A Phase 1b, Randomized 2-Part Single-Center Study to Evaluate the PK and Safety of Multiple Ascending Oral Doses of PF614 and the Food Effect and BA/BE of Single Oral Doses of PF614 Relative to OxyContin in Healthy Adult Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 84
- 试验地点
- 1
- 主要终点
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
研究概览
简要总结
This is a single-center study incorporating 2 parts: A Multiple Ascending Dose Study (Part A) and a comparative Bioavailability/Bioequivalence and Food Effect study (Part B). Both parts of the study will be conducted in healthy adult subjects.
详细描述
This study is intended to evaluate the pharmacokinetics of OxyContin (oxycodone ER) and PF614, as well as PF614 fragments, following administration of multiple ascending doses of PF614, and to compare to steady-state pharmacokinetics to those of OxyContin. (Part A)
In addition, oral bioavailability of oxycodone derived from single doses of PF614 of the to-be-marketed capsule formulation will be compared to that of the reference drug, OxyContin, in the fasted and fed condition. A pivotal food effect assessment will be incorporated into the study to determine the impact of a high fat meal on the bioavailability of oxycodone, following oral single-dose administration of PF614 (Part B).
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 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Males or females, ages 18-50 years in good general health,
- •BMI between 18 and 32 kg/m (inclusive)
- •Subjects must have a negative screen for drugs of abuse, nicotine, alcohol, Hepatitis B, Hepatitis C, and HIV.
- •Female subjects of child bearing potential must have a negative serum pregnancy test at randomization
- •Females must be of non-child bearing potential (e.g. postmenopausal) or of childbearing potential and agree to use a highly effective form of contraception from the time of screening to two weeks after last dose of study medication.
- •Subjects must have normal findings in a physical examination and 12 lead ECG and normal Vital Signs
- •Clinical laboratory values must be Within Normal limits as defined by the clinical laboratory
- •Subjects must be able to provide coherent written informed consent
- •Subjects must be willing and able to follow study instructions and be likely to complete all study requirements.
排除标准
- •History of allergy or sensitivity to oxycodone
- •History of loud snoring or sleep apnea
- •History of medical problems encountered with opioid therapy
- •Urinary cotinine levels indicative of smoking or history of smoking or regular tobacco use with 2 months prior to screening
- •History of alcoholism or drug abuse
- •Use of prescription medications within 14 days of study drug administration with exception of contraceptives used by female subjects
- •Use of any opioid within 30 days prior to screening
- •History of allergy or sensitivity to naltrexone
- •History of allergy or sensitivity to naloxone
- •Donation of blood within 30 days prior to screening
- •Donation of plasma within 30 days prior to screening
- •Acute illness at admission of clinical study unit
- •History of GI disturbance requiring use of antacid twice weekly or more
- •Females who are breastfeeding
- •Anticipated need for surgery or hospitalization during the study
- •Enrollment in an investigational drug study within 30 days prior to screening
- •Any condition that in the Investigator's opinion puts the subject at significant risk, could confound the study results, or may interfere significantly with the subject's participation in the study.
研究组 & 干预措施
PF614
Part A will utilize a randomized, open-label, multiple-ascending dose design with up to 3 separate dose groups of 8 subjects. Within each dose group, subjects will be randomized to receive repeated BID doses, planned to be 12 hours apart over a 5 day period, for a total of 9 doses. Dose escalation to Dose Groups 2 and 3 will follow a review of pharmacokinetic, safety and tolerability data up to Day 10 of the preceding group. The doses or dosing regimen for Dose groups 2 and 3 may be modified based on a review of the data.
干预措施: PF614 (Drug)
PF614
Part A will utilize a randomized, open-label, multiple-ascending dose design with up to 3 separate dose groups of 8 subjects. Within each dose group, subjects will be randomized to receive repeated BID doses, planned to be 12 hours apart over a 5 day period, for a total of 9 doses. Dose escalation to Dose Groups 2 and 3 will follow a review of pharmacokinetic, safety and tolerability data up to Day 10 of the preceding group. The doses or dosing regimen for Dose groups 2 and 3 may be modified based on a review of the data.
干预措施: Naltrexone Hydrochloride (Drug)
Part B Compare Bioavailability and Bioequivalence
Part B will utilize an open-label, single-dose, randomized, 4-way crossover design. Following confirmation of eligibility, subjects will be randomized to receive each of the single oral doses of study drugs (one at each treatment period).
PF614 100 mg administered under fasted conditions; PF614 100 mg administered under fed conditions; OxyContin 40 mg administered under fasted conditions; OxyContin 40 mg administered under fed conditions
干预措施: PF614 (Drug)
Part B Compare Bioavailability and Bioequivalence
Part B will utilize an open-label, single-dose, randomized, 4-way crossover design. Following confirmation of eligibility, subjects will be randomized to receive each of the single oral doses of study drugs (one at each treatment period).
PF614 100 mg administered under fasted conditions; PF614 100 mg administered under fed conditions; OxyContin 40 mg administered under fasted conditions; OxyContin 40 mg administered under fed conditions
干预措施: Naltrexone Hydrochloride (Drug)
Part B Compare Bioavailability and Bioequivalence
Part B will utilize an open-label, single-dose, randomized, 4-way crossover design. Following confirmation of eligibility, subjects will be randomized to receive each of the single oral doses of study drugs (one at each treatment period).
PF614 100 mg administered under fasted conditions; PF614 100 mg administered under fed conditions; OxyContin 40 mg administered under fasted conditions; OxyContin 40 mg administered under fed conditions
干预措施: OxyContin (Drug)
结局指标
主要结局
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
时间窗: 30 days
Adverse Events, Significant Adverse Events, Adverse Events leading to discontinuation
Pharmacokinetics t1/2 [Half-life]
时间窗: PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours
Terminal elimination half-life
Pharmacokinetics Ctrough [Minimum Plasma Concentration before next dose]
时间窗: Prior to dosing on Days 2, 3, and 4
Concentrations prior to dosing
Pharmacokinetics Part B Cmax
时间窗: PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours
Maximum (peak) plasma concentration in fed vs fasted state
Bioavailability and Bioequivalence
时间窗: PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours
Bioavailability and Bioequivalence of single oral doses of PF614 prodrug and oxycodone derived from from PF614 vs. oxycodone derived from OxyContin in healthy adult subjects (Part B)
Pharmacokinetics AUC [Area Under the Curve]
时间窗: Full PK sampling time points will be 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours
Area under the concentration-time curve from the time of dosing to the start of the next dosing interval using PF614 concentrations and oxycodone concentrations in plasma.
Pharmacokinetics Cmax [Maximum Plasma Concentration]
时间窗: PK sampling time points will be 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours
Maximum (peak) plasma concentration first dose
Pharmacokinetics Tlag [Time to first measurable plasma concentration]
时间窗: PK sampling time points will be 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours
Time prior to the time corresponding to the first measurable (non-zero) concentration
Pharmacokinetics Vz/F [Volume of Distribution]
时间窗: PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours
Apparent volume of distribution during the terminal-elimination phase
Pharmacokinetics Tmax [Time to maximum plasma concentration]
时间窗: PK sampling time points 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours
Time to maximum plasma concentration on Day 1 (first dose)
Pharmacokinetics CL/F [Clearance]
时间窗: PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours
Apparent total systemic clearance
Pharmacokinetics Part B AUC
时间窗: PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours
Area under the concentration-time curve from the time of dosing extrapolated to time infinity in fed vs fasted state
Pharmacokinetics AUC, Steady State
时间窗: PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours
Steady-state (Day 5) area under the concentration-time curve from the time of dosing extrapolated to time infinity
Pharmacokinetics Cmax, Steady State
时间窗: PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours
Maximum (peak) plasma concentration at steady-state on Day 5
Pharmacokinetics elimination rate
时间窗: PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours
Terminal elimination rate/constant
Pharmacokinetics Tmax, Steady State
时间窗: PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours
Time to maximum plasma concentration on Day 5
Pharmacokinetics Part B AUC 0-t
时间窗: PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours
Area under the concentration-time curve from the time of dosing to the last measurable concentration in fed vs fasted state
次要结局
- Pharmacokinetics Part B Terminal elimination rate(PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours)
- Pharmacokinetics Part B Tmax(PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours)
- Plasma Concentration of inactive metabolic fragment #1(PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours)
- Plasma Concentration of inactive metabolic fragment #2(PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours)
- Pharmacokinetics Part B CL/F(PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours)
- Pharmacokinetics Part B pAUC(PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours)
- Pharmacokinetics Part B Tlag(PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours)
- Pharmacokinetics Part B Vz/F(PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours)
- Pharmacokinetics Part B t1/2(PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours)