Investigation of the Effect of Riociguat, Administered as 2.5 mg IR-tablets TID Over 14 Days, on Bone Metabolism in a Randomized, Placebo-controlled, Double-blind, 2-fold Cross-over Design in Healthy Male Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Bayer
- 入组人数
- 17
- 主要终点
- Cmax
研究概览
简要总结
Investigation of the effect of Riociguat, administered as 2.5 mg IR-tablets TID over 14 days, on bone metabolism.
详细描述
Clinical pharmacology
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 45 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Healthy male white subjects
- •18 to 45 years of age
- •BMI between 18 and 28 kg/m2
- •Subjects who are able to understand and follow instructions and who are able to participate in the study for the entire period
排除标准
- •Relevant deviation from the normal range in the clinical examination; in clinical chemistry, hematology, or urinalysis
- •Resting heart rate in the awake subject below 45 BPM or above 90 BPM
- •Systolic blood pressure below 100 mmHg or above 145 mmHg
- •Diastolic blood pressure above 95 mmHg
- •Relevant pathological changes in the ECG such as a second or third-degree AV block, prolongation of the QRS complex over 120 msec or of the QT / QTc-interval over 450 msec for males
- •History of genetic muscle or bone disease of any kind
- •Completely sedentary or extremely fit subjects
- •Fractures in the preceding 12 months
- •Psychiatric diseases
- •History of peptic ulcers or relevant gastro-esophageal reflux disease
- •Subjects with hypersensitivity to the investigational drug riociguat or ranitidine, or to inactive constituents
- •Regular daily consumption of more than half a liter of usual beer or the equivalent quantity of approximately 20 g of alcohol in another form, more than 1 L of xanthine-containing beverages, recent smoking history
- •Use of medication within the 2 weeks preceding the study which could have interfered with the investigational drug riociguat or ranitidine
- •Subjects with a medical disorder, condition or history of such that would have impaired the subject's ability to participate or complete this study in the opinion of the investigator or the sponsor
研究组 & 干预措施
Riociguat
Subjects received multiple doses of riociguat (thrice a day) with concomitant administration of ranitidine (once daily) for 14 days
干预措施: Riociguat (Adempas, BAY63-2521) immediate release tablet of 2.5 mg (Drug)
Placebo
Subjects received placebo (thrice a day) with concomitant administration of ranitidine (once daily) for 14 days
干预措施: Placebo (Drug)
结局指标
主要结局
Cmax
时间窗: Pre-dose and up to 7 hours post-dose on Day 0
Maximum drug concentration in plasma after single dose administration for riociguat and its metabolite M-1 (BAY60-4552)
Cmax,ss
时间窗: Pre-dose and up to 7 hours post-dose on Day 13
Maximum drug concentration in plasma at steady state during a dosage interval for riociguat and its metabolite M-1 (BAY60-4552)
AUC(0-7)
时间窗: Pre-dose and up to 7 hours post-dose on Day 0
Area under the plasma concentration vs time curve (AUC) from zero to 7 hours after single (first) dose for riociguat and its metabolite M-1 (BAY60-4552)
AUC(0-7)ss
时间窗: Pre-dose and up to 7 hours post-dose on Day 13
AUC(0-7) at steady state
Urinary excretion (over 24 hours) of C-terminal cross-linking telopeptides of type I collagen (CTX)
时间窗: From Day -01 to 16
Marker of bone resorption
次要结局
- Cmax,norm(Pre-dose and up to 7 hours post-dose on Day 0)
- tmax(Pre-dose and up to 7 hours post-dose on Day 0)
- Aeur(0-7)(Pre-dose and up to 7 hours post-dose)
- Number of participants with adverse events(Approximately 12 weeks)
- tmax,ss(Pre-dose and up to 7 hours post-dose on Day 13)
- %Aeur(0-7)(Pre-dose and up to 7 hours post-dose)
- Urinary excretion (over 24 hours) of N-terminal cross-linking telopeptides of type I collagen (NTX)(From -01 to 16 Days)
- Creatinine(From -01 to 16 Days)
- Ctrough(On Days 03 and 08)
- AUC(0-7)norm(Pre-dose and up to 7 hours post-dose on Day 0)
- AUC(0-7)ss,norm(Pre-dose and up to 7 hours post-dose on Day 13)
- Cmax,ss,norm(Pre-dose and up to 7 hours post-dose on Day 13)
- Serum CTX(From -01 to 16 Days)
- Serum N-terminal propeptide of type I collagen (PINP)(From -01 to 16 Days)
- Serum bone-specific alkaline phosphatase (bAP)(From -01 to 16 Days)
- Serum albumin, protein(From -01 to 16 Days)
- Cyclic guanosine monophosphate (cGMP)(From -01 to 16 Days)
- Calcium, sodium, potassium(From -01 to 16 Days)
- Urine volume(From -01 to 16 Days)
- Renin(From -01 to 16 Days)
- Serum osteocalcin(From -01 to 16 Days)
- Phosphate(From -01 to 16 Days)
- Creatinine clearance(From -01 to 16 Days)
- Parathyroid hormone (PTH)(From -01 to 16 Days)