An Open-label Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Two Iloperidone Depot Formulations Followed by a Dose-ranging Phase of One Selected Formulation in Schizophrenic Patients Given Depot Injections Every 28 Days
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 81
- 试验地点
- 1
- 主要终点
- Maximum Observed Plasma Concentration (Cmax) of Iloperidone Divided by the Average Plasma Concentration (Cav) of Iloperidone (Cmax/Cav) - Phase B
研究概览
简要总结
This study is designed as a 3-part trial to evaluate the safety of a novel depot formulation of iloperidone, compare 2 depot dosage forms, and perform dose ranging of 1 chosen form in support of a monthly depot dosing regimen. In Phase A, the study is designed to evaluate the safety of a crystalline iloperidone depot formulation. In Phase B, the pharmacokinetic and safety profile of 2 depot clinical dosage forms will be compared, and 1 form will be selected for assessment in Phase C. Phase C of this study is designed to define the dose-exposure relationship of the selected form and to provide information that will permit a comparison of the risk-benefit ratio of several doses of the study drug to enable optimal dose selection for later studies.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with schizophrenia that have been stable for 3 months.
排除标准
- •Women who can become or are currently pregnant or lactating.
- •Hypersensitivity to iloperidone or related drugs.
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
Iloperidone 50 mg crystalline formulation - Phase A
Participants received a crystalline formulation of iloperidone 50 mg in a depot intramuscular (IM) injection 1 time. Prior to receiving IM iloperidone, participants were gradually titrated up with oral iloperidone for at least 7 days to stable doses of 12 to 24 mg daily.
干预措施: Iloperidone crystalline formulation (Drug)
Iloperidone 50 mg crystalline formulation - Phase A
Participants received a crystalline formulation of iloperidone 50 mg in a depot intramuscular (IM) injection 1 time. Prior to receiving IM iloperidone, participants were gradually titrated up with oral iloperidone for at least 7 days to stable doses of 12 to 24 mg daily.
干预措施: Oral iloperidone (Drug)
Iloperidone 125 mg crystalline formulation - Phase A
Participants received a crystalline formulation of iloperidone 125 mg in a depot IM injection 1 time. Prior to receiving IM iloperidone, participants were gradually titrated up with oral iloperidone for at least 7 days to stable doses of 12 to 24 mg daily.
干预措施: Iloperidone crystalline formulation (Drug)
Iloperidone 125 mg crystalline formulation - Phase A
Participants received a crystalline formulation of iloperidone 125 mg in a depot IM injection 1 time. Prior to receiving IM iloperidone, participants were gradually titrated up with oral iloperidone for at least 7 days to stable doses of 12 to 24 mg daily.
干预措施: Oral iloperidone (Drug)
Iloperidone 250 mg crystalline formulation - Phase B
Participants received a crystalline formulation of iloperidone 250 mg in a depot IM injection 1 time. Prior to receiving IM iloperidone, participants were gradually titrated up with oral iloperidone for at least 10 to 14 days to stable doses of 12 to 24 mg daily.
干预措施: Iloperidone crystalline formulation (Drug)
Iloperidone 250 mg crystalline formulation - Phase B
Participants received a crystalline formulation of iloperidone 250 mg in a depot IM injection 1 time. Prior to receiving IM iloperidone, participants were gradually titrated up with oral iloperidone for at least 10 to 14 days to stable doses of 12 to 24 mg daily.
干预措施: Oral iloperidone (Drug)
Iloperidone 250 mg microparticle formulation - Phase B
Participants received a microparticle formulation of iloperidone 250 mg in a depot IM injection 1 time. Prior to receiving IM iloperidone, participants were gradually titrated up with oral iloperidone for at least 10 to 14 days to stable doses of 12 to 24 mg daily.
干预措施: Iloperidone microparticle formulation (Drug)
Iloperidone 250 mg microparticle formulation - Phase B
Participants received a microparticle formulation of iloperidone 250 mg in a depot IM injection 1 time. Prior to receiving IM iloperidone, participants were gradually titrated up with oral iloperidone for at least 10 to 14 days to stable doses of 12 to 24 mg daily.
干预措施: Oral iloperidone (Drug)
Iloperidone 250 mg microparticle formulation - Phase C
Participants received a microparticle formulation of iloperidone 250 mg in a depot IM injection 2 times 28 days apart. Prior to receiving IM iloperidone, participants were gradually titrated up with oral iloperidone for at least 10 to 14 days to stable doses of 12 to 24 mg daily.
干预措施: Iloperidone microparticle formulation (Drug)
Iloperidone 250 mg microparticle formulation - Phase C
Participants received a microparticle formulation of iloperidone 250 mg in a depot IM injection 2 times 28 days apart. Prior to receiving IM iloperidone, participants were gradually titrated up with oral iloperidone for at least 10 to 14 days to stable doses of 12 to 24 mg daily.
干预措施: Oral iloperidone (Drug)
Iloperidone 500 mg microparticle formulation - Phase C
Participants received a microparticle formulation of iloperidone 500 mg in a depot IM injection 2 times 28 days apart. Prior to receiving IM iloperidone, participants were gradually titrated up with oral iloperidone for at least 10 to 14 days to stable doses of 12 to 24 mg daily.
干预措施: Iloperidone microparticle formulation (Drug)
Iloperidone 500 mg microparticle formulation - Phase C
Participants received a microparticle formulation of iloperidone 500 mg in a depot IM injection 2 times 28 days apart. Prior to receiving IM iloperidone, participants were gradually titrated up with oral iloperidone for at least 10 to 14 days to stable doses of 12 to 24 mg daily.
干预措施: Oral iloperidone (Drug)
Iloperidone 625 mg microparticle formulation - Phase C
Participants received a microparticle formulation of iloperidone 625 mg in a depot IM injection 2 times 28 days apart. Prior to receiving IM iloperidone, participants were gradually titrated up with oral iloperidone for at least 10 to 14 days to stable doses of 12 to 24 mg daily.
干预措施: Iloperidone microparticle formulation (Drug)
Iloperidone 625 mg microparticle formulation - Phase C
Participants received a microparticle formulation of iloperidone 625 mg in a depot IM injection 2 times 28 days apart. Prior to receiving IM iloperidone, participants were gradually titrated up with oral iloperidone for at least 10 to 14 days to stable doses of 12 to 24 mg daily.
干预措施: Oral iloperidone (Drug)
结局指标
主要结局
Maximum Observed Plasma Concentration (Cmax) of Iloperidone Divided by the Average Plasma Concentration (Cav) of Iloperidone (Cmax/Cav) - Phase B
时间窗: Pre-dose to 26 days post-dose
Blood samples for pharmacokinetic (PK) evaluation were drawn pre-dose and at 3, 6, and 12 hours on Day 1; at 0 and 12 hours on Day 2; and on Days 3, 4, 6, 8, 10, 14, 18, 22, and 26 following administration of iloperidone. PK parameters were calculated from plasma concentration-time data using non-compartmental methods.
The Average Plasma Concentration (Cav) of Iloperidone - Phase C
时间窗: Pre-dose to 26 days post-dose
Blood samples for pharmacokinetic (PK) evaluation were drawn pre-dose and at 3, 6, and 12 hours on Day 1; at 0 and 12 hours on Day 2; and on Days 3, 4, 6, 8, 10, 14, 18, 22, and 26 following administration of iloperidone. Blood samples were collected after each depot injection. PK parameters were calculated from plasma concentration-time data using non-compartmental methods. Cav was calculated as AUC0-672h/672 h.
次要结局
- Time to Reach the Maximum Plasma Concentration (Tmax) of Iloperidone - Phase B(Pre-dose to 26 days post-dose)
- Maximum Observed Plasma Concentration (Cmax) of Iloperidone - Phase B(Pre-dose to 26 days post-dose)
- Area Under the Plasma Concentration-time Curve From 0 to the Last Measurable Concentration (AUClast) of Iloperidone - Phase B(Pre-dose to 26 days post-dose)
- The Average Plasma Concentration (Cav) of Iloperidone - Phase B(Pre-dose to 26 days post-dose)
- Duration That the Concentration of Iloperidone Was Above 4 ng/mL (Teff) - Phase B(Pre-dose to 26 days post-dose)
- Time to Reach the Maximum Plasma Concentration (Tmax) of Iloperidone - Phase C(Pre-dose to 26 days post-dose)
- Maximum Observed Plasma Concentration (Cmax) of Iloperidone - Phase C(Pre-dose to 26 days post-dose)
- Area Under the Plasma Concentration-time Curve From 0 to the End of the Dosing Period (AUCtau) of Iloperidone - Phase B(Pre-dose to 26 days post-dose)
- Area Under the Plasma Concentration-time Curve From 0 to the End of the Dosing Period (AUCtau) of Iloperidone - Phase C(Pre-dose to 26 days post-dose)
- The Average Plasma Concentration (Cav) of Iloperidone Divided by Dose - Phase C(Pre-dose to 26 days post-dose)