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 A new formulation of S-ketamine as an intranasal spray device was tested in our hospital in 8 healthy volunteers (unpublished data, EKBB 351/08). 20 mg of S-ketamine were administered intranasally and compared with S-ketamine i.v. and i.m..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.
New Dosage	NCT02435563 ↗	Dose Adaptation to Offset the Interaction Between Ticagrelor and Ritonavir by Population-based PK Modeling	Completed	University Hospital, Geneva	Phase 2	2014-08-01	Ticagrelor is a new generation antiplatelet agent with higher efficacy as compared to clopidogrel and prasugrel in treatment of patients with moderate and high ischemic risks. Ticagrelor is active as such and its hepatic metabolism by CYP3A generates also an active metabolite. Because of the remarkable progress in HIV therapies the number of older age patients is on the rise, requiring adequate cardiovascular treatment. Since frontline HIV therapies include ritonavir, a strong inhibitor of CYP3A enzyme, ticagrelor is contraindicated in these patients because of the expected interaction and bleeding risk. A lower efficacy of clopidogrel and prasugrel, which are both pro-drugs, in the presence of ritonavir has been already demonstrated. Therefore, administration of a lower dose of ticagrelor may be a good alternative in HIV patients in order to lessen the impact of this pharmacokinetic interaction. The aim of this study is to adjust the dose of ticagrelor in case of co-treatment with ritonavir to achieve the same pharmacokinetic profile as administered alone using a physiologically-based pharmacokinetic (PBPK) model. As the first step, a pharmacokinetic (PK) model for ticagrelor and its active metabolite will be created based on available in vitro and in vivo parameters in healthy volunteers. An open-label, 2 sessions cross over study will be conducted with 20 healthy male volunteers at Clinical Research Center (CRC) of Geneva University Hospitals (HUG). During the first session of the clinical trial, a single dose 180 mg ticagrelor will be administered to the volunteers and obtained pharmacokinetic data will be fitted into the model for optimization. Thereafter a simulated trial by the Simcyp® simulator in presence of a single dose 100 mg ritonavir will allow evaluating the impact of CYP3A inhibition on the concentration-time profile of ticagrelor and its active metabolite. The necessary dose of ticagrelor to minimize the magnitude of this interaction will be calculated. This new dose will be co-administered with ritonavir in the same volunteers during the second session of the clinical trial. The purpose is to obtain the same PK profile with single dose of 180 mg ticagrelor administered alone and with an adapted dose of ticagrelor co-administered with a single dose 100 mg ritonavir. Moreover, the pharmacodynamic effect of ticagrelor will be measured in both sessions of the clinical trial using two specific platelet function tests: the VAsodilator-Stimulated Phosphoprotein assay (VASP) and VerifyNow® P2Y12. With the same PK profile, the same pharmacodynamic activity is expected. The modulation of activity of CYP3A and P-gp by ritonavir will be also monitored using micro dose midazolam and fexofenadine as probe substrates. The purpose of this study is to use the Simcyp® Simulator mechanistic PBPK modeling to broaden the application field of ticagrelor, especially in HIV patients. Since PK models are often created after clinical observations, the prospective aspect of this study is of particular value as the model will be first created and then applied to an unknown clinical scenario.

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.
NCT00030004 ↗	Pilot Study of Spinal Manipulation for Chronic Neck Pain	Terminated	National Center for Complementary and Integrative Health (NCCIH)	Phase 1	2000-05-01	This study is designed to determine whether a medicine that can produce temporary amnesia (midazolam) can be used to block the memory of treatment with spinal manipulation. This is important since any study that is designed to determine whether spinal manipulation is effective would be better if patients were not aware of whether or not they were treated. This would allow a true assessment of treatment effects without the complication of a strong placebo effect that manipulative treatment may produce.

Clinical Trial Conditions for Midazolam

Condition Name

Condition Name for Midazolam
Intervention	Trials
Healthy	95
Pain	49
Anesthesia	43
Sedation	41

Condition MeSH

Condition MeSH for Midazolam
Intervention	Trials
Pain, Postoperative	91
Delirium	38
Depression	36
Depressive Disorder	32

Clinical Trial Locations for Midazolam

Trials by Country

Trials by Country for Midazolam
Location	Trials
Egypt	140
China	110
Canada	74
Germany	74
Korea, Republic of	60

Trials by US State

Trials by US State for Midazolam
Location	Trials
Texas	94
California	85
New York	70
Florida	56
Pennsylvania	51

Clinical Trial Progress for Midazolam

Clinical Trial Phase

Clinical Trial Phase for Midazolam
Clinical Trial Phase	Trials
Phase 4	388
Phase 3	124
Phase 2/Phase 3	44

Clinical Trial Status

Clinical Trial Status for Midazolam
Clinical Trial Phase	Trials
Completed	824
Recruiting	178
Not yet recruiting	155

Clinical Trial Sponsors for Midazolam

Sponsor Name

Sponsor Name for Midazolam
Sponsor	Trials
Boehringer Ingelheim	28
Assiut University	24
Pfizer	24

Sponsor Type

Sponsor Type for Midazolam
Sponsor	Trials
Other	1465
Industry	492
NIH	48