None listed
Conditions
Brief summary
RLS-2202 is an intravenous formulation of oral SEROQUEL® tablet and is being tested for treatment of delirium and acute agitation in critically ill patients. The study is designed to characterise the pharmacokinetics (PK) and safety profile of the formulation RLS-2202, which is an intravenous formulation of quetiapine fumarate and compare it to the approved, oral tablet of quetiapine fumarate, which has the trade name SEROQUEL®. This trial is designed in two parts. The first is a pharmacokinetic assessment, where 4 healthy volunteers are given a single oral dose of 25mg tablet. Blood sampling will occur at timepoints pre-dose, 15, 30, 60,90 minutes and then at 2, 4 an 8 hours. These samples will be tested to observe how long it takes for the medication to be absorbed and metabolised by the body. The healthy volunteers will undergo a wash out period to ensure that there is no medication remaining in circulation. After the washout period, the healthy volunteers will be given an intravenous dose of the RLS-2202. Blood samples will be taken at same timepoints and the samples will be tested in exactly the same way as the first blood samples to see how long the intravenous RLS-2202 takes to be absorbed and metabolised by the body. These results will be compared and the dose for the second part of the study will be determined by a panel of doctors and scientists. The second part involves 12 health volunteers, where a single dose, determined from results of part 1, will be given intravenously and blood sampling will occur over 48 hour period. The healthy volunteers will then undergo a wash out period before being given a dose of oral Seroquel 50mg. Blood sampling will be conducted over the 48 hour period. All samples will then be analysed, as previously described. It is hypothesized that this intravenous formulation will be fast-acting, easier to administer to critically ill patients and significantly reduce the number of side effects, compared to the oral tablet.
Interventions
This clinical trial is designed as an open-label, 2-cohort, single-dose crossover study in healthy adults volunteers, aged 18-65 years old. The investigational product is RLS-2202, a intra-venous (I.V) Quetiapine Fumarate formulation and will be compared to oral SEROQUEL®, Quetiapine Fumarate, which is commercially available, via prescription.
This clinical trial is designed as an open-label, 2-cohort, single-dose crossover study in healthy adults volunteers, aged 18-65 years old. The investigational product is RLS-2202, a intra-venous (I.V) Quetiapine Fumarate formulation and will be compared to oral SEROQUEL®, Quetiapine Fumarate, which is commercially available, via prescription. The study consists of two cohorts: Cohort 1 is the exploratory PK and IV dose characterisation, where 4 healthy volunteers will receive a single dose of 25mg oral SEROQUEL® on Day 1, Period 1. Blood sampling over an 8 hour period at pre-dose, 1-2, 10, 30, 60, 90mins, then at 2, 4 and 8 hour will occur to analyse the pharmacokinetics of oral SEROQUEL®. Safety assessments will be performed throughout the 8 hours to ensure wellbeing of volunteers, prior to departing the clinical trial unit. Volunteers will then undergo a washout period of 96 hours before returning to the clinical trial unit for Day 5, Period 2 to receive a single dose of the investigational product, Intra venous RLS-2202, 1mg will be dosed over 1-2 minutes. Blood sampling over an 8 hours period at pre-dose, 1-2, 10, 30, 60, 90mins, then at 2, 4 and 8 hour timepoints to analyse the pharmacokinetics of I.V formulation RLS-2202. Safety assessments will be performed throughout the 8 hours to ensure wellbeing of volunteers, prior to departing the clinical trial unit. Cohort 2 will consist of 12 healthy adult volunteers who will be admitted to clinic on Day -1 and discharged at Day 7. The volunteers will dosed with IV RLS-2202 at a dose that will be determined by the Safety Review Committee analysis and review of PK data from cohort 1. The Cohort 2 IV dose will not exceed 10mg of RLS-2202. Cohort 2 study design is to determine PK and safety for the determined dose. A single dose will be administered, via I.V. and PK sampling will be conducted over timepoints pre-dose, 1-2mins, 15,20,30 minutes, then at 1,2,4,8,12,24,36 and 48 hours. Safety assessments will also be conducted during this period. The volunteers undergo a washout of 96 hours where a 50mg oral dose of SEROQUEL® will be administered at Day 5. PK sampling will be conducted over a timepoints pre-dose, 15,30,60,90 minutes, 2,3,4,12,24 and 48 hours. Safety assessments will also be conducted during this period. Safety assessments will be performed throughout the confinement period to ensure wellbeing of volunteers and prior to departing the clinical trial unit.
Sponsors
Patrys Ltd
Study design
Allocation
Non-randomised trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
Participants who meet all of the following criteria will be eligible to participate: 1) Must be able to provide written, personally signed and dated informed consent to participate in the study before completing any study related procedures. 2) Male or female aged 18 to 65 years, inclusive, at the time of consent. 3) Body mass index (BMI) greater or equal to 18.0 to less than or equal to 30.0 kg per m² with a body weight greater or equal to 50 kg. 4) Nonsmokers or light tobacco/nicotine user (e.g., smokers, electronic cigarettes, vaping, and smokeless tobacco/nicotine products limited to 5 cigarette equivalents per week in last month), that are willing to abstain from nicotine use throughout the study (Day-1 through End of Study). 5) No Clinically significant abnormalities as determined by the Principal Investigator or delegate based on review of medical history, physical examination, ECG, vital signs (including blood pressure and heart rate) and clinical laboratory tests. 6) Females of childbearing potential must agree to use a highly effective method of contraception from the time of consent through to at least 30 days after the last dose of the study drug. Highly effective methods of contraception include established use of a intrauterine device, intrauterine system, contraceptive implant, combined injectable contraceptives, hormonal oral contraceptives when used in combination with male condoms. Sexual abstinence, defined as refraining from heterosexual intercourse, when this is in line with the preferred and usual lifestyle of the participant. Female participants with male partner(s) must utilize highly effective forms of contraception and their male partner(s) must use a male condom. Female of childbearing potential should refrain from donating ova for 30 days after the last dose of study medication. 7) Females of nonchildbearing potential must be postmenopausal (defined as a minimum of 12 consecutive months of spontaneous amenorrhea and / or FSH greater than 40.0 IU/L) or surgically sterile (hysterectomy, bilateral oophorectomy, bilateral salpingectomy, bilateral tubal ligation or bilateral tubal occlusion). Females of nonchildbearing potential are exempt from contraception requirements. 8) Male participants are eligible to participate if they are: Permanently sterile (via a vasectomy performed at least 3 months prior to Screening with documented confirmation of azoospermia, or due to a medical condition); OR Are non-sterile but agree to use a male condom (barrier contraception) during the study and for at least 90 days after the final dose of the study drug, and their female partner of childbearing potential agrees to use a highly effective method of contraception. All male participants must refrain from donating sperm during this period. 9) Must not take any prescription with the exception of contraceptives, HRT, or over the counter pain medications during the study unless otherwise approved by the Principal Investigator or delegate. 10) Participants may be included if they have a history of the following conditions, provided they are clinically stable and, in the opinion of the investigator, do not pose an increased risk or interfere with study participation or interpretation of results: - Prior cholecystectomy (gallbladder removal) - Gilbert’s syndrome, provided there is no evidence of clinically significant liver dysfunction beyond benign unconjugated hyperbilirubinemia - History of childhood asthma that is no longer active or requires no ongoing treatment - History of depression that is stable, adequately managed, and does not interfere with compliance with study procedures Individuals with these conditions may be enrolled at the principal investigator or delegate’s discretion, provided all other inclusion and exclusion criteria are met.
Exclusion criteria
Any of the following medical conditions: a. Any significant acute illness within 30 days prior to Screening which, in the opinion of the Principal Investigator or delegate and / or study Medical Monitor, could interfere with the participant's safety or study objectives. b. History of hypotension (systolic BP < 95) or orthostatic hypotension (systolic BP less than 90, or a greater than 20mmHg fall in systolic BP on standing) at screening, OR in the morning prior to dosing c. Positive tests at Screening for HIV, hepatitis B or hepatitis C. d. Previous malignant disease (except basal cell carcinoma of skin and cervical carcinoma in situ/dysplasia). 2) Must not have a history of organic heart disease including coronary artery disease, myocardial infarction, angina, clinically significant abnormal ECGs, QTcF interval greater than 450 msec for males and grater than 470 msec for females, congestive heart failure, valvular heart disease and congenital heart disease. 3) Use of concomitant medications that prolong the QT/QTc interval or triptan medications for migraine headaches within 28 days before dosing. 4) Must not have a history of excessive alcohol use (on average more than 14 standard drinks per week), or any other substance use disorder (excluding nicotine) currently or within 1 year prior to enrolment based on the discretion of the investigator. 5) Must not test positive for a substance of abuse or have a positive alcohol breath test at the time of screening or check in. Re-tests will not be allowed for a positive screen of an illicit drug or alcohol. 6) Positive pregnancy test at screening or check in or is breastfeeding/lactating. 7) Symptoms or history suggestive of a recent systemic illness or febrile illness within 7 days prior to check in based on the Principal Investigator or delegate’s discretion. Participants with a positive test for flu, or other viral infections may isolate and be rescreened for the study. 8) Cannot tolerate venipuncture, has poor venous access that would cause difficulty for collecting blood samples and absence of tattoos at intended injection site that in the opinion of the Investigator would obscure the evaluation of local injection site reactions. 9) Use of any prescription medication (excluding contraceptives) within 14 days or 5 half-lives (whichever is longer) prior to first dose. 10) Use of over-the-counter medications, herbal and nutritional supplements including St. John’s Wort within 14 days or 5 half-lives (whichever is longer) prior to first dose. 11) Use of CYP450 3A inhibitors or inducers within 28 days before dosing. 12) Donation of greater than 450 mL blood within 3 months, or plasma and platelet donation within 6 weeks, prior to first dose. 13) Hypersensitivity or contraindication to QTP or any excipient of the IV or oral formulations. 14) Has taken other investigational drug or participated in any clinical study within 30 days prior to dosing or is currently participating in another clinical study. 15) Clinically significant laboratory (blood or urine) abnormality as defined by the investigator. Liver enzymes (Total Bilirubin, AST/ALT, ALP, GGT) may not be greater than 1.5 times the upper limit of normal (ULN) at baseline (day -1 for Period 1). If values exceed this threshold, repeat testing may be performed at the discretion of the investigator; eligibility will be based on the repeat result. 16) Unwilling or unlikely to comply with the requirements of the study.
Outcome results
None listed