Multicenter, Open-label, Two-arm, Parallel-design, Repeat-dose Clinical Trial to Evaluate the PK, Safety, and Tolerability of Four Intramuscular Injections of Risperidone ISM® 75 mg, at 28 Day Intervals in Patients With Schizophrenia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 70
- 试验地点
- 1
- 主要终点
- Peak Plasma Concentration (Cmax) for Active Moiety
研究概览
简要总结
To characterize the pharmacokinetics (PK) of the injectable intramuscular (IM) long-acting formulation (in situ microparticle, ISM) of risperidone over four IM injections in the gluteal and deltoid muscle at 28-day intervals and at one dose strength (75 mg) in patients with schizophrenia.
详细描述
This was a multicenter, open-label, two-arm, parallel-design, repeat-dose clinical study designed to evaluate the PK, safety, and tolerability of Risperidone ISM®, a new long-acting injectable formulation of the licensed drug risperidone, administered in the gluteal muscle or the deltoid muscle. Participants were patients with a diagnosis of schizophrenia capable of understanding, signing, and consenting to study participation on their own.
Objectives:
Primary Objective
• To characterize the pharmacokinetics (PK) of the injectable intramuscular (IM) long-acting formulation of risperidone over four IM injections in the gluteal and deltoid muscle at 28 day intervals and at one dose strength (75 mg) in patients with schizophrenia.
Secondary Objectives
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
- •Capable of providing informed consent.
- •Male or female aged ≥18 years to ≤65 years.
- •Current diagnosis of schizophrenia, according to Diagnostic and Statistical Manual
- •Body mass index (BMI) ≥17 kg/m2 but ≤35 kg/m
- •Medically stable over the last month, and psychiatrically stable
- •On oral stable dosage of risperidone ≥4 mg daily as maintenance therapy.
- •Total score ≤70 on the Positive and Negative Syndrome Scale.
- •Using a medically accepted contraceptive method
- •Agrees to washout all prohibited medications prior to baseline (day -1)
排除标准
- •Informed consent obtained from a third party.
- •Prisoners or patients who are compulsorily detained.
- •Females who are breast-feeding and/or who have a positive pregnancy test.
- •Presence of an uncontrolled, unstable clinically significant medical condition.
- •Positive serology for Hepatitis B, Hepatitis C or anti-HIV 1 and 2 at screening.
- •History of neuroleptic malignant syndrome.
- •Current or past history of tardive dyskinesia.
- •Positive urine drug or alcohol screen finding.
- •Risk of committing self-harm or harm based on Columbia Suicidal Rating Scale.
- •Taking more than one antidepressant.
- •Use of depot antipsychotics within the last three months.
- •Use of strong or moderate cytochrome P450 isoenzyme 3A4inducers
- •Use of electroconvulsive therapy (ECT) within the last three months.
- •Receipt of any investigational drugs within the last three months.
- •Known or suspected allergy or hypersensitivity to risperidone
- •Previous non-responder to risperidone treatment.
研究组 & 干预措施
Deltoid (Risperdione ISM)
Risperidone ISM (75 mg) injection in the deltoid muscle at 28-day intervals
干预措施: Risperidone ISM (Drug)
Gluteus (Risperidone ISM)
Risperidone ISM (75 mg) injection in the gluteal muscle at 28-day intervals
干预措施: Risperidone ISM (Drug)
结局指标
主要结局
Peak Plasma Concentration (Cmax) for Active Moiety
时间窗: Dose 1, 2 and 3: Pre-dose; at 2, 8, 12, 24 and 48 hours post-dose; 5, 7, 10, 14, 18, and 21 days post-dose. Dose 4: Pre dose; at 2, 8, 12, 24, and 48 hours post-dose; at 5, 7, 10, 14, 18, 21, 25, 28, 32, 37, 42, 60, 75, 90, 105, and 120 days post-dose.
AUCτ for Active Moiety
时间窗: Dose 1, 2 and 3: Pre-dose; at 2, 8, 12, 24 and 48 hours post-dose; 5, 7, 10, 14, 18, and 21 days post-dose. Dose 4: Pre dose; at 2, 8, 12, 24, and 48 hours post-dose; at 5, 7, 10, 14, 18, 21, 25, 28, 32, 37, 42, 60, 75, 90, 105, and 120 days post-dose.
AUCτ is the area under the curve over the dosing interval (τ), where the dosing interval is 28 days
Terminal Half-life (t1/2) for Active Moiety
时间窗: Dose 1, 2 and 3: Pre-dose; at 2, 8, 12, 24 and 48 hours post-dose; 5, 7, 10, 14, 18, and 21 days post-dose. Dose 4: Pre dose; at 2, 8, 12, 24, and 48 hours post-dose; at 5, 7, 10, 14, 18, 21, 25, 28, 32, 37, 42, 60, 75, 90, 105, and 120 days post-dose.
Time to Peak Concentration (Tmax) for Active Moiety
时间窗: Dose 1, 2 and 3: Pre-dose; at 2, 8, 12, 24 and 48 hours post-dose; 5, 7, 10, 14, 18, and 21 days post-dose. Dose 4: Pre dose; at 2, 8, 12, 24, and 48 hours post-dose; at 5, 7, 10, 14, 18, 21, 25, 28, 32, 37, 42, 60, 75, 90, 105, and 120 days post-dose.
PTF for Active Moiety
时间窗: Dose 1, 2 and 3: Pre-dose; at 2, 8, 12, 24 and 48 hours post-dose; 5, 7, 10, 14, 18, and 21 days post-dose. Dose 4: Pre dose; at 2, 8, 12, 24, and 48 hours post-dose; at 5, 7, 10, 14, 18, 21, 25, 28, 32, 37, 42, 60, 75, 90, 105, and 120 days post-dose.
Peak to Trough Fluctuation ratio for the Active Moiety
Trough Plasma Concentration (Cmin) for Active Moiety
时间窗: Dose 1, 2 and 3: Pre-dose; at 2, 8, 12, 24 and 48 hours post-dose; 5, 7, 10, 14, 18, and 21 days post-dose. Dose 4: Pre dose; at 2, 8, 12, 24, and 48 hours post-dose; at 5, 7, 10, 14, 18, 21, 25, 28, 32, 37, 42, 60, 75, 90, 105, and 120 days post-dose.
Area Under the Curve to the Last Quantified Concentration (AUClast) for Active Moiety
时间窗: Dose 1, 2 and 3: Pre-dose; at 2, 8, 12, 24 and 48 hours post-dose; 5, 7, 10, 14, 18, and 21 days post-dose. Dose 4: Pre dose; at 2, 8, 12, 24, and 48 hours post-dose; at 5, 7, 10, 14, 18, 21, 25, 28, 32, 37, 42, 60, 75, 90, 105, and 120 days post-dose.
Area Under the Curve Extrapolated to Infinity (AUC∞) for Active Moiety
时间窗: Dose 1, 2 and 3: Pre-dose; at 2, 8, 12, 24 and 48 hours post-dose; 5, 7, 10, 14, 18, and 21 days post-dose. Dose 4: Pre dose; at 2, 8, 12, 24, and 48 hours post-dose; at 5, 7, 10, 14, 18, 21, 25, 28, 32, 37, 42, 60, 75, 90, 105, and 120 days post-dose.
次要结局
- Accumulation Ratio (RA) for Active Moiety(Dose 1, 2 and 3: Pre-dose; at 2, 8, 12, 24 and 48 hours post-dose; 5, 7, 10, 14, 18, and 21 days post-dose. Dose 4: Pre dose; at 2, 8, 12, 24, and 48 hours post-dose; at 5, 7, 10, 14, 18, 21, 25, 28, 32, 37, 42, 60, 75, 90, 105, and 120 days post-dose.)