None listed
Conditions
Brief summary
Otsuka Pharmaceutical Development & Commercialization, Inc (OPDC) is studying an investigational drug called OPC-224333. This drug is not available for sale in any country. OPC-224333 is being studied as a possible treatment for epileptic diseases including drug-resistant and rare epilepsies such as Dravet, Lennox-Gastaut, West, and Doose syndrome. Epilepsy is a condition that causes people to have repeated seizures. Seizures are caused by abnormal electrical activity in the brain. Seizures can make you have convulsions, pass out, shaking movements in just one arm or in a part of your face, suddenly stop responding and stare for a few seconds, or behave strangely. Epilepsy can start at any age. You are invited to take part in this research study. The reason for this study is to find out potential benefits and safety of OPC-224333. About 72 participants will be in the study and the study is being done at one research site, CMAX Clinical Research Pty Ltd, in Australia. We are looking for a total of 72 healthy male or non-childbearing potential female participants between the ages of 18 and 55 years (inclusive) who have a body mass index between 19-32 kg/m2 (inclusive). The study will involve: • A screening visit (2 – 3 hours), within 28 days of the study starting • 8 night in-house stay (Day -1 to Day 8) • Follow-up phone call 30 days after your last dose (approximately 15 minutes) Expected study duration for Arm 1 is up to approximately 59 days.
Interventions
OPC-224333
Participants are planned to be dosed in 9 ascending dose groups, with 8 participants in each group. There will be 9 ascending doses of Investigational Medicinal Product (IMP) (1 dose per each of the 9 groups; 8 participants in each group [6 active and 2 placebo]). There is a single dose on Day 1 of Treatment.
Dose groups 1, 2, 3, 4, 5, 6, 7, 8, and 9 correspond to planned doses of 3, 10, 30, 100, 200, 400, 600, 800,and 1000 mg, respectively.
However, the planned doses and escalat
OPC-224333 Participants are planned to be dosed in 9 ascending dose groups, with 8 participants in each group. There will be 9 ascending doses of Investigational Medicinal Product (IMP) (1 dose per each of the 9 groups; 8 participants in each group [6 active and 2 placebo]). There is a single dose on Day 1 of Treatment. Dose groups 1, 2, 3, 4, 5, 6, 7, 8, and 9 correspond to planned doses of 3, 10, 30, 100, 200, 400, 600, 800,and 1000 mg, respectively. However, the planned doses and escalation scheme may be modified, including dose reductions or repeating a dose, based on available Pharmacokinetic (PK) and safety information. Doses will be given using the least number of tablets as possible. Treatment will be administered following an overnight (at least 10 hours) fast and participants will continue to fast for at least 4 hours after dosing. In case the maximum tolerated dose (MTD) is determined in less than 9 dosing cohorts, lower doses may be explored. In each cohort, a sentinel group consisting of 2 healthy participants (1 active:1 placebo) will be dosed first. The remaining participants in the cohort will be dosed at least 48 hours after dosing in the sentinel group. All oral doses of IMP will be administered with 240 mL of still water. Water may be increased by up to 240mL more for higher doses. Except with water given with the dose, water will be restricted beginning 1 hour prior to dosing.
Sponsors
Otsuka Pharmaceutical Development & Commercialization, Inc
Study design
Allocation
Randomised controlled trial
Intervention model
Other
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
Participants are required to meet the following inclusion criteria when assessed: 1) Male and nonchildbearing potential (NCBP) female participants between 18 and 55 years of age, inclusive. 2) Body mass index (BMI) between 19.0 to 32.0 kg/m2 (inclusive). 3) In good health as determined by: a) Medical history b) Physical examination c) Neurological examination d) Electrocardiogram (ECG) e) Serum/urine biochemistry, hematology, and serology tests. 4) Ability to provide written, informed consent prior to initiation of any trial-related procedures, and ability, in the opinion of the principal investigator, to comply with all the requirements of the trial. 5) Female participants who are surgically sterile (ie, have undergone bilateral oophorectomy or hysterectomy) or who have been postmenopausal for at least 12 consecutive months. This will be confirmed with follicle-stimulating hormone (FSH) assessment. 6) Male participants must agree to remain abstinent or to practice double-barrier forms of birth control and refrain from sperm donation from trial screening through 90 days from the last dose of the IMP. 7) Participants who are nonsmokers (with an acceptable cotinine test), nontobacco users, and nonvapers.
Exclusion criteria
Participants will be excluded if they meet any of the following exclusion criteria when assessed: 1) Clinically significant abnormality in past medical history or at the screening physical examination (including but not limited to clinical laboratory tests), that in the investigator’s or sponsor’s opinion may place the subject at risk or interfere with outcome variables including absorption, distribution, metabolism, and excretion of the IMP. This includes, but is not limited to, history of or concurrent cardiac, hepatic (liver function tests > 1.5 × upper limit of normal [ULN] at screening/baseline), renal (estimated glomerular filtration rate per chronic kidney disease epidemiology formula <60 mL/min), neurologic, endocrine, gastrointestinal, respiratory, hematologic, and immunologic disease. 2) History of drug and/or alcohol abuse within 2 years prior to screening. 3) History of or current hepatitis or acquired immunodeficiency syndrome or carriers of hepatitis B surface antigen (HBsAg), hepatitis C antibodies (anti-HCV), and/or human immunodeficiency virus (HIV) antibodies. Exceptions are permitted for subjects with a prior history of infection with hepatitis A who have fully recovered and are experiencing no liver sequelae, or with hepatitis C who have been adequately treated to be considered cured with no liver sequelae. 4) History of any medically significant allergy. 5) A positive urine or breath alcohol test and/or a positive urine drug screen for substance of abuse at screening or upon check-in to the trial site. 6) Subject having taken an investigational drug within 30 days preceding screening or a biological investigational drug within 30 days or 5 half-lives (whichever is longer) preceding screening, 7) Any history of significant bleeding or hemorrhagic tendencies. 8) Any history of difficulty in donating blood. 9) Donation of blood or plasma within 30 days prior to dosing. 10) Subjects without a permanent physical residence. 11) Consumption of alcohol and/or food and beverages containing methylxanthines (caffeinated coffee, caffeinated tea, caffeinated soda, and chocolate), pomelo, grapefruit, grapefruit juice, Seville oranges, or Seville orange juice within 3 days prior to dosing. 12) Use of prescription drugs, over-the-counter drugs, herbal medication, or vitamin supplements within 14 days or 5 half-lives, whichever is longer, prior to dosing and antibiotics within 30 days prior to dosing. The sponsor may allow exceptions only if the medication’s administration is deemed unlikely to impact the pharmacokinetic (PK) results. 13) Exposure to any substances known to stimulate hepatic microsomal enzymes within 30 days prior to screening (eg, occupational exposure to pesticides, organic solvents). 14) Use of tobacco products or daily exposure to second-hand smoke within 2 months prior to screening, which result in urine cotinine concentrations > 500 ng/mL, or serum cotinine concentrations > 20 ng/mL at screening or at check-in to the trial site. 15) Uncontrolled hypertension, defined as supine systolic blood pressure = greater than or equal to 140 mmHg and/or supine diastolic blood pressure = greater than or equal to 90 mmHg at screening or check-in, or symptomatic hypotension or orthostatic hypotension, which is defined as a decrease of = greater than or equal to 20 mmHg in systolic blood pressure and/or a decrease of = greater than or equal to 10 mmHg in diastolic blood pressure after at least 3 minutes of standing compared with the previous supine blood pressure, at screening or check-in. 16) Supine heart rate (HR), after resting for at least 3 minutes, outside the range of 45 to 100 beats per minute. The sponsor may allow exceptions if the results are not considered to be clinically significant; however, this will need to be approved by the medical monitor. Note: If the first HR measurement is abnormal, it can be repeated at the investigator’s discretion, in which case a third (confirmatory) measurement may also be required. 17) Clinically relevant changes on ECG such as atrioventricular block (ie, PR > 220 msec), prolongation of the QRS complex over 120 msec, or a QT interval corrected for heart rate using Fridericia’s formula (QTcF) = greater than or equal to 450 msec in males or = greater than or equal to 470 msec in females. 18) Sexually active males or females of childbearing potential (FOCBP), or their partners, who do not agree to practice 2 different approved methods of birth control or remain fully abstinent (periodic abstinence or withdrawal are not acceptable methods of contraception) during the trial and for 90 days after the last dose of IMP. If employing birth control, 2 of the following methods must be used: vasectomy, tubal ligation, nonhormonal intrauterine device, condom or occlusive cap (vaginal diaphragm or cervical/vault cap). 19) History of serious mental disorders that, in the opinion of the investigator, would exclude the subject from participating in this trial. 20) Any subject who, in the opinion of the investigator, should not participate in the trial.
Outcome results
None listed