CLINICAL TRIALS PROFILE FOR MIDAZOLAM

505(b)(2) Clinical Trials for midazolam

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
New Formulation	NCT01275547 ↗	The Analgesic Effect of Combined Treatment With Intranasal S-ketamine and Intranasal Midazolam	Completed	University Hospital, Basel, Switzerland	Phase 2/Phase 3	2011-01-01	Introduction Ketamine is an old and generally well accepted analgesic used in the intra- and perioperative setting. Several studies demonstrated the effectiveness of ketamine in the postoperative setting. A new formulation of S-ketamine as an intranasal spray device was tested in our hospital in 8 healthy volunteers (unpublished data, EKBB 351/08). 20 mg of S-ketamine were administered intranasally and compared with S-ketamine i.v. and i.m.. None of the volunteers had serious adverse effects or complications. A preliminary data analysis shows a clear analgesic effect and good absorption of the intranasal S-ketamine. As a next step we would like to investigate the effect of S-ketamine intranasal spray combined with midazolam intranasal spray in a group of postoperative spinal surgery patients. The rational for the combination of intranasal S-ketamine and midazolam is the well known midazolam antagonising effect of ketamine induced psychomimetic adverse effects. Furthermore we know from other studies (EKBB 106/06) that midazolam intranasal spray has relaxant and anxiolytic effects. As far as we know, this is the first study which will examine the combination of S-ketamine and midazolam intranasal sprays in adult patients. Study work plan This prospective, randomized, double-blinded non inferiority study will address pain ratings and patient satisfaction in a postoperative setting in two treatment scenarios: 1. Alternating S-ketamine intranasal unit-dose spray (6 mg per dose) with midazolam intranasal spray (0.75 mg per dose) patient controlled application with a lock-out interval of 20 minutes between two applications and placebo patient controlled analgesia (PCA) with a lock-out interval of 12 minutes with saline 0.9% i.v. for 72 hours or until 40 unit-dose sprays are delivered 2. PCA with 2 mg morphine with a lock-out interval of 12 minutes i.v. with placebo intranasal spray (saline 0.9% + chitosan) with a minimum lock-out interval of 20 minutes for 72 hours or until 40 unit-dose sprays are delivered Patient number We will examine 36 patients, 18 patients in each group. The study duration for an individual patient will be at latest 72 hours, the total study duration is 4 to 5 months. Study importance An intranasal spray is an ideal application form for surgery patients, either in- or outpatients. On the other hand, ketamine and S-ketamine is quite often used in the perioperative setting as a rescue analgesic. In higher doses it could be used as an emergency tool in emergency prehospital medicine. In the perioperative setting it is important to evaluate the efficacy and safety of S-ketamine intranasal spray combined with midazolam intranasal spray in patients. If our study shows that S-ketamine intranasal spray is effective as an analgesic and has good patient acceptance, S-ketamine intranasal spay could be considered as an alternative, completely non-invasive analgesic procedure in a postoperative outpatient setting. As a consequence development of a nasal multidose-applicator combining S-ketamine and midazolam would be of interest.
New Formulation	NCT01349140 ↗	EXPAREL Dose-Response for Single-Injection Femoral Nerve Blocks	Completed	Pacira Pharmaceuticals, Inc	Phase 1	2012-02-01	EXPAREL™, an investigational drug product, is a new formulation of a local anesthetic (numbing medicine) that is designed to be longer acting than the currently-available local anesthetics. The purpose of this study is to define the dose-response curve of EXPAREL, an investigational extended-duration formulation of the local anesthetic bupivacaine, on both motor and sensory block when applied in a fixed volume adjacent to the femoral nerve.
New Formulation	NCT01349140 ↗	EXPAREL Dose-Response for Single-Injection Femoral Nerve Blocks	Completed	University of California, San Diego	Phase 1	2012-02-01	EXPAREL™, an investigational drug product, is a new formulation of a local anesthetic (numbing medicine) that is designed to be longer acting than the currently-available local anesthetics. The purpose of this study is to define the dose-response curve of EXPAREL, an investigational extended-duration formulation of the local anesthetic bupivacaine, on both motor and sensory block when applied in a fixed volume adjacent to the femoral nerve.
OTC	NCT01691690 ↗	Analgesic Effect of IV Acetaminophen in Tonsillectomies	Completed	Nationwide Children's Hospital	Phase 2	2012-10-01	Acetaminophen (paracetamol) is a first-line antipyretic and analgesic for mild and moderate pain for pediatric patients. Its common use (particularly in oral form) is underscored by its wide therapeutic window, safety profile, over the counter accessibility, lack of adverse systemic effects (as compared with NSAIDS and opioids) when given in appropriate doses. Although the exact anti-nociceptive mechanisms of acetaminophen continue to be elucidated, these mechanisms appear to be multi-factorial and include central inhibition of the cyclo-oxygenase (COX) enzyme leading to decreased production of prostaglandins from arachidonic acid, interference with serotonergic descending pain pathways, indirect activation of cannabinoid 1 (CB1) receptors and inhibition of nitric oxide pathways through N-methyl-D-aspartate (NMDA) or substance P. Of the above mechanisms, the most commonly known is that of central inhibition of COX enzymes by which the decreased production of prostaglandins diminish the release of excitatory transmitters of substance P and glutamate which are both involved in nociceptive transmission (Anderson, 2008; Smith, 2011). To date, several studies have shown acetaminophen's opioid sparing effect in the pediatric population when given by the rectal or intravenous routes (Korpela et al, 1999; Dashti et al, 2009; Hong et al, 2010).
New Formulation	NCT01754116 ↗	A Randomized Study to Assess the Relative Bioavailability of New Formulations of GSK1265744 Long Acting Parental (LAP) in Healthy Adult Subjects	Completed	GlaxoSmithKline	Phase 1	2013-01-01	This is a single-center, randomized, open-label, 3 parallel treatment study in healthy adult subjects to assess the relative bioavailability of new formulations of GSK1265744 LAP 400 mg intra muscular compared to the current GSK1265744 LAP 400 mg nanomilled formulation. This study will evaluate LAP formulations of GSK1265744 with different particle sizes. Following a 14 day lead in period with oral GSK1265744, forty-five subjects will receive 400 mg of one of three GSK1265744 formulations which vary in particle size from 200 nm to 5 um by intramuscular injection. Samples for determination of GSK1265744 concentrations will be collected for 12 weeks post-injection. Safety will be evaluated by adverse event recording and laboratory values at frequent intervals throughout the trial. A subgroup of 12 subjects will receive a 3 mg dose of oral midazolam at baseline on Day-29 and then again on the last day of the oral GSK1265744 lead in period to evaluate the effect of GSK1265744 on CYP3A enzymes. The subjects will undergo follow-up evaluations for a minimum of 12 weeks.
New Formulation	NCT01754116 ↗	A Randomized Study to Assess the Relative Bioavailability of New Formulations of GSK1265744 Long Acting Parental (LAP) in Healthy Adult Subjects	Completed	ViiV Healthcare	Phase 1	2013-01-01	This is a single-center, randomized, open-label, 3 parallel treatment study in healthy adult subjects to assess the relative bioavailability of new formulations of GSK1265744 LAP 400 mg intra muscular compared to the current GSK1265744 LAP 400 mg nanomilled formulation. This study will evaluate LAP formulations of GSK1265744 with different particle sizes. Following a 14 day lead in period with oral GSK1265744, forty-five subjects will receive 400 mg of one of three GSK1265744 formulations which vary in particle size from 200 nm to 5 um by intramuscular injection. Samples for determination of GSK1265744 concentrations will be collected for 12 weeks post-injection. Safety will be evaluated by adverse event recording and laboratory values at frequent intervals throughout the trial. A subgroup of 12 subjects will receive a 3 mg dose of oral midazolam at baseline on Day-29 and then again on the last day of the oral GSK1265744 lead in period to evaluate the effect of GSK1265744 on CYP3A enzymes. The subjects will undergo follow-up evaluations for a minimum of 12 weeks.

All Clinical Trials for midazolam

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00001570 ↗	A Phase I Study of Continuous Intravenous Infusion of PSC 833 and Vinblastine in Patients With Metastatic Renal Cancer	Completed	National Cancer Institute (NCI)	Phase 1	1997-02-01	Bolus PSC 833 is administered on Day 1 simultaneously with initiation of 24 hour continuous infusion of PSC 833, followed by another continuous infusion lasting an additional 6 days. To ensure the safety of a 7 day infusion of PSC 833, one patient is treated for 5 days and a second for 6 days, before the first cohort is enrolled. Vinblastine is administered in escalating doses on days 2-5. At least 3 patients are entered at each dose level. The MTD will be defined as the dose immediately below that at which 2 patients experience dose limiting toxicity. Treatment continues every 28 days.
NCT00004424 ↗	Randomized Study of Propofol Versus Fentanyl and Midazolam in Pediatric Patients Requiring Mechanical Ventilation and Sedation Therapy	Completed	Case Western Reserve University	N/A	1996-07-01	OBJECTIVES: I. Assess the degree of amnesia afforded by study sedatives relative to the patient's intensive care unit experiences. II. Evaluate the efficacy and safety of propofol monotherapy compared to a conventional sedative regimen consisting of continuous infusion fentanyl and midazolam. III. Perform a detailed pharmacoeconomic evaluation of propofol sedation compared to combination drug therapy in acutely ill, mechanically ventilated pediatric patients.
NCT00004424 ↗	Randomized Study of Propofol Versus Fentanyl and Midazolam in Pediatric Patients Requiring Mechanical Ventilation and Sedation Therapy	Completed	FDA Office of Orphan Products Development	N/A	1996-07-01	OBJECTIVES: I. Assess the degree of amnesia afforded by study sedatives relative to the patient's intensive care unit experiences. II. Evaluate the efficacy and safety of propofol monotherapy compared to a conventional sedative regimen consisting of continuous infusion fentanyl and midazolam. III. Perform a detailed pharmacoeconomic evaluation of propofol sedation compared to combination drug therapy in acutely ill, mechanically ventilated pediatric patients.
NCT00006299 ↗	Celebrex for Pain Relief After Oral Surgery	Completed	National Institute of Dental and Craniofacial Research (NIDCR)	Phase 2	1999-12-01	This study will evaluate the effects of the new anti-inflammatory drug, Celebrex, on relieving pain after oral surgery. It is also designed to assess the drug's selective inhibition of a chemical called cyclooxygenase-2 and not its closely related form, cyclooxygenase-1. This selective inhibition allows pain alleviation without the adverse side effects (e.g., bleeding and stomach upset) often associated with anti-inflammatory drugs. Healthy volunteers who require removal of their third molars are eligible for this study. Participants will have oral surgery for tooth extraction after receiving a local anesthetic (lidocaine) in the mouth and a sedative (midazolam) through an arm vein. On the evening before and 1 hour before surgery, patients will be given a dose of either the standard anti-inflammatory drug ibuprofen (Advil, Nuprin, Motrin), or Celebrex, or a placebo (a pill with no active ingredient). After surgery, a small piece of tubing will be placed in each extraction site and tied to an adjacent tooth to hold it in place. Samples will be collected from the tubing to measure chemicals involved in pain and inflammation. Patients will stay in the clinic for up to 6 hours after surgery while the anesthetic wears off and will complete pain questionnaires. During that time, they may receive acetaminophen plus codeine (Tylenol 3), if needed, for pain. The tubing then will be removed and the patient discharged with standard pain medication.
NCT00026819 ↗	Rofecoxib to Prevent Pain After Third Molar (Wisdom Tooth) Extraction	Completed	National Institute of Dental and Craniofacial Research (NIDCR)	Phase 2	2001-11-01	This study will evaluate the ability of a new non-steroidal anti-inflammatory drug (NSAID) called rofecoxib to prevent pain following third molar (wisdom tooth) extraction. The Food and Drug Administration approved rofecoxib in 1999 to treat the symptoms of arthritis, menstrual cramps, and pain. Healthy normal volunteers between 16 and 35 years of age in general good health who require third molar (wisdom tooth) extraction may be eligible for this study. Candidates will be screened with a medical history and oral examination, including dental x-rays as needed to confirm the need for third molar removal. Participants will have all four wisdom teeth extracted, and a biopsy (removal of a small piece of tissue) will be taken from the inside of the cheek around the area behind the lower wisdom tooth. On the morning of surgery, patients will be given a dose of either the standard anti-inflammatory drug ibuprofen (Advil, Nuprin, Motrin), or rofecoxib, or a placebo (a pill with no active ingredient). Before surgery, they will be given a local anesthetic (lidocaine) in the mouth and a sedative (midazolam) through an arm vein. After the surgery, patients will remain in the clinic for up to 4 hours to monitor pain and the effects of the drug. Patients will complete pain questionnaires. Patients whose pain is unrelieved an hour after surgery may request and receive morphine intravenously (through a vein). After 4 hours, patients will be discharged with additional pain medicines (Tylenol with codeine and the study drug) and instructions for their use. They will also be given a pain diary to record pain ratings and medications taken at home. A clinic staff member will telephone patients at home the morning after surgery to ensure they are rating their pain intensity at the proper time and are taking their medications as instructed. Patients will return to the clinic 48 hours after surgery with the pain diary and pain relievers. At this visit, another biopsy will be taken under local anesthetic.
NCT00027014 ↗	Herb-Opioid Interactions	Completed	National Center for Complementary and Integrative Health (NCCIH)	Phase 4	2001-09-01	This is a series of studies in healthy volunteers to assess the potential for adverse interactions between St. John's wort (SJW) extract and two narcotic (opioid) pain medications: oxycodone and fentanyl. In the case of oxycodone, we are interested in whether SJW treatment promotes the metabolism of oxycodone, such that it lowers the effectiveness of standard doses of oxycodone in treating pain problems. For the fentanyl study, we will investigate whether SJW treatment will interfere with the delivery of fentanyl to the brain and diminish it's effectiveness to relieve pain. There is evidence to suggest that SJW treatment may increase the activity of a transporter protein, named P-glycoprotein (Pgp), in the blood-brain barrier (BBB) that protects the brain from exposure to drugs and other dietary and environmental toxins.

Clinical Trial Conditions for midazolam

Condition Name

Condition Name for midazolam
Intervention	Trials
Healthy	110
Anesthesia	53
Pain	53
Sedation	47

Condition MeSH

Condition MeSH for midazolam
Intervention	Trials
Pain, Postoperative	114
Delirium	42
Depression	40
Emergence Delirium	36

Clinical Trial Locations for midazolam

Trials by Country

Trials by Country for midazolam
Location	Trials
Egypt	192
China	156
Canada	83
Germany	79
Korea, Republic of	62

Trials by US State

Trials by US State for midazolam
Location	Trials
Texas	105
California	98
New York	73
Florida	62
Pennsylvania	53

Clinical Trial Progress for midazolam

Clinical Trial Phase

Clinical Trial Phase for midazolam
Clinical Trial Phase	Trials
PHASE4	41
PHASE3	18
PHASE2	23

Clinical Trial Status

Clinical Trial Status for midazolam
Clinical Trial Phase	Trials
Completed	909
Recruiting	259
Not yet recruiting	166

Clinical Trial Sponsors for midazolam

Sponsor Name

Sponsor Name for midazolam
Sponsor	Trials
Boehringer Ingelheim	35
Ain Shams University	34
Pfizer	31

Sponsor Type

Sponsor Type for midazolam
Sponsor	Trials
Other	1665
Industry	577
NIH	52

Midazolam Clinical Trials Update and Market Analysis (2018-2026)

Last updated: April 26, 2026

What is midazolam’s current clinical and regulatory position?

Midazolam is an established benzodiazepine used for sedation, anesthesia induction, procedural sedation, and seizure-related indications. Its late-stage development is largely consolidated into product reformulations (route, delivery system, dosing form) rather than new molecular entities.

Core labeled use categories (commercial reality)

• Procedural sedation and premedication in clinical settings
• General anesthesia induction and maintenance support
• Treatment of acute seizures/status epilepticus (route-dependent)
• ICU sedation (route and formulation dependent)

Trial activity pattern

• Ongoing clinical activity concentrates in:
  • Alternative delivery routes (e.g., intranasal, buccal/oromucosal, sublingual)
  • Pediatric and emergency-use regimens
  • Pharmacokinetic (PK), safety, and onset time studies for reformulated products
• Midazolam’s “new approval” pipeline tends to occur via formulation/route and label expansions rather than first-in-class development cycles.

Clinical trial discovery coverage Public databases show substantial ongoing studies on midazolam delivery methods and seizure/acute management protocols, with many trials focusing on comparative PK, time-to-sedation, time-to-clinical effect, and rescue therapy rates. (Source: ClinicalTrials.gov search results for “midazolam”). [1]

What do recent clinical trials signal about where development is heading?

Midazolam clinical trials over the past several years have been dominated by performance metrics that matter to payers and hospitals: onset time, depth of sedation consistency, usability in non-anesthetist settings, and rescue efficacy.

Most common endpoints used in midazolam studies

• Time to onset (sedation and/or seizure suppression depending on indication)
• Proportion achieving target sedation scale without rescue
• Rescue use rate (repeat dosing, alternative rescue meds)
• Safety outcomes: respiratory depression, hypotension, bradycardia, hypoxia events
• PK parameters: Cmax, Tmax, AUC; exposure variability
• In pediatric cohorts: age stratification, dosing alignment, and caregiver-administration feasibility (where applicable)

Development direction by use-case

• Procedural sedation: reformulations targeting faster onset and predictable sedation depth with simplified administration.
• Seizure and emergency use: non-IV routes (intranasal/buccal) that reduce delays to treatment outside controlled OR settings.
• ICU sedation: use protocols and route options that reduce variability and ease titration.

(Trial evidence base: ClinicalTrials.gov listings for midazolam across sedation and seizure-related entries.) [1]

What is the midazolam market structure and how do products compete?

Midazolam market competition is driven by:

• Route of administration (IV, IM, oral, buccal, intranasal)
• Formulation convenience (ready-to-use units, metered dosing, device usability)
• Regulatory labeling (pediatric age claims, procedural sedation claims, seizure claims)
• Reimbursement and hospital contracting (formulary status and bundled anesthesia/ED pathways)

Product segmentation (practical)

1. IV and IM midazolam
   Dominant in hospitals for anesthesia and ICU sedation where IV access exists.
2. Oral tablets/syrup (where used)
   Used in premedication and certain sedation workflows.
3. Buccal/oromucosal and intranasal midazolam
   Competes on speed to treatment and ease of administration in ED, EMS-adjacent settings, and home/caregiver use models where labels permit.

Competitive battlegrounds

• Onset time and dose precision: delivery devices and formulation affect how quickly therapeutic exposure is reached.
• Safety management: respiratory events and the need for monitoring and reversal readiness drive hospital procurement.
• Payer preference: products that reduce rescue medication use and shorten room/transfer times can win procurement.

How big is the midazolam market and what matters for projections?

Public market sizing varies widely due to definitional differences (including or excluding anesthetic adjuvants and excluding/including seizure and prefilled device markets). Market modeling therefore should focus on drivers and constraints rather than a single headline number.

Key demand drivers

• High baseline use in anesthesia and sedation across surgical and procedural volumes
• ED throughput pressure and early seizure treatment protocols
• Growth in community and out-of-hospital seizure action pathways (where labels and payer policies support)
• Switching toward formulations that reduce administration friction (non-IV products)

Key constraints

• Mature molecule with limited “brand-new” competitive entry at the API level
• Generics and biosimilar-style dynamics at the molecular level (price compression)
• Stringent sedation safety requirements (monitoring protocols and contraindications)
• Supply chain and manufacturing scale constraints for certain prefilled/device formats

What is the forecast logic: base case vs. upside?

Midazolam projections typically hinge on how the market values delivery and usability versus price.

Base case projection (most likely)

• Value growth at or slightly above inflation in regions where sedation and seizure protocols tighten around standardized pathways.
• Unit growth tied to procedural volumes and ED seizure management adoption.
• Share shifts toward device/delivery products (intranasal/buccal) in seizure indications where labels support outpatient or caregiver administration.

Upside scenario

• Faster adoption of non-IV seizure rescue protocols in ED and community settings due to guideline alignment.
• Payer preference for products that reduce time-to-treatment and resource utilization.
• Additional pediatric label expansions for non-IV formulations.

Downside scenario

• Continued generic pricing compression outweighs uptake of higher-priced device formats.
• Payer restrictions on reimbursement for device formats without evidence of improved outcomes in local workflows.

Where are major regulatory and evidence anchors for market adoption?

Midazolam’s penetration is supported by longstanding clinical use and label breadth across many geographies. The incremental market dynamics are driven by:

• Pediatric claims and route-specific approvals
• Clinical performance tied to sedation scales and seizure suppression endpoints
• Device usability and real-world administration workflows

For seizure-related use in many jurisdictions, adoption tends to track guideline and protocol uptake rather than new mechanism innovation, which is typical for established benzodiazepines.

(Clinical development and trial evidence base: ClinicalTrials.gov listings and ongoing studies.) [1]
(General reference positioning for benzodiazepines and midazolam’s pharmacology/usage: FDA and other regulator and authoritative drug references are consistent with this established utility framework.) [2]

What does ongoing clinical trial activity imply for next-cycle product differentiation?

The likely next differentiation cycles concentrate on:

• More consistent time-to-effect across populations (pediatric stratification is recurring)
• Simplified administration with fewer steps and better dose accuracy
• Protocol-aligned endpoints that map to operational outcomes (ED length of stay, need for rescue, monitoring intensity)
• Safety characterization for respiratory depression risk in faster-onset formulations

The trial mix on ClinicalTrials.gov shows a sustained stream of midazolam studies across routes and settings. [1]

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Market Outlook Snapshot (2018-2026)

Demand drivers by setting

Setting	Primary use	Differentiation lever	Market impact direction
Operating room / anesthesia	Induction, perioperative sedation	IV workflow standardization	Stable-to-moderate growth
ICU	Ongoing sedation support	PK stability, titration usability	Stable
ED	Procedural sedation, acute seizures	Rapid onset, rescue protocol fit	Uptick in device routes
Outpatient/community (where labeled)	Seizure rescue	Caregiver-friendly non-IV delivery	Potential for share gains

Competitive forces

• Generics compress commoditized IV/oral segments.
• Device/delivery products can sustain premium pricing if procurement ties to operational endpoints.
• Hospital formularies reward standardized sedation protocols and predictable administration.

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Key Takeaways

• Midazolam’s clinical pipeline is active but focused on route and formulation optimization, not new molecular innovation. [1]
• Development targets time-to-effect, sedation depth consistency, and safety management in sedation and acute seizure contexts.
• Market outcomes will be driven by delivery convenience and protocol adoption, partially offset by generic price compression in commoditized segments.
• Near-to-mid term (through 2026), the most defensible growth outlook is in non-IV seizure rescue and emergency workflow-aligned formulations, contingent on label scope and reimbursement acceptance.

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FAQs

1) Is midazolam still seeing new clinical trials?
Yes. ClinicalTrials.gov continues to list midazolam studies focused on sedation and acute seizure use, including route and PK/safety evaluations. [1]

2) What trial endpoints matter most for commercial differentiation?
Time to onset/effect, proportion achieving target sedation without rescue, rescue medication rates, respiratory-related safety events, and PK variability are the common decision metrics. [1]

3) What segment is most exposed to price compression?
IV and oral formulations of the established molecule face the strongest generic pricing pressure, since the API is mature and widely available.

4) Where does the market premium typically come from?
Non-IV delivery systems (intranasal/buccal/oromucosal) can command premium positioning when they simplify administration and align with emergency or caregiver workflows.

5) What drives adoption in emergency and seizure protocols?
Operational protocol fit, speed to treatment, and achievable outcomes under real-world monitoring constraints.

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References

[1] U.S. National Library of Medicine. (n.d.). ClinicalTrials.gov: Midazolam studies (search results). https://clinicaltrials.gov/
[2] U.S. Food and Drug Administration. (n.d.). Drug approvals and labeling resources for benzodiazepines and midazolam-related products. https://www.fda.gov/drugs