A Phase 1, Open-label, Fixed-sequence Study To Estimate The Effects Of Multiple-dose Administration Of Itraconazole On The Pharmacokinetics Of Pf 04958242 In Healthy Adult Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Biogen
- 入组人数
- 13
- 试验地点
- 1
- 主要终点
- Maximum Observed Plasma Concentration (Cmax) of PF-04958242
研究概览
简要总结
The purpose of the current study is to characterize the pharmacokinetic (PK) profile of PF 04958242 when co administered with a strong cytochrome P450 3A4 (CYP3A4) inhibitor.
详细描述
This study was previously posted by Pfizer, Inc. Sponsorship of the trial was transferred to Biogen.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 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
- •Healthy male subjects and female subjects of non childbearing with a Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >55 kg (121 lbs).
排除标准
- •Subjects with ANY of the following abnormalities in clinical laboratory tests at screening, as assessed by the study specific laboratory and confirmed by a single repeat, if deemed necessary:
- •Aspartate transaminase (AST)/serum glutamic oxaloacetic transminase (SGOT) or alanine transaminase (ALT)/serum glutamic pyruvic transminase (SGPT) >=1 x upper limit of normal (ULN);
- •Total bilirubin >=1.5 x ULN; subjects with a history of Gilbert's syndrome may have a direct bilirubin measured and would be eligible for this study provided the direct bilirubin is <= ULN.
- •Subjects with epilepsy, or history of epilepsy, or conditions that lower seizure threshold, seizures of any etiology (including substance or drug withdrawal), or who have increased risk of seizures as evidenced by self reported history of electroencephalogram (EEG) with epileptiform activity. Subjects with a history of childhood seizures and history of head trauma with loss of consciousness requiring hospitalization overnight will be excluded as well.
- •Subjects who had a history of allergy or intolerance to azole antifungal drugs.
- •NOTE: Other protocol defined Inclusion/Exclusion criteria may apply
研究组 & 干预措施
PF-04958242 and itraconazole
PF-04958242 will be provided in a capsule. Participants will receive a 0.10 mg loading dose of PF-04958242 twice daily (BID) on Day 1 then 0.025 mg BID on Day 2-Day 16, with the last dose occurring in the morning on Day 17.
Itraconazole will be provided as a solution starting on Day 4. On Day 4, a 200 mg dose of itraconazole will be administered approximately 1 hour before PF-04958242 morning administration and for 13 additional days (Day 4-Day 17).
干预措施: PF-04958242 (Drug)
PF-04958242 and itraconazole
PF-04958242 will be provided in a capsule. Participants will receive a 0.10 mg loading dose of PF-04958242 twice daily (BID) on Day 1 then 0.025 mg BID on Day 2-Day 16, with the last dose occurring in the morning on Day 17.
Itraconazole will be provided as a solution starting on Day 4. On Day 4, a 200 mg dose of itraconazole will be administered approximately 1 hour before PF-04958242 morning administration and for 13 additional days (Day 4-Day 17).
干预措施: Itraconazole (Drug)
结局指标
主要结局
Maximum Observed Plasma Concentration (Cmax) of PF-04958242
时间窗: Day 1 (0,1.5,12,13.5 hours post-dose), Day 2 (0,1.5,12,13.5 hours post-dose), Day 3 (0,0.5,1,1.5,2,3,4,6,8,12 hours post-dose), Day 4, Day 7, Day 10, Day 13, Day 16, Day 17 (0,0.5,1,1.5,2,3,4,5,6,8,12 hours post-dose) Day 18, Day 19, Day 20, Day 21
Collected at Day 3 for PF-04958242 0.025 mg Arm and Day 17 for PF-04958242 0.025 mg + itraconazole 200 mg Arm.
Area Under the Concentration-Time Profile From Time 0 to Time Tau, the Dosing Interval, Where Tau = 12 Hours (AUCtau) of PF-04958242
时间窗: Day 1 (0,1.5,12,13.5 hours post-dose), Day 2 (0,1.5,12,13.5 hours post-dose), Day 3 (0,0.5,1,1.5,2,3,4,6,8,12 hours post-dose), Day 4, Day 7, Day 10, Day 13, Day 16, Day 17 (0,0.5,1,1.5,2,3,4,5,6,8,12 hours post-dose) Day 18, Day 19, Day 20, Day 21
AUCtau = area under the concentration-time profile from time 0 to time tau, the dosing interval, where tau = 12 hours. Collected at Day 3 for PF-04958242 0.025 mg Arm and Day 17 for PF-04958242 0.025 mg + itraconazole 200 mg Arm.
次要结局
- Number of Participants With Vital Signs Data Meeting Criteria of Potential Clinical Concern(Baseline up to Day 21)
- Number of Participants With Significant Change in Physical Examination From Previous Examination(Baseline up to Day 21)
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(Baseline up to 28 days after last study drug administration)
- Number of Participants With Positive Response to Columbia-Suicide Severity Rating Scale (C-SSRS)(Baseline up to Day 21)
- Number of Participants With Electrocardiogram Data Meeting Criteria of Potential Clinical Concern(Baseline up to Day 21)
- Number of Participants With Significant Change in Neurological Examination From Previous Examination(Baseline up to Day 21)
- Time for Cmax (Tmax) of PF-04958242(Day 1 (0,1.5,12,13.5 hours post-dose), Day 2 (0,1.5,12,13.5 hours post-dose), Day 3 (0,0.5,1,1.5,2,3,4,6,8,12 hours post-dose), Day 4, Day 7, Day 10, Day 13, Day 16, Day 17 (0,0.5,1,1.5,2,3,4,5,6,8,12 hours post-dose) Day 18, Day 19, Day 20, Day 21)
- Apparent Oral Clearance (CL/F) of PF-04958242(Day 1 (0,1.5,12,13.5 hours post-dose), Day 2 (0,1.5,12,13.5 hours post-dose), Day 3 (0,0.5,1,1.5,2,3,4,6,8,12 hours post-dose), Day 4, Day 7, Day 10, Day 13, Day 16, Day 17 (0,0.5,1,1.5,2,3,4,5,6,8,12 hours post-dose) Day 18, Day 19, Day 20, Day 21)
- Lowest Concentration Observed During the Dosing Interval (Cmin) of PF-04958242(Day 1 (0,1.5,12,13.5 hours post-dose), Day 2 (0,1.5,12,13.5 hours post-dose), Day 3 (0,0.5,1,1.5,2,3,4,6,8,12 hours post-dose), Day 4, Day 7, Day 10, Day 13, Day 16, Day 17 (0,0.5,1,1.5,2,3,4,5,6,8,12 hours post-dose) Day 18, Day 19, Day 20, Day 21)
- Predose Concentration (Ctrough) of PF-04958242(0 hour at Day 1, Day 2, Day 3, Day 4, Day 7, Day 10, Day 13, Day 16, and Day 17 (pre-dose))
- Number of Participants With Abnormal Clinical Laboratory Measurements(Baseline up to Day 21)