Dose-Finding Safety Study Evaluating CNS 7056 in Patients Undergoing Diagnostic Upper GI Endoscopy - Full Text View

Purpose

The purpose of this study is 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.

Condition	Intervention	Phase
Procedural Sedation Endoscopy	Drug: CNS 7056 Drug: Midazolam	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Endoscopy

Drug Information available for: Midazolam hydrochloride

U.S. FDA Resources

Further study details as provided by Paion UK Ltd.:

Primary Outcome Measures:

MOAA/S scores ≤4 on three consecutive measurements after administration of study drug AND completion of the endoscopy procedure without requiring rescue sedative medication AND without requiring manual or mechanical ventilation [ Time Frame: From start of study drug injection to patient discharge ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Time to fully alert (time to first of 3 consecutive MOAA/S scores of 5) [ Time Frame: At 1, 1.5, 2, 2.5, and 3 minutes after start of study drug injection; then every 2 minutes up to and including 15 minutes; then every 5 minutes until fully alert criteria are reached. ] [ Designated as safety issue: No ]
Time to ready for discharge (time to first of 3 consecutive Aldrete scores ≥9) [ Time Frame: Beginning immediately after the end of the endoscopy procedure; then every 5 minutes up to 120 minutes or until 3 consecutive Aldrete scores of ≥9 are reached, whichever occurs first ] [ Designated as safety issue: No ]
No requirement for rescue sedative medication [ Time Frame: From the start of study drug injection to end of endoscopy procedure ] [ Designated as safety issue: No ]
No manual or mechanical ventilation [ Time Frame: From start of study drug injection to patient discharge ] [ Designated as safety issue: Yes ]
MOAA/S score at specified time points [ Time Frame: Within 15 minutes prior to start of study drug administration and at 1, 1.5, 2, 2.5, and 3 minutes after study drug injection; then every 2 minutes up to and including 15 minutes; then every 5 minutes until fully alert criteria are reached ] [ Designated as safety issue: No ]
Drowsiness intensity rating on VAS at specified time points [ Time Frame: Within 15 minutes prior to start of study drug administration and at 5, 10, 15, 25, 35,45,60, 90 and 120 minutes after study drug injection or until fully alert criteria are reached, whichever comes first ] [ Designated as safety issue: No ]
HVLT-R Score [ Time Frame: Administered within 30 minutes prior to study drug administration and 5 minutes after fully alert criteria are reached, but no less than 20 minutes after the preprocedure assessment ] [ Designated as safety issue: No ]
Brice Questionnaire [ Time Frame: Administered after fully alert criteria are reached and then at the Follow-up/Early termination Visit ] [ Designated as safety issue: No ]

Enrollment:	102
Study Start Date:	March 2009
Study Completion Date:	September 2009
Primary Completion Date:	September 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 CNS 7056 0.10 mg/kg	Drug: CNS 7056 Administered as a single intravenous injection by a syringe driver over 1 minute
Experimental: 2 CNS 7056 0.15 mg/kg	Drug: CNS 7056 Administered as a single intravenous injection by a syringe driver over 1 minute
Experimental: 3 CNS 7056 0.20 mg/kg	Drug: CNS 7056 Administered as a single intravenous injection by a syringe driver over 1 minute
Experimental: 4 Midazolam 0.075 mg/kg	Drug: Midazolam Administered as a single intravenous injection by a syringe driver over 1 minute

Detailed Description:

This is 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 meet all study entry criteria and complete screening procedures will be 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 will receive their assigned treatment administered as a single intravenous injection by a syringe driver over 1 minute. The endoscopy will be 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) will be permitted at the discretion of the administering physician.

Efficacy assessments will consist of the MOAA/S scores, Aldrete scores, and drowsiness measures using a Visual Analogue Scale (VAS). Cognitive function will be assessed by the HVLT-R™ and memory for the procedure by the Brice Questionnaire.

Safety assessments will include adverse events, physical examinations, vital signs, ECGs, pulse oximetry measurements, clinical laboratory tests, and pain on injection using a VAS.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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 ICF that is approved by an 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:

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).

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00869440

Locations

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

Sponsors and Collaborators

Paion UK Ltd.

Investigators

Study Director:

James P Lees, B.Sc. MedSci

Paion UK Ltd.

More Information

No publications provided

Responsible Party:	Jim Lees, Clinical Development Manager, Paion UK Ltd.
ClinicalTrials.gov Identifier:	NCT00869440 History of Changes
Other Study ID Numbers:	CNS 7056-003
Study First Received:	March 25, 2009
Last Updated:	September 8, 2010
Health Authority:	United States: Food and Drug Administration

Keywords provided by Paion UK Ltd.:

CNS 7056
Procedural Sedation
Sedation
Endoscopy

Additional relevant MeSH terms:

Midazolam
Adjuvants, Anesthesia
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Anxiety Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs

Psychotropic Drugs
Hypnotics and Sedatives
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on June 18, 2013