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Dexmedetomidine

Phase 3

Anesthesia | Small molecule | Pain |Pfizer, Inc.|Last Updated: Mar 22, 2021

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLEDDMC
Total Trials2
Total Enrollment332

FDA Designations

No designations recorded

Clinical trial landscape

Dexmedetomidine · 9 trials · 6 indications

Phase 3 6Phase 2 3
NCT02757625Study of DA-9501 In Pediatric Subjects In The Intensive Care UnitICU Sedation
COMPLETED63 Analytics
NCT01438957Clinical Study to Investigate the Efficacy and the Safety of DA-9501 in Sedation During the Surgery With Epidural Anesthesia or Spinal Anesthesia Without IntubationSedation
COMPLETED119 Analytics
NCT00875550Study Evaluating Safety and Efficacy of Dexmedetomidine (DEX) in Intubated and Mechanically Ventilated Pediatric Intensive Care Unit (PICU) SubjectsSedation
COMPLETED175 Analytics
NCT00526760Long-term Clinical Study Evaluating the Safety and Efficacy of Dexmedetomidine in ICU SubjectsSedation
COMPLETED80 Analytics
NCT00398827A Safety and Efficacy Study of Dexmedetomidine in Patients Requiring Sedation During Monitored Anesthesia Care (MAC)Anesthesia
COMPLETED326 Analytics
NCT00383890A Safety and Efficacy Study of Dexmedetomidine in Patients Requiring Sedation for Elective Awake Fiberoptic IntubationAwake Fiberoptic Intubation
COMPLETED124 Analytics
PHASE3COMPLETED
Study of DA-9501 In Pediatric Subjects In The Intensive Care Unit
ICU SedationUnlock trial analytics
PHASE3COMPLETED
Clinical Study to Investigate the Efficacy and the Safety of DA-9501 in Sedation During the Surgery With Epidural Anesthesia or Spinal Anesthesia Without Intubation
SedationUnlock trial analytics
PHASE3COMPLETED
Study Evaluating Safety and Efficacy of Dexmedetomidine (DEX) in Intubated and Mechanically Ventilated Pediatric Intensive Care Unit (PICU) Subjects
SedationUnlock trial analytics
PHASE3COMPLETED
Long-term Clinical Study Evaluating the Safety and Efficacy of Dexmedetomidine in ICU Subjects
SedationUnlock trial analytics
PHASE3COMPLETED
A Safety and Efficacy Study of Dexmedetomidine in Patients Requiring Sedation During Monitored Anesthesia Care (MAC)
AnesthesiaUnlock trial analytics
PHASE3COMPLETED
A Safety and Efficacy Study of Dexmedetomidine in Patients Requiring Sedation for Elective Awake Fiberoptic Intubation
Awake Fiberoptic IntubationUnlock trial analytics

Study Endpoints

Primary Endpoints

Percentage of Participants Who Did Not Require a Rescue Sedative Within 24 Hours of Dosing of Study Drug
From start of study drug administration on Day 1 up to 24 hours of study drug dosing or at the conclusion of mechanical ventilation or the end of study drug administration, whichever is earliest (up to maximum of 28 days)

Percentage of participants who did not require rescue medication for Sedation (Midazolam) based on the data of investigator's judgement and State Behavioral Scale (SBS) (which was a sedation assessment instrument for intubated participants and its score ranges from 2 to -3, where 2= agitated, 1= restless and difficult to calm, 0= awake and able to calm, -1= responsive to gentle touch or voice, -2= responsive to noxious stimuli and -3= unresponsive. During intubation \[placement of a flexible plastic tube into the trachea to maintain an open airway or to serve as a conduit through which to administer certain drugs\], the target sedation depth by SBS was -2 to 0, where higher score indicated more responsive and after extubation \[removal of endotracheal tube\], the target sedation depth was -1 to 0, where higher score indicated more responsive) were reported.

Percentage of Patients Who Did Not Require Rescue Administration of Propofol to Achieve and Maintain Observer's Assessment of Alertness/Sedation (OAA/S) Score ≤4 During the Study Drug Administration.
Pre-dose, every 5 ± 2 minutes after start of study drug infusion and every 15 ± 2 minutes until 1 hour after study drug infusion. Before additional administration of sedative.
Percentage of Subjects That do Not Require Rescue Midazolam (MDZ) for Sedation Based on Achieving and Maintaining a Target University of Michigan Sedation Scale (UMSS) Score of 1 to 3 While Intubated.
6 to 24 hours

Clinical Score Level of Sedation 0 Awake/Alert 1. Minimally Sedated: Tired/sleepy, appropriate response to verbal conversation and/or sounds. 2. Moderately Sedated: Somnolent/sleeping, easily aroused with light tactile stimulation. 3. Deeply sedated: Deep sleep, arousable only with significant physical stimulation. 4. Unarousable

Incidence rate of adverse drug reactions of hypotension, hypertension and bradycardia which correspond to the protocol definitions
Prior to study drug infusion, during the study drug infusion and 24 hours after study drug infusion end; maximum ≤28 days.

Definition: * Hypotension: dosing start or dose increase of vasopressor drug or use of fluid bolus ≥500 mL within 1 hour resulting from SBP\<60mmHg, DBP\<40mmHg or ≥50% lower than baseline. * Hypertension: dosing start or dose increase of intravenous anti-hypertensive medication resulting from SBP\>160, DBP\>100 or. ≥50% higher than baseline. * Bradycardia: dosing start or dose increase of positive chronotropic medication or use of pacemaker resulting from heart rate \<40bpm or ≥50% lower than baseline.

Percent of patients not requiring midazolam for rescue sedation based on achieving and/or maintaining an Observer's Assessment of Alertness/Sedation Scale (OAA/S) score ≤4
Prior to start of study drug, 15 minutes after start of study drug infusion, every 5 minutes thereafter throughout the study drug infusion and every 15 minutes while the subject is in the post anesthesia care unit.

Observer's Assessment of Alertness/Sedation Scale (OAA/S) score ≤4 (Responsiveness: Lethargic response to name spoken in normal tone; Speech: Mild slowing or thickening; Facial Expression: Mild relaxation; Eyes: Glazed or mild ptosis \[less than half the eye\])

The percentage of subjects requiring rescue midazolam to achieve and/or maintain proper sedation levels throughout the study drug infusion
At baseline and 15 minutes after starting study drug (prior to topicalization), and every 3 minutes thereafter throughout study drug infusion, at the end of topicalization, and prior to administration of any rescue medication.

Sedation levels (Ramsay Sedation Scale \[RSS\] score ≥2 \[Patient is cooperative, oriented and tranquil\])

Percent of Subjects Requiring Rescue Midazolam for Sedation
During the study drug administration (ie., loading dose 10 or 20 minutes and maintenance infusion minimum of 6 hours up to 24 hours) and during the post drug administration (up to 24 hours).
Area Under the Plasma Concentration-time Curve (AUC0-∞)
30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MI

Area under the plasma concentration-time curve of dexmedetomidine at 0 to Infinity hours

Observed Peak Plasma Concentration (Cmax)
30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MI

Maximum observed concentration of dexmedetomidine in plasma

Steady State Concentration (Css)
30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MI

Concentration of dexmedetomidine at steady state in plasma

Terminal Elimination Half-life (t1/2)
30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MI

Terminal elimination half-life of dexmedetomidine. Half-life is the time required for plasma concentration of the drug to decrease by 50%.

Time to Reach Maximum Plasma Concentration (Tmax)
30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MI

Observed time to reach maximum plasma concentration of dexmedetomidine, expressed in hours

Weight-Adjusted Plasma Clearance (CLw)
30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MI

Weight-Adjusted Plasma Clearance of dexmedetomidine after intravenous administration.

Plasma Clearance (CL)
30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MI

Clearance of dexmedetomidine after intravenous administration. Clearance is the rate at which the drug is removed from the plasma after the dose.

Volume of Distribution (Vd)
30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MI

Volume of distribution of dexmedetomidine after intravenous administration. Volume of distribution measures how much the drug spreads through the body after the dose.

Weight-Adjusted Volume of Distribution (Vdw)
30 minutes prior to loading dose (LD); 5 minutes before finishing LD; 0.5, 1, 2 and 4-6 hours during maintenance infusion (MI); 30 minutes prior (within 24 hours of start of MI) and 10 minutes, 0.5, 1, 2, 4 and 10 hours end of MI

Weight-Adjusted Volume of distribution of dexmedetomidine after intravenous administration.

Average Total Faces, Legs, Activity, Cry, and Consolability (FLACC) Score
Prior to loading dose and every hour during the maintenance infusion; within 5 minutes after any fentanyl administration during DEX infusion or every 4 hours in case of continuous fentanyl infusion; within 5 minutes prior and after titration of fentanyl

FLACC scale is a 5 category observational measure to assess pediatric pain on face, legs, activity, cry and consolability. Responses in each category are scored between 0 to 2 (0 = normal, relaxed to 2 = upset, rigid), for a maximum total score of 10.

Absolute Time That Subject is in UMSS Range 2-4 During Treatment Period
During the treatment (6 to 24 hours)

The level of sedation will be assessed using the University of Michigan Sedation Scale (UMSS). Score 0 (awake/alert); Score 1 (sleepy/responds appropriately); Score 2 (somnolent/arouses to light stimuli); Score 3 (deep sleep/arouses to deeper physical stimuli); Score 4 (unarousable). The UMSS scores obtained just prior the loading dose (LD) and 5 and 10 minutes during LD; 0, 5, 10, 15, 30, and 60 minutes and thereafter every 4 hours of the maintenance infusion; within 5 minutes of obtaining each pharmacokinetic sample; within 5 minutes prior and after any midazolam rescue during dexmedetomidine infusion period.

Number of Subjects Who Received Rescue Medication for Sedation and Analgesic
During the treatment (6 to 24 hours)

Participants who received rescue medication midazolam for sedation and/or fentanyl for analgesic during study drug Infusion

Percentage of Subjects Who Received Rescue Medication Midazolam for Sedation During Dexmedetomidine Infusion
During study drug administration (6 to 24 hours)

Secondary Endpoints

Percentage of Participants Who Did Not Require Administration of a Rescue Analgesic Within 24 Hours of Dosing of Study Drug
From start of study drug administration on Day 1 up to 24 hours of study drug dosing or at the conclusion of mechanical ventilation or the end of study drug administration, whichever is earliest (up to maximum of 28 days)
Total Amount of Rescue Sedative Administered Within 24 Hours of Dosing of Study Drug
From start of study drug administration on Day 1 up to 24 hours of study drug dosing or at the conclusion of mechanical ventilation or the end of study drug administration, whichever is earliest (up to maximum of 28 days)
Body Weight Adjusted Total Amount (Per Kg) of Rescue Sedative Taken Within 24 Hours of Dosing of Study Drug
From start of study drug administration on Day 1 up to 24 hours of study drug dosing or at the conclusion of mechanical ventilation or the end of study drug administration, whichever is earliest (up to maximum of 28 days)
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Study Design & Arms

AllocationNA
MaskingNONE
ModelSINGLE_GROUP
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
DA-9501EXPERIMENTALA single vial contains an injection solution with 2 mL of dexmedetomidine hydrochloride solution (100 µg/mL as dexmedetomidine) dissolved in physiological saline
PlaceboPLACEBO_COMPARATORDexmedetomidine 0 mcg/kg/hr 10 min Initial dose + Dexmedetomidine 0 mcg/kg/hr Maintenance dose
Dexmedetomidine 0.067 mcg/kgEXPERIMENTALDexmedetomidine 0.4 mcg/kg/hr 10 min Initial dose + Dexmedetomidine 0.2 - 0.7 mcg/kg/hr Maintenance dose
Dexmedetomidine 0.25 mcg/kgEXPERIMENTALDexmedetomidine 1.5 mcg/kg/hr 10 min Initial dose + Dexmedetomidine 0.2 - 0.7 mcg/kg/hr Maintenance dose
Dexmedetomidine 0.5 mcg/kgEXPERIMENTALDexmedetomidine 3 mcg/kg/hr 10 min Initial dose + Dexmedetomidine 0.2 - 0.7 mcg/kg/hr Maintenance dose
Dexmedetomidine 1.0 mcg/kgEXPERIMENTALDexmedetomidine 6 mcg/kg/hr 10 min Initial dose + Dexmedetomidine 0.2 - 0.7 mcg/kg/hr Maintenance dose
Dexmedetomidine Low DoseACTIVE_COMPARATOR -
Dexmedetomidine High doseACTIVE_COMPARATOR -
DexmedetomidineEXPERIMENTAL -
Dexmedetomidine 0.5 mcg/kg loadEXPERIMENTAL -
Dexmedetomidine 1 mcg/kg loadEXPERIMENTAL -
Placebo (PBO)PLACEBO_COMPARATORPlacebo load for 10 min and Placebo maintenance for 15 min
Dose level 1EXPERIMENTALDexmedetomidine 0.7 mcg/kg loading dose and 0.5 mcg/kg/hr maintenance infusion
Dose level 2EXPERIMENTALDexmedetomidine 1.0 mcg/kg loading dose and 0.75 mcg/kg/hr maintenance infusion
Dexmedetomidine 0.05 mcg/kgEXPERIMENTALDexmedetomidine loading dose 0.05 mcg/kg; maintenance infusion: 0.05 mcg/kg/hr.
Dexmedetomidine 0.1 mcg/kgEXPERIMENTALDexmedetomidine loading dose: 0.1 mcg/kg; maintenance infusion 0.1 mcg/kg/hr.
Dexmedetomidine 0.2 mcg/kgEXPERIMENTALDexmedetomidine loading dose 0.2 mcg/kg; maintenance infusion 0.2 mcg/kg/hr.

Interventions

NameTypeDescription
Dexmedetomidine hydrochlorideDRUG* 45 weeks CGA to \< 6 years old: Maintenance infusion will be started at 0.2 µg/kg/h. The infusion rate will be adjusted within a range of 0.2 to 1.4 µg/kg/h according to the pediatric subject's sedative state * 6 years old to \< 17 years old: Maintenance infusion will be started at 0.2 µg/kg/h. The infusion rate will be adjusted within a range of 0.2 to 1.0 µg/kg/h according to the pediatric subject's sedative state
PlaceboDRUG -
DexmedetomidineDRUGStudy drug titrated up or down to maintain target UMSS range.
MidazolamDRUGRescue medication for sedation according to UMSS scores
FentanylDRUGRescue medication for pain based on UMSS scores
MorphineDRUGRescue medication for pain based on UMSS scores.
Dexmedetomidine HCL InjectionDRUG -
Fentanyl/MorphineDRUGPer package insert, N-PASS scores and investigator discretion.
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Eligibility Criteria

Age Range45 Weeks to 16 Years
SexALL
Healthy VolunteersNo
Study Sites12

Inclusion Criteria: 1. Subjects whose consent is obtained in writing prior to the clinical trial from a guardian after a full explanation. For subjects over 7 years old, it is desirable that an informed assent is also obtained from the pediatric subject him/herself when possible. 2. Subjects aged ≥...

Countries:JapanUnited StatesCanadaGuatemala
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Competitive Landscape -Anesthesia and Sedation 4 trials (matched to "Anesthesia")

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Frequently asked questions about Dexmedetomidine

What is Dexmedetomidine used for?

Dexmedetomidine is an investigational small molecule being studied for use in awake fiberoptic intubation, sedation, ICU sedation, anesthesia, and in intubated and mechanically ventilated pediatric subjects. It is being developed by Pfizer, Inc. (PFE) and is currently in Phase 3 clinical development.

What does Dexmedetomidine target?

Dexmedetomidine is a small molecule that acts as a selective alpha-2 adrenergic receptor agonist. By binding to these receptors, it produces sedative, analgesic, and anxiolytic effects, which are being studied for applications in sedation and anesthesia across various patient populations.

Who makes Dexmedetomidine?

Dexmedetomidine is being developed by Pfizer, Inc., a biopharmaceutical company traded on the New York Stock Exchange under the ticker symbol PFE. Pfizer is conducting clinical trials to evaluate the drug's safety and efficacy in sedation and anesthesia indications.

What phase is Dexmedetomidine in?

Dexmedetomidine is in Phase 3 clinical development. While it has completed Phase 2 trials in pediatric sedation and intubated subjects, it remains investigational and has not been approved by regulatory authorities. The drug is still undergoing clinical evaluation to establish its safety and efficacy profile.

What clinical trials is Dexmedetomidine in?

Dexmedetomidine has completed five clinical trials, including Phase 2 studies (NCT00652028, NCT01159262, NCT01378988) and a Phase 3 study (NCT02757625). These trials evaluated the drug in pediatric subjects for sedation, ICU sedation, and intubated and mechanically ventilated conditions across the United States, Guatemala, and Japan.

Is Dexmedetomidine the same as DA-9501?

Yes, Dexmedetomidine is the same as DA-9501. The Phase 3 clinical trial NCT02757625, titled 'Study of DA-9501 In Pediatric Subjects In The Intensive Care Unit,' evaluates Dexmedetomidine for ICU sedation in pediatric subjects in Japan.