A Double-blind, Randomized, Placebo-controlled, Sequential Group Pilot Study to Assess Safety, Tolerability, and Effectiveness of TC-5214 as Augmentation Therapy in Patients With Refractory Hypertension
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- Mean difference between TC-5214 and placebo in change at 3 hours from baseline SBP
研究概览
简要总结
A pilot study of subjects with refractory hypertension (on 3 concomitant agents with SBP > 140 mmHg and a DBP > 90 mmHg) randomized in a double-blind fashion to receive 4 single escalating doses of study medication in clinic.
详细描述
12 subjects with refractory hypertension will be randomized in a double-blind fashion to receive single escalating doses of study medication in-clinic: on Day 1 (1mg), Day 8 (2mg), Day 15 (4mg) and Day 22 (8mg). On each of these 4 days, 10 subjects will receive TC-5214, and 2 subjects will receive placebo. Placebo treatments will be pooled across the 4 days of single-dose to produce an equivalent reference cohort (n = 8) for each treatment dose (n=10). Following the single-dose administration of 8mg in the clinic on Day 22, subjects will continue with two weeks (Days 23 - 35) of outpatient self-administration of TC-5214 (4mg BID; n = 6), or matching placebo (BID; n = 6). On Day 36, subjects will return for a final in-clinic dose of either TC-5214 (4mg, n = 6) or placebo (n = 6). There will be a 1-week follow-up period at the end of the treatment period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
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
- •Refractory hypertension, defined as a SBP of >140mmHg and a DBP > 90mmHg, on stable doses of at least 3 concomitant antihypertensive treatment (which must include a diuretic and an ACEI, ARB or RA) for 8 weeks prior to Screening. All approved antihypertensive treatments are allowed except for alpha-adrenergic blockers, hydralazine, clonidine, guanethidine, guanadrel, and rauwolfia alkaloids.
- •Stable hypertension, as defined by: a. mean SBP on Day -7 that is within 20mmHg of the mean SBP on Day 1, with both mean SBPs > 140mmHg; and b. mean DBP on Day -7 that is within 10mm of the mean DBP on Day 1, with both mean DBPs > 90mmHg.
- •Outpatient with stable housing.
- •Subjects must be able to stay in the clinic for 8 hrs on Day 1, Day 8, Day 15, Day 22, and Day
- •Able to give and to sign informed consent.
排除标准
- •Any unstable medical condition other than hypertension;
- •Stage 3 hypertension (SBP > 180mmHg and/or DBP > 110mmHg);
- •Heart rate > 100 beats per minute;
- •WOCBP who is pregnant or who is planning to become pregnant during the study;
- •History within past year of alcohol or illicit drug abuse;
- •Unable to comply with study procedures in opinion of investigator;
- •Concomitant medications for any medical condition that is uncontrolled for more than 2 weeks prior to study entry;
- •Current use of alpha-adrenergic blocker, hydralazine, clonidine, guanethidine, guanadrel, or rauwolfia alkaloids;
- •History of myocardial infarction or angina pectoris;
- •Current seizure disorder;
- •Renal insufficiency as defined by a serum creatinine > 2.0;
- •Uncontrolled hypothyroidism, vitamin B12 or folic acid deficiency;
- •History of or concurrent ileus, glaucoma, or urinary retention;
- •Inability of subject to understand and sign the ICF;
- •Known systemic infection (HBV, HCV, HIV, TB);
- •Current use of smoking cessation therapy within 4 weeks of screening;
- •Use of herbal supplements;
- •Clinically significant finding on physical exam;
- •Clinically significant laboratory or ECG abnormality, including QTcF > 460 msec;
- •Participation in another clinical trial in last month;
- •Body Mass Index (BMI) >
- •Body weight < 100 pounds.
- •Site staff or family member of study site staff.
研究组 & 干预措施
Placebo
Subjects may receive a single, oral dose of placebo (capsule) in one of 4 crossover periods. Also, subjects may receive placebo orally, twice daily for 14 days in the last phase of the study.
干预措施: Placebo (Drug)
1 mg TC-5214
Subjects may receive a single, oral capsule of 1 mg TC-5214 in one of 4 crossover periods.
干预措施: TC-5214 (Drug)
2 mg TC-5214
Subjects may receive a single, oral capsule of 2 mg TC-5214 in one of 4 crossover periods.
干预措施: TC-5214 (Drug)
4 mg TC-5214
Subjects may receive a single, oral capsule of 4 mg TC-5214 in one of 4 crossover periods. Also, subjects may receive 4 mg TC-5214 orally, twice daily for 14 days in the last phase of the study.
干预措施: TC-5214 (Drug)
8 mg TC-5214
Subjects may receive a single, oral capsule of 8 mg TC-5214 in one of 4 crossover periods.
干预措施: TC-5214 (Drug)
结局指标
主要结局
Mean difference between TC-5214 and placebo in change at 3 hours from baseline SBP
时间窗: Following dosing, 3 manual seated BP measurements and orthostatic BP measurements will be obtained in an identical fashion, at 30 minutes post-dose and at 1, 2, 3, 4, 5, 6, 7, and 8 hrs post-dose.
次要结局
- Safety and tolerability of TC-5214 in patients with refractory hypertension and obtain preliminary dose-response estimates(Days 1, 8, 15, 22 and 36)