Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as AZD1722, Tenapanor, AZD1722 (in-patient)
RDX5791 · 17 trials · 12 indications
Durable complete spontaneous bowel movements (CSBM) response is defined as achieving the weekly CSBM response for ≥9 out of the first 12 weeks of the randomized treatment period and and for ≥3 of the last 4 weeks of the first 12 weeks of randomized treatment period
Incidence of AEs, SAEs and drug related adverse events
Descriptive summaries of ECG parameters (heart rate, PR-interval, QRS-duration, QT-interval, QTc-interval, and RR-interval)
6/12-week APS (abdominal pain and SBM (spontaneous bowel movement)) +2 response, defined as achieving the weekly APS +2 response criteria (i.e., achieving both weekly SBM +2 response and weekly abdominal pain response during the same week) for ≥6 out of the 12 weeks of the RTP. * The weekly SBM +2 response is defined as having an increase of ≥2 from baseline in the average weekly SBM frequency for a given week * The weekly abdominal pain response is defined as having ≥30% reduction from baseline in the average weekly abdominal pain score for a given week
Patients with at least a 1.2 mg/dL decrease in serum phosphorus during the first 26 weeks of the study were defined as the responder population.
Safety assessments will be based on adverse events, clinical laboratory tests, vital signs, ECG, and physical exams
Serum phosphorus difference between placebo and tenapanor in the change from the end of the 8 week treatment period to the end of the randomized withdrawal period in Efficacy Analysis Set. The efficacy analysis was pre-defined to be a pooled analysis of all tenapanor treated patients with a minimum of a 1.2 mg/dL decrease in serum phosphorus during the 8-week treatment period
An overall responder is defined as a weekly responder for the first 6/12 weeks where both CSBM and abdominal pain response criteria were met for the week. The CSBM response criteria are defined as an increase of one or more change in average weekly CSBMs from baseline. The definition of a CSBM is as follows: A CSBM is a spontaneous bowel movement (SBM) for which the subject responds "yes" to the following question; "Did you feel like you completely emptied your bowels?" The abdominal pain response criterion is defined as a decrease of 30% or more of percent change in average weekly worst abdominal pain from baseline.
An overall responder is defined as a weekly responder for the first 6/12 weeks where both CSBM and abdominal pain response criteria were met for the week. The CSBM response criteria are defined as an increase of one or more change in average weekly CSBMs from baseline. The definition of a CSBM is as follows: A CSBM is a spontaneous bowel movement (SBM) for which the subject responds "yes" to the following question; "Did you feel like you completely emptied your bowels?" The abdominal pain response criterion is defined as a decrease of 30% or more of percent change in average weekly worst abdominal pain from baseline.
Our primary endpoint will be CSBM response, defined as an increase of at least one CSBM per week compared to baseline for at least 6 of the 12 treatment weeks. A CSBM is defined as a bowel movement that occurs naturally and is accompanied by a feeling of complete evacuation
Change from baseline in average weekly SBM frequency in Week 4
Difference in mean change from baseline in s-P level at Week 4 between the tenapanor and placebo groups.
Change in serum phosphate levels from the end of wash out (pre randomization value) to end of treatment
Weekly complete spontaneous bowel movement resaponders defined as an increase of one or more bowel movement per week from baseline for 6 of the 12 weeks
The difference between tenapanor and placebo in the change in UACR from baseline to the end of 12 weeks of treatment
Patients are weighed pre dialysis prior to their first dialysis of the week. This measure looks at the change in pre-dialysis weight over time
Patients complete a phone diary daily. They are asked "how many bowel movements have you had today?" they are then asked for each spontaneous bowel movement (unaided with laxative use) wether there was its was a complete evacuation. if it was then it is a complete spontaneous bowel movement. All CSBMs are added and adjusted for a mean compete sponteneous bowel movement.
The primary objective of the study is to determine the maximum observed milk concentration (Cmax) of tenapanor and its primary metabolite AZ13792925 in the breast milk of lactating female subjects.
| Arm | Type | Description |
|---|---|---|
| Tenapanor 5 mg BID | EXPERIMENTAL | Patients will be randomized to receive 5 mg tenapanor twice daily. |
| Tenapanor 25 mg BID | EXPERIMENTAL | Patients will be randomized to receive 25 mg tenapanor twice daily. |
| Tenapanor 50 mg BID | EXPERIMENTAL | Patients will be randomized to receive 50 mg tenapanor twice daily. |
| Placebo Comparator | PLACEBO_COMPARATOR | Patients will be randomized to receive matching placebo twice daily. |
| Tenapanor | EXPERIMENTAL | Eligible patients from the parent study will continue tenapanor at the same dose assigned in the parent study which can be titrated to either 50 mg BID or 25 mg BID per Investigator guidance after a patient's first week on the assigned dose. |
| Tenpanor 50 mg BID | EXPERIMENTAL | Patients will be randomized to receive 50 mg tenapanor twice daily |
| Tenpanor 25 mg BID | EXPERIMENTAL | Patients will be randomized to receive 25 mg tenapanor twice daily |
| Tenapanor 10 mg, 20 mg, 30 mg BID | EXPERIMENTAL | During the 26-week open label part, all enrolled subjects will receive 30 mg BID doses of tenapanor. Investigators may decrease or increase the dose in 10 mg increments to a minimum of 10 g BIDor a maximum of 30 mg BID |
| Placebo | PLACEBO_COMPARATOR | Placebo |
| Sevelamer Carbonate | ACTIVE_COMPARATOR | Subjects randomized into the active control group, for safety analysis, will receive sevelamer carbonate, open label, for the entire 52-week study period. Sevelamer carbonate will be dosed based on package insert instructions (standard of care) |
| 50mg BID | EXPERIMENTAL | Tenapanor, 50 mg BID (100 mg total) |
| 3mg BID | EXPERIMENTAL | Tenapanor, 3mg BID (6mg total) |
| 10mg BID | EXPERIMENTAL | Tenapanor, 10mg BID (20mg total) |
| Dose Titration | EXPERIMENTAL | Tenapanor, patients start at 30mg BID and can down titrate weekly to 20, 15, 10, and 3mg BID, sequentially based on a GI tolerability question |
| Tenapanor Cohort 1 | EXPERIMENTAL | Tenapanor 2 mg BID |
| Tenapanor Cohort 2 | EXPERIMENTAL | Tenapanor 5 mg BID |
| Tenapanor Cohort 3 | EXPERIMENTAL | Tenapanor 10 mg BID |
| Tenapanor Cohort 4 | EXPERIMENTAL | Tenapanor 15 mg BID |
| Tenapanor Cohort 5 | EXPERIMENTAL | Tenapanor 20 mg BID |
| Tenapanor Cohort 6 | EXPERIMENTAL | Tenapanor 25 mg BID |
| Tenapanor 30 mg BID | EXPERIMENTAL | During the Double-Blind Treatment Period, subjects will receive tenapanor starting at a dose of 30 mg bid (three 10 mg tablets each time). Investigators may decrease or increase the dose of study medication based on s-P levels and/or gastrointestinal (GI) tolerability in 10 mg increments to a minimum of 10 mg bid or a maximum of 30 mg bid at any time during the Double-Blind Treatment Period. |
| 1 mg bid | EXPERIMENTAL | 1 mg AZD1722 bid |
| 3 mg bid | EXPERIMENTAL | 3 mg AZD1722 bid |
| 10 mg bid | EXPERIMENTAL | 10 mg AZD1722 bid |
| 30 mg bid | EXPERIMENTAL | 30 mg AZD1722 bid |
| 3 mg od | EXPERIMENTAL | 3 mg AZD1722 od |
| 30 mg od | EXPERIMENTAL | 30 mg AZD1722 od |
| 5 mg BID | EXPERIMENTAL | AZD1722 |
| 20 mg BID | EXPERIMENTAL | AZD1722 |
| 50 mg BID | EXPERIMENTAL | AZD1722 |
| AZD1722 | ACTIVE_COMPARATOR | AZD1722 in 5, 15, 30, or 60 mg capsules. Starting dose is 15 mg BID PO for 12 Weeks |
| AZD1722- in patient | EXPERIMENTAL | Tenapanor administered in a clinical pharmacology unit |
| Placebo- in patient | PLACEBO_COMPARATOR | Placebo (size and color matched to experimental drug) administered in a clinical pharmacology unit |
| AZD1722 out-patient | EXPERIMENTAL | Tenapanor |
| Placebo out-patient | EXPERIMENTAL | Placebo |
| Low Dose | EXPERIMENTAL | 10 mg capsule of tenapanor |
| Mid Dose | EXPERIMENTAL | 30 mg capsule of tenapanor |
| High Dose | EXPERIMENTAL | 100 mg capsule of tenapanor |
| Treatment Arm | EXPERIMENTAL | Eligible subjects will be enrolled to receive the study drug |
| Name | Type | Description |
|---|---|---|
| Tenapanor 5 mg BID | DRUG | Patients will receive tenapanor 5 mg BID (total of 10 mg daily) |
| Tenapanor 25 mg BID | DRUG | Patients will receive tenapanor 25 mg BID (total of 50 mg daily) |
| Tenapanor 50 mg BID | DRUG | Patients will receive tenapanor 50 mg BID (total of 100 mg daily) |
| Placebo | DRUG | Patients will receive matching placebo BID |
| Tenapanor | DRUG | Eligible patients from the parent study will continue tenapanor at the same dose assigned in the parent study. Doses can be titrated to either 50 mg BID or 25 mg BID |
| Tenapanor 50 MG | DRUG | Participants will receive tenapanor 50 mg BID (total of 100 mg daily) |
| Sevelamer Carbonate | DRUG | Active control |
| Phosphate Binder Agents | DRUG | standard of care phosphate binder use at study entry was maintained throughout the entire study |
| AZD1722 | DRUG | AZD1722, oral tablet |
| AZD1722 (in-patient) | DRUG | doses between 5 and 60 mg BID may be administered based on tolerability in a CPU setting |
| Placebo (in-patient) | DRUG | Placebo, size and color matched to experimental drug administered in a CPU |
| AZD1722 (out-patient) | DRUG | doses between 5 and 45 mg BID |
| RDX5791 | DRUG | Capsule, QD |
Inclusion Criteria: 1. Patients ≥18 to ≤80 years old at the Screening visit (Visit 1). 2. Meet the Rome IV Diagnostic Criteria for functional constipation. 3. Females of non-childbearing potential, or agree to the use of an acceptable means of contraception for up to 30 days following the last dose...
RDX5791 is an investigational small molecule developed by Ardelyx, Inc. for the treatment of constipation predominant irritable bowel syndrome, commonly called IBS-C. It has been studied in a Phase 2 clinical trial. RDX5791 is not approved and remains in clinical development.
RDX5791 was studied as a treatment for constipation predominant irritable bowel syndrome, or IBS-C, a gastrointestinal condition. The Phase 2 trial enrolled adults 18 years and older with IBS-C in the United States. RDX5791 is investigational and has not been approved for this or any other use.
RDX5791 is developed by Ardelyx, Inc., a biopharmaceutical company that trades under the ticker ARDX. Ardelyx sponsored the Phase 2 study of RDX5791 in constipation predominant irritable bowel syndrome. No other developer or partnership for RDX5791 has been announced.
RDX5791 is in Phase 2 development. One Phase 2 trial has been completed, and no trials are currently active. The study evaluated RDX5791 for constipation predominant irritable bowel syndrome. RDX5791 is investigational and has not received FDA approval.
RDX5791 has been studied in one completed Phase 2 trial, NCT01340053, titled a study to evaluate the safety and efficacy of RDX5791 for the treatment of constipation predominant irritable bowel syndrome. The trial enrolled 186 participants in the United States and was randomized, double blind, and placebo controlled.
The Phase 2 trial of RDX5791, NCT01340053, was a randomized, double blind, placebo controlled study in adults with constipation predominant irritable bowel syndrome. It enrolled 186 participants aged 18 years and older in the United States and has been completed. No biomarker selection was used in the study.