A Phase I Randomized, Double-Blind, Crossover, Exploratory Study of the Pharmacokinetics of a Single Oral Dose of Form I Versus Form V Capsules of the Anti-Orthopoxvirus Compound ST-246® in Fed Normal Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Pharmacokinetic Parameters for a Single Dose of ST-246 Form I vs. Form V: t½
研究概览
简要总结
The purpose of this study was to evaluate the pharmacokinetic parameters and safety of a single dose of ST-246 400mg Form I versus ST-246 400mg Form V capsules in fed normal healthy volunteers.
详细描述
This was a Phase I, double-blind, cross-over, single-dose study of the orally administered anti-orthopoxvirus compound, ST-246, to 12 healthy, fed volunteers between the ages of 18 and 50 years. Subjects were randomized such that 6 subjects received either ST-246 Form I (monohydrate) followed 10 days later after a wash-out period by Form V (hemihydrate), and 6 subjects received ST-246 Form V followed by Form I, as for the previous group.
Both forms of ST-246 were similar in the way they were manufactured. The only difference between Form I and Form V may be related to how it dissolves, and this may affect the way that it is absorbed in the human body. Information about any side-effects that may occur will also be collected in this study.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •18 to 50 years
- •Available for clinical follow-up duration of study.
- •Able/willing to give written consent.
- •Good general health; no clinically significant medical history.
- •Refrain from taking any medications from screening through 72 hours after last dose.
- •Adequate venous access.
- •PE and lab results without clinically significant findings within 28 days prior to receipt of drug.
- •Meet Lab Criteria within 28 days prior to receipt of drug.
- •Negative pregnancy test
- •Non smokers
- •No alcohol or caffeine
- •Participant or partner has undergone surgical sterilization, or the participant agrees either to be abstinent or use two non-hormonal methods of contraception for duration of the study
排除标准
- •Marked baseline prolongation of QT/corrected QT interval (QTc) interval (
- •History of additional risk factors for Torsade de Pointes
- •Clinically significant abnormal ECG
- •Personal history of cardiac disease, symptomatic or asymptomatic arrhythmias, syncopal episodes, or prolongation of the PR interval
- •Family history of Sudden Cardiac Death not clearly due to acute myocardial infarction.
- •History of any clinically significant conditions including:
- •Diabetes mellitus
- •History of thyroidectomy or thyroid disease
- •Serious angioedema episodes
- •Head trauma resulting in a diagnosis of TBI other than concussion
- •Seizure or history of seizure
- •Bleeding disorder diagnosed by a doctor or significant bruising or bleeding difficulties with intramuscular injections or blood draws
- •Malignancy
- •Family history of idiopathic seizures
- •History or presence of neutropenia or other blood dyscrasia
- •Known Hepatitis B or Hepatitis C infection
- •Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome illness.
- •Current or recent history of a clinically significant bacterial, fungal, or mycobacterial infection.
- •Known clinically significant chronic viral infection (or current clinically significant viral infection
- •History of frequent or severe headaches or migraines
- •Known chronic bacterial, mycobacterial, fungal, parasitic, or protozoal infection
- •Woman who is pregnant or is breast-feeding or planning to become pregnant
- •On any concomitant medications
- •History of drug allergy that, in the opinion of the PI, contraindicates participation in the trial.
- •Inability to swallow medication
- •Body Mass Index above 35 or below 18,
- •Current drug abuse or alcohol abuse.
- •Inability to refrain from physical exercise for a period of 24 hr before and after a PK day or refrain from consuming xanthines, grapefruit or grapefruit juice
- •Clinically significant lactose intolerance
- •Received experimental drug within 30 days
- •Vaccination within 30 days
- •Total of more than 350 milliliters (mL) of blood drawn in 2 months
- •Treatment with any immunosuppressant or immunomodulatory medication in 3 months
- •Any condition occupational reason or other responsibility that, in the judgment of the PI, would jeopardize the safety or rights of a subject participating in the trial or would render the subject unable to comply with the protocol
- •History or diagnosis that would affect absorption of study medication
研究组 & 干预措施
Group ST-246 Form I (followed by Form V)
Each of six subjects receive a single oral 400 mg dose (2×200 mg) of ST-246 Form I (monohydrate) in the first intervention period, followed 10 days later (3 days post-treatment monitoring and 7 days wash-out period) in the second intervention period by a single oral 400 mg dose (2×200 mg) of ST-246 Form V (hemihydrate). Both forms of drug are orally administered within 30 minutes after a standard light meal consisting of 400-450 calories and approximately 25% fat.
干预措施: ST-246 Days 1 - 3 (Drug)
Group ST-246 Form I (followed by Form V)
Each of six subjects receive a single oral 400 mg dose (2×200 mg) of ST-246 Form I (monohydrate) in the first intervention period, followed 10 days later (3 days post-treatment monitoring and 7 days wash-out period) in the second intervention period by a single oral 400 mg dose (2×200 mg) of ST-246 Form V (hemihydrate). Both forms of drug are orally administered within 30 minutes after a standard light meal consisting of 400-450 calories and approximately 25% fat.
干预措施: ST-246 Days 11 - 13 (Drug)
Group ST-246 Form V (followed by Form I)
Each of six subjects receive a single oral 400 mg dose (2×200 mg) of ST-246 Form V (hemihydrate) in the first intervention period, followed 10 days later (3 days post-treatment monitoring and 7 days wash-out period) in the second intervention period by a single oral 400 mg dose (2×200 mg) of ST-246 Form I (monohydrate). Both forms of drug are orally administered within 30 minutes after a standard light meal consisting of 400-450 calories and approximately 25% fat.
干预措施: ST-246 Days 1 - 3 (Drug)
Group ST-246 Form V (followed by Form I)
Each of six subjects receive a single oral 400 mg dose (2×200 mg) of ST-246 Form V (hemihydrate) in the first intervention period, followed 10 days later (3 days post-treatment monitoring and 7 days wash-out period) in the second intervention period by a single oral 400 mg dose (2×200 mg) of ST-246 Form I (monohydrate). Both forms of drug are orally administered within 30 minutes after a standard light meal consisting of 400-450 calories and approximately 25% fat.
干预措施: ST-246 Days 11 - 13 (Drug)
结局指标
主要结局
Pharmacokinetic Parameters for a Single Dose of ST-246 Form I vs. Form V: t½
时间窗: Post-dose samples at 0.5,1,2,3,4,8,12,24,36,48,72 hrs
Mean terminal half-life (t½; hrs) for Forms I and V were calculated from \[plasma\] vs time profiles.
Pharmacokinetic Parameters for a Single Dose of ST-246 Form I vs. Form V: AUC0-τ
时间窗: Post-dose samples at 0.5,1,2,3,4,8,12,24,36,48,72 hrs
Area under the drug concentration-time curve from time zero to time t, where t is the last timepoint with a drug concentration ≥ lowest obtainable quantification (AUC0-τ; ng\*hr/mL).
Pharmacokinetic Parameters for a Single Dose of ST-246 Form I vs. Form V: AUC0-∞
时间窗: Post-dose samples at 0.5,1,2,3,4,8,12,24,36,48,72 hrs
Area under the drug concentration-time curve from time zero to infinity (AUC0-∞; ng\*hr/mL).
Pharmacokinetic Parameters for a Single Dose of ST-246 Form I vs. Form V: Cmax
时间窗: Post-dose samples at 0.5,1,2,3,4,8,12,24,36,48,72 hrs
Maximum drug concentration in plasma, determined directly from individual concentration-time data (Cmax)
Pharmacokinetic Parameters for a Single Dose of ST-246 Form I vs. Form V: Tmax
时间窗: Post-dose samples at 0.5,1,2,3,4,8,12,24,36,48,72 hrs
Time to maximum plasma concentration(Tmax; hrs) for Forms I and V were calculated from \[plasma\] vs time profiles.
次要结局
- Number of Study Participants Who Tolerated a Single Dose of ST-246 Form I vs. Form V as Determined by No Clinically Significant Changes in Safety Parameters(4 weeks)