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| Name | Class |
|---|---|
| Premier Research | OTHER |
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A prospective, double-blind, randomized, placebo and active controlled, multi-center, parallel group study comparing remimazolam to placebo, with an additional open-label arm for midazolam, in patients undergoing a colonoscopy for diagnostic or therapeutic reasons.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Remimazolam | Experimental | Remimazolam iv 5 mg for sedation induction, and 2.5 mg top-ups for sedation maintenance. Fentanyl pre-treatment: 50 μg (or less for elderly/disabled subjects) and 25 μg top-up doses |
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| Placebo | Placebo Comparator | Inactive control arm Fentanyl pre-treatment: 50 μg (or less for elderly/disabled subjects) and 25 μg top-up doses |
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| Midazolam | Active Comparator | Midazolam iv 1.75 mg* for sedation induction and 1.0 mg* for sedation maintenance. *1.0 mg for induction and 0.5 mg for maintenance in adults over 60, debilitated or chronically ill Fentanyl pre-treatment: 50 μg (or less for elderly/disabled subjects) and 25 μg top-up doses |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Remimazolam | Drug | For induction and maintenance of sedation |
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| Measure | Description | Time Frame |
|---|---|---|
| Success Rates of the Procedure | Success of the Procedure is measured by completion of colonoscopy, no requirement for an alternative sedative and no requirement for more than 5 top-ups of study medication within any 15 minute period in the blinded arms (remimazolam/placebo) or no requirement for more than 3 doses within any 12 minute window in the midazolam arm. | From administration of the first dose of the study drug to the end of colonoscopy |
| Measure | Description | Time Frame |
|---|---|---|
| Time to Start of Procedure | The time to the start of the procedure after administration of the first dose of randomized study drug | From first dose of study drug until insertion of the colonoscope |
| Time to Fully Alert |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Douglas K Rex, MD | Indiana University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of South Alabama | Mobile | Alabama | 36688 | United States | ||
| Advanced Clinical Research Institute |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22190555 | Background | Antonik LJ, Goldwater DR, Kilpatrick GJ, Tilbrook GS, Borkett KM. A placebo- and midazolam-controlled phase I single ascending-dose study evaluating the safety, pharmacokinetics, and pharmacodynamics of remimazolam (CNS 7056): Part I. Safety, efficacy, and basic pharmacokinetics. Anesth Analg. 2012 Aug;115(2):274-83. doi: 10.1213/ANE.0b013e31823f0c28. Epub 2011 Dec 20. | |
| 22253270 |
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| ID | Title | Description |
|---|---|---|
| FG000 | Remimazolam | Double-blind Remimazolam iv arm: 5 mg for sedation induction, and 2.5 mg top-ups for sedation maintenance. |
| FG001 | Placebo | Double-blind Placebo iv arm: as an inactive control |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Midazolam | Drug | For induction of maintenance and sedation |
|
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| Placebo | Drug | Inactive control arm |
|
The time to fully alert (time to first of three consecutive Modified Observer's Assessment of Alertness/Sedation [MOAA/S] scores of 5) after the end of colonoscopy procedure [colonoscope out], and after the last dose of study drug or rescue sedative medication
| From the end of colonoscopy (colonoscope out) until the patient has recovered to fully alert and from the last injection of the study drug or rescue sedative medication until the patient has recovered to fully alert |
| Time to Ready for Discharge | The time after the end of colonoscopy procedure (colonoscope out) and after the last injection of study drug or rescue sedative medication, until discharge (defined as ability to walk unassisted). | From the end of the colonoscopy until discharge (expected to be the same day). After the last dose of study drug or rescue sedative, until discharge (expected to be the same day). |
| Anaheim |
| California |
| 92801 |
| United States |
| Precision Research Institute | Chula Vista | California | 91910 | United States |
| Precision Research Institute | San Diego | California | 92114 | United States |
| Borland-Grover Clinic, P.A | Jacksonville | Florida | 32256 | United States |
| Indiana University Health | Indianapolis | Indiana | 46202 | United States |
| Delta Research Partners Inc | Monroe | Louisiana | 71201 | United States |
| Washington University School of Medicine | St Louis | Missouri | 63110 | United States |
| Wake Research Associates | Raleigh | North Carolina | 27612 | United States |
| Cleveland Clinic Foundation | Cleveland | Ohio | 44195 | United States |
| Thomas Jefferson Medical College | Philadelphia | Pennsylvania | 19107 | United States |
| Nashville Medical Research Institute | Nashville | Tennessee | 37205 | United States |
| Gastroenterology Associates of Tidewater | Chesapeake | Virginia | 23320 | United States |
| Background |
| Wiltshire HR, Kilpatrick GJ, Tilbrook GS, Borkett KM. A placebo- and midazolam-controlled phase I single ascending-dose study evaluating the safety, pharmacokinetics, and pharmacodynamics of remimazolam (CNS 7056): Part II. Population pharmacokinetic and pharmacodynamic modeling and simulation. Anesth Analg. 2012 Aug;115(2):284-96. doi: 10.1213/ANE.0b013e318241f68a. Epub 2012 Jan 16. |
| 24108261 | Background | Worthington MT, Antonik LJ, Goldwater DR, Lees JP, Wilhelm-Ogunbiyi K, Borkett KM, Mitchell MC. A phase Ib, dose-finding study of multiple doses of remimazolam (CNS 7056) in volunteers undergoing colonoscopy. Anesth Analg. 2013 Nov;117(5):1093-100. doi: 10.1213/ANE.0b013e3182a705ae. |
| 25502841 | Background | Borkett KM, Riff DS, Schwartz HI, Winkle PJ, Pambianco DJ, Lees JP, Wilhelm-Ogunbiyi K. A Phase IIa, randomized, double-blind study of remimazolam (CNS 7056) versus midazolam for sedation in upper gastrointestinal endoscopy. Anesth Analg. 2015 Apr;120(4):771-80. doi: 10.1213/ANE.0000000000000548. |
| 26363333 | Background | Pambianco DJ, Borkett KM, Riff DS, Winkle PJ, Schwartz HI, Melson TI, Wilhelm-Ogunbiyi K. A phase IIb study comparing the safety and efficacy of remimazolam and midazolam in patients undergoing colonoscopy. Gastrointest Endosc. 2016 May;83(5):984-92. doi: 10.1016/j.gie.2015.08.062. Epub 2015 Sep 9. |
| Result | Douglas K. Rex, MD, MACG, Raj Bhandari, MD, Taddese Desta MD, Michael DeMicco MD, Cynthia Schaeffer MD, Kyle Etzkorn, Charles Barish MD, Ronald Pruitt MD, Brooks Cash MD, FACG, Daniel Quirk MD, Felix Tiongco MD, David Bernstein MD, FACG. REMIMAZOLAM IS A SAFE AND EFFECTIVE AGENT FOR SEDATION IN OUTPATIENT COLONOSCOPY: RESULTS OF A PHASE 3, MULTICENTER, RANDOMIZED, PLACEBO CONTROLLED TRIAL. Program No. ACG 2016 Annual Scientific Meeting Abstracts. Las Vegas, NV: American College of Gastroenterology. |
| 29723512 | Result | Rex DK, Bhandari R, Desta T, DeMicco MP, Schaeffer C, Etzkorn K, Barish CF, Pruitt R, Cash BD, Quirk D, Tiongco F, Sullivan S, Bernstein D. A phase III study evaluating the efficacy and safety of remimazolam (CNS 7056) compared with placebo and midazolam in patients undergoing colonoscopy. Gastrointest Endosc. 2018 Sep;88(3):427-437.e6. doi: 10.1016/j.gie.2018.04.2351. Epub 2018 Apr 30. |
| FG002 | Midazolam | Open-label Midazolam iv arm: 1.75 mg* for sedation induction and 1.0 mg* for sedation maintenance. *1.0 mg for induction and 0.5 mg for maintenance in adults over 60, debilitated or chronically ill |
| Modified Intention to Treat (mITT) | All ITT population who received at least 1 complete dose of study medication |
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| Safety Population | All randomized patients who received any amount of study drug and were analyzed as treated |
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| COMPLETED |
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| NOT COMPLETED |
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Baseline Analysis Population is the safety population
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| ID | Title | Description |
|---|---|---|
| BG000 | Remimazolam | Double-blind Remimazolam iv arm: 5 mg for sedation induction, and 2.5 mg top-ups for sedation maintenance. |
| BG001 | Placebo | Double-blind Placebo iv arm: inactive control arm |
| BG002 | Midazolam | Open-label Midazolam iv arm: 1.75 mg* for sedation induction and 1.0 mg* for sedation maintenance. *1.0 mg for induction and 0.5 mg for maintenance in adults over 60, debilitated or chronically ill |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Age, Customized | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Weight | Mean | Standard Deviation | Kg |
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| Height | Mean | Standard Deviation | cm |
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| Body Max Index (BMI) | Mean | Standard Deviation | kg/m2 |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Success Rates of the Procedure | Success of the Procedure is measured by completion of colonoscopy, no requirement for an alternative sedative and no requirement for more than 5 top-ups of study medication within any 15 minute period in the blinded arms (remimazolam/placebo) or no requirement for more than 3 doses within any 12 minute window in the midazolam arm. | Posted | Count of Participants | Participants | From administration of the first dose of the study drug to the end of colonoscopy |
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| Secondary | Time to Start of Procedure | The time to the start of the procedure after administration of the first dose of randomized study drug | Patients who do not reach the endpoint are excluded from the analysis. | Posted | Median | Inter-Quartile Range | minutes | From first dose of study drug until insertion of the colonoscope |
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| Secondary | Time to Fully Alert | The time to fully alert (time to first of three consecutive Modified Observer's Assessment of Alertness/Sedation [MOAA/S] scores of 5) after the end of colonoscopy procedure [colonoscope out], and after the last dose of study drug or rescue sedative medication | Patients who do not reach the endpoint are censored at last MOAA/S | Posted | Median | 95% Confidence Interval | minutes | From the end of colonoscopy (colonoscope out) until the patient has recovered to fully alert and from the last injection of the study drug or rescue sedative medication until the patient has recovered to fully alert |
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| Secondary | Time to Ready for Discharge | The time after the end of colonoscopy procedure (colonoscope out) and after the last injection of study drug or rescue sedative medication, until discharge (defined as ability to walk unassisted). | Posted | Median | 95% Confidence Interval | minutes | From the end of the colonoscopy until discharge (expected to be the same day). After the last dose of study drug or rescue sedative, until discharge (expected to be the same day). |
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From first dose of study drug until Day 4, or resolution of any ongoing adverse events
Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a non serious Treatment-emergent Adverse Event (TEAE). The listing of participants with Preferred Term (PT)TEAEs is reported with a threshold of 5% in any of the arms
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Remimazolam | Double-blind Remimazolam iv arm: 5 mg for sedation induction, and 2.5 mg top-ups for sedation maintenance. | 0 | 296 | 0 | 296 | 218 | 296 |
| EG001 | Placebo | Double-blind Placebo iv arm: as an inactive control | 0 | 60 | 0 | 60 | 47 | 60 |
| EG002 | Midazolam | Open-label Midazolam iv arm: 1.75 mg* for sedation induction and 1.0 mg* for sedation maintenance. *1.0 mg for induction and 0.5 mg for maintenance in adults over 60, debilitated or chronically ill | 0 | 102 | 0 | 102 | 93 | 102 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypotension | Vascular disorders | MedDRA (18.0) | Systematic Assessment |
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| Hypertension | Vascular disorders | MedDRA (18.0) | Non-systematic Assessment |
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| Bradycardia | Cardiac disorders | MedDRA (18.0) | Systematic Assessment |
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| Diastolic Hypertension | Vascular disorders | MedDRA (18.0) | Non-systematic Assessment |
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| Diastolic Hypotension | Vascular disorders | MedDRA (18.0) | Systematic Assessment |
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| Systolic hypertension | Vascular disorders | MedDRA (18.0) | Systematic Assessment |
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| Tachycardia | Cardiac disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (18.0) | Non-systematic Assessment |
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At least 60 days prior to submission of communications, sponsor shall review and comment on the communications. Sponsor shall have the right to require institution and investigator to remove specifically identified confidential information and to delay the proposed publication an additional 60 days to enable sponsor to seek patent protection.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Trial Information | PAION UK Ltd | +49 2414453101 | reg_paion@paion.com |
| ID | Term |
|---|---|
| C522201 | remimazolam |
| D008874 | Midazolam |
| ID | Term |
|---|---|
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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| ≥65 years |
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| Male |
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| Units | Counts |
|---|---|
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