A Phase 1, Single-Center, Single-Blind, Placebo and Propofol Controlled Study in Healthy Subjects to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Ascending Intravenous (IV) Infusion Doses of ABP-700|
|- candidate number||19290|
|- NTR Number||NTR4735|
|- ISRCTN||ISRCTN no longer applicable|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||13-aug-2014|
|- Secondary IDs||ANVN-02 Annovation - 140369 QPS|
|- Public Title||A Phase 1, Single-Center, Single-Blind, Placebo and Propofol Controlled Study in Healthy Subjects to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Ascending Intravenous (IV) Infusion Doses of ABP-700|
|- Scientific Title||A Phase 1, Single-Center, Single-Blind, Placebo and Propofol Controlled Study in Healthy Subjects to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Ascending Intravenous (IV) Infusion Doses of ABP-700|
|- hypothesis||Assess the safety and tolerability of single ascending Intravenous (IV) infusion doses of ABP-700|
|- Healt Condition(s) or Problem(s) studied|
|- Inclusion criteria||1.Healthy, adult, men and women, 18-45 years of age, inclusive. |
2.Continuous non-smoker who has not used nicotine-containing products for at least 6 months prior to the first dose.
3.Body Mass Index (BMI) ≥ 17.5 and ≤ 30.0 kg/m2, inclusive, and a total body weight >50 kg, at screening and check-in.
4.Medically healthy with no clinically significant laboratory findings, vital signs or ECGs, as deemed by the PI.
5.Women must be of non-childbearing potential, i.e., must have undergone one of the following sterilization procedures at least 6 months prior to the first dose:
b.bilateral tubal ligation or bilateral salpingectomy;
or be postmenopausal with amenorrhea for at least 1 year prior to the first dose and FSH serum levels consistent with postmenopausal status.
6.Non-vasectomized men must agree to use a condom with spermicide or abstain from sexual intercourse during the study until 90 days beyond the last dose of study medication. Men who have been vasectomized less than 4 months prior to study start must follow the same restrictions as non-vasectomized men.
7.Men must agree not to donate sperm from the first dose until 90 days after dosing.
8.Obtain a score of I or II using the Modified Mallampati Scoring.
9.Understand the study procedures in the informed consent form(s) (ICF(s)), and be willing and able to comply with the protocol.
10.Agree not to make any public disclosure of personal medical data related to the study or other information related to the study, including posting on any website or social media site (e.g., Facebook, Twitter, etc.).
|- Exclusion criteria||1. 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.).|
2.History or presence of significant pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological (inclusive of any seizure disorder), or psychiatric disease.
3.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 subject by their participation in 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.History or presence of alcoholism, drug abuse or illicit drug use within the past 2 years.
7.History of regular alcohol consumption exceeding 7 drinks/week for women or 14 drinks/week for men (1 drink = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor) within 6 months of screening.
8.Hypersensitivity or idiosyncratic reaction to components of ABP-700 or placebo (meglumine and/or sulfobutylether-beta-cyclodextrin) propofol, midazolam, fentanyl, egg, egg products, soybeans, soy, or to compounds related to the study medications.
9.History or presence of adrenal insufficiency as defined by serum cortisol level <6 Ķg/dL at screening (as defined by Debono et al.,).
10.Women who are pregnant or lactating.
11.Women who have FSH levels less than 30 IU/L.
12.Positive results for the urine drug screen and alcohol breath test at screening or check-in (Day -1).
13.Positive urine cotinine at screening.
14.Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HCV).
15.Single 12-lead ECG demonstrating QTcF interval >450 msec at screening and Day -1.
16.Vital signs demonstrating HR <50 bpm at screening and Day -1.
17.Unable to refrain from or anticipates the use of any drug, including prescription and non-prescription medications, herbal remedies, or vitamin supplements beginning approximately 14 days prior to dosing (with exception of Lidocaine which will be used for arterial line placement) and throughout the study. Ibuprofen (1.2 g per 24 hour period) may be permitted during the study at the PIís discretion.
18.Use of any drugs known to be hormonal replacement therapy, inducers of cytochrome P450 (CYP) enzymes, including St. Johnís Wort, within 28 days prior to the first dose of study medication. Appropriate sources will be consulted by the PI to confirm lack of PK/PD interaction with study medication(s).
19.Have a diet incompatible with the on-study diet, in the opinion of the PI, within the 28 days prior to the first dose of study medication(s), and throughout the study.
20.Blood donation or significant blood loss within 90 days prior to dosing.
21.Plasma donation within 7 days prior to dosing.
22.Participation in another 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.
23.Subjects who previously received ABP-700.
|- mec approval received||yes|
|- multicenter trial||no|
|- Type||2 or more arms, randomized|
|- planned startdate ||25-aug-2014|
|- planned closingdate||30-nov-2014|
|- Target number of participants||48|
|- Interventions||ABP-700, Propofol or Placebo|
|- Primary outcome||To assess the safety and tolerability of a single ascending intravenous (IV) infusion doses of ABP-700.
To determine the maximum tolerated dose (MTD) of intravenous infusion doses of ABP-700.
|- Secondary outcome||To characterize the pharmacokinetics (PK) of ABP-700 and its primary metabolite (CPM-acid).
To assess the pharmacodynamics (PD) of ABP-700.
To investigate the dose-response and PK/PD relationships.
|- Timepoints||Days 1, 2 and 5|
|- Trial web site|
|- status||recruitement status not public|
|- CONTACT FOR PUBLIC QUERIES|| M.C.E. Beukers-Reuvers|
|- CONTACT for SCIENTIFIC QUERIES||Prof. dr. M.M.R.F. Struys|
|- Sponsor/Initiator ||Annovation Biopharma, University Medical Center Groningen (UMCG)|
(Source(s) of Monetary or Material Support)
|- Brief summary||Background: The highly dynamic nature of surgical and procedural intervention, as well as the short duration of these procedures, demands the development of potent yet rapidly reversible anesthetic agents. Ideally, the pharmacokinetics (PK) and pharmacodynamics (PD) of these anesthetic agents should be better matched to both the procedures being performed. ABP-700 is a newly developed, potent, positive allosteric modulator of the GABAA receptor. Its mechanism of action is via potentiation of GABAA receptor activation produces its sedative and anesthetic effects. ABP-700 contains an ester bond that was precisely designed to undergo rapid hydrolysis in the body by nonspecific tissue esterases that produce an inactive carboxylic acid metabolite.|
Purpose: To assess the safety and tolerability of single ascending IV infusion doses of ABP-700
Design: This is a Single-Center, Single-Blind, Placebo and Propofol Controlled Study in Healthy Subjects to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Ascending Intravenous (IV) Infusion Doses of ABP-700. Safety and tolerability of ABP-700 will be assessed through AEs, physical examination, safety laboratory tests (serum chemistry, hematology, arterial blood gas, urinalysis, and coagulation), serum methanol concentration, vital signs (blood pressure [including mean arterial pressure], heart rate, RR, SpO2 and body temperature), ECGs (12-lead ECG and 3-lead ECG), infusion site reaction monitoring, and respiratory function (respiratory pattern and occurrence of apnea).
The evaluation of cortisol levels before dosing and after synthetic ACTH administration will be evaluated to assess the effect of ABP-700 on adrenal function. The PK properties of ABP-700 and it's primary metabolite will also be evaluated.
|- Main changes (audit trail)|
|- RECORD||13-aug-2014 - 13-sep-2014|
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