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

Paion

Status and phase: Completed; Phase 2

Conditions: Sedation

Treatments: Drug: D. Midazolam; Drug: A. CNS 7056; Drug: C. CNS 7056; Drug: B. CNS 7056

Study type: Interventional

Funder types: Industry

Identifiers

NCT01145222

CNS 7056-004

Details and patient eligibility

About

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.

Full 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.

Enrollment: 162 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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

• 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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162 participants in 4 patient groups

A. Remimazolam (CNS 7056)

Experimental group

Description:

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.

Treatment:

Drug: A. CNS 7056

B. Remimazolam (CNS 7056)

Experimental group

Description:

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.

Treatment:

Drug: B. CNS 7056

C. Remimazolam (CNS 7056)

Experimental group

Description:

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.

Treatment:

Drug: C. CNS 7056

D. Midazolam

Active Comparator group

Description:

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

Treatment:

Drug: D. Midazolam