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Ranolazine

Phase 3

Type 2 Diabetes Mellitus | Small molecule | Metabolic |Gilead Sciences, Inc.|Last Updated: Nov 18, 2014

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
RandomizedDouble-BlindACTIVE_CONTROLLEDDMCBiomarker
Total Trials6
Total Enrollment1,411
FDA Designations
No designations recorded
Clinical Trials (6)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT01555164A Phase 3 Study of Ranolazine in Subjects With Type 2 Diabetes Who Are Inadequately Controlled on Metformin AlonePHASE3 COMPLETED 442Jun 1, 2012Oct 1, 2013Sep 23, 2014146 United States, Canada +9
NCT01494987Ranolazine When Added to Glimepiride in Subjects With Type 2 Diabetes MellitusPHASE3 COMPLETED 431Jan 1, 2012Aug 1, 2013Nov 18, 2014140 United States, Czechia +10
NCT01472185Ranolazine Monotherapy in Subjects With Type 2 Diabetes MellitusPHASE3 COMPLETED 465Nov 1, 2011Oct 1, 2013Oct 24, 2014159 United States, Czechia +8
NCT01843127A Study to Evaluate the Effect of Ranolazine on Postprandial Glucagon in Subjects With Type 2 Diabetes.PHASE1 COMPLETED 24Apr 1, 2013Sep 1, 2013Mar 31, 20143 United States
NCT01546558Single Cohort, 2-Period Study to Assess Pharmacokinetics of Metformin Alone and in Combination With Ranolazine 500 mgPHASE1 COMPLETED 25Feb 1, 2012Mar 1, 2012Jul 11, 20121 United States
NCT01546597Single Cohort 4-period Study to Assess Pharmacokinetics of Metformin Alone and in Combination With RanolazinePHASE1 COMPLETED 24Feb 1, 2012Mar 1, 2012Jul 11, 20121 United States
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Study Endpoints
Primary Endpoints
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24
Baseline; Week 24

The average (mean) change from baseline in HbA1c at Week 24 was analyzed.

Area under the concentration-time curve (AUC) of plasma glucagon during the standard meal test (SMT)
Days 5, 10, and 14
Maximum observed plasma concentration (Cmax) of metformin
0, 0.5, 1,1.5, 2, 3, 4, 6, 8, 10 and 12 hours post-dose on Days 5 and 10
Area under the plasma concentration vs time curve over the dosing interval, at steady state (AUCtau) of metformin
0, 0.5, 1,1.5, 2, 3, 4, 6, 8, 10 and 12 hours post-dose on Days 5 and 10
Time to reach maximum observed plasma concentration (Cmax) of metformin
0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours post-dose on Days 5, 10, 15 and 20
Area under the plasma concentration versus time curve over the dosing interval, at steady state (AUCtau) of metformin
0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours post-dose on Days 5, 10, 15 and 20
Secondary Endpoints
Change From Baseline in Fasting Serum Glucose at Week 24
Baseline; Week 24
Change From Baseline in 2-hour Postprandial Serum Glucose at Week 24
Baseline; Week 24
Change From Baseline in Incremental Change of 2-hour Postprandial Serum Glucose at Week 24
Baseline; Week 24
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Study Design & Arms
AllocationRANDOMIZED
MaskingDOUBLE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
Ranolazine+metforminEXPERIMENTALQualifying 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+metforminPLACEBO_COMPARATORQualifying 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+glimepirideEXPERIMENTALGlimepiride 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+glimepiridePLACEBO_COMPARATORGlimepiride 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.
PlaceboPLACEBO_COMPARATORQualifying 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.
RanolazineEXPERIMENTALQualifying Period: Placebo to match ranolazine (1 tablet twice daily) for 14 days. Treatment Period: Ranolazine tablets (Days 1-7: 1 × 500 mg twice daily; 2 × 500 mg twice daily thereafter) for up to 24 weeks. Participants were required to maintain their diet and exercise regimen.
Placebo, Ranolazine, ExenatideACTIVE_COMPARATOR -
Ranolazine, Placebo, ExenatideACTIVE_COMPARATOR -
Metformin, RanolazineEXPERIMENTALSingle 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
Interventions
NameTypeDescription
RanolazineDRUGRanolazine tablet(s) administered orally
Placebo to match ranolazineDRUGPlacebo to match ranolazine for the duration of the study
MetforminDRUGMetformin tablet(s) administered orally once daily
Placebo to match metforminDRUGPlacebo to match metformin for the duration of the study
DietBEHAVIORALParticipants are instructed to continue the diet regimen prescribed by their physician.
ExerciseBEHAVIORALParticipants are instructed to continue the exercise regimen prescribed by their physician.
PlaceboDRUGPlacebo to match ranolazine for the duration of the study
GlimepirideDRUGGlimepiride 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.
ExenatideDRUG -
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Eligibility Criteria
Age Range18 Years — 75 Years
SexALL
Healthy VolunteersNo
Study Sites146

Inclusion Criteria: * Documented history of T2DM * Metformin therapy at a stable total daily dose ≥ 1500 mg and ≤ 2550 mg in addition to diet and exercise for ≥ 8 weeks prior to Screening * Body mass index (BMI) 25 to 45 kg/m\^2, inclusive, at Screening * HbA1c within specified ranges at Screening ...

Countries:United StatesCanadaCzechiaHungaryIndiaIsraelMexicoPolandRussiaSouth AfricaUkraineMalaysiaRomaniaSerbiaSlovakiaThailand
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