A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Intravenous Pregabalin and Acetaminophen (Ofirmev®) in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 63
- 试验地点
- 1
- 主要终点
- Treatment related Drowsiness and Dizziness
研究概览
简要总结
This is a Phase 1, randomized, double-blind, placebo-controlled, single and multiple ascending dose study to determine a maximum tolerated dose of IV PGB and to evaluate the safety, tolerability, and PK of an admixture of IV PGB and a fixed dose of 1300 mg IV APAP in healthy adult volunteers.
详细描述
This is a Phase 1, randomized, double-blind, placebo-controlled, single and multiple ascending dose study to determine a maximum tolerated dose (MTD) of IV PGB and to evaluate the safety, tolerability, and PK of an admixture of IV PGB and a fixed dose of 1300 mg IV APAP in healthy adult volunteers.
Up to 60 subjects will be enrolled into one (1) of six (6) sequential cohorts (n=10 per cohort [8 APAP + PGB and 2 placebo]).
The dose for the first cohort will be 1300 mg APAP and 100 mg PGB. For subsequent cohorts, the dose of APAP will remain constant at 1300 mg while the dose of PGB will be varied (will start with 100 mg TID and then based on tolerability will be either increased or decreased by 25 mg) based on Safety Monitoring Committee decision.
The placebo will be the saline solution.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Up to 60 healthy male and female volunteers will be enrolled into one (1) of up to six (6) cohorts (n=10 per cohort).
Within each cohort, subjects will be randomized at a ratio of 4:1 to receive IP (1300 mg of IV APAP plus a cohort specific dose of IV PGB) or placebo (saline) (8 active:2 placebo).
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
- •Male or female aged 18 to 55 years, inclusive at time of Screening
- •Body mass index (BMI) between 18.5 and 28.0 kg/m2 inclusive, with a minimum weight of 50 kg and a maximum of 100 kg
- •Healthy as determined by pre-study medical history, physical examination, vital signs, complete neurological examination, and 12-lead ECG confirming normal sinus rhythm
- •Negative tests for Hepatitis B surface antigen (HbsAg), hepatitis C virus antibody (anti-HCV), human immunodeficiency virus (HIV)-1 and HIV-2 antibody at Screening
- •Routine clinical laboratory tests should be within normal limits at Screening and Admission (Day -1) or abnormalities deemed not clinically significant by the Investigator; for liver function tests, AST and ALT values should not be greater than 1.5 times the upper limit of normal range
- •Negative screen for drugs of abuse or exhibit detectable alcohol levels by breathalyzer at the time of Screening or Admission
- •Non-smokers or ex-smokers (must have ceased smoking ≥3 months prior Screening visit)
- •Female subjects:
- •Must be of non-childbearing potential by surgical sterilization or postmenopausal OR Must not be pregnant, breast feeding, or planning to become pregnant AND must be practicing both a highly effective method of birth control from Screening until at least 90 days after the last dose of study drug.
- •Women of childbearing potential must have a negative pregnancy test result at Screening and upon admission to the Clinical Trial Unit.
排除标准
- •Has a clinically relevant history or presence of respiratory, gastrointestinal, renal, hepatic, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, endocrine, connective tissue diseases or disorders
- •Has a history of severe drug allergy, or severe hypersensitivity or severe food allergy, including anaphylaxis or known allergy or sensitivity to any component of PGB or APAP
- •Has a history of alcoholism or drug abuse
- •Has acute gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea) at the time of Screening or Admission
- •Consumption of drugs with enzyme-inducing properties, within 3 weeks prior to the initial dose of study drug and throughout the treatment phase
- •Has used any prescription medicines, over the counter medicines, or herbal supplements, within 7 days of dosing
- •Has used any investigational product or participated in any clinical trial within 30 days prior to Screening
- •Has donated or received any blood or blood products within the 3 months prior to Screening;
- •Not able to comply with the requirements of this study, including assessments, duration of admission of the study and expected follow up visits
- •Is unwilling or unable to give written informed consent
研究组 & 干预措施
1300 mg Acetaminophen and 100 mg IV Pregabalin
The dose for the first cohort will be 1300 mg APAP and 100 mg PGB. For subsequent cohorts, the dose of APAP will remain constant at 1300 mg while the dose of PGB will be varied (will start with 100 mg TID and then based on tolerability will be either increased or decreased by 25 mg based on Safety Monitoring Committee decision).
干预措施: Pregabalin 100mg (Drug)
1300 mg Acetaminophen and 100 mg IV Pregabalin
The dose for the first cohort will be 1300 mg APAP and 100 mg PGB. For subsequent cohorts, the dose of APAP will remain constant at 1300 mg while the dose of PGB will be varied (will start with 100 mg TID and then based on tolerability will be either increased or decreased by 25 mg based on Safety Monitoring Committee decision).
干预措施: Acetaminophen 1300mg (Drug)
1300 mg Acetaminophen and 100 mg +/- 25 IV Pregabalin
Decisions to escalate or decrease the dose for Cohorts 2 through 6 will be dependent upon blinded review of emerging safety and tolerability data by the Safety Monitoring Committee (SMC). However, PK data is not part of the SMC review, but may be reviewed by a SMC designee at a later time.
干预措施: Pregabalin 100mg (Drug)
1300 mg Acetaminophen and 100 mg +/- 25 IV Pregabalin
Decisions to escalate or decrease the dose for Cohorts 2 through 6 will be dependent upon blinded review of emerging safety and tolerability data by the Safety Monitoring Committee (SMC). However, PK data is not part of the SMC review, but may be reviewed by a SMC designee at a later time.
干预措施: Acetaminophen 1300mg (Drug)
结局指标
主要结局
Treatment related Drowsiness and Dizziness
时间窗: 7 days
The incidence and severity of somnolence and dizziness
Treatment Related Adverse Events
时间窗: 7 days
The incidence and severity of treatment-emergent adverse events
次要结局
- Plasma PK endpoints for APAP and PGB, SAD Phase, Tmax(7 days)
- Plasma PK endpoints for APAP and PGB, SAD Phase, λz(7 days)
- Plasma PK endpoints for APAP and PGB, multiple doses at steady state, Vz, ss(7 days)
- Plasma PK endpoints for APAP and PGB, SAD Phase, Cmax(7 days)
- Plasma PK endpoints for APAP and PGB, SAD Phase, t1/2(7 days)
- Plasma PK endpoints for APAP and PGB, SAD Phase, AUC0-last(7 days)
- Plasma PK endpoints for APAP and PGB, SAD Phase, CL(7 days)
- Plasma PK endpoints for APAP and PGB, SAD Phase, AUC0-inf(7 days)
- Plasma PK endpoints for APAP and PGB, SAD Phase, Vz(7 days)
- Plasma PK endpoints for APAP and PGB, multiple doses at steady state, Cmin,ss(7 dyas)
- Plasma PK endpoints for APAP and PGB, multiple doses at steady state, R(7 days)
- Plasma PK endpoints for APAP and PGB, multiple doses at steady state, AUCτ(7 days)
- Plasma PK endpoints for APAP and PGB, multiple doses at steady state, Cmax,ss(7 days)
- Plasma PK endpoints for APAP and PGB, multiple doses at steady state, CLss(7 days)
- Plasma PK endpoints for APAP and PGB, multiple doses at steady state(7 days)
- Plasma PK endpoints for APAP and PGB, multiple doses at steady state, Tmax,ss(7 days)
- Plasma PK endpoints for APAP and PGB, multiple doses at steady state, Cav,ss(7 days)
- Plasma PK endpoints for APAP and PGB, multiple doses at steady state, λz,ss(7 days)
- Plasma PK endpoints for APAP and PGB, multiple doses at steady state, LF(7 days)