizziness, and vomiting. Notably, dizziness was more prevalent in subjects aged 60 and above[4].

Efficacy Findings

The clinical trials showed that the combination was superior to either naproxen or diphenhydramine alone in several sleep-related endpoints. Specifically, the combination reduced WASO by 70 minutes and sleep latency by 15.9 minutes compared to naproxen alone and diphenhydramine alone, respectively[4].

Pharmacokinetics

Naproxen Sodium

Naproxen sodium is well-absorbed, with peak plasma concentrations achieved within 1-4 hours. Food can delay its absorption but does not affect its overall exposure. The analgesic action is exerted at plasma concentrations of about 15 μg/mL[5].

Diphenhydramine Hydrochloride

Diphenhydramine is also well-absorbed, with peak plasma concentrations reached within 1-4 hours. It undergoes first-pass metabolism, with only 40-60% of the oral dose reaching systemic circulation. The elimination half-life of diphenhydramine is prolonged with age, particularly in elderly patients[5].

Market Analysis

Market Position

Aleve PM, the combination product, fills a niche in the OTC market by addressing both pain and sleep disturbances. It competes with other analgesic/sleep-aid combination products but offers a unique combination of naproxen and diphenhydramine, which has been shown to be effective in clinical trials[2].

Consumer Demand

There is a significant demand for products that can manage both pain and sleep issues, especially among individuals with chronic pain conditions. The convenience of a single product that addresses both symptoms is a key selling point for Aleve PM.

Regulatory Approval

Bayer Healthcare – Consumer Care submitted a New Drug Application (NDA) for Aleve PM, which was approved based on the efficacy and safety data from the clinical trials. The FDA review highlighted the combination's effectiveness and safety profile, although it noted some limitations in the study designs and generalizability[2][4].

Market Projections

Growth Potential

The market for OTC pain and sleep aids is expected to grow, driven by an aging population and increasing awareness of sleep health. Aleve PM is well-positioned to capture a significant share of this market due to its unique formulation and clinical evidence supporting its efficacy.

Competitive Landscape

While there are other combination products available, Aleve PM's specific formulation and the strength of its clinical data make it a strong competitor. However, the market is highly competitive, and ongoing marketing and educational efforts will be necessary to maintain and grow market share.

Future Developments

Future studies may focus on expanding the indications for Aleve PM, such as exploring its use in different pain conditions or populations. Additionally, there could be further research into the long-term safety and efficacy of the combination, particularly in elderly patients who may be more susceptible to adverse effects.

Key Takeaways

• Clinical Efficacy: The combination of naproxen sodium and diphenhydramine hydrochloride has been shown to be effective in reducing pain and improving sleep quality.
• Safety Profile: The combination is generally safe, with a profile consistent with the individual components, although dizziness is more common in older adults.
• Market Position: Aleve PM fills a unique niche in the OTC market, addressing both pain and sleep disturbances.
• Growth Potential: The product is expected to grow in market share due to increasing demand for effective pain and sleep management solutions.

FAQs

Q: What is the primary indication for Aleve PM?

A: Aleve PM is indicated for the temporary relief of minor aches and pains and to help fall asleep and stay asleep.

Q: What are the common adverse events associated with Aleve PM?

A: Common adverse events include nausea, headache, dizziness, and vomiting.

Q: How does food affect the absorption of naproxen sodium and diphenhydramine hydrochloride?

A: Food can delay the absorption of naproxen sodium but does not affect its overall exposure. For diphenhydramine, food intake can delay the time to peak plasma concentration but does not significantly affect its bioavailability[2].

Q: Is Aleve PM suitable for all age groups?

A: While generally safe, elderly patients may experience a higher incidence of dizziness and prolonged elimination half-life of diphenhydramine.

Q: Are there any ongoing or planned studies for Aleve PM?

A: Future studies may focus on expanding indications, long-term safety, and efficacy, particularly in different populations.

Sources

1. Clinical Trials Explorer - Bayer: Study 15560.
2. FDA: NDA 205352Orig1s000 Cross Discipline Team Leader Review.
3. FDA: N205-352 Naproxen & Diphenhydramine Clinical PREA.
4. FDA: N205-352 Aleve PM (naproxen sodium+diphenhydramine hydrochloride) Clinical Review.
5. Health Canada: ALEVE® Nighttime.