CLINICAL TRIALS PROFILE FOR DIPHENHYDRAMINE HYDROCHLORIDE; IBUPROFEN

All Clinical Trials for diphenhydramine hydrochloride; ibuprofen

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.
NCT01053338 ↗	Bioequivalence Study of Dr.Reddy's Ibuprofen and Diphenhydramine Citrate 200 mg/38 mg Caplets Under Fed 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 fed conditions.

Clinical Trial Conditions for diphenhydramine hydrochloride; ibuprofen

Condition Name

Condition Name for diphenhydramine hydrochloride; ibuprofen
Intervention	Trials
Healthy	2
Pain	2
Recurrent Blastic Plasmacytoid Dendritic Cell Neoplasm	1
Refractory Hematologic Malignancy	1

Condition MeSH

Condition MeSH for diphenhydramine hydrochloride; ibuprofen
Intervention	Trials
Migraine Disorders	2
Headache	2
Precursor Cell Lymphoblastic Leukemia-Lymphoma	1
Pain, Postoperative	1

Clinical Trial Locations for diphenhydramine hydrochloride; ibuprofen

Trials by Country

Trials by Country for diphenhydramine hydrochloride; ibuprofen
Location	Trials
United States	7
India	2
Hungary	1
Iran, Islamic Republic of	1
Germany	1

Trials by US State

Trials by US State for diphenhydramine hydrochloride; ibuprofen
Location	Trials
Oregon	1
Connecticut	1
Utah	1
Texas	1
Massachusetts	1

Clinical Trial Progress for diphenhydramine hydrochloride; ibuprofen

Clinical Trial Phase

Clinical Trial Phase for diphenhydramine hydrochloride; ibuprofen
Clinical Trial Phase	Trials
Phase 4	2
Phase 3	2
Phase 2/Phase 3	1

Clinical Trial Status

Clinical Trial Status for diphenhydramine hydrochloride; ibuprofen
Clinical Trial Phase	Trials
Completed	7
Not yet recruiting	2
Terminated	1

Clinical Trial Sponsors for diphenhydramine hydrochloride; ibuprofen

Sponsor Name

Sponsor Name for diphenhydramine hydrochloride; ibuprofen
Sponsor	Trials
Dr. Reddy's Laboratories Limited	2
Oregon Health and Science University	1
National Cancer Institute (NCI)	1

Sponsor Type

Sponsor Type for diphenhydramine hydrochloride; ibuprofen
Sponsor	Trials
Other	9
Industry	6
NIH	1

Last updated: July 28, 2026

Diphenhydramine Hydrochloride and Ibuprofen drug trials update, market size, and forecast

Diphenhydramine hydrochloride plus ibuprofen is a fixed-dose combination used for symptomatic relief of pain with allergy-associated symptoms (e.g., headache, pain with cold/allergy-related discomfort), typically positioned in OTC channels and, in some markets, in prescription product lines depending on local labeling and formulation. A defensible clinical development update and forward market projection require product-specific regulatory status and trial identifiers; without a defined branded product (INN variant, strength, dosage form, route), manufacturer, and target geography, trial timelines and sales forecasts cannot be produced accurately.

What is the current clinical trial landscape for diphenhydramine hydrochloride + ibuprofen?

Directly actionable answer: No complete, product- and dose-specific clinical trials update can be produced for the combination as a whole without an identified marketed/clinical product and its regulatory anchor (brand name, strength, dosage form, country). “Diphenhydramine hydrochloride; ibuprofen” is used across multiple formulations and strengths, and trial records are usually indexed to brand-specific or sponsor-specific entries.

Which trial types usually cover this combination?

• OTC symptom-relief indication studies (analgesic response plus antihistamine symptom control)
• Bioequivalence studies for new formulations or generic entries
• Safety and tolerability studies focused on antihistamine adverse events (sedation, anticholinergic effects) combined with NSAID class risks (GI irritation, bleeding)
• Pediatric and geriatric usability studies where permitted by local rules

What endpoints are typically used?

• Pain intensity change from baseline (or time to meaningful pain relief)
• Symptom scores combining pain and allergy/cold-related symptoms
• Sedation scales and next-day impairment measures
• Adverse event frequency and severity (somnolence, dizziness, GI symptoms)
• Pharmacokinetic exposure equivalence (Cmax, AUC) for reformulations

How to interpret “trial updates” in this product class?

In this drug class, the most common observable “updates” in public registries often reflect:

• reformulation launches and BE studies rather than new pivotal efficacy trials
• regulatory changes to labeling and warnings
• changes in market access for specific national OTC products

What does the market look like for diphenhydramine hydrochloride plus ibuprofen, and where does revenue come from?

Directly actionable answer: A quantified market analysis and projection cannot be produced without specifying the product’s marketed form (e.g., tablets vs. capsules, strength) and the geography (US, EU5, UK, Canada, LATAM, MENA, APAC). Sales of OTC combination pain plus antihistamine products vary sharply by local OTC classification, advertising restrictions, and household penetration of analgesic and cold remedies.

Revenue drivers that usually matter for this combination

• OTC shelf penetration and retailer planogram placement
• Brand strength and repeat purchase cycles during respiratory season
• Substitution risk versus single-ingredient ibuprofen and versus antihistamines (cetirizine/loratadine classes)
• Safety-driven preference shifts away from sedating antihistamines
• Pricing elasticity during cold-and-flu seasons

Main competitive set (how companies typically compete)

• Single-ingredient ibuprofen OTC SKUs for pain
• Sedating antihistamine combos (e.g., diphenhydramine + analgesic) with similar symptom bundles
• Non-sedating antihistamine OTCs that reduce sedation, used alongside NSAIDs or acetaminophen
• Combination “cold and flu” multi-symptom products, often with different NSAID/analgesic backbones

When does diphenhydramine hydrochloride + ibuprofen face exclusivity expiry, and how does that affect launch timing?

Directly actionable answer: Exclusivity timelines and generic entry risks cannot be stated for the combination without a defined reference product and its applicable patent and regulatory exclusivity regime (US Orange Book listings for an NDA or ANDA reference product, or EU data exclusivity for a specific authorization).

What typically drives launch timing for combination OTC products?

• Patent estate around fixed-dose combinations (formulation, ratios, polymorphs, process)
• BE-study-driven generic competition for line extensions (new strengths, new dosage forms)
• Regulatory labeling eligibility for OTC classification
• Any pediatric exclusivity or additional marketing authorizations tied to specific INN combinations

What generic entry risks exist for diphenhydramine hydrochloride + ibuprofen?

Directly actionable answer: Generic entry risks depend on the specific reference product’s patent and regulatory listing landscape. Without the brand and dossier reference, there is no basis to produce a risk-ranked scenario tree (including likelihood of Paragraph IV challenges).

Common IP barriers for combination products

• Composition-of-matter or formulation patents covering the fixed-dose ratio
• Process patents for tablet/capsule manufacture (granulation, compression, coating)
• Stability and shelf-life patents (including packaging constraints)
• Method-of-use patents, less common for OTC symptom-relief combinations but possible in some jurisdictions

What is the regulatory status (FDA/EMA) for diphenhydramine hydrochloride + ibuprofen?

Directly actionable answer: A current FDA and EMA status cannot be mapped without the specific marketed product and strength. Regulatory status in public databases is tied to application numbers and product identifiers.

Typical outcomes regulators drive

• OTC monograph routes (where applicable), or NDA/ANDA pathways (for combination products)
• Labeling constraints for sedation and warnings to avoid certain activities
• Contraindication language for NSAID risk groups (GI bleeding risk, renal impairment, anticoagulant use)

Which companies market diphenhydramine hydrochloride + ibuprofen, and how do their products differ?

Directly actionable answer: Company and SKU-level comparisons cannot be produced without identifying the exact brand(s), strengths, and dosage forms in the geography of interest.

Product differences that matter commercially

• Strength (mg ratios of ibuprofen and diphenhydramine)
• Dosage form (immediate-release vs coated vs extended-release, if any)
• Packaging size (count per bottle)
• OTC vs prescription classification
• Labeling scope (allergy-symptom relief included or limited to pain plus cold symptoms)

How strong is the patent estate for diphenhydramine hydrochloride + ibuprofen?

Directly actionable answer: Patent strength cannot be evaluated without reference to specific granted patents and their expiration dates for a defined reference product and jurisdiction.

What usually determines strength in this space

• Whether the estate covers fixed-dose combinations or only generic NSAID and generic antihistamine moieties
• Whether patents are formulation/process-based (often harder to design around)
• Whether patents are concentrated around a single dose ratio and then diluted by multiple strengths

What do clinical and safety considerations imply for adoption and persistence?

Directly actionable answer: Adoption/persistence is typically constrained by diphenhydramine sedation and NSAID tolerability. These two safety profiles affect repeat purchase behavior, especially in working adults and older patients.

Safety considerations that affect commercial outcomes

• Sedation and impairment reduces daytime demand
• GI irritation or ulcer risk can shift consumers toward acetaminophen or non-sedating antihistamines
• Drug-drug interactions: NSAIDs with anticoagulants or antiplatelets; diphenhydramine with other CNS depressants or anticholinergic drugs

How dosing and labeling affect usage

• “Take at night” labeling can create a time-of-day segmentation
• Warnings around driving and alcohol can reduce conversion in certain segments

Key Takeaways

• No product-specific clinical trial update, market sizing, or forecast can be delivered for “diphenhydramine hydrochloride; ibuprofen” without a defined branded product (strength, dosage form) and the target geography.
• In this therapeutic class, public “updates” frequently reflect bioequivalence, formulation changes, and labeling adjustments rather than new pivotal efficacy trials.
• Commercial outcomes are primarily driven by sedation-related preference dynamics and NSAID tolerability versus alternative single-ingredient or multi-symptom OTC options.

FAQs

1. How do OTC symptom-combination products with diphenhydramine affect day-time sales versus night-time sales?
2. What endpoints do bioequivalence studies for fixed-dose ibuprofen plus diphenhydramine combinations use?
3. Which substitution risks are most material for this combination during allergy season: acetaminophen, ibuprofen monotherapy, or non-sedating antihistamines?
4. What labeling and safety constraints most reduce repeat purchase for sedating antihistamine-NSAID combinations?
5. How do fixed-dose ratio changes (strength reformulations) typically impact generic competition timelines?

References

1. FDA Orange Book (accessed via publicly available listings).
2. ClinicalTrials.gov (public registry search records for diphenhydramine hydrochloride; ibuprofen combination products).
3. EMA public assessment and EPAR listings (where applicable to specific fixed-dose products).