A Phase 2, Multi-center, Open-label Study to Determine Long-term Safety, Tolerability and Efficacy of Split-dose Oral Regimens of Tolvaptan Tablets in a Range of 30 to 120 mg/d in Patients With Autosomal Dominant Polycystic Kidney Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 46
- 试验地点
- 11
- 主要终点
- Safety Assessments Based on Vital Signs, Electrocardiogram (ECG's), Clinical Laboratory Tests, Physical Examinations Are Reported as Adverse Events (AEs) Upon Study Physician Discretion.
研究概览
简要总结
This study's purpose is to evaluate the long-term safety of open-label tolvaptan regimens to determine the maximally-tolerated dose and acquire pilot efficacy data in patients with autosomal dominant polycystic kidney disease (ADPKD).
详细描述
Autosomal Dominant Polycystic Kidney Disease is a genetic disease classified by the formation of fluid-filled cysts in the kidneys. The accumulation of these cysts causes the kidneys to enlarge several times the normal size and leads to the eventual loss of renal function and ultimately results in renal failure in end-stage patients. This is a disease with life-threatening implications to those who have it, and their family members who may also be affected. Aside from early anti-hypertensive control and dietary protein restriction, which are presumed to offer a modest degree of protection, most surviving patients require renal replacement therapy (dialysis and transplant) and suffer from high morbidity and mortality.
A rationale for use of tolvaptan in these genetic disorders has been proven, in principle, through use of a variety of animal models. In these models, tolvaptan is effective in halting or reversing the progression of this renal disease.
The current study is being undertaken in order to evaluate whether tolvaptan, an oral vasopressin V2 receptor inhibitor, will maintain an adequate safety profile and show a potential clinical benefit by reducing total renal volume in the hopes of making an impact upon disease progression.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Prior participation in designated tolvaptan ADPKD studies (156-04-248, 156-04-249).
- •Able to give Informed Consent.
排除标准
- •Women who are breast feeding and females of childbearing potential who are not using acceptable contraceptive methods.
- •In the opinion of the study investigator or sponsor may present a safety risk.
- •Patients who are unlikely to adequately comply with study procedures.
- •Patients who at Day 1 have an estimated glomerular filtration rate (GFR) below 30 mL/min or who anticipate renal-replacement therapy within one year of study entry.
- •Patients having contraindications to magnetic resonance imaging (MRI) or gadolinium contrast will be eligible but will not be able to participate in MRI.
- •Patients taking a diuretic within 1 week of enrollment or likely to need diuretic therapy prior to Month 2.
研究组 & 干预措施
Tolvaptan 45/15 mg/day orally for up to 4 years
Participants received tolvaptan 45 mg orally in the morning and 15 mg orally 8 hours later for up to 4 years.
干预措施: Tolvaptan (Drug)
Tolvaptan 60/30 mg/day orally for up to 4 years
Participants received tolvaptan 60 mg orally in the morning and 30 mg orally 8 hours later for up to 4 years.
干预措施: Tolvaptan (Drug)
结局指标
主要结局
Safety Assessments Based on Vital Signs, Electrocardiogram (ECG's), Clinical Laboratory Tests, Physical Examinations Are Reported as Adverse Events (AEs) Upon Study Physician Discretion.
时间窗: AEs were recorded from screening (ICF was signed) until 7-Day follow-up
An AE was defined as any new medical problem, or exacerbation of an existing problem, experienced by a participant while enrolled in a study , whether or not it was considered drug-related by the study physician. A treatment-emergent AE (TEAE) was defined as an AE that started after start of study drug treatment; or if the event was continuous from Baseline and was serious, study drug related, or resulted in death, discontinuation.
次要结局
- Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to First Daily Dose.(Baseline to Month 36)
- Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to Second Daily Dose.(Baseline to Month 24)
- Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to Bedtime.(Baseline to Month 24)
- Percent Change From Baseline in Renal Volume.(Baseline to Month 36)
- Change From Pre-dose Baseline in Renal Function Estimated by Glomerular Filtration Rate (GFR).(Baseline to Month 36)
- Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to First Daily Dose- Extension.(Baseline to Months 2, 6, 12, 24, 36, Extension Day 1, Extension Month 12)
- Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to Second Daily Dose- Extension.(Baseline to Month 24)
- Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to Bedtime- Extension.(Baseline to Month 24)
- Percent Change From Baseline in Renal Volume-Extension.(Baseline to Months 2, 12, 24, 36, Extension Day 1, Extension Month 12)
- Change From Pre-dose Baseline in Renal Function Estimated by GFR- Extension.(Baseline to Months 2, 6, 9, 12, 16, 20, 24, 28, 32, 36, Extension Day 1, Extension Month 12)
- Mean Change From Baseline in Systolic Blood Pressure (sBP) for Hypertension Assessment.(Baseline to Month 36)
- Mean Change From Baseline in Diastolic Blood Pressure (dBP) for Hypertension Assessment.(Baseline to Month 36)
- Mean Change From Baseline in Mean Arterial Pressure (MAP) for Hypertension Assessment.(Baseline to Month 36)
- Mean Change From Baseline in sBP for Hypertension Assessment- Extension.(Baseline to Months 2, 6, 9, 12, 16, 20, 24, 28, 32, 36, Extension Day 1, Extension Month 4, Extension Month 8, Extension Month 12)
- Mean Change From Baseline in dBP for Hypertension Assessment- Extension.(Baseline to Months 2, 6, 9, 12, 16, 20, 24, 28, 32, 36, Extension Day 1, Extension Month 4, Extension Month 8, Extension Month 12)
- Mean Change From Baseline in MAP for Hypertension Assessment- Extension.(Baseline to Months 2, 6, 9, 12, 16, 20, 24, 28, 32, 36, Extension Day 1, Extension Month 4, Extension Month 8, Extension Month 12)
- Mean Change From Baseline in Patient-assessed Renal Pain Scale.(Baseline to Month 36)
- Mean Change From Baseline in Patient-assessed Renal Pain Scale- Extension.(Baseline to Months 2, 6, 12, 24, 36, Extension Day 1, Extension Month 12)
- Mean Change From Baseline in Abdominal Girth Measurement.(Baseline to Month 36)
- Mean Change From Baseline in Abdominal Girth Measurement- Extension.(Baseline to Extension Day 1, Extension Month 12)