A Study to Assess the Pharmacokinetics and Relative Bioavailability of Crystalline LTG-001 Immediate Release Tablets Compared to LTG-001 SDD Formulation in Healthy Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 14
- 试验地点
- 1
- 主要终点
- Determine the relative bioavailability of two different LTG-001 crystalline formulations (test) compared to the LTG-001 SDD formulation (reference) in the fasted state.
研究概览
简要总结
This is a single-center, open-label, part-randomized, crossover study in 14 healthy participants to assess the PK and safety profile of an SDD formulation of LTG-001 and two crystalline LTG-001 Instant Release tablet formulations, one of which will also be assessed at a differing dose level.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •Must be able to understand a written informed consent, which must be obtained prior to initiation of study procedures.
- •Must be willing and able to comply with all study requirements Aged 18 to 55 years inclusive at the time of signing informed consent.
- •Must agree to use an adequate method of contraception (as defined in Section 9.
- •Healthy males or non-pregnant, non-lactating, healthy females.
- •Body mass index of 18.0 to 32.0 kg/m2 as measured at screening.
- •Weight ≥50 kg at screening.
排除标准
- •Serious adverse reaction or serious hypersensitivity to any drug or formulation excipients.
- •Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hay fever is allowed unless it is active.
- •Significant serious skin disease, including rash, food allergy, eczema, psoriasis, or urticaria.
- •History of clinically significant cardiovascular, renal, hepatic, chronic respiratory or gastrointestinal disease (except cholecystectomy), neurological or psychiatric disorder, as judged by the investigator.
- •Have poor venous access that limits phlebotomy.
- •Clinically significant abnormal clinical chemistry, hematology or urinalysis as judged by the investigator (laboratory parameters are listed in Appendix 1). Participants with Gilbert's Syndrome are allowed.
- •Has ALT or AST >1.5 × ULN; Total bilirubin >1.5 × ULN (for participants with known Gilbert's syndrome these criteria only apply if the total bilirubin >1.5 × ULN as long as direct bilirubin is ≤1.5 × ULN) at screening.
- •Evidence of renal impairment at screening, as indicated by an estimated creatinine clearance (CLcr) of <90 mL/min using the Cockcroft-Gault equation
- •Positive HBsAg, HCV Ab or HIV antibody results at screening.
- •Positive serum pregnancy test at screening or positive urine pregnancy test at first
- •Participants who have received any IMP in a clinical research study within 5 half-lives or within 30 days prior to first dose. However, in no event shall the time between last receipt of IMP and first dose be less than 30 days.
- •Participants who report to have previously received LTG-
- •admission. Those who are pregnant or lactating will be excluded.
- •Personal or family history of long QT syndrome or a QTcF interval > 450 msec for men or > 470 for women on screening or first admission ECG. Participants who are taking, or have taken, any prescribed or over-the-counter drug or herbal remedies (other than up to 4 g per day acetaminophen, HRT or oral contraception) in the 14 days before IMP administration (see Section 11.4). Exceptions may apply on a case-by-case basis, if considered not to interfere with the objectives of the study, as determined by the investigator.
- •Participants who have had any vaccine within 15 days before first IMP administration History of any drug or alcohol abuse in the past 2 years.
- •Regular alcohol consumption in males >21 units per week and females >14 units per week (1 unit = 12 oz 1 bottle/can of beer, 1 oz 40% spirit, or 5 oz glass of wine).
- •A confirmed positive alcohol urine test at screening or first admission.
- •Current smokers and those who have smoked within the last 12 months.
- •Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months.
- •A confirmed positive urine cotinine test at screening or first admission.
- •Positive drug screen test result at screening or first admission (drug of abuse tests are listed in Appendix 1) Donation of blood within 2 months or donation of plasma within 7 days prior to first dose of study medication.
- •Participants who are, or are immediate family members of, a study site or sponsor employee.
- •Failure to satisfy the investigator of fitness to participate for any other reason.
研究组 & 干预措施
Period 1 Regimen A SDD Tablet
干预措施: LTG-001 SDD (Drug)
Period 2 Regimen B
干预措施: LTG-001 Formulation A Prototype 1 (Drug)
Period 3 Regimen C
干预措施: LTG-001 Formulation B Prototype 2 (Drug)
Period 4 Regimen D
干预措施: LTG-001 Formulation B prototype 2 (Drug)
结局指标
主要结局
Determine the relative bioavailability of two different LTG-001 crystalline formulations (test) compared to the LTG-001 SDD formulation (reference) in the fasted state.
时间窗: From enrollment to Period 4, Day 3 Discharge
results of LTG001 peak plasma concentration (Cmax)
Determine the relative bioavailability of two different LTG-001 crystalline formulations (test) compared to the LTG-001 SDD formulation (reference) in the fasted state
时间窗: from enrollment to Period 4, Day 3 discharge
Results of LTG001 Area under the plasma concentration versus time curve, (AUC (0-last))
Determine the relative bioavailability of two different LTG-001 crystalline formulations (test) compared to the LTG-001 SDD formulation (reference) in the fasted state.
时间窗: from enrollment to Period 4, Day 3 discharge
Results of LTG001 Area under the plasma concentration versus time curve, (AUC (0-inf))
To characterize the PK of LTG-001 and metabolites LTGO-4247 and LTGO-4449, following single administrations of up to two dose levels of two different LTG-001 IR tablet formulations in the fasted state.
时间窗: From Enrollment to Period 4, Day 3 discharge
Results of Cmax
To characterize the PK of LTG-001 and metabolites LTGO-4247 and LTGO-4449, following single administrations of up to two dose levels of two different LTG-001 IR tablet formulations in the fasted state
时间窗: From enrollment to period 4, Day 3 Discharge
Results of Tmax
To characterize the PK of LTG-001 and metabolites LTGO-4247 and LTGO-4449, following single administrations of up to two dose levels of two different LTG-001 IR tablet formulations in the fasted state.
时间窗: enrollment to Period 4, Day 3 discharge
Results of AUC(0-last)
To characterize the PK of LTG-001 and metabolites LTGO-4247 and LTGO-4449, following single administrations of up to two dose levels of two different LTG-001 IR tablet formulations in the fasted state.
时间窗: from enrollment to Period 4, Day 3 discharge
Results of AUC (0-inf)
次要结局
- Secondary Objective(from enrollment to Follow up phone call)