Investigation of Pharmacodynamic and Pharmacokinetic Interactions Between 25 mg BI 10773 and 25 mg Hydrochlorothiazide or 5 mg Torasemide Under Steady State Conditions in Patients With Type 2 Diabetes Mellitus in an Open-label, Randomised, Cross-over Trial
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 23
- 试验地点
- 1
- 主要终点
- Change in Serum Concentration of Renin, Intact Parathyroid Hormone (iPTH) and 1,25-dihydroxyvitamin D From Baseline
研究概览
简要总结
The primary objective of the study is to investigate the effect of BI 10773, hydrochlorothiazide and torasemide on changes in serum and urine electrolytes. Furthermore the pharmacodynamic and pharmacokinetic interactions between BI 10773 and diuretics should be assessed.
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
- None
入排标准
- 年龄范围
- 20 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Test 1
administration of BI 10773 + HTC once daily for 5 days (10 patients)
干预措施: BI 10773 (Drug)
Reference 1
administration of BI 10773 once daily for 5 days (20 patients)
干预措施: BI 10773 (Drug)
Reference 2
administration of hydrochlorothiazide (HTC) once daily for 4 days (10 patients)
干预措施: hydrochlorothiazide (Drug)
Reference 3
administration of torasemide (TOR) once daily for 4 days (10 patients)
干预措施: torasemide (Drug)
Test 1
administration of BI 10773 + HTC once daily for 5 days (10 patients)
干预措施: hydrochlorothiazide (Drug)
Test 2
administration of BI 10773 + TOR once daily for 5 days (10 patients)
干预措施: BI 10773 (Drug)
Test 2
administration of BI 10773 + TOR once daily for 5 days (10 patients)
干预措施: torasemide (Drug)
结局指标
主要结局
Change in Serum Concentration of Renin, Intact Parathyroid Hormone (iPTH) and 1,25-dihydroxyvitamin D From Baseline
时间窗: baseline and then day 6 for Empa, day 5 for TOR and HCT, day 10 for Empa+TOR and Empa+HCT
Change in serum concentration of Renin, intact parathyroid hormone (iPTH) and 1,25-dihydroxyvitamin D from baseline , where baseline was defined as the measurement obtained before first drug administration in the first period The mean change from baseline was evaluated as: Empa: day 6- baseline, HCT: day 5-baseline, TOR: day 5-baseline, Empa+ HCT: day 10- baseline, Empa+ TOR: day 10- baseline, The means for the Empa arm represent combined adjusted means of all four sequences that is Empa administered before or after the administration of either TOR, HCT and their combination with Empa
Change in Serum Concentration of Aldosterone From Baseline
时间窗: baseline and then day 6 for Empa, day 5 for TOR and HCT, day 10 for Empa+TOR and Empa+HCT
Change in serum concentration of Aldosterone from baseline , where baseline was defined as the measurement obtained before first drug administration in the first period The mean change from baseline was evaluated as: Empa: day 6- baseline, HCT: day 5-baseline, TOR: day 5-baseline, Empa+ HCT: day 10- baseline, Empa+ TOR: day 10- baseline, The mean for the Empa arm represent combined adjusted means of all four sequences that is Empa administered before or after the administration of either TOR, HCT and their combination with Empa
The Change in Micturition Frequency From the Baseline
时间窗: Baseline and day 5
For this endpoint the change in total micturition frequency from the baseline was only examined for EMPA where baseline was defined as the day before the first drug administration.
Change in Serum Concentration of Fibroblast Growth Factor-23 (FGF- 23) From Baseline
时间窗: baseline and then day 6 for Empa, day 5 for TOR and HCT, day 10 for Empa+TOR and Empa+HCT
Change in serum concentration of fibroblast growth factor-23 (FGF- 23) from baseline, where baseline was defined as the measurement obtained before first drug administration in the first period The mean change from baseline was evaluated as: Empa: day 6- baseline, HCT: day 5-baseline, TOR: day 5-baseline, Empa+ HCT: day 10- baseline, Empa+ TOR: day 10- baseline, The mean for the Empa arm represent combined adjusted means of all four sequences that is Empa administered before or after the administration of either TOR, HCT and their combination with Empa
Change in Urine pH From Baseline
时间窗: baseline and then day 6 for Empa, day 5 for TOR and HCT, day 10 for Empa+TOR and Empa+HCT
Change in urine pH from baseline, where baseline was defined as the measurement obtained before first drug administration in the first period The mean change from baseline was evaluated as: Empa: day 6- baseline, HCT: day 5-baseline, TOR: day 5-baseline, Empa+ HCT: day 10- baseline, Empa+ TOR: day 10- baseline, The mean for the Empa arm represent combined adjusted means of all four sequences that is Empa administered before or after the administration of either TOR, HCT and their combination with Empa
Changes in Bicarbonate Concentrations of Calcium, Bicarbonate Ions and Base Excess in Capillary or Arterialised Blood From Baseline
时间窗: baseline and then day 6 for Empa, day 5 for TOR and HCT, day 10 for Empa+TOR and Empa+HCT
Changes in bicarbonate concentrations of calcium, bicarbonate ions and base excess in capillary or arterialised blood from baseline, where baseline was defined as the last measurement before trial drug administration of each treatment period The mean change from baseline was evaluated as: Empa: day 6- baseline, HCT: day 5-baseline, TOR: day 5-baseline, Empa+ HCT: day 10- baseline, Empa+ TOR: day 10- baseline, The means for the Empa arm represent combined adjusted means of all four sequences that is Empa administered before or after the administration of either TOR, HCT and their combination with Empa
Change in Body Weight From Baseline
时间窗: baseline and then day 6 for Empa, day 5 for TOR and HCT, day 10 for Empa+TOR and Empa+HCT
Change in body weight from baseline , where baseline was defined as the last measurement before trial drug administration of each treatment period The mean change from baseline was evaluated as: Empa: day 6- baseline, HCT: day 5-baseline, TOR: day 5-baseline, Empa+ HCT: day 10- baseline, Empa+ TOR: day 10- baseline, The mean for the Empa arm represent combined adjusted means of all four sequences that is Empa administered before or after the administration of either TOR, HCT and their combination with Empa
The Change in Total Muscle Sympathetic Nerve Activity (MSNA) From Off- Treatment
时间窗: One day before the drug administration, then day 4 after the first drug administration
The change in total Muscle sympathetic nerve activity (MSNA) that represents an area under the curve of all C-fiber action potentials per minute. This endpoint was evaluated only for Empa. For this endpoint a baseline value was not defined. However, the parameters obtained at 2 measurements time points during the trial were compared.
Change in Urinary Excretion in a 24-hour Period of Sodium, Potassium, Magnesium, Chloride, Calcium, Phosphate, Creatinine, Uric Acid, Glucose From Baseline
时间窗: 24 hour sampling interval at baseline and then day 5 for Empa, day 4 for TOR and HCT, day 9 for Empa+TOR and Empa+HCT
Change in urinary excretion in a 24-hour period of sodium, potassium, magnesium, chloride, calcium, phosphate, creatinine, uric acid, glucose from baseline, where baseline was defined as the value obtained from the last 24-hour (h) collection period before the first drug administration in the first treatment period. This applies also to sodium excretion in urine, which is additionally obtained one day before the drug administration before the second period. The mean change from baseline was evaluated as: Empa: day 5- baseline, HCT: day 4-baseline, TOR: day 4-baseline, Empa+ HCT: day 9- baseline, Empa+ TOR: day 9- baseline, The means for the Empa arm represent combined adjusted means of all four sequences that is Empa administered before or after the administration of either TOR, HCT and their combination with Empa
Change in Urinary Excretion in a 24-hour Period of N-terminal Telopeptide (NTx) From Baseline
时间窗: 24 hour sampling interval at baseline and then day 5 for Empa, day 4 for TOR and HCT, day 9 for Empa+TOR and Empa+HCT
Change in urinary excretion in a 24-hour period of N-terminal telopeptide (NTx) from baseline, where baseline was defined as the value obtained from the last 24-hour (h) collection period before the first drug administration in the first treatment period. The mean change from baseline was evaluated as: Empa: day 5- baseline, HCT: day 4-baseline, TOR: day 4-baseline, Empa+ HCT: day 9- baseline, Empa+ TOR: day 9- baseline, The means for the Empa arm represent combined adjusted means of all four sequences that is Empa administered before or after the administration of either TOR, HCT and their combination with Empa
Change in Serum Osmolality From Baseline
时间窗: baseline and then day 6 for Empa, day 5 for TOR and HCT, day 10 for Empa+TOR and Empa+HCT
Changes in serum osmolality from baseline based on a blood sample. Baseline was defined as the measurement obtained before the first drug administration in the first period. The mean change from baseline was evaluated as: Empa: day 6- baseline, HCT: day 5-baseline, TOR: day 5-baseline, Empa+ HCT: day 10- baseline, Empa+ TOR: day 10- baseline, The mean for the Empa arm represent combined adjusted means of all four sequences that is Empa administered before or after the administration of either TOR, HCT and their combination with Empa
Change in Urine Osmolality From Baseline
时间窗: baseline and then day 6 for Empa, day 5 for TOR and HCT, day 10 for Empa+TOR and Empa+HCT
Change in urine osmolality from baseline, where baseline was defined as the measurement obtained before first drug administration in the first period The mean change from baseline was evaluated as: Empa: day 6- baseline, HCT: day 5-baseline, TOR: day 5-baseline, Empa+ HCT: day 10- baseline, Empa+ TOR: day 10- baseline, The mean for the Empa arm represent combined adjusted means of all four sequences that is Empa administered before or after the administration of either TOR, HCT and their combination with Empa
Change in Clearance of Sodium, Potassium, Creatinine, Magnesium, Chloride,Calcium, Phosphate and Uric Acid From Baseline
时间窗: 24 hour sampling interval at baseline and then day 5 for Empa, day 4 for TOR and HCT, day 9 for Empa+TOR and Empa+HCT
Change in clearance of sodium, potassium, creatinine, magnesium, chloride,calcium, phosphate and uric acid from baseline, where baseline is defined as the value obtained from the last 24-h collection period before the first drug administration in the first treatment period. The mean change from baseline was evaluated as: Empa: day 5- baseline, HCT: day 4-baseline, TOR: day 4-baseline, Empa+ HCT: day 9- baseline, Empa+ TOR: day 9- baseline, The means for the Empa arm represent combined adjusted means of all four sequences that is Empa administered before or after the administration of either TOR, HCT and their combination with Empa
Change in Serum Concentration of Sodium, Potassium, Magnesium, Calcium, Chloride, Phosphate, Glucose and Urea From Baseline
时间窗: baseline and then day 6 for Empa, day 5 for TOR and HCT, day 10 for Empa+TOR and Empa+HCT
Change in serum concentration of sodium, potassium, magnesium, calcium, chloride, phosphate, glucose and urea from baseline, where baseline was defined as the measurement obtained before first drug administration in the first period The mean change from baseline was evaluated as: Empa: day 6- baseline, HCT: day 5-baseline, TOR: day 5-baseline, Empa+ HCT: day 10- baseline, Empa+ TOR: day 10- baseline, The means for the Empa arm represent combined adjusted means of all four sequences that is Empa administered before or after the administration of either TOR, HCT and their combination with Empa
Change in Serum Concentration of Creatinine and Uric Acid From Baseline
时间窗: baseline and then day 5 for Empa, day 4 for TOR and HCT, day 9 for Empa+TOR and Empa+HCT
Change in serum concentration of Creatinine and Uric acid from baseline, where baseline was defined as the measurement obtained before first drug administration in the first period The mean change from baseline was evaluated as: Empa: day 5- baseline, HCT: day 4-baseline, TOR: day 4-baseline, Empa+ HCT: day 9- baseline, Empa+ TOR: day 9- baseline, The means for the Empa arm represent combined adjusted means of all four sequences that is Empa administered before or after the administration of either TOR, HCT and their combination with Empa
Change in Serum Concentration of Alkaline Phosphatase (ALP) From Baseline
时间窗: baseline and then day 6 for Empa, day 5 for TOR and HCT, day 10 for Empa+TOR and Empa+HCT
Change in serum concentration of ALP from baseline, where baseline was defined as the measurement obtained before first drug administration in the first period The mean change from baseline was evaluated as: Empa: day 6- baseline, HCT: day 5-baseline, TOR: day 5-baseline, Empa+ HCT: day 10- baseline, Empa+ TOR: day 10- baseline, The mean for the Empa arm represent combined adjusted means of all four sequences that is Empa administered before or after the administration of either TOR, HCT and their combination with Empa
Change in pH in Capillary or Arterialised Blood From Baseline
时间窗: baseline and then day 6 for Empa, day 5 for TOR and HCT, day 10 for Empa+TOR and Empa+HCT
Change in pH in capillary or arterialised blood from baseline, where baseline was defined as the last measurement before trial drug administration of each treatment period The mean change from baseline was evaluated as: Empa: day 6- baseline, HCT: day 5-baseline, TOR: day 5-baseline, Empa+ HCT: day 10- baseline, Empa+ TOR: day 10- baseline, The mean for the Empa arm represent combined adjusted means of all four sequences that is Empa administered before or after the administration of either TOR, HCT and their combination with Empa
Change in Urea Concentration in Urine
时间窗: baseline and then day 6 for Empa, day 5 for TOR and HCT, day 10 for Empa+TOR and Empa+HCT
Change in urea concentration in urine from baseline, where baseline was defined as the measurement obtained before first drug administration in the first period The mean change from baseline was evaluated as: Empa: day 6- baseline, HCT: day 5-baseline, TOR: day 5-baseline, Empa+ HCT: day 10- baseline, Empa+ TOR: day 10- baseline, The mean for the Empa arm represent combined adjusted means of all four sequences that is Empa administered before or after the administration of either TOR, HCT and their combination with Empa
Change in Urinary Weight From Baseline
时间窗: 24 hour sampling interval at baseline and then day 5 for Empa, day 4 for TOR and HCT, day 9 for Empa+TOR and Empa+HCT
Change from baseline in urinary weight in a 24 hour (h)- collection period, where baseline is the last 24-h collection period before first trial drug administration in each treatment period. The mean change from baseline was evaluated as: Empa: day 5- baseline, HCT: day 4-baseline, TOR: day 4-baseline, Empa+ HCT: day 9- baseline, Empa+ TOR: day 9- baseline, The mean for the Empa arm represent combined adjusted means of all four sequences that is Empa administered before or after the administration of either TOR, HCT and their combination with Empa
Urinary Sodium Excretion Over 24-hour run-in Periods
时间窗: Day 3, 2 and 1 before the first drug administration
Urinary sodium excretion over 24-hour run-in periods to assess the harmonisation of electrolytes after intake of a standardised diet
次要结局
- Area Under the Concentration-time Curve of Empa in Plasma (AUCτ,ss)(Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, and 24 post-dose on Day 5 with EMPA alone and on Day 9 with EMPA plus diuretic. The Pre-dose values were averaged over Days 1 to 4 with EMPA alone and on Days 7 & 8 with EMPA plus diuretic)
- Maximum Measured Concentration of Empa in Plasma (Cmax, ss)(Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, and 24 post-dose on Day 5 with EMPA alone and on Day 9 with EMPA plus diuretic. The Pre-dose values were averaged over Days 1 to 4 with EMPA alone and on Days 7 & 8 with EMPA plus diuretic)
- Area Under the Concentration-time Curve of HCT in Plasma (AUCτ,ss)(Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, and 24 post-dose on Day 4 with HCT alone and on Day 9 with EMPA plus HCT. The Pre-dose values were averaged over Days 1 to 3 with HCT alone and on Days 7 & 8 with EMPA plus HCT)
- Maximum Measured Concentration of HCT in Plasma (Cmax, ss)(Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, and 24 post-dose on Day 4 with HCT alone and on Day 9 with EMPA plus HCT. The Pre-dose values were averaged over Days 1 to 3 with HCT alone and on Days 7 & 8 with EMPA plus HCT)
- Area Under the Concentration-time Curve of TOR in Plasma (AUCτ,ss)(Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, and 24 post-dose on Day 4 with TOR alone and on Day 9 with EMPA plus TOR. The Pre-dose values were averaged over Days 1 to 3 with TOR alone and on Days 7 & 8 with EMPA plus TOR)
- Maximum Measured Concentration of TOR in Plasma (Cmax, ss)(Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, and 24 post-dose on Day 4 with TOR alone and on Day 9 with EMPA plus TOR. The Pre-dose values were averaged over Days 1 to 3 with TOR alone and on Days 7 & 8 with EMPA plus TOR)
- Number of Subjects With Clinical Relevant Abnormalities in Vital Signs, Clinical Laboratory Tests, 12-lead Resting Electrocardiogram (ECG), Physical Examination and Assessment of Tolerability by the Investigator(From first drug administration until up to 14 days after the last drug administration, up to 35 days)