CompletedNCT00869440Updated Jan 8, 2019Results posted

Dose-Finding Safety Study Evaluating Remimazolam (CNS 7056) in Patients Undergoing Diagnostic Upper GI Endoscopy

A Phase 2 interventional study of CNS 7056 and Midazolam in Procedural Sedation and Endoscopy, sponsored by Paion UK Ltd.. Completed at 7 sites in United States. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2019-01-08.

Sponsored by Paion UK Ltd. · Phase 2, Interventional, and Treatment

Phase: Phase 2
Study type: Interventional
Enrollment: 100
Allocation: Randomized
Ages: 18 Years to 65 Years
Sex: All

Study 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 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 studied

Procedural Sedation
Endoscopy

Keywords

CNS 7056
Procedural Sedation
Sedation
Endoscopy

In context

Lead sponsor

Paion UK Ltd. is the lead sponsor of 14 studies on the registry; none are open to participants now.

Of its 9 completed or terminated interventional studies of FDA-regulated products, 5 (56%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 65 Years
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

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.
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.

Exclusion criteria

Exclusion Criteria:

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).
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).

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Double (Participant, Investigator)
Enrollment: 100 participants (actual)

Study arms

Experimental
1: Remimazolam (CNS 7056) 0.10 mg/kg
Remimazolam (CNS 7056) 0.10 mg/kg iv
Drug: CNS 7056
Experimental
2: Remimazolam (CNS 7056) 0.15 mg/kg
Remimazolam (CNS 7056) 0.15 mg/kg iv
Drug: CNS 7056
Experimental
3: Remimazolam (CNS 7056) 0.20 mg/kg
Remimazolam (CNS 7056) 0.20 mg/kg iv
Drug: CNS 7056
Experimental
4: Midazolam 0.075 mg/kg
Midazolam 0.075 mg/kg iv
Drug: Midazolam

Interventions

DrugCNS 7056
Administered as a single intravenous injection by a syringe driver over 1 minute
Also known as: remimazolam
DrugMidazolam
Administered as a single intravenous injection by a syringe driver over 1 minute
Also known as: Versed

What researchers measure

Primary outcomes

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
Time frame: From start of study drug injection to patient discharge

Secondary outcomes

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
Time frame: 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
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

Posted Jan 8, 2019

Participant flow

Participant flow — Overall Study
Milestone	1: CNS 7056 0.10 mg/kg	2: CNS 7056 0.15 mg/kg	3: CNS 7056 0.20 mg/kg	4: Midazolam 0.075 mg/kg
Started	25	25	25	25
Completed	23	24	25	25
Not completed	2	1	0	0
Withdrew: Withdrawal by subject	1	0	0	0
Withdrew: Physician decision	1	1	0	0

Outcome measures

PrimarySuccess 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

Time frame:: From start of study drug injection to patient discharge
Reported as:: Count of participants · Participants

Success Rates of the Procedure
Participants	1: CNS 7056 0.10 mg/kg	2: CNS 7056 0.15 mg/kg	3: CNS 7056 0.20 mg/kg	4: Midazolam 0.075 mg/kg
Success Rates of the Procedure	8	14	16	11

SecondaryTime 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

Time frame:: From study drug administration until fully alert criteria are reached
Reported as:: Mean · minutes

Time to Fully Alert
minutes	1: CNS 7056 0.10 mg/kg	2: CNS 7056 0.15 mg/kg	3: CNS 7056 0.20 mg/kg	4: Midazolam 0.075 mg/kg
Time to Fully Alert	11 ± 10.04	13.4 ± 6.51	12.1 ± 5.26	17.2 ± 16.71

SecondaryTime to Ready for Discharge

Time to first of 3 consecutive Aldrete scores ≥9 after the end endoscopy procedure

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
Reported as:: Mean · minutes

Time to Ready for Discharge
minutes	1: CNS 7056 0.10 mg/kg	2: CNS 7056 0.15 mg/kg	3: CNS 7056 0.20 mg/kg	4: Midazolam 0.075 mg/kg
Time to Ready for Discharge	14 ± 9.96	12.8 ± 5.96	11.8 ± 4.96	17.2 ± 12.81

Adverse events

Collected over Treatment-emergent adverse events (TEAEs) were collected from Time 0 on Day 1 to the Follow-up Visit on Day 4, and were followed until resolution (with or without sequelae) up to a maximum of 30 days after Time 0.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
1: CNS 7056 0.10 mg/kg	0/25 (0%)	0/25 (0%)	6/25 (24%)
2: CNS 7056 0.15 mg/kg	0/25 (0%)	0/25 (0%)	8/25 (32%)
3: CNS 7056 0.20 mg/kg	0/25 (0%)	0/25 (0%)	9/25 (36%)
4: Midazolam 0.075 mg/kg	0/25 (0%)	0/25 (0%)	10/25 (40%)

Most frequent other events

Most frequent other events
Event	1: CNS 7056 0.10 mg/kg	2: CNS 7056 0.15 mg/kg	3: CNS 7056 0.20 mg/kg	4: Midazolam 0.075 mg/kg
Oxygen saturation decreasedInvestigations	4/25	5/25	6/25	5/25
Abdominal painGastrointestinal disorders	0/25	0/25	2/25	0/25
DizzinessNervous system disorders	0/25	0/25	0/25	2/25
HeadacheNervous system disorders	2/25	2/25	2/25	2/25
Pharyngeolaryngeal painRespiratory, thoracic and mediastinal disorders	1/25	1/25	0/25	2/25

Baseline characteristics

Age, Continuous
Age, Continuous(years)	1: CNS 7056 0.10 mg/kg	2: CNS 7056 0.15 mg/kg	3: CNS 7056 0.20 mg/kg	4: Midazolam 0.075 mg/kg	Total
Mean	37.7 ± 13.33	38.8 ± 14.08	43.2 ± 13.95	44.6 ± 13.64	41.1 ± 13.86

Sex: Female, Male
Sex: Female, Male(Participants)	1: CNS 7056 0.10 mg/kg	2: CNS 7056 0.15 mg/kg	3: CNS 7056 0.20 mg/kg	4: Midazolam 0.075 mg/kg	Total
Female	13	13	16	12	54
Male	12	12	9	13	46

Region of Enrollment
Region of Enrollment(participants)	1: CNS 7056 0.10 mg/kg	2: CNS 7056 0.15 mg/kg	3: CNS 7056 0.20 mg/kg	4: Midazolam 0.075 mg/kg	Total
United States	25	25	25	25	100

Height
Height(cm)	1: CNS 7056 0.10 mg/kg	2: CNS 7056 0.15 mg/kg	3: CNS 7056 0.20 mg/kg	4: Midazolam 0.075 mg/kg	Total
Mean	169.33 ± 9.603	168.42 ± 10.283	168.97 ± 7.432	171.55 ± 9.650	169.57 ± 9.241

Weight
Weight(kg)	1: CNS 7056 0.10 mg/kg	2: CNS 7056 0.15 mg/kg	3: CNS 7056 0.20 mg/kg	4: Midazolam 0.075 mg/kg	Total
Mean	73.22 ± 10.583	75.17 ± 10.869	75.13 ± 11.027	75.45 ± 10.099	74.74 ± 10.526

Body Mass Index (BMI)
Body Mass Index (BMI)(Kg/m2)	1: CNS 7056 0.10 mg/kg	2: CNS 7056 0.15 mg/kg	3: CNS 7056 0.20 mg/kg	4: Midazolam 0.075 mg/kg	Total
Mean	25.47 ± 2.091	26.43 ± 2.158	26.24 ± 2.725	25.59 ± 2.262	25.93 ± 2.324

Study locations

7 sites

Helen Keller Hospital
Sheffield, Alabama 35660, United States
HOPE Research Institute
Phoenix, Arizona 85050, United States
Advanced Clinical Research Institute
Anaheim, California 92801, United States
Miami Research Associates
South Miami, Florida 33143, United States
Stony Brook University Medical Center
Stony Brook, New York 11794, United States
Wake Research Associates
Raleigh, North Carolina 27612, United States
Charlottesville Medical Research
Charlottesville, Virginia 22911, United States

References and documents

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 ↗

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Jan 8, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00869440
Lead sponsor: Paion UK Ltd.
Collaborators: Premier Research Group plc
Responsible party: Sponsor
First posted: Mar 26, 2009
Start date: Mar 2009
Primary completion: Sep 2009
Completion: Sep 2009
Results posted: Jan 8, 2019
Last update: Jan 8, 2019

Oversight

Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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