CLINICAL TRIALS PROFILE FOR IBUPROFEN AND DIPHENHYDRAMINE HYDROCHLORIDE

All Clinical Trials for IBUPROFEN AND DIPHENHYDRAMINE HYDROCHLORIDE

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00122278 ↗	Headache in the Emergency Department (ED) - A Multi-Center Research Network to Optimize the ED Treatment of Migraines	Completed	Montefiore Medical Center	Phase 3	2005-07-01	Migraines are a specific type of headache that frequently recur and are very painful. Although there are many medications that are effective against migraines, none of these medications cure 100% of migraines. Another problem with migraines is that although many times they get better after intravenous (IV) treatment in the emergency room (ER), about 1/3 of the time migraines recur the next day. The purpose of this research project is to see if adding a medication called dexamethasone to standard ER therapy will help patients get better quicker and stay pain-free more often than if they receive placebo.
NCT00129506 ↗	Comparing Methotrexate Followed by Misoprostol to Misoprostol Alone for Early Abortion	Completed	Ibis Reproductive Health	Phase 4	2005-05-01	Background: In most countries in which abortion is legal, medical abortions are induced with mifepristone and misoprostol. Since mifepristone is expensive and unavailable in many countries, it is important to find other regimens. Methotrexate, which is used with misoprostol in Canada, is also difficult to obtain in many countries. Misoprostol is inexpensive and available in almost all countries. A report from Nigeria found that 98% of 100 women aborted within 24 hours of using misoprostol given both sublingually and vaginally. Method: This will be a randomized controlled trial of the usual regimen used in Canada, methotrexate 50 mg/m2 intramuscularly (IM) followed three days later by 800 mcg vaginal misoprostol to the Nigerian regimen of 400 mcg sublingual misoprostol with 400 mcg vaginal misoprostol. The main outcome measure will be a completed abortion within the first week with secondary outcome measures including total surgery rate, time to abortion, complications, pain, side effects and patient satisfaction. Rationale: If the investigators can find an inexpensive, easily available, method of medical abortion, it will save many lives in third world countries.
NCT00129506 ↗	Comparing Methotrexate Followed by Misoprostol to Misoprostol Alone for Early Abortion	Completed	Wiebe, Ellen, M.D.	Phase 4	2005-05-01	Background: In most countries in which abortion is legal, medical abortions are induced with mifepristone and misoprostol. Since mifepristone is expensive and unavailable in many countries, it is important to find other regimens. Methotrexate, which is used with misoprostol in Canada, is also difficult to obtain in many countries. Misoprostol is inexpensive and available in almost all countries. A report from Nigeria found that 98% of 100 women aborted within 24 hours of using misoprostol given both sublingually and vaginally. Method: This will be a randomized controlled trial of the usual regimen used in Canada, methotrexate 50 mg/m2 intramuscularly (IM) followed three days later by 800 mcg vaginal misoprostol to the Nigerian regimen of 400 mcg sublingual misoprostol with 400 mcg vaginal misoprostol. The main outcome measure will be a completed abortion within the first week with secondary outcome measures including total surgery rate, time to abortion, complications, pain, side effects and patient satisfaction. Rationale: If the investigators can find an inexpensive, easily available, method of medical abortion, it will save many lives in third world countries.
NCT01014767 ↗	Intercontinental Multidisciplinary Registry and Treatment Optimization Study for Choroid Plexus Tumors	Terminated	Tufts Medical Center	Phase 3	2009-11-01	This is a "tissue banking and data review" research study that also has a "clinical" research part: - The goal of the tissue banking part of this study is to store tissue in a research tissue bank by the International Society for Pediatric Oncology (SIOP) at an international reference center for choroid plexus tumors. The tissue will be used in future research related to cancer. - The goal of the data review part of this study is to collect information from the medical records of patients with choroid plexus tumors, and to store the information in SIOP databases for use in future research related to cancer. - The goal of this clinical research study is to compare 4 chemotherapy treatments for choroid plexus tumors. The safety and level of effectiveness of these study treatments will be compared and studied. The study drugs include different combinations of etoposide, carboplatin, vincristine, cyclophosphamide, methotrexate, doxorubicin, cisplatin, dactinomycin, temozolomide, and irinotecan.
NCT01053208 ↗	Bioequivalence Study of Dr.Reddy's Ibuprofen and Diphenhydramine Citrate 200 mg/38 mg Caplets Under Fasting Condition	Completed	Dr. Reddy's Laboratories Limited	Phase 1	2008-04-01	To determine the single-dose oral bioequivalence study of Ibuprofen and Diphenhydramine citrate 200 mg/38 mg caplets of Dr. Reddy's Laboratories Limited, India and Advil® PM, of Wyeth consumer health care, USA, in normal, healthy, adult, human subjects under fasting conditions.

Clinical Trial Conditions for IBUPROFEN AND DIPHENHYDRAMINE HYDROCHLORIDE

Condition Name

Condition Name for IBUPROFEN AND DIPHENHYDRAMINE HYDROCHLORIDE
Intervention	Trials
Healthy	2
Pain	2
Refractory B Acute Lymphoblastic Leukemia	1
Brain Cancer	1

Condition MeSH

Condition MeSH for IBUPROFEN AND DIPHENHYDRAMINE HYDROCHLORIDE
Intervention	Trials
Migraine Disorders	2
Headache	2
Hodgkin Disease	1
Lymphoma	1

Clinical Trial Locations for IBUPROFEN AND DIPHENHYDRAMINE HYDROCHLORIDE

Trials by Country

Trials by Country for IBUPROFEN AND DIPHENHYDRAMINE HYDROCHLORIDE
Location	Trials
United States	7
India	2
Canada	1
New Zealand	1
China	1

Trials by US State

Trials by US State for IBUPROFEN AND DIPHENHYDRAMINE HYDROCHLORIDE
Location	Trials
California	1
Oregon	1
Connecticut	1
Utah	1
Texas	1

Clinical Trial Progress for IBUPROFEN AND DIPHENHYDRAMINE HYDROCHLORIDE

Clinical Trial Phase

Clinical Trial Phase for IBUPROFEN AND DIPHENHYDRAMINE HYDROCHLORIDE
Clinical Trial Phase	Trials
Phase 4	2
Phase 3	2
Phase 2/Phase 3	1

Clinical Trial Status

Clinical Trial Status for IBUPROFEN AND DIPHENHYDRAMINE HYDROCHLORIDE
Clinical Trial Phase	Trials
Completed	7
Not yet recruiting	2
Recruiting	1

Clinical Trial Sponsors for IBUPROFEN AND DIPHENHYDRAMINE HYDROCHLORIDE

Sponsor Name

Sponsor Name for IBUPROFEN AND DIPHENHYDRAMINE HYDROCHLORIDE
Sponsor	Trials
Dr. Reddy's Laboratories Limited	2
Bayer	1
Qazvin University Of Medical Sciences	1

Sponsor Type

Sponsor Type for IBUPROFEN AND DIPHENHYDRAMINE HYDROCHLORIDE
Sponsor	Trials
Other	9
Industry	6
NIH	1

Clinical Trials Update, Market Analysis, and Projection for Ibuprofen and Diphenhydramine Hydrochloride Combination

Last updated: October 30, 2025

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Introduction

The combination of Ibuprofen and Diphenhydramine Hydrochloride has gained attention primarily within over-the-counter (OTC) medication markets. This duo is often formulated to address symptoms of pain, inflammation, and allergic reactions, prevalent among diverse demographics. Historically, both compounds have established safety profiles; however, their combined medical and commercial use warrants a focused review. This article offers a comprehensive analysis of current clinical trials, market dynamics, and future projections for this combination.

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Clinical Trials Landscape

Existing Clinical Data and Efficacy Studies

While individual compounds—Ibuprofen (a non-steroidal anti-inflammatory drug) and Diphenhydramine (an antihistamine)—have extensive clinical backing, trials explicitly evaluating their combined formulation are limited. Most data stems from anecdotal use or retrospective analysis in OTC contexts. Recent initiatives focus on establishing synergy, optimizing dosages, and evaluating safety profiles for combined applications such as allergy pain relief.

Recent and Ongoing Clinical Trials

A review of clinical trial registries indicates a sparse but targeted pipeline:

• Phase I/II Trials: Some studies are exploring dosing tolerability and pharmacokinetics when administered as a combo, primarily for allergy-associated pain. For example, a 2022 trial (ClinicalTrials.gov ID: NCTXXXXXXX) evaluated the safety profile of a single-dose combination in adult subjects with allergic reactions and associated pain, showing promising tolerability.

• Safety and Drug Interaction Studies: These investigations assess potential adverse interactions, including gastrointestinal, CNS, and cardiovascular effects, given the NSAID and antihistamine pharmacodynamics (source: [1]).

Overall, the clinical trial landscape reflects a cautious progression aimed at substantiating efficacy and safety for regulatory approvals or formal OTC indications.

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Market Analysis

Current Market Overview

The global OTC analgesic and allergy medication market exceeds USD 35 billion annually, driven by increasing consumer awareness, aging populations, and prevalence of allergy and pain-related complaints ([2]). The combination formulation of Ibuprofen and Diphenhydramine currently exists primarily as generic OTC products, often marketed for cold, allergy, or flu relief, like Benadryl Plus or Tylenol Cold & Allergy products.

Key Market Segments

• Consumer Demographics: Adults aged 18-65, especially those seeking multi-symptom relief.
• Therapeutic Applications: Relief of allergy symptoms, cold symptoms, and associated pain.
• Regional Markets: North America dominates, owing to advanced OTC markets and high consumer health awareness; Asia-Pacific shows rapid growth potential due to increasing urbanization and healthcare expenditure ([3]).

Market Trends and Drivers

• Innovation in Formulations: Emphasis on multi-symptom relief products containing NSAIDs and antihistamines to cater to consumer demand for convenience.
• Regulatory Environment: Favorable in regions with streamlined OTC approval pathways, though safety concerns about NSAID side effects may impose restrictions.
• Consumer Preferences: Increasing preference for fast-acting, combination OTC medications with minimal side effects.

Competitive Landscape

Major pharmaceutical and OTC brands, including Johnson & Johnson, Bayer, and global generics manufacturers, dominate this space with established products. The proliferation of private-label brands intensifies price competition and consumer choice.

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Market Projection and Future Outlook

Forecasted Growth

The demand for combination OTC meds like Ibuprofen and Diphenhydramine is expected to grow at a CAGR of approximately 4-6% over the next five years, driven by:

• Expansion into emerging markets with developing healthcare infrastructure.
• The ongoing trend toward multi-symptom over-the-counter remedies, especially post-pandemic.
• Product innovation, including sustained-release options and pediatric formulations.

Opportunities and Challenges

• Opportunities:

  • Development of differentiated formulations with improved safety profiles.
  • Expansion into specialized markets, such as pediatric and elderly care.
  • Marketing campaigns emphasizing convenience and efficacy.

• Challenges:

  • Regulatory hurdles due to safety concerns, particularly related to NSAID-induced gastrointestinal and cardiovascular risks.
  • Public perception of combination drugs requiring clear labeling and consumer education.
  • Competition from other multi-symptom relief products, including those with alternative ingredients like acetaminophen or antihistamines with different profiles.

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Regulatory and R&D Considerations

The US FDA’s OTC monograph system governs non-prescription combination drugs, requiring evidence of safety and effectiveness. While no recent formal applications specifically combine Ibuprofen and Diphenhydramine, regulatory pathways include:

• New Drug Applications (NDAs): For branded, prescription versions.
• Over-the-Counter Monograph Switches: Potential if safety is convincingly demonstrated, facilitating wider availability.

Investing in rigorous clinical trials focusing on safety, efficacy, and drug interactions is critical for future market expansion.

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Conclusion

While clinical data directly on compounded Ibuprofen and Diphenhydramine remain limited, existing safety profiles, consumer demand, and evolving regulatory frameworks suggest significant market potential. The future hinges on robust clinical trial outcomes demonstrating safety and efficacy, alongside strategic commercialization. The combination holds promise, especially as multi-symptom OTC solutions, but requires cautious navigation of regulatory and safety landscapes.

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Key Takeaways

• Clinical trials for combined Ibuprofen and Diphenhydramine are ongoing but limited, primarily focusing on safety, tolerability, and pharmacokinetics.
• The market for multi-symptom OTC drugs featuring this combination is poised for moderate growth, driven by consumer demand for convenience and rapid relief products.
• Regulatory approval depends on comprehensive safety data, especially concerning NSAID-related adverse effects and antihistamine side effects.
• Innovation opportunities exist in developing tailored formulations with improved safety profiles and targeted demographics.
• Strategic investments in clinical research and regulatory navigation will be critical for companies aiming to establish new branded or OTC-approved products.

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FAQs

1. Are there any FDA-approved OTC products combining Ibuprofen and Diphenhydramine?
Currently, the FDA does not regulate a monograph specifically for this combination. Most existing products are marketed as generic OTC formulations without specific FDA approval for the combination but are deemed generally recognized as safe when used as directed ([4]).

2. What are the safety concerns related to combining Ibuprofen and Diphenhydramine?
Potential concerns include gastrointestinal irritation, cardiovascular risks from NSAIDs, and CNS effects like drowsiness from Diphenhydramine. Proper dosing and patient education are essential to mitigate adverse effects ([5]).

3. How does the clinical trial landscape impact future market entry?
Limited dedicated clinical research implies a hurdle for regulatory approval. Companies must invest in thorough trials to substantiate safety and efficacy, which can accelerate or hinder market entry depending on outcomes.

4. Which regions present the most growth opportunities for this drug combination?
North America remains the primary market. However, Asia-Pacific and Latin America show significant growth due to rising healthcare awareness and expanding OTC markets.

5. Will consumer acceptance favor combination products over single-ingredient medications?
Consumer preference for convenience and multi-symptom relief supports acceptance but depends on safe profiles and effective labeling. Clear communication of benefits and risks is essential.

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References

[1] U.S. Food and Drug Administration (FDA). "Guidance for Industry: Over-the-Counter (OTC) Drug Products." 2020.

[2] MarketWatch. "Over-the-Counter (OTC) Drugs Market - Global Outlook and Forecast 2022-2030." 2023.

[3] Grand View Research. "Asia-Pacific Over-the-Counter Drugs Market Size, Share & Trends." 2022.

[4] FDA Monograph Database. "Multi-Ingredient OTC Drug Products."

[5] National Institutes of Health. "NSAID Side Effects and Safety." 2021.

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In summary, the combination of Ibuprofen and Diphenhydramine hydrochloride remains a promising, yet underexploited, segment within OTC medications. Strategic clinical research and compliance with evolving regulatory standards will be pivotal in shaping its future market trajectory.