A Phase 1, Two-part, Single Dose, Randomised, Double-blind, Placebo-controlled Parallel Study to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of Subcutaneous TRV250 Following Glyceryl Trinitrate Infusion
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Trevena Inc.
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- The primary outcome of this study is the proportion of patients who experienced a headache from dosing up to 4 hours post-dose, that exceeds a verbal numerical rating scale (NRS) headache rating of ≥2 points.
研究概览
简要总结
A trial to assess the efficacy, safety, tolerability and effect of a drug (code name TRV250) given as an injection to subjects who have received an injection of a drug called glyceryl trinitrate (GTN) which is clinically known to induce an immediate headache of short duration (under 30 minutes), known as the "GTN immediate headache"
详细描述
This is a Phase 1, two-part, single dose, randomised, double-blind, placebo-controlled parallel study to evaluate the efficacy, safety, tolerability and pharmacokinetics of subcutaneous TRV250 following glyceryl trinitrate infusion-evoked migraine type headache.
Approximately 360 patients (120 in Part A and 240 in Part B) are planned to complete dosing and assessments.
Part A will be a proof of concept study; approximately 120 patients will be randomised to 1 of 2 treatments (60 patients per treatment arm). Patients will receive either TRV250 (20 mg) or placebo administered subcutaneously in a double-blind manner. Part B will be a dose-ranging study; approximately 240 patients will be randomised to 1 of 4 treatments (60 patients per treatment arm). Patients will receive 1 of 3 doses of TRV250 or placebo administered subcutaneously in a double-blind manner.
The study will consist of 3 phases: Screening, Confinement, and Follow-Up. Patients will participate in an outpatient Screening visit, a 3-day inpatient Confinement Phase that comprises GTN-infusion and treatment with TRV250 or placebo, and an outpatient safety Follow-Up visit 5 to 7 days post-dose.
The expected duration of participation is up to 6 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- Double (Participant, Investigator)
盲法说明
Patients will be randomised to receive TRV250 20 mg or placebo in Part A and 1 of 3 doses of TRV250 or placebo in Part B. The study will be conducted in a double-blinded fashion (Investigator- and patient -blinded). Only unblinded personnel will have access to the randomisation list before official unblinding of treatment assignment. Interim analyses will be conducted at the end of Part A of the study prior to proceeding to Part B and the preliminary efficacy pharmacokinetic, safety and tolerability data will be evaluated unblinded at the end of Part A and shared with the Investigators in an unblinded manner, prior to starting Part B.
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient is male or female, aged between 18 and 55 years inclusive.
- •Patient's Body Mass Index (BMI) is between 18 and 32 kg/m2 inclusive.
- •Patient should have a clinical diagnosis of migraine without aura (IHS criteria 1.1) and experience between 1 migraine attack every other month to 8 migraine attacks per month. They should have had a positive outcome with Triptans, for their migraine attacks (Triptan Responders).
排除标准
- •Patient has previous exposure to TRV
- •Abnormal EEG at screening or risk factors of increased seizure potential, such as previous seizures, history of febrile seizures, cerebral tumor, stroke, cerebrovascular disease, or significant traumatic brain injury.
- •Patient with a history of hypotension or hypertension, including where this is currently under control.
- •Patient taking prophylactic migraine treatments such as beta blockers 28 days before GTN infusion on Day
- •Resting heart rate <45 beats per minute on assessment of vital signs at screening or pre-GTN infusion on Day
- •QTcF >450 msec at screening (mean of three ECGs) or pre-GTN infusion on Day
- •Patient with another headache disorder such as menstrual migraine, chronic migraine, cluster headache, tension headache or other chronic headache states.
- •Patient who have a history, or family history of any vascular intracranial lesion such as subarachnoid aneurysm or similar and patients with a relevant neurological history.
- •Patients who have any allergies/contraindications for Triptan administration.
研究组 & 干预措施
Part A: Placebo for SC injection
2 SC injections (identical to the TRV250)
干预措施: Placebo (Drug)
Part B: Placebo for SC injection
Placebo (using syringes identical to the TRV250 arms)
干预措施: Placebo (Drug)
结局指标
主要结局
The primary outcome of this study is the proportion of patients who experienced a headache from dosing up to 4 hours post-dose, that exceeds a verbal numerical rating scale (NRS) headache rating of ≥2 points.
时间窗: 0-4 hours post-dose
Verbal Numerical Rating (NRS) and Headache Characteristics (Pain Response, Pain Freedom, Nausea, Photophobia) Assessment: 0 minutes prestart of GTN infusion and every 15 minutes until 4 hours post-dose
次要结局
- The PK data model for each patient/dose combination: AUC(0-24)(up to 24 hours post dose)
- The PK data model for each patient/dose combination: Cmax (ng/mL) o Tmax - Time of maximum concentration (hours) o t1/2 - half-life (hours)(up to 24 hours post dose)
- The PK data model for each patient/dose combination: Tmax(up to 24 hours post dose)
- The PK data model for each patient/dose combination: t1/2(up to 24 hours post dose)
- The proportion of patients who experienced a headache occurring at various timepoints from dosing up to 8 hours post-dose, that exceeds a verbal NRS headache rating of ≥2 points(0-8 hours post-dose)
- The proportion of patients who experience a headache occurring at various timepoints from dosing up to 8 hours post-dose, that exceeds a verbal NRS headache rating of ≥3 points.(0-8 hours post-dose)
- PF at 2-hour time point following injection of TRV250 or placebo.(every 2 hours for 24 hours)
- Absence of nausea between 2 and 24 hours in patients with nausea from 60 minutes post-start of GTN infusion(up to 24 hours post dose)
- The proportion of patients who experience a headache occurring at various timepoints from dosing up to 8 hours post-dose, that exceeds a verbal NRS headache rating of ≥4 points.(0-8 hours post-dose)
- Sustained pain response between 2 and 24 hours (2-24H SPR): PR at 2 hours after TRV250 or placebo administration, with no administration of any rescue medication and no occurrence of migraine type headache with verbal NRS score of ≥4 points(up to 24 hours post dose)
- Absence of photophobia between 2 and 24 hours in patients with photophobia from 60 minutes post-start of GTN infusion.(up to 24 hours post dose)
- The effect of TRV250 on cardiac repolarisation (Cardiac Telemetry)(Continuous Cardiac Telemetry: min 8hrs pre-GTN to 24hrs post dose)
- Safety Assessment - Injection Site Assessment(at time of GTN-infusion (0 hours) up to 24hrs post-dose)
- Pain Response (PR) at 2-hour time point following injection of TRV250 or placebo(every 2 hours for 24 hours)
- The effect of TRV250 on cardiac repolarisation (Electrocardiogram)(12-lead ECG: screening, Day-1 and up to 24 hours post dose)
- The PK data model for each patient/dose combination: AUC(0-∞)(up to 24 hours post dose)
- Proportion of patients requiring use of rescue medication at various timepoints.(up to 24 hours of follow-up)
- The effect of TRV250 on cardiac repolarisation determined from cardiac telemetry(Continuous Cardiac Telemetry: min 8hrs pre-GTN to 24hrs post dose)