Procedural SedationPhase 2NCT00869440
Dose-Finding Safety Study Evaluating Remimazolam (CNS 7056) in Patients Undergoing Diagnostic Upper GI Endoscopy
A Phase 2 study testing CNS 7056 and Midazolam in people with Procedural Sedation and Endoscopy, run by Paion UK Ltd. at 7 sites in United States.
Trial summary
The purpose of this study was to assess the safety and efficacy of CNS 7056 as a procedural sedative at three dose levels compared to midazolam during a diagnostic upper GI endoscopy. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Procedural Sedation, Endoscopy
- What is being tested?
- CNS 7056 and Midazolam
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 7 sitesUnited States
- Study dates
- Mar 2009to Sep 2009
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male and female patients, aged 18 to 65 years inclusive, scheduled to undergo diagnostic upper GI endoscopy.
- American Society of Anesthesiologists Physical Status (ASA PS) Score I or II.
- Weight range 60 to 120 kg inclusive.
- Body mass index (BMI) 18 to < 30 kg/m2.
- Patients with no clinically significant abnormalities in 12 lead ECG recorded at Screening.
- Female with a negative serum human chorionic gonadotropin (hCG) pregnancy test result at Screening and negative urine hCG pregnancy test result on Day 1 before the endoscopy procedure.
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- Patients with negative drugs of abuse serum result at Screening and negative drugs of abuse urine result on Day 1 before the endoscopy procedure.
- Patient has a negative serum ethanol test result at Screening and a negative ethanol saliva test result on Day 1 before the endoscopy procedure.
- Patient voluntarily signs and dates an informed consent form (ICF) that is approved by an investigational review board (IRB) prior to the conduct of any study procedure.
- Patient is willing and able to comply with study requirements and return for a Follow up Visit (Visit 3 ± 1 day) after the endoscopy procedure.
Who cannot join
- Patients with a suspected upper GI bleed an conditions predisposing to hemorrhage at the discretion of the investigator.
- Has a known sensitivity to benzodiazepines, flumazenil, or anesthetic agents, or a medical condition such that these agents are contraindicated.
- Patients with evidence of uncontrolled renal, hepatic, central nervous system, respiratory, cardiovascular, or metabolic dysfunction, in the opinion of the investigator or medical monitor.
- Patients taking an agent that inhibits cytochrome P450 subtype 3A4 (CYP3A4) or patients who have taken such an agent within 14 days prior to study start or within the duration of 7 half lives of the drug, whichever is longer.
- Patients in receipt of any investigational drug within 30 days or less than 7 half lives (whichever is longer) before the start of the study, or scheduled to receive one during the study period.
- Chronic use of benzodiazepines for any indication (eg, insomnia, anxiety, spasticity).
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- Has known or suspected history of alcoholism or drug abuse or misuse within 2 years of Screening or evidence of tolerance or physical dependence before dosing with study drug.
- Patients with clinically significant findings at Screening that, in the investigator's opinion, should exclude them from the study.
- Patients with a history of laboratory results that show the presence of hepatitis B surface antigen (HBs Ag), hepatitis C antibody (HCV Ab), or human immunodeficiency virus (HIV).
- Patients with an inability to communicate well in English with the investigator.
- Lactating female patients.
- Patients in whom management of airway is judged to be difficult due to:
- obesity (weight > 120 kg, or BMI ≥ 30 kg/m2),
- thyro mental distance ≤ 4 cm ("short neck"), or
- Mallampati score of 4 (Appendix IV).
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Advanced Clinical Research Institute
Anaheim, California, 92801
Charlottesville Medical Research
Charlottesville, Virginia, 22911
HOPE Research Institute
Phoenix, Arizona, 85050
Wake Research Associates
Raleigh, North Carolina, 27612
Helen Keller Hospital
Sheffield, Alabama, 35660
Miami Research Associates
South Miami, Florida, 33143
Stony Brook University Medical Center
Stony Brook, New York, 11794
About this study
Official title: A Phase IIa, Randomized, Controlled, Double-Blind, Dose-Finding Study Evaluating the Safety and Pharmacodynamics of CNS 7056 in Patients Undergoing Diagnostic Upper GI Endoscopy
The purpose of this study was to assess the safety and efficacy of CNS 7056 as a procedural sedative at three dose levels compared to midazolam during a diagnostic upper GI endoscopy.
Read the detailed description
This was a randomized, double-blind, parallel-group, dose-finding study assessing the safety and efficacy of three dose levels of CNS 7056 compared with midazolam in patients undergoing diagnostic upper GI endoscopy.
Patients who met all study entry criteria and completed screening procedures were randomly assigned to 1 of 4 treatment groups: CNS 7056 0.10 mg/kg,0.15 mg/kg, or 0.20 mg/kg; or midazolam 0.075 mg/kg. Patients received their assigned treatment administered as a single intravenous injection by a syringe driver over 1 minute. The endoscopy started when a Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score of ≤3 has been reached, but no earlier than 90 seconds after Time 0 (the start of study drug injection). Rescue with sedative medication (midazolam 1-2 mg) was be permitted at the discretion of the administering physician.
Efficacy assessments consisted of the MOAA/S scores, Aldrete scores, and drowsiness measures using a Visual Analogue Scale (VAS). Cognitive function was assessed by the Hopkins Verbal Learning Test-Revised™ (HVLT-R™) and memory for the procedure by the Brice Questionnaire.
Safety assessments included adverse events, physical examinations, vital signs, ECGs, pulse oximetry measurements, clinical laboratory tests, and pain on injection using a VAS.
- Conditions
- Procedural Sedation, Endoscopy
- Being tested
- CNS 7056, Midazolam
- Keywords
- CNS 7056, Procedural Sedation, Sedation, Endoscopy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CNS 7056Drug
Also called remimazolam
Administered as a single intravenous injection by a syringe driver over 1 minute
MidazolamDrug
Also called Versed
Administered as a single intravenous injection by a syringe driver over 1 minute
| Study group | Role | What they receive |
|---|---|---|
| 1: Remimazolam (CNS 7056) 0.10 mg/kg | Experimental | Remimazolam (CNS 7056) 0.10 mg/kg iv Receives: Drug: CNS 7056 |
| 2: Remimazolam (CNS 7056) 0.15 mg/kg | Experimental | Remimazolam (CNS 7056) 0.15 mg/kg iv Receives: Drug: CNS 7056 |
| 3: Remimazolam (CNS 7056) 0.20 mg/kg | Experimental | Remimazolam (CNS 7056) 0.20 mg/kg iv Receives: Drug: CNS 7056 |
| 4: Midazolam 0.075 mg/kg | Experimental | Midazolam 0.075 mg/kg iv Receives: Drug: Midazolam |
What is being measured
The primary outcome is the main question the study is designed to answer.
Success Rates of the Procedure
Success of the procedure is a composite endpoint consisting of: MOAA/S scores ≤4 on three consecutive measurements after administration of study drug AND completion of the endoscopy procedure AND no requirement for rescue sedative medication AND no requirement for manual or mechanical ventilation
Measured: From start of study drug injection to patient discharge
Secondary outcomes (2)
Time to Fully Alert
Time to first of 3 consecutive Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scores of 5 following study drug administration in patients who underwent the endoscopy procedure
Measured: From study drug administration until fully alert criteria are reached
Time to Ready for Discharge
Time to first of 3 consecutive Aldrete scores ≥9 after the end endoscopy procedure
Measured: From the end of the endoscopy procedure up to 120 minutes or until 3 consecutive Aldrete scores of ≥9 are reached, whichever occurs first
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Mar 2009 (estimated)
- Study startMar 2009
- Primary completionSep 2009
- Study completionSep 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Procedural SedationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Paion UK Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Premier Research
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00869440
- Sponsor's protocol ID
- CNS 7056-003
- Status last verified
- Dec 2018
- First submitted
- 25 Mar 2009
- Last updated
- 8 Jan 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 25502841
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IIa, Randomized, Controlled, Double-Blind, Dose-Finding Study Evaluating the Safety and Pharmacodynamics of CNS 7056 in Patients Undergoing Diagnostic Upper GI Endoscopy
- ClinicalTrials.gov ID
- NCT00869440
- Acronym / sponsor ID
- CNS 7056-003
- Conditions
- Procedural Sedation, Endoscopy
- Keywords
- CNS 7056, Procedural Sedation, Sedation, Endoscopy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Paion UK Ltd.Industry (pharma, biotech, devices)
- Collaborators
- Premier Research
- Study start
- Mar 2009
- Primary completion
- Sep 2009 (actual)
- Study completion
- Sep 2009 (actual)
- First posted
- 26 Mar 2009 (estimated)
- Results
- Posted 8 Jan 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study was to assess the safety and efficacy of CNS 7056 as a procedural sedative at three dose levels compared to midazolam during a diagnostic upper GI endoscopy.
Detailed description
This was a randomized, double-blind, parallel-group, dose-finding study assessing the safety and efficacy of three dose levels of CNS 7056 compared with midazolam in patients undergoing diagnostic upper GI endoscopy.
Patients who met all study entry criteria and completed screening procedures were randomly assigned to 1 of 4 treatment groups: CNS 7056 0.10 mg/kg,0.15 mg/kg, or 0.20 mg/kg; or midazolam 0.075 mg/kg. Patients received their assigned treatment administered as a single intravenous injection by a syringe driver over 1 minute. The endoscopy started when a Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score of ≤3 has been reached, but no earlier than 90 seconds after Time 0 (the start of study drug injection). Rescue with sedative medication (midazolam 1-2 mg) was be permitted at the discretion of the administering physician.
Efficacy assessments consisted of the MOAA/S scores, Aldrete scores, and drowsiness measures using a Visual Analogue Scale (VAS). Cognitive function was assessed by the Hopkins Verbal Learning Test-Revised™ (HVLT-R™) and memory for the procedure by the Brice Questionnaire.
Safety assessments included adverse events, physical examinations, vital signs, ECGs, pulse oximetry measurements, clinical laboratory tests, and pain on injection using a VAS.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 1: Remimazolam (CNS 7056) 0.10 mg/kg | Experimental | Drug: CNS 7056Remimazolam (CNS 7056) 0.10 mg/kg iv |
| 2: Remimazolam (CNS 7056) 0.15 mg/kg | Experimental | Drug: CNS 7056Remimazolam (CNS 7056) 0.15 mg/kg iv |
| 3: Remimazolam (CNS 7056) 0.20 mg/kg | Experimental | Drug: CNS 7056Remimazolam (CNS 7056) 0.20 mg/kg iv |
| 4: Midazolam 0.075 mg/kg | Experimental | Drug: MidazolamMidazolam 0.075 mg/kg iv |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Male and female patients, aged 18 to 65 years inclusive, scheduled to undergo diagnostic upper GI endoscopy.
- American Society of Anesthesiologists Physical Status (ASA PS) Score I or II.
- Weight range 60 to 120 kg inclusive.
- Body mass index (BMI) 18 to < 30 kg/m2.
- Patients with no clinically significant abnormalities in 12 lead ECG recorded at Screening.
Key exclusion criteria (15 listed)
- Patients with a suspected upper GI bleed an conditions predisposing to hemorrhage at the discretion of the investigator.
- Has a known sensitivity to benzodiazepines, flumazenil, or anesthetic agents, or a medical condition such that these agents are contraindicated.
- Patients with evidence of uncontrolled renal, hepatic, central nervous system, respiratory, cardiovascular, or metabolic dysfunction, in the opinion of the investigator or medical monitor.
- Patients taking an agent that inhibits cytochrome P450 subtype 3A4 (CYP3A4) or patients who have taken such an agent within 14 days prior to study start or within the duration of 7 half lives of the drug, whichever is longer.
- Patients in receipt of any investigational drug within 30 days or less than 7 half lives (whichever is longer) before the start of the study, or scheduled to receive one during the study period.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CNS 7056Also: remimazolamAdministered as a single intravenous injection by a syringe driver over 1 minute | Drug | 1: Remimazolam (CNS 7056) 0.10 mg/kg, 2: Remimazolam (CNS 7056) 0.15 mg/kg, 3: Remimazolam (CNS 7056) 0.20 mg/kg |
| MidazolamAlso: VersedAdministered as a single intravenous injection by a syringe driver over 1 minute | Drug | 4: Midazolam 0.075 mg/kg |
Primary outcome
Success Rates of the Procedure
Time frame: From start of study drug injection to patient discharge
Success of the procedure is a composite endpoint consisting of: MOAA/S scores ≤4 on three consecutive measurements after administration of study drug AND completion of the endoscopy procedure AND no requirement for rescue sedative medication AND no requirement for manual or mechanical ventilation
2 secondary outcomes
Time to Fully Alert
Time frame: From study drug administration until fully alert criteria are reached
Time to Ready for Discharge
Time frame: From the end of the endoscopy procedure up to 120 minutes or until 3 consecutive Aldrete scores of ≥9 are reached, whichever occurs first
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 25502841Borkett 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing CNS 7056 and Midazolam in people with Procedural Sedation and Endoscopy, run by Paion UK Ltd. at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Success Rates of the Procedure (time frame: From start of study drug injection to patient discharge). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00869440, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jan 2019.