A phase II, randomized, single-blind study to investigate the safety and efficacy of 3 dosing regimens of ABP-700 for procedural sedation in adult patients undergoing colonoscopy.

INTERVENTION: ABP‐700 (cyclopropyl‐MOC‐metomidate, CPMM), is an intravenous (IV) anesthetic being developed for sedation, monitored anesthesia care (MAC) and/or general anesthesia in patients undergoing therapeutic or diagnostic procedures such as colonoscopies. ABP‐700 is a potent, positive allosteric modulator of the GABAA receptor which produces its sedative and anesthetic effects via potentiation of endogenous GABAA receptor activation. ABP‐700 contains an ester bond that was designed to undergo rapid hydrolysis by nonspecific tissue esterases that produce an inactive carboxylic acid metabolite. This chemical approach has been used previously in approved drugs such as remifentanil, esmolol, and clevidipine, resulting in rapid inactivation of pharmacologic activity and a unique PK profile. This study is designed to test if 3 different ABP‐700 infusion regimens can safely and consistently produce satisfactory conditions for a colonoscopy. It is also intended to quantify pharmacodynamic effects, readiness for discharge, cognitive and memory function and both patient and provider satisfaction related to these dosing regimens. Patients will be randomized in a single‐blinded manner, in a 1:1:1 ratio to a low, mid or high‐dose ABP‐700 fixed two/stage infusion regimen. The procedure may begin no sooner than 5 minutes from the start of the ABP‐700 infusion regimen. After the start of the procedure, up to 2 supplemental ABP‐700 bolus doses of 50 µg/kg are allowed at the discretion of the anesthesia provider to maintain conditions acceptable for procedure completion. These bolus doses can occur no more frequently than every 5 minutes with no more than 3 boluses allowed. CONDITION: Diagnosis, Colonoscopy ; ; PRIMARY OUTCOME: The primary objective of this study is to test if ABP‐700 infusion regimens that produce a range of sedation effects enable successful completion of a colonoscopy in adult patients. Success of the procedure is defined as, procedure completion without the use of alternative rescue sedative medication, or major respiratory impairment as assessed by oxygen saturation off less than 90% or the need for assisted positive pressure ventilation (manual or mechanical). SECONDARY OUTCOME: Secondary objectives of this study are to quantify the pharmacodynamic effect of ABP‐700 including time to procedure start, sedation depth, patient recovery and readiness for discharge; and to quantify the cardio‐respiratory effects of sedation doses of ABP‐700. ; Further exploratory objectives include: ; ; ‐ To determine endoscopist and anesthesiologist satisfaction with the procedure ; ; ‐ To determine patient satisfaction with the procedure ; ; ‐ To determine patient procedural recall. ; ; ‐ To evaluate cognition and memory function of the patient. ; INCLUSION CRITERIA: Patients may be included in the study if they meet all of the following criteria: 1. Patient must be male or female 18 ‐ 65 years of age, inclusive. 2. Patient must give written informed consent before initiation of any study‐related procedures 3. Patient is scheduled to undergo elective colonoscopy 4. BMI 18.0 – 29.0 kg/m2 5. ASA class I – II 6. Modified Mallampati score I – II 7. If female and of child‐bearing potential, patient has negative pregnancy test during screening and is not breast‐feeding 8. If patient is a sexually active male or a sexually active female of child‐bearing potential, patient agrees to use a medically accepted form of contraception from the time of consent to completion of all follow‐up study visits.