A Dose Calibration and Dose Equivalence Pharmacokinetic Study in Healthy Volunteers Comparing IkT-001Pro to Imatinib Mesylate 400mg
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 64
- 试验地点
- 1
- 主要终点
- Exposure of imatinib after administration of IkT-001Pro and imatinib mesylate, as measured by area under the concentration-time curve for imatinib from time zero to infinity (AUC0-inf)
研究概览
简要总结
This study investigates the safety, tolerability and dose equivalence of drug IkT-001Pro in healthy volunteers (18 to 55 years old) in comparison to imatinib mesylate. This study is designed in 3 parts.
Part A consists of 3 cohorts. In cohort 1 healthy participants will take a single, oral dose of 400mg IkT-001Pro then will be followed by a single dose of 400mg Imatinib mesylate after a 7-day washout. Cohort 2 and 3 will follow the same structure as cohort 1 with a different Ikt-001Pro dose.
Part B will be chosen using Part A data by statistical procedures. Part B will enroll 32 subjects to demonstrate the bioequivalence of IkT-001Pro (the 'Test') to 400 mg imatinib delivered as imatinib mesylase (the 'Reference').
Part C (Dose Equivalence at 600 mg):
Part C will enroll up to eight (8) subjects to demonstrate bioequivalence of imatinib delivered as 800 mg IkT-001Pro (the 'Test') to 600 mg imatinib delivered as imatinib mesylate ('the Reference')
详细描述
Part A, Dose Calibration Cohort:
This is a crossover design dose calibration study in healthy volunteers to identify a dose of IkT-001Pro film-coated tablets that would be equivalent to imatinib free base 400 mg film-coated tablets containing imatinib mesylate.
Dose calibration cohorts will each consist of eight (8) subjects who will receive a single dose of IkT-001Pro at 400, 500 or 600 mg and then crossover to a single dose of imatinib 400 mg delivered as imatinib mesylate following a 7-day washout. The three cohorts will have staggered starting points. The 400 mg IkT-001Pro dose, washout and 400 mg imatinib delivered as imatinib mesylate will be completed first including full PK analysis. Following review of the PK data at 400 mg IkT-001Pro, the 500 mg and 600 mg cohorts will be enrolled approximately simultaneously.
Pharmacokinetic plasma samples for all three cohorts will be drawn pre-dose at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72 and 96 hours after dosing. A 7-day washout period will take place between dosing of IkT-001Pro and dosing of 400 mg imatinib delivered as imatinib mesylate. PK plasma samples for the imatinib mesylate arm will be obtained on the same sampling schedule as the IkT-001Pro arm.
Part B- Dose Equivalence Cohort:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Subject must have all questions about the study answered and must have signed the informed consent document before any study-specific procedures are performed.
- •Healthy ambulatory male and female subjects > 18 to < 55 years of age at the Screening visit, with no history or evidence of clinically relevant medical disorders as determined by the Investigator in consultation with the Sponsor.
- •Bodyweight > 50 kg and body mass index (BMI) > 18.0 and < 32.0 kg/m2 at the screening visit.
- •Physical examination, clinical laboratory values, vital signs, and electrocardiogram (ECG) data. Vital signs and clinical laboratory values must be within the normal range and or deemed not clinically significant by the PI and ECG tracings must be normal at baseline and/or deemed not clinically significant by the PI.
- •Female subjects must be postmenopausal, permanently sterile (bilateral tubal occlusion), or of childbearing potential with a negative pregnancy test, non-breastfeeding, and using two highly effective methods of birth control prior to screening and through completion of the last follow-up visit. If a subject discontinues early after receiving a dose of study drug, she must continue this method of birth control for at least 7 days following the last dose of the study drug. Highly effective methods of birth control are defined as follows: hormonal (ie, established use of oral, implantable, injectable, or transdermal hormonal methods of contraception); placement of an intrauterine device; placement of an intrauterine system; and mechanical /barrier method of contraception (ie, condom or occlusive cap [diaphragm or cervical/vault cap] in conjunction with spermicide [foam, gel, film, cream or suppository]).
- •Male subjects must agree to practice an acceptable method of highly effective birth control from the Screening visit, while on study and for 7 days after receiving the last dose of study drug. Highly effective methods of birth control include sexual abstinence; vasectomy; or a condom with spermicide (men) in combination with their partner's highly effective method.
- •Males must be willing to abstain from sperm donation from the screening visit, while on study and through 30 days after receiving the last dose of study drug.
排除标准
- •Any subject with previous exposure to imatinib or known hypersensitivity to imatinib.
- •Clinically significant abnormal values for hematology, clinical chemistry or urinalysis at the screening and admission visits. Abnormalities considered to be non-clinically significant by the Investigator are acceptable.
- •Clinically significant abnormal physical examination or 12-lead electrocardiogram (ECG) at the screening or admission visits. NOTE: QTcF interval of > 450 msec in males or > 470 msec in females will be the basis for exclusion from the study. ECG may be repeated for confirmatory purposes if initial values obtained exceed the limits specified.
- •Clinically significant abnormal renal function defined as a creatinine clearance rate < 90 mL/min
- •Significant history (within six months prior to receiving the study drug) and/or presence of hepatic, renal, cardiovascular, pulmonary, gastrointestinal, endocrinological, hematological, dermatological, psychiatric, neurological, immunologic, ophthalmologic, metabolic, fluid retention and edema, bleeding disorders including hemorrhage or oncological disease.
- •Any subject with a history, presence and/or current evidence of serologic positive result for hepatitis B surface antigen, hepatitis C antibodies, or HIV antibodies 1 or
- •Recent history (within previous six months prior to screening) of alcohol or drug abuse (as judged by the investigator), or has consumed > 2 alcohol drinks/day during the last three months prior to screening (one glass is approximately equivalent to: beer [284 mL], wine [125 mL/4 ounces], or distilled spirits [25 mL/1 ounce]). Subjects that consume three glasses of alcoholic beverages per day but less than 14 glasses per week may be enrolled at the discretion of the Investigator. Positive screens for alcohol or controlled substances at the screening or admission visits will disqualify a subject from study participation.
- •Any subject who currently uses or has regularly used tobacco or tobacco-containing products (cigarettes, pipes, etc.) for at least 30 days prior to screening or positive urine cotinine screen (>300 ng/mL) at the screening or admission visits.
- •Any subject who has received treatment with an investigational drug during the 30 days prior to screening. Exposure to an investigational medical device within 30 days of screening.
- •Use of agents known to affect drug metabolism: use of any known CYP3A4 inducers and/or inhibitors or consumed grapefruit juice, grapefruit, Seville oranges or St John's Wort or products containing these within 14 days prior to first administration of study drug. Strong inducers of CYP3A4 include dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifampicin and phenobarbital. Strong inhibitors of CYP3A4 include ketoconazole, itroconazole, clarythromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin and voriconazole.
- •Investigative site personnel or their immediate families (spouse, parent, child or sibling whether biological or legally adopted).
- •Any subject unwilling or unable to comply with study procedures.
- •Pregnant or nursing women.
- •Anyone who does not meet the requirements for exclusion of certain concomitant medications as defined in Section 7.5.
研究组 & 干预措施
Dose Calibration
In Part A, cohorts will consist of 8 subjects who will receive a single dose of Ikt-001Pro and then cross over to a single does of imatinib following a 7 day washout.
干预措施: Imatinib Mesylate (Drug)
Dose Calibration
In Part A, cohorts will consist of 8 subjects who will receive a single dose of Ikt-001Pro and then cross over to a single does of imatinib following a 7 day washout.
干预措施: IkT-001Pro (Drug)
Dose Equivalance
In Part B, up to 16 subjects will receive IkT001-Pro and up to 16 subjects will receive 400mg of imatinib mesylate. After a 7 day washout period the subjects will switch to receive the drug they did not previously receive.
干预措施: Imatinib Mesylate (Drug)
Dose Equivalance
In Part B, up to 16 subjects will receive IkT001-Pro and up to 16 subjects will receive 400mg of imatinib mesylate. After a 7 day washout period the subjects will switch to receive the drug they did not previously receive.
干预措施: IkT-001Pro (Drug)
Dose Equivalence at 600 mg):
In Part C, up to eight (8) subjects will be administered a single dose of 800 mg IkT-001Pro. After a 7-day washout period, the subjects will switch to 600 mg imatinib.
干预措施: Imatinib Mesylate (Drug)
Dose Equivalence at 600 mg):
In Part C, up to eight (8) subjects will be administered a single dose of 800 mg IkT-001Pro. After a 7-day washout period, the subjects will switch to 600 mg imatinib.
干预措施: IkT-001Pro (Drug)
结局指标
主要结局
Exposure of imatinib after administration of IkT-001Pro and imatinib mesylate, as measured by area under the concentration-time curve for imatinib from time zero to infinity (AUC0-inf)
时间窗: Day 1 through day 12
Area under the concentration-time curve for imatinib from time zero to infinity (AUC(0-inf))
Safety: Proportion of those in each dosing cohort who discontinued the assigned regimen
时间窗: Day 1 through day 12
Proportion of those in each dosing cohort who discontinued the assigned regimen
Exposure of imatinib after administration of IkT-001Pro and imatinib mesylate, as measured by area under the concentration-time curve for imatinib from time zero to last measurable concentration (AUC(0-last))
时间窗: Day 1 through day 12
Area under the concentration-time curve for imatinib from time zero to last measurable concentration (AUC0-last)
Safety: Incidence and temporal profile of treatment-emergent adverse events (TEAEs) evaluated by type/nature, severity/intensity, seriousness, and relationship to study intervention
时间窗: Day 1 through day 12
Incidence and temporal profile of treatment-emergent adverse events (TEAEs)
Exposure of imatinib after administration of IkT-001Pro and imatinib mesylate, as measured by the maximum plasma concentration (Cmax) of imatinib
时间窗: Day 1 through day 12
The maximum plasma concentration (Cmax) of imatinib
次要结局
- Exposure of imatinib after administration of IkT-001Pro and imatinib mesylate, as measured by imatinib pharmacokinetic parameters for dose normalized maximum concentration(Day 1 through day 12)
- Exposure of imatinib after administration of IkT-001Pro and imatinib mesylate, as measured by imatinib pharmacokinetic parameters for time to maximum concentration(Day 1 through day 12)
- Exposure of imatinib after administration of IkT-001Pro and imatinib mesylate, as measured by imatinib pharmacokinetic parameters for dose normalized area under the time concentration curve to last time point(Day 1 through day 12)
- Exposure of imatinib after administration of IkT-001Pro and imatinib mesylate, as measured by imatinib pharmacokinetic parameters for dose-normalized area under the time concentration curve from 0 to infinite time(Day 1 through day 12)
- Exposure of imatinib after administration of IkT-001Pro and imatinib mesylate, as measured by imatinib pharmacokinetic parameters for terminal rate constant(Day 1 through day 12)
- Exposure of imatinib after administration of IkT-001Pro and imatinib mesylate, as measured by imatinib pharmacokinetic parameters for terminal half-life(Day 1 through day 12)