Open-label, Randomised, Drug Interaction Study of Pyramax (Pyronaridine Artesunate) and the Protease Inhibitor Ritonavir in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 34
- 试验地点
- 1
- 主要终点
- Pharmacokinetics Analysis: Cmax
研究概览
简要总结
The primary objective of the study is to determine any drug interaction between the antimalarial Pyramax (pyronaridine artesunate) and the protease inhibitor ritonavir in healthy subjects. The secondary objective of the study is to assess further the safety of Pyramax in this setting.
详细描述
This is a phase I, open label, randomized study to determine any drug interaction between Pyramax (pyronaridine/artesunate) and the protease inhibitor ritonavir in healthy volunteers. A total of 34 healthy volunteers (17 per treatment arm) will be enrolled in the study so that at least 30 (15 per treatment arm) will complete it. Subjects will be randomly assigned in a 1:1 ratio to receive either ritonavir (100 mg) twice daily for 17 days from Day 1-17 plus Pyramax (180:60 mg) once daily for 3 days from Day 8-10 in Arm A or pyronaridine/artesunate (180:60 mg) alone once daily for 3 days from Day 1-3 in Arm B.
Subjects will come to the clinic the evening before first dosing of Pyramax / ritonavir. If enrolled, and according to the treatment arm, subjects will stay in the clinic and attend subsequent visits as follows:
Arm A:
- Inpatient day -1 (evening) to day 17
- Ambulatory clinic visit once daily (morning) on day 22, 29, 36, 43 and 50 (end of study visit)
Arm B:
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
- 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
- •Male or female subjects between the ages of 18 and 55 years with a body weight between 50 and 90 kg and a body mass index calculated using Quetelet's Index - weight (kg)/height (m2) between 18.5-30.0
- •Signed and dated a written informed consent form (ICF) before undergoing any study related activities, including discontinuation of any prohibited medications
- •Medically normal subjects with no significant abnormal findings at the screening physical examination as evaluated by the investigator
- •Strictly normal values of ALT, AST and bilirubin and normal or abnormal and clinically insignificant results (if agreed by the Investigator and the Sponsor on a case by case evaluation) of the other blood and urine laboratory parameters at screening
- •Female subjects of non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who was post-menopausal (i.e., one year without menses) or who has undergone sterilization (via hysterectomy or bilateral tubal ligation)
- •Female subjects of childbearing potential with a negative urine pregnancy test at screening and a negative plasma pregnancy test prior to inclusion and who agreed to one of the following methods:
- •Double barrier method of contraception for 2 weeks before first study drug administration and throughout the entire study follow up period
- •Partner(s) who had undergone vasectomy and has been negative for sperm for at least 6 months
- •The ability to understand the requirements of the study and willingness to comply with all study procedures
排除标准
- •Known history or evidence of clinically significant disorders such as cardiovascular (including arrhythmia, acute QTc interval greater or equal to 450 mseconds), respiratory (including active tuberculosis), hepatic, renal, gastrointestinal, immunological (including active HIV-AIDS), neurological (including auditory), endocrine, infectious, malignancy, psychiatric or other clinical abnormality
- •Known history of hypersensitivity, allergic or adverse reactions to pyronaridine or artesunate or other artemisinins or ritonavir
- •Known active Hepatitis A IgM (HAV-IgM), Hepatitis B surface antigen (HBsAg) or Hepatitis C antibody (HCV Ab)
- •Seropositive HIV antibody
- •Previous participation in any clinical study with Pyramax
- •Presence or recent history (last two years) of tobacco abuse (≥10 cigarettes/day)
- •Known or suspected alcohol abuse or illicit drug use in the last 10 years before the study start or positive findings on urine drug screen
- •Intake of grapefruit and grapefruit juice alcoholic beverages or caffeine-containing food or beverages, such as coffee, tea, chocolate, or cola, 48 hours before study drug administration
- •Use of over-the-counter (OTC) medications, including vitamins, analgesics, or antacids, 1 week before the study start
- •Use of prescription medications 14 days before the study start or required chronic use of any prescription medication
- •Use of enzyme-altering agents (e.g., barbiturates, phenothiazines, cimetidine, etc.) within 30 days or 5 half lives, whichever the longer, before the study start
- •Plasma donation 1 month before the study start
- •Blood donation of 450 mL or more in the last 3 months before the study start
- •Participation in any clinical study in last 2 months
研究组 & 干预措施
Arm A Ritonavir plus Pyramax
7 days of ritonavir followed by 3 days of ritonavir plus Pyramax followed by 7 days of ritonavir followed by a 33 day follow-up period (40 days since last Pyramax dosing) and a study completion evaluation.
干预措施: Ritonavir and Pyramax (Drug)
Arm B Pyramax
3 day treatment course of Pyramax, followed by a follow up period of 40 days since last Pyramax dosing and a study completion evaluation.
干预措施: Pyramax (Drug)
结局指标
主要结局
Pharmacokinetics Analysis: Cmax
时间窗: Until Day 50 for Arm A and until Day 43 for Arm B
Cmax for pyronaridine, artesunate, DHA: Cmax - maximum peak observed concentration Blood samples for pyronaridine analysis were taken at Day 8 predose, Day 9 predose, Day 10 predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours postdose, and Days 11,12, 13, 15, 22, 29, 36 and 43. Blood samples for artesunate / DHA analysis were taken at Day 10 predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours postdose.
Pharmacokinetics Analysis: Half-life, Tmax
时间窗: Until Day 50 for Arm A and until Day 43 for Arm B
Half-life and Tmax for pyronaridine, artesunate, DHA: Tmax - time of the maximum observed concentration Half life - apparent plasma terminal elimination half-life, computed as ln (2)/Kel Blood samples for pyronaridine analysis were taken at Day 8 predose, Day 9 predose, Day 10 predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours postdose, and Days 11,12, 13, 15, 22, 29, 36 and 43. Blood samples for artesunate / DHA analysis were taken at Day 10 predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours postdose.
Pharmacokinetics Analysis: AUC0-tau, AUC0-∞
时间窗: Until Day 50 for Arm A and until Day 43 for Arm B
AUC0-tau, AUC0-∞ for pyronaridine, artesunate, DHA: AUC0-tau - area under the concentration-time curve from Hour 0 to the scheduled time of the next dose AUC0-∞ - area under the concentration-time curve from Hour 0 through the last quantifiable concentration time Blood samples for pyronaridine analysis were taken at Day 8 predose, Day 9 predose, Day 10 predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours postdose, and Days 11,12, 13, 15, 22, 29, 36 and 43. Blood samples for artesunate / DHA analysis were taken at Day 10 predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours postdose.
次要结局
- Summary of Treatment Emergent Adverse Events(Throughout the study)