A Phase 1, Single-Center, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single- and Multiple-Ascending Doses of RDX5791 in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Ardelyx
- 入组人数
- 80
- 主要终点
- Adverse events
研究概览
简要总结
A Phase I, single-center, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single-and multiple-ascending doses of RDX5791 in healthy male and female subjects.
详细描述
In the single-ascending dose (SAD), 5 separate cohorts received RDX5791 at various doses once po fasting. Each cohort of 8 subjects (6 RDX5791, 2 placebo) received a diet standardized fro Na+ content wile in the clinical pharmacology unit (CPU).
The PK data from the 50-mg dose and the safety data from the 150-mg dose of the SAD study were evaluated prior to proceeding with the multiple-ascending dose (MAD) phase. Doses of RDX5791 are 3, 10, 30, and 100 mg administered once daily po fasting. Four cohorts of 10 subjects each (8 RDX5791, 2 placebo) received a diet standardized for Na+ content while in the CPU.
Safety assessments including clinical assessment and vital signs, clinical laboratory evaluations, ECGs, and AE monitoring were performed at regular intervals. Plasma was collected at regular intervals for PK analysis. The PD assessment included stool frequency and consistency, as well as changes in urinary Na+ excretion. All bowel movements were collected and analyzed for Na+ content outside this study protocol.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 19 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •BMI between 18 and 29.9 kg/m², inclusive
- •Females must be of non-childbearing potential; If of child-bearing potential, must have negative pregnancy test and confirm the use of one of the appropriate means of contraception
- •Males must agree to use appropriate methods of barrier contraception or have documented surgical sterilization
排除标准
- •Diagnosis or treatment of any clinically symptomatic biochemical or structural abnormality of the GI tract
- •Any surgery on the small intestine or colon, excluding appendectomy
- •Loose stools (Bristol Stool Form Score of 6 or 7) ≥2 days in the past 7 days
- •Hepatic dysfunction ([ALT] or [AST]) >1.5 times the upper limit of normal or renal impairment
- •Any evidence of or treatment of malignancy, excluding non-melanomatous malignancies of the skin
- •Use of diuretic medications, medications that are known to affect stool consistency and/or GI motility
- •Use of an investigational agent within 30 days prior to Day -2
- •Positive virology, alcohol, or drugs of abuse test during screening
- •Use of any prescription medication within 7 days before admission to the CPU
- •Have had significant blood loss (>450 mL) or have donated 1 or more units of blood or plasma within 8 weeks prior to study entry
研究组 & 干预措施
RDX5791 10mg QD (MAD phase)
10mg of RDX5791 administered once daily PO fasting
干预措施: Placebo (Drug)
RDX5791 10mg QD (SAD phase)
10mg of RDX5791 administered once daily PO fasting
干预措施: RDX5791 (Drug)
RDX5791 10mg QD (SAD phase)
10mg of RDX5791 administered once daily PO fasting
干预措施: Placebo (Drug)
RDX5791 50mg QD (SAD phase)
50mg of RDX5791 administered once daily PO fasting
干预措施: RDX5791 (Drug)
RDX5791 50mg QD (SAD phase)
50mg of RDX5791 administered once daily PO fasting
干预措施: Placebo (Drug)
RDX5791 150mg QD (SAD phase)
150mg of RDX5791 administered once daily PO fasting
干预措施: RDX5791 (Drug)
RDX5791 450mg QD (SAD phase)
450mg of RDX5791 administered once daily PO fasting
干预措施: Placebo (Drug)
RDX5791 150mg QD (SAD phase)
150mg of RDX5791 administered once daily PO fasting
干预措施: Placebo (Drug)
RDX5791 450mg QD (SAD phase)
450mg of RDX5791 administered once daily PO fasting
干预措施: RDX5791 (Drug)
RDX5791 900mg QD (SAD phase)
900mg of RDX5791 administered once daily PO fasting
干预措施: RDX5791 (Drug)
RDX5791 900mg QD (SAD phase)
900mg of RDX5791 administered once daily PO fasting
干预措施: Placebo (Drug)
RDX5791 3mg QD (MAD phase)
3mg of RDX5791 administered once daily PO fasting
干预措施: RDX5791 (Drug)
RDX5791 3mg QD (MAD phase)
3mg of RDX5791 administered once daily PO fasting
干预措施: Placebo (Drug)
RDX5791 10mg QD (MAD phase)
10mg of RDX5791 administered once daily PO fasting
干预措施: RDX5791 (Drug)
RDX5791 30 mg QD (MAD phase)
30mg of RDX5791 administered once daily PO fasting
干预措施: RDX5791 (Drug)
RDX5791 30 mg QD (MAD phase)
30mg of RDX5791 administered once daily PO fasting
干预措施: Placebo (Drug)
RDX5791 100 mg QD (MAD phase)
100mg of RDX5791 administered once daily PO fasting
干预措施: RDX5791 (Drug)
RDX5791 100 mg QD (MAD phase)
100mg of RDX5791 administered once daily PO fasting
干预措施: Placebo (Drug)
结局指标
主要结局
Adverse events
时间窗: 7 days
serum chemistry and hematology, ECGs, and clinical signs and symptoms
次要结局
- Pharmacokinetics of RDX5791(7 days)
- Urinary and fecal sodium levels(7 days)
- Urinary and fecal phosphorus levels(7 days)