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.|
|- candidate number||24279|
|- NTR Number||NTR5832|
|- ISRCTN||ISRCTN no longer applicable|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||20-apr-2016|
|- Secondary IDs||MDCO-ABP-15-01 2015-004019-19|
|- Public Title||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.|
|- Scientific Title||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.|
|- ACRONYM||N. Appl.|
|- hypothesis||Phase I testing of ABP-700 alone and with remifentanil co-infusions have shown the ability to produce consistent dose dependent sedation effects with conditions favorable for procedural care including minimal involuntary muscle movement, stable hemodynamics and little respiratory depression. When ABP-700 is given as a single-stage 30-minute continuous infusion, a delay (> 10 minutes) was observed in the attainment of arterial steady state plasma concentrations and stable clinical effect. Subsequent testing showed that a dual stage “step down” infusion methodology quickly achieved and maintained plasma concentrations required to produce a desired clinical effect while also minimizing the peak plasma concentrations produced during bolus administration. With these dual stage infusions, steady state arterial plasma concentrations were attained in 3-4 minutes and thereafter maintained steady state concentrations of approximately ± 10-15% of the target plasma concentration over the course of a 30-minute infusion. This study aims to test three dual stage infusion regimens which are intended to produce a range of clinical sedation effects in order to determine their ability to support procedural care when the procedural stimulation profile is generally uniform and of low-moderate intensity.|
|- Healt Condition(s) or Problem(s) studied||Diagnosis, Colonoscopy|
|- 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.
|- Exclusion criteria||1. Any ASA physical status III or worse, or history of one or more of the following:|
- History or presence of significant cardiovascular disease, or cardiovascular disease risk factors, hyperlipidemia, coronary artery disease, or any known genetic pre disposition to cardiac arrhythmia (including long QT syndrome, > 450 msec)
- History of any neurological or seizure disorder or psychiatric disease
- History or presence of significant pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic or dermatologic disease
- History of any illness that, in the opinion of the PI, might confound the results of the study or pose an additional risk to the patient by their participation in the study
2. History of any recent illness (e.g., upper respiratory infection) that does not satisfy ASA III or greater requirements but in the opinion of the PI, may pose an additional risk to the patient by their participation in the study.
3. Patients with a history of essential hypertension well controlled on medication will be accepted. Subjects should have been diagnosed with hypertension for at least 6 months and should have been on stable therapy for at least 4 weeks prior to the study.
4. Surgery within the past 90 days prior to dosing judged by the PI to be clinically relevant.
5. History of febrile illness within 5 days prior to dosing.
6. Patients in whom airway management is judged to be potentially difficult; thyromental distance ≤4 cm or Mallampati scores of 3 or 4 or per the discretion of the anesthesiologist based on history.
7. History or presence of alcoholism, drug abuse or illicit drug use within the past 2 years.
8. Hypersensitivity or idiosyncratic reaction to components of ABP-700 (sulfobutylether-beta-cyclodextrin, citrate buffer, sodium hydroxide), remifentanil or midazolam.
9. Patient is the Investigator or his/her deputy, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the study.
10. Participation in another interventional clinical trial within 90 days prior to dosing. The 90-day window will be derived from the date of the last study procedure (such as last blood collection or dosing) in the previous study to Day 1 of the current study.
11. Patients who, for any reason, are deemed by the Investigator to be inappropriate for this study, including patients who are unable to communicate or to cooperate with the Investigator.
|- mec approval received||yes|
|- multicenter trial||yes|
|- control||Not applicable|
|- Type||2 or more arms, randomized|
|- planned startdate ||25-apr-2016|
|- planned closingdate|
|- Target number of participants||75|
|- Interventions||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.
|- 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.
|- Timepoints||Screening (Day -14 to Day 1), |
Randomization/Sedation/Procedure (Day 1), Telephone follow-up / Safety evaluation (Day 5-7)
|- Trial web site||N. Appl. |
|- CONTACT FOR PUBLIC QUERIES|| Marieke Geel|
|- CONTACT for SCIENTIFIC QUERIES|| A.R. Absalom|
|- Sponsor/Initiator ||The Medicines Company|
(Source(s) of Monetary or Material Support)
|- Publications||Submission status: no results submitted at 04-04-2016.|
|- Brief summary||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. 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. 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. 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. 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).
Recruitment sites will be located in The Netherlands.
|- Main changes (audit trail)|
|- RECORD||20-apr-2016 - 15-sep-2017|
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