Safety, Tolerability, and Pharmacodynamics of RDX5791 in Healthy Volunteers

A Phase I, Single-center, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of Different Multiple Dose Regimens of RDX5791 in Healthy Volunteers

A Phase 1, single-center, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerabiltiy, and pharmacodynamics of different multiple dose regimens of RDX5791 in healthy volunteers.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: RDX5791

Detailed Description

The starting doses for this study are based on the results from the multiple ascending-dose study performed on RDX5791 (Protocol RDX5791-101). Subjects will be screened within 3 weeks of check in to the CPU. Each cohort of 15 subjects (12 RDX5791, 3 placebo) will check in to the CPU on Day -5 before dinner. Each subject will receive a diet standardized for Na+ content while in the CPU. Subjects will receive doses of RDX5791 with approximately 240 mL of non-carbonated water on Days 1 to 7 (just prior to meals, depending on QD, bid, or tid regimens). Subjects will be provided standardized meals within 10 minutes after dosing. Doses can be administered with breakfast, lunch, or dinner.

• Study Type: Interventional
• Enrollment (Actual): 105
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Body mass index between 18 and 29.9 kg/m², inclusive
• No clinically significant abnormalities in medical history
• Females must be non-pregnant, non-lactating, and either postmenopausal for at least 12 months or have agreed to use an effective form of contraception from the time of signing the informed consent until 45 days after end of study
• Men must be either sterile, abstinent, or agreed to use an approved method of contraception from check-in until 45 days after final study visit

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: QUADRUPLE

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 30 mg bid; 30 mg of RDX5791 administered twice daily PO (60 mg total dose/day).	Drug: Placebo; Placebo; Drug: RDX5791; Other Names: Tenapanor; AZD1722
EXPERIMENTAL: 30 mg tid; 30 mg of RDX5791 administered three times daily PO (90 mg total dose/day).	Drug: Placebo; Placebo; Drug: RDX5791; Other Names: Tenapanor; AZD1722
EXPERIMENTAL: 60 mg bid; 60 mg of RDX5791 administered two times daily (120 mg total dose/day).	Drug: Placebo; Placebo; Drug: RDX5791; Other Names: Tenapanor; AZD1722
EXPERIMENTAL: 15 mg bid; 15 mg of RDX5791 administered two times daily (30 mg total dose/day).	Drug: Placebo; Placebo; Drug: RDX5791; Other Names: Tenapanor; AZD1722
EXPERIMENTAL: 30 mg QD; 30 mg of RDX5791 administered once daily (30 mg total dose/day).	Drug: Placebo; Placebo; Drug: RDX5791; Other Names: Tenapanor; AZD1722
EXPERIMENTAL: Escalating dose bid; 15 mg or 30 mg or 45 mg of RDX5791 administered two times daily (30, 60, or 90 mg total dose/day respectively). The stopping criteria for the dose escalation is based on Bristol Stool Score and AEs.	Drug: Placebo; Placebo; Drug: RDX5791; Other Names: Tenapanor; AZD1722
EXPERIMENTAL: 30 mg bid with psyllium; 30 mg of RDX5791 administered two times daily (60 mg total dose/day) with psyllium taken up to three times per day (maximum of 15 g psyllium/day).	Drug: Placebo; Placebo; Drug: RDX5791; Other Names: Tenapanor; AZD1722

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of different dosing regimens of RDX5791	Safety assessments will be based on adverse events, clinical laboratory tests, vital signs, ECG, and physical exams.	7 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacodynamics of different dosing regimens of RDX5791	Pharmacodynamics of different dosing regimens of RDX5791 will be assessed by bowel movement timing, consistency, frequency, and by urine and stool sodium (Na+) excretion.	7 Days

Collaborators and Investigators

• Sponsor: Ardelyx

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (ACTUAL): October 1, 2011
• Study Completion (ACTUAL): April 1, 2012

Study Registration Dates

• First Submitted: June 7, 2016
• First Submitted That Met QC Criteria: June 7, 2016
• First Posted (ESTIMATE): June 10, 2016

Study Record Updates

• Last Update Posted (ESTIMATE): June 10, 2016
• Last Update Submitted That Met QC Criteria: June 7, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: Healthy; Phase I; Pharmacodynamics
• Other Study ID Numbers: RDX5791-102