CompletedNCT01145222Updated Jan 8, 2019Results posted

Multiple Dose Safety and Efficacy Study Evaluating CNS 7056 Versus Midazolam in Patients Undergoing Colonoscopy

A Phase 2 interventional study of A. CNS 7056 and B. CNS 7056 in Sedation, sponsored by Paion UK Ltd.. Completed at 9 sites in United States. Open to participants aged 18 Years to 70 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: 162
Allocation: Randomized
Ages: 18 Years to 70 Years
Sex: All

Study summary

The purpose of this dose-response study is to assess the safety and efficacy of CNS 7056 compared with midazolam to maintain suitable sedation levels in patients undergoing colonoscopy.

Read the detailed description

This is a double-blind, randomized, parallel group, dose-response study to assess the safety and efficacy of three dose levels of CNS 7056 compared with midazolam to maintain suitable sedation levels in patients undergoing colonoscopy.

Safety assessment will include physical examinations, vital signs, ECGs, pulse oximetry measurements, capnography, clinical chemistry and hematology laboratory tests, routine drug and ethanol screening, urinalysis, pregnancy test, pain on injection using a verbal scale, and monitoring of adverse events.

Conditions studied

Sedation

Keywords

CNS 7056
Procedural Sedation
Colonoscopy

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 70 Years
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

Male and female patients, aged 18 to 70 years inclusive, scheduled to undergo a standard colonoscopy.
American Society of Anesthesiologists Physical Status (ASA PS) Score I, II, or III.
Weight range 55 to 130 kg inclusive.
Body mass index (BMI) range 18 to 33 kg/m2 inclusive
Patients of child-bearing potential and their partners must have been willing to use adequate contraception such as an intrauterine device, diaphragm or condom during the study and until 1 month after the last study drug administration. Childbearing potential was defined as "all patients unless they were a female post menopausal for at least 2 years, or were surgically sterile."
Patient voluntarily signed and dated an ICF that was approved by an IRB prior to the conduct of any study procedure.
Patient was willing and able to comply with study requirements and return for a Follow up Visit (Day 4 ± 3 day) after the colonoscopy.

Exclusion criteria

Exclusion Criteria:

Expected duration of colonoscopy > 30 minutes.
Patients with a suspected or diagnosed pathology of the lower GI tract that would have added to the risk of colonoscopy, such as strictures, active inflammatory bowel disease.
ASA III patients with history of sleep apnea.
ASA III patients with obesity (BMI ≥ 30 kg/m2).
Patients with evidence of uncontrolled renal, hepatic, central nervous system, respiratory, cardiovascular or metabolic dysfunction, or other clinically significant (CS) findings at screening that, in the investigator's or medical monitor's opinion, should have excluded them from the study.
Patients with clinically significant abnormalities in 12 lead ECG recorded at screening.
Female patients with a positive serum human chorionic gonadotropin (HCG) pregnancy test at screening or baseline.
Lactating female patients.
Patients with positive drugs of abuse screen at baseline.
Patients with positive serum ethanol at baseline.
Patient with a history of drug or ethanol abuse.
Patients in receipt of any investigational drug within 30 days or less than 7 half lives (whichever was longer) before the start of the study, or scheduled to receive one during the study period.
Patients with a known sensitivity to benzodiazepines, flumazenil, opioids, naloxone, or a medical condition such that these agents were contraindicated.
Patients with an inability to communicate well with the investigator.
Patients in whom management of airway was judged to be difficult due to, e.g., thyro-mental distance ≤ 4 cm ("short neck"), or Mallampati score of 4.

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Double (Participant, Investigator)
Enrollment: 162 participants (actual)

Study arms

Experimental
A. Remimazolam (CNS 7056)
Initial 8 mg iv for sedation induction, and 3 mg iv top-ups for sedation maintenance. Fentanyl pre-treatment: up to 100 μg (at the discretion of the investigator) and 25 μg top-up doses.
Drug: A. CNS 7056
Experimental
B. Remimazolam (CNS 7056)
Initial 7 mg iv for sedation induction, and 2 mg iv top-ups for sedation maintenance. Fentanyl pre-treatment: up to 100 μg (at the discretion of the investigator) and 25 μg top-up doses.
Drug: B. CNS 7056
Experimental
C. Remimazolam (CNS 7056)
Initial 5 mg iv for sedation induction, and 3 mg iv top-ups for sedation maintenance. Fentanyl pre-treatment: up to 100 μg (at the discretion of the investigator) and 25 μg top-up doses.
Drug: C. CNS 7056
Active comparator
D. Midazolam
Initial 2.5 mg iv for sedation induction, and 1 mg iv top-ups for sedation maintenance. Fentanyl pre-treatment: up to 100 μg (at the discretion of the investigator) and 25 μg top-up doses
Drug: D. Midazolam

Interventions

DrugA. CNS 7056
Initial low dose plus supplemental doses as necessary.
Also known as: CAS No. 1001415-66-2, Remimazolam
DrugB. CNS 7056
Initial intermediate dose plus supplemental doses as necessary.
Also known as: CAS No. 1001415-66-2, Remimazolam
DrugC. CNS 7056
Initial high dose plus supplemental doses as necessary.
Also known as: CAS No. 1001415-66-2, Remimazolam
DrugD. Midazolam
Initial standardized dose plus supplemental doses as necessary.
Also known as: CAS No. 59467-96-8

What researchers measure

Primary outcomes

Success Rates of the Procedure
Success of the procedure is a composite endpoint consisting of: Modified Observer's Assessment for Alertness/Sedation (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 MOAA/S scores of 5 after the last injection of double-blind study medication
Time frame: From last injection of double-blind study medication until fully alert criteria are reached
Time to Ready for Discharge
Time of the first of 3 consecutive Aldrete scores ≥ 9
Time frame: After the Last Injection of Double-Blind Study Medication AND after end of colonoscopy until first of 3 consecutive Aldrete scores ≥ 9

Results

Posted Jan 8, 2019

Participant flow

Participant flow — Overall Study
Milestone	Remimazolam 8.0/3.0 mg	Remimazolam 7.0/2.0 mg	Remimazolam 5.0/3.0 mg	Midazolam 2.5/1.0
Started	40	40	41	41
Safety population	40	40	40	41
Intention to treat (itt) population	40	40	40	40
Completed	40	40	40	40
Not completed	0	0	1	1
Withdrew: Procedure not done (no anesthesiologist)	0	0	1	0
Withdrew: Poor bowel preparation	0	0	0	1

Outcome measures

PrimarySuccess Rates of the Procedure

Success of the procedure is a composite endpoint consisting of: Modified Observer's Assessment for Alertness/Sedation (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	Remimazolam 8.0/3.0 mg	Remimazolam 7.0/2.0 mg	Remimazolam 5.0/3.0 mg	Midazolam 2.5/1.0
Success Rates of the Procedure	37	38	39	30

Statistical analysis

Remimazolam 8.0/3.0 mg vs Remimazolam 7.0/2.0 mg vs Remimazolam 5.0/3.0 mg vs Midazolam 2.5/1.0 · Fisher Exact · p = 0.007

SecondaryTime to Fully Alert

Time to first of 3 consecutive MOAA/S scores of 5 after the last injection of double-blind study medication

Time frame:: From last injection of double-blind study medication until fully alert criteria are reached
Reported as:: Mean · minutes

Time to Fully Alert
minutes	Remimazolam 8.0/3.0 mg	Remimazolam 7.0/2.0 mg	Remimazolam 5.0/3.0 mg	Midazolam 2.5/1.0
Time to Fully Alert	13.6 ± 7.48	11.3 ± 5.69	13.3 ± 7.21	15.2 ± 7.43

SecondaryTime to Ready for Discharge

Time of the first of 3 consecutive Aldrete scores ≥ 9

Time frame:: After the Last Injection of Double-Blind Study Medication AND after end of colonoscopy until first of 3 consecutive Aldrete scores ≥ 9
Reported as:: Mean · minutes

Time to Ready for Discharge
minutes	Remimazolam 8.0/3.0 mg	Remimazolam 7.0/2.0 mg	Remimazolam 5.0/3.0 mg	Midazolam 2.5/1.0
After last injection	14.6 ± 8.52	12.4 ± 6.72	11.3 ± 4.86	15.3 ± 8.13
After end of colonoscopy	5.0 ± 6.29	4.6 ± 4.58	3.8 ± 4.16	5.5 ± 6.59

Adverse events

Collected over Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug until Day 4 ± 3 days, and were followed until resolution of any ongoing TEAE up to 30 days. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Remimazolam 8.0/3.0 mg	0/40 (0%)	0/40 (0%)	10/40 (25%)
Remimazolam 7.0/2.0 mg	0/40 (0%)	0/40 (0%)	8/40 (20%)
Remimazolam 5.0/3.0 mg	0/40 (0%)	0/40 (0%)	9/40 (22.5%)
Midazolam 2.5/1.0	0/41 (0%)	0/41 (0%)	6/41 (14.6%)

Most frequent other events

Most frequent other events
Event	Remimazolam 8.0/3.0 mg	Remimazolam 7.0/2.0 mg	Remimazolam 5.0/3.0 mg	Midazolam 2.5/1.0
HypertensionVascular disorders	3/40	0/40	1/40	4/41
BradycardiaCardiac disorders	3/40	1/40	0/40	0/41
Abdominal painGastrointestinal disorders	1/40	2/40	3/40	0/41
VomitingGastrointestinal disorders	1/40	2/40	3/40	2/41
HeadacheNervous system disorders	1/40	3/40	3/40	2/41
NauseaGastrointestinal disorders	3/40	2/40	2/40	1/41
DizzinessNervous system disorders	0/40	1/40	2/40	0/41

Baseline characteristics

Baseline Analysis Population is the Safety Population

Age, Continuous
Age, Continuous(years)	Remimazolam 8.0/3.0 mg	Remimazolam 7.0/2.0 mg	Remimazolam 5.0/3.0 mg	Midazolam 2.5/1.0	Total
Mean	54.5 ± 11.22	54.5 ± 8.07	54.0 ± 10.30	55.5 ± 5.86	54.6 ± 9.02

Sex: Female, Male
Sex: Female, Male(Participants)	Remimazolam 8.0/3.0 mg	Remimazolam 7.0/2.0 mg	Remimazolam 5.0/3.0 mg	Midazolam 2.5/1.0	Total
Female	22	25	22	20	89
Male	18	15	18	21	72

Region of Enrollment
Region of Enrollment(participants)	Remimazolam 8.0/3.0 mg	Remimazolam 7.0/2.0 mg	Remimazolam 5.0/3.0 mg	Midazolam 2.5/1.0	Total
United States	40	40	40	41	161

Height
Height(cm)	Remimazolam 8.0/3.0 mg	Remimazolam 7.0/2.0 mg	Remimazolam 5.0/3.0 mg	Midazolam 2.5/1.0	Total
Mean	169.15 ± 11.0	168.18 ± 8.3	169.01 ± 11.3	169.87 ± 10.1	169.06 ± 10.2

Weight
Weight(kg)	Remimazolam 8.0/3.0 mg	Remimazolam 7.0/2.0 mg	Remimazolam 5.0/3.0 mg	Midazolam 2.5/1.0	Total
Mean	79.68 ± 13.4	76.23 ± 11.6	76.79 ± 14.5	76.95 ± 13.6	77.41 ± 13.3

Body Mass Index (BMI)
Body Mass Index (BMI)(Kg/m2)	Remimazolam 8.0/3.0 mg	Remimazolam 7.0/2.0 mg	Remimazolam 5.0/3.0 mg	Midazolam 2.5/1.0	Total
Mean	27.79 ± 3.451	27.02 ± 4.042	26.73 ± 3.063	26.58 ± 3.515	27.03 ± 3.533

Study locations

9 sites

Helen Keller Hospital
Sheffield, Alabama 35660, United States
HOPE Research Institute
Phoenix, Arizona 85050, United States
ACRI Phase I LLC
Anaheim, California 92801, United States
Advanced Clinical Research Associates
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
Options Health Research
Tulsa, Oklahoma 74104, United States
Charlottesville Medical Research
Charlottesville, Virginia 22911, United States

References and documents

Publications

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. PubMed 26363333 ↗

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: NCT01145222
Lead sponsor: Paion UK Ltd.
Collaborators: Premier Research Group plc
Responsible party: Sponsor
First posted: Jun 16, 2010
Start date: May 2010
Primary completion: Sep 2010
Completion: Oct 2010
Results posted: Jan 8, 2019
Last update: Jan 8, 2019

Oversight

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

View the source record on ClinicalTrials.gov ↗

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