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

NCT00869440 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: CNS 7056-003
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 7

Brief 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.

Conditions

Procedural Sedation; Endoscopy

Keywords

CNS 7056; Procedural Sedation; Sedation; Endoscopy

Outcome Measures

Primary Outcomes (1)

• 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

  From start of study drug injection to patient discharge

Secondary Outcomes (2)

• Time to Fully Alert

  From study drug administration until fully alert criteria are reached

• Time to Ready for Discharge

  From the end of the endoscopy procedure up to 120 minutes or until 3 consecutive Aldrete scores of ≥9 are reached, whichever occurs first

Study Arms (4)

1: Remimazolam (CNS 7056) 0.10 mg/kg

EXPERIMENTAL

Remimazolam (CNS 7056) 0.10 mg/kg iv

Drug: CNS 7056

2: Remimazolam (CNS 7056) 0.15 mg/kg

EXPERIMENTAL

Remimazolam (CNS 7056) 0.15 mg/kg iv

Drug: CNS 7056

3: Remimazolam (CNS 7056) 0.20 mg/kg

EXPERIMENTAL

Remimazolam (CNS 7056) 0.20 mg/kg iv

Drug: CNS 7056

4: Midazolam 0.075 mg/kg

EXPERIMENTAL

Midazolam 0.075 mg/kg iv

Drug: Midazolam

Interventions

CNS 7056 DRUG

Administered as a single intravenous injection by a syringe driver over 1 minute

Also known as: remimazolam

1: Remimazolam (CNS 7056) 0.10 mg/kg; 2: Remimazolam (CNS 7056) 0.15 mg/kg; 3: Remimazolam (CNS 7056) 0.20 mg/kg

Midazolam DRUG

Administered as a single intravenous injection by a syringe driver over 1 minute

Also known as: Versed

4: Midazolam 0.075 mg/kg

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Paion UK Ltd.: lead
• Premier Research: collaborator

Study Sites (7)

Helen Keller Hospital

Sheffield, Alabama, 35660, United States

Location

HOPE Research Institute

Phoenix, Arizona, 85050, United States

Location

Advanced Clinical Research Institute

Anaheim, California, 92801, United States

Location

Miami Research Associates

South Miami, Florida, 33143, United States

Location

Stony Brook University Medical Center

Stony Brook, New York, 11794, United States

Location

Wake Research Associates

Raleigh, North Carolina, 27612, United States

Location

Charlottesville Medical Research

Charlottesville, Virginia, 22911, United States

Location

Related Publications (1)

• 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.

  PMID: 25502841 RESULT

MeSH Terms

Interventions

remimazolam; Midazolam

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Trial Information
• Organization: PAION UK Ltd

reg_paion@paion.com

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2009
• First Posted: March 26, 2009
• Study Start: March 1, 2009
• Primary Completion: September 1, 2009
• Study Completion: September 1, 2009
• Last Updated: January 8, 2019
• Results First Posted: January 8, 2019

Record last verified: 2018-12

Locations

US (7)