Riociguat (BAY 63-2521), a Stimulator of Soluble Guanylate Cyclase (sGC) - Cerebral Vasodilation and Headache Induction in Healthy Volunteers
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Change in superficial temporal artery (STA) diameter from baseline to 90 minutes in healthy volunteers after receiving riociguat compared to placebo.
研究概览
简要总结
This double-blind, randomized, placebo-controlled cross-over clinical trial aims to investigate the effects of riocigaut on cerebral arteries and headache inducing properties in healthy volunteers.
详细描述
The investigators believe that activation of sGC could play a role in migraine pathophysiology and propose that stimulation with riociguat causes cranial arterial dilation alongside headache in healthy volunteers.
Twelve healthy volunteers participate at a screening visit, and if eligible, on two separate study days, where participants, in a randomized cross-over fashion, will ingest either riociguat (active comparator arm) or placebo (placebo comparator arm), serving as their own controls. On the two separate study days the investigators will measure change in diameter of superficial temporal artery and middle cerebral artery blood flow velocity and register possible headache until 4 hours after intake of riociguat or placebo. At home participants are expected to fill out a headache diary until 12 hours from intake of riociguat or placebo.
Leading up to the main study described above, the investigators will conduct a pilot dose-finding study (experimental arm) of increasing doses of riociguat, 2,5mg and 5mg respectively, on two separate study days in 5 healthy volunteers, to ensure an appropriate dose is applied in the main study.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Ability to provide written informed consent and receive participant privacy and rights information.
- •Male or female participants aged 18-45 years.
- •Weight between 50-100kg
- •Non-smokers
排除标准
- •Any current or previous known primary or secondary headache disorder(s) apart from tension type headache ≤ 1 day per month.
- •Headache <48 hours before study start.
- •Daily use of any medication except contraceptives. Specifically use of nitrates or nitric oxide donors or phosphodiesterase inhibitors.
- •Intake of any pro necessitate medication later than 4 times plasma half-life for the specific drug before study start, except for contraceptives
- •Women of child-bearing potential not currently using safe contraceptives. Women of child-bearing potential does not include hysterectomized women and women who have been in menopause for at least 2 years. Safe contraceptives include either IUD, birth control pills, surgical sterilization of the woman, depositary gestagen, barrier prevention or sexual abstinence.
- •Pregnant or breastfeeding women
- •Positive pregnancy urin screening on screening day or study days.
- •A medical history or clinical signs of
- •Hypertension (systolic blood pressure >140mmHg and/or diastolic blood pressure >90mmHg)
- •Hypotension (systolic blood pressure <100mmHg and/or diastolic blood pressure <50mmHg)
- •Electrocardiogram (ECG) with any clinically significant abnormalities at screening determined by the investigator, including but not limited to, prolonged PQ or QTc interval, signs of arrythmias, ischemia or left/right ventricle dysfunction/hypertrophy.
- •Blood work at screening with signs of anemia.
- •Blood work at screening with signs of abnormal kidney and liver function.
- •A medical history or clinical signs of cardiovascular disease including cerebrovascular disease.
- •A medical history or clinical signs of pulmonary disease.
- •A medical history or clinical signs of liver, renal, gastrointestinal, endocrine, hematological or neurological disease.
- •A medical history or clinical signs of psychiatric illness or substance abuse
- •A medical history or clinical signs of drug or alcohol abuse
- •A medical history or clinical signs of disease of any origin that the investigative doctor finds relevant for participation in the study
- •A family history of severe cardiac disease.
- •Any history of hypersensitivity to riociguat.
- •Subjects who do not want information about crucial pathological findings during the study
研究组 & 干预措施
Dose Riociguat 2,5 or 5mg
Riociguat dose finding pilot experiment, 2,5mg and 5mg
干预措施: Dose Riociguat 2,5 or 5mg (Drug)
Riociguat
Riociguat orally
干预措施: Riociguat (Drug)
Placebo
Placebo orally
干预措施: Placebo (Drug)
结局指标
主要结局
Change in superficial temporal artery (STA) diameter from baseline to 90 minutes in healthy volunteers after receiving riociguat compared to placebo.
时间窗: 0 - 90 minutes
Measured by high resolution ultrasonography.
次要结局
- Incidence of headache (>0 on Numeric Rating Scale (NRS) from 0 to 10, 0="no pain" versus 1-10="pain") in healthy volunteers until 12 hours after receiving riociguat compared to placebo.(0 - 12 hours)
- Change in middle cerebral artery (MCA) blood flow velocity in healthy volunteers after receiving riociguat compared to placebo.(0 - 4 hours)
- Changes in heart rate in healthy volunteers after receiving riociguat compared to placebo.(0 - 4 hours)
研究者
Messoud Ashina, MD
MD, Ph.D., DMSc., Chief Consultant Neurologist
Danish Headache Center