Clinical trial NCT02819687: Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RDX5791 in Healthy Volunteers
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Phase I
Healthy
Pharmacokinetics
Pharmacodynamics
Lead sponsor: Ardelyx
Sponsor class: INDUSTRY
First posted: 2016-06-30
Enrollment: 80
Sex: ALL
Minimum age (years): 19
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Adverse events
timeFrame: 7 days
Secondary outcomes:
measure: Pharmacokinetics of RDX5791
timeFrame: 7 days
measure: Urinary and fecal sodium levels
timeFrame: 7 days
measure: Urinary and fecal phosphorus levels
timeFrame: 7 days
Other outcomes:
Locations:
Study officials:
affiliation: Ardelyx, Inc.
name: David P. Rosenbaum, Ph.D
role: STUDY_CHAIR
References:
citation: Rosenbaum DP, Yan A, Jacobs JW. Pharmacodynamics, Safety, and Tolerability of the NHE3 Inhibitor Tenapanor: Two Trials in Healthy Volunteers. Clin Drug Investig. 2018 Apr;38(4):341-351. doi: 10.1007/s40261-017-0614-0.