Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Ranexa
Ranolazine · 16 trials · 14 indications
Assessed as average improvement in WHO Functional Class. The WHO Functional Class score ranges from 1 to 4, with higher scores indicating more impairment
Improve Exercise Capacity measured by 6-Minute Walk Test
The Kansas City Cardiomyopathy Questionnaire is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. The scores are averaged and transformed to a range of 0-100, in which higher scores reflect better health status and was performed at the conclusion of the study.
The average (mean) change from baseline in HbA1c at Week 24 was analyzed.
Time to event distributions were estimated by the Kaplan-Meier (KM) method. 1 month = 28 days; 1 calendar year = 365 days.
Change in QTc at 2 months on ranolazine vs. at 1 month on placebo. This was prespecified outcome.
The change in scores of the angina frequency dimension of the Seattle Angina Questionnaire (SAQ) after 12 weeks therapy with ranolazine or placebo are presented. Change at 12 weeks was calculated as (Endpoint Value at 12 weeks - Endpoint Value at Baseline)/Endpoint Value at Baseline. Individual dimensions of the Seattle Angina Questionnaire are transformed to be a score from 0 to 100, where higher scores indicate better health. A positive number for the angina frequency dimension means that the participants are experiencing fewer episodes of angina at week 12 than they were at the baseline visit.
AFB was defined as the total time a participant was in atrial tachycardia (AT)/atrial fibrillation (AF) expressed as a percentage of total recording time. Geometric mean is the mean of log-transformed AFB exponentiated.
AFB was defined as the total time a participant was in atrial tachycardia (AT)/atrial fibrillation (AF) expressed as a percentage of total recording time. Data are presented for baseline-adjusted AFB over 12 weeks of treatment. Geometric mean is the mean of log-transformed AFB exponentiated.
AFB is defined as the total time a participant is in AT/AF expressed as a percentage of total recording time. Data are presented for baseline-adjusted AFB over 12 weeks of treatment.
HbA1c is a blood test to measure blood sugar control over the prior 3-month period. The last observation carried forward (LOCF) method was used: the last observed post-baseline measurements prior to Week 12 carried forward for participants with no available Week 12 values. Participants were summarized according to the actual treatment received regardless of the allocated treatment.
2-hour postprandial serum glucose was defined as the average of serum glucose measurement at 120 minutes and 125 minutes following a standardized meal. The LOCF method was used. Participants were summarized according to the actual treatment received regardless of the allocated treatment.
Serum glucose was measured following an overnight fast. The LOCF method was used. Participants were summarized according to the actual treatment received regardless of the allocated treatment.
Change from baseline to 30 minutes from initiation of study drug bolus No.1 in cardiac catheterization hemodynamic parameters at both resting and paced conditions: Time-constant of relaxation (tau) Left ventricular end-diastolic pressure (LVEDP) dP/dtmin (minimal rate of LV pressure change)
quality of life measurements for overall health and neuromuscular disease
The subject is observed and timed while rising from an arm chair, walking 3 meters, turning, walking back, and sitting down again
To see if the electrical potentials produced by the muscle fibers change.
| Arm | Type | Description |
|---|---|---|
| Ranolazine | EXPERIMENTAL | 1000 mg PO BID |
| Ranolazine+metformin | EXPERIMENTAL | Qualifying Period: Participants will receive metformin 1000 mg + placebo to match ranolazine twice daily for either 2 or 8 weeks (dependent on metformin dose and HbA1c level at Screening). Treatment Period: Participants will receive ranolazine 500 mg + metformin 500 mg + placebo to match metformin twice daily on Days 1 through 7, followed by ranolazine 1000 mg + metformin 500 mg + placebo to match metformin twice daily from Day 8 through Week 24. Participants are required to maintain their diet and exercise regimen. |
| Placebo+metformin | PLACEBO_COMPARATOR | Qualifying Period: Participants will receive metformin 1000 mg + placebo to match ranolazine twice daily for either 2 or 8 weeks (dependent on metformin dose and HbA1c level at Screening). Treatment Period: Participants will receive metformin 1000 mg + placebo to match ranolazine twice daily through Week 24. Participants are required to maintain their diet and exercise regimen. |
| Ranolazine+glimepiride | EXPERIMENTAL | Glimepiride stabilization period (up to 8 weeks): participants not on stable glimepiride will receive glimepiride 2 mg once daily, and if tolerated the dose will be increased on Day 8 (+ 2 days) to 4 mg once daily. Qualifying period: participants will receive placebo to match ranolazine twice daily in addition to glimepiride for 14 days (+ 2 days) and if ≥ 80% compliant and meeting eligibility criteria will continue to the treatment period. Treatment period: participants will be randomized to receive ranolazine 500 mg twice daily plus glimepiride 4 mg once daily on Days 1 through 7, followed by ranolazine 1000 mg twice daily plus glimepiride 4 mg once daily from Day 8 (or by Day 16 if not well tolerated) through Week 24. Participants will be required to maintain their diet and exercise regimen. |
| Placebo+glimepiride | PLACEBO_COMPARATOR | Glimepiride stabilization period (up to 8 weeks): participants not on stable glimepiride will receive glimepiride 2 mg once daily, and if tolerated the dose will be increased on Day 8 (+ 2 days) to 4 mg once daily. Qualifying period: participants will receive placebo to match ranolazine twice daily in addition to glimepiride for 14 days (+ 2 days) and if ≥ 80% compliant and meeting eligibility criteria will continue to the treatment period. Treatment period: participants will be randomized to receive placebo to match ranolazine plus glimepiride 4 mg once daily for 24 weeks. Participants will be required to maintain their diet and exercise regimen. |
| Placebo | PLACEBO_COMPARATOR | Qualifying Period: Placebo to match ranolazine (1 tablet twice daily) for 14 days. Treatment Period: Placebo to match ranolazine (Days 1-7: 1 tablet twice daily; 2 tablets twice daily thereafter) for up to 24 weeks. Participants were required to maintain their diet and exercise regimen. |
| 1 | EXPERIMENTAL | Ranolazine |
| 2 | PLACEBO_COMPARATOR | Placebo |
| Placebo followed by Ranolazine Administration | EXPERIMENTAL | Placebo for 1 month and Ranolazine for 5 months. |
| Ranolazine 750 mg | EXPERIMENTAL | Ranolazine 750 mg plus dronedarone placebo for 12 weeks. |
| Dronedarone 225 mg | EXPERIMENTAL | Ranolazine placebo plus dronedarone 225 mg for 12 weeks. |
| Ranolazine 750 mg + Dronedarone 225 mg | EXPERIMENTAL | Ranolazine 750 mg plus dronedarone 225 mg for 12 weeks. |
| Ranolazine 750 mg + Dronedarone 150 mg | EXPERIMENTAL | Ranolazine 750 mg plus dronedarone 150 mg for 12 weeks. |
| Saline 0.9% | PLACEBO_COMPARATOR | Saline 0.9% and placebo tablet |
| Placebo, Ranolazine, Exenatide | ACTIVE_COMPARATOR | - |
| Ranolazine, Placebo, Exenatide | ACTIVE_COMPARATOR | - |
| Metformin, Ranolazine | EXPERIMENTAL | Single cohort, 2-period study: * Period 1, metformin 1000 mg bid on Days 1-5 * Period 2, metformin 1000 mg bid + ranolazine 500 mg bid on Days 6-10 |
| Name | Type | Description |
|---|---|---|
| Ranolazine | DRUG | ranolazine 1000 mg PO BID for 3 months |
| Placebo to match ranolazine | DRUG | Placebo to match ranolazine for the duration of the study |
| Metformin | DRUG | Metformin tablet(s) administered orally once daily |
| Placebo to match metformin | DRUG | Placebo to match metformin for the duration of the study |
| Diet | BEHAVIORAL | Participants are instructed to continue the diet regimen prescribed by their physician. |
| Exercise | BEHAVIORAL | Participants are instructed to continue the exercise regimen prescribed by their physician. |
| Placebo | DRUG | Placebo to match ranolazine for the duration of the study |
| Glimepiride | DRUG | Glimepiride tablets (2 mg or 4 mg) administered orally once daily with the morning dose of study drug or placebo. The target dosing regimen for glimepiride is 4 mg once daily. |
| Dronedarone | DRUG | Capsule administered orally twice daily |
| Ranolazine placebo | DRUG | Tablets administered orally twice daily. |
| Dronedarone placebo | DRUG | Capsules administered orally twice daily |
| Saline 0.9% and placebo tablet | OTHER | Intravenous treatment followed by oral treatment for 13 days |
| Exenatide | DRUG | - |
Inclusion criteria: 1. World Health Organization (WHO) Group 1 PAH, defined as a pulmonary hypertension with mean pulmonary artery pressure \> 25 mmHg, pulmonary capillary wedge pressure \< 15 mmHg, and pulmonary vascular resistance \> 3 Wood units. 2. Right ventricular dysfunction, defined as RV f...
Ranolazine is a small molecule under development for cardiovascular and related conditions, including angina, atrial fibrillation, coronary artery disease, diastolic heart failure, long QT syndrome, and microvascular angina. It has also been studied in myotonia congenita, paramyotonia congenita, myotonic dystrophy type 1, and type 2 diabetes. It is investigational and not approved.
Ranolazine targets the sodium channels SCN5A and SCN4A. It acts as a blocker of these channels, which are involved in cardiac and skeletal muscle electrical signaling. This mechanism underlies its evaluation across cardiac conditions and certain muscle disorders.
Ranolazine is being developed by Gilead Sciences, Inc., which trades on the Nasdaq under the ticker GILD. The company is the sponsor of the clinical development program for this small molecule.
Ranolazine is in Phase 3 development. It is an investigational drug and has not been approved by the FDA for the indications being studied. The program includes completed Phase 1 and Phase 2 trials, with a total of seven trials and 6,560 participants enrolled.
Ranolazine has been studied in completed trials including NCT02251457 in myotonia congenita, paramyotonia congenita, and myotonic dystrophy type 1; NCT02147067 in microvascular angina; NCT01843127 in type 2 diabetes; and NCT01648205 in long QT syndrome. All seven trials are completed, with no active trials.