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ABT335

Phase 3

Dyslipidemia | Small molecule | Metabolic |Abbott Laboratories|Last Updated: Feb 29, 2016

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_CONTROLLEDBiomarker
Total Trials4
Total Enrollment4,038
FDA Designations
No designations recorded
Clinical Trials (4)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT00300430Study to Evaluate the Long-Term Safety and Efficacy of ABT-335, in Combination With Three Different Statins in Subjects With Mixed Dyslipidemia.PHASE3 COMPLETED 1,911Sep 1, 2006 -Jul 23, 20091 United States
NCT00300456Evaluate Safety and Efficacy of ABT-335 in Combination With Simvastatin in Subjects With Multiple Abnormal Lipid Levels in the BloodPHASE3 COMPLETED 657Mar 1, 2006 -Jun 3, 20091 United States
NCT00300482Evaluate Safety and Efficacy of ABT-335 in Combination With Rosuvastatin Calcium in Subjects With Multiple Abnormal Lipid Levels in the BloodPHASE3 COMPLETED 1,445Mar 1, 2006 -Jun 10, 20091 United States
NCT00728910Combined Effects of Non-statin Treatments on Apolipoprotein A-I Up-Regulation (CENTAUR): A Feasibility StudyPHASE2 COMPLETED 25Jun 1, 2008Aug 1, 2009Feb 29, 20161 United States
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Study Endpoints
Primary Endpoints
Percentage of Subjects Reporting Adverse Events During Combination Therapy, Either in the Preceding Double-blind Studies or in This Open-label Study
Anytime after initiation of combination therapy (either in the double-blind or open-label study) to within 30 days after the last dose of combination therapy
Mean Percent Change in Triglycerides From Baseline to Final Visit
Baseline to 12 Weeks (Final Visit)

\[(Week 12 triglycerides minus baseline triglycerides)/baseline triglycerides\] x 100

Mean Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Final Visit
Baseline to 12 Weeks (Final Visit)

\[(Week 12 HDL-C minus baseline HDL-C)/baseline HDL-C\] x 100

Mean Percent Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to Final Visit
Baseline to 12 Weeks (Final Visit)

\[(Week 12 LDL-C minus baseline LDL-C)/baseline LDL-C\] x 100

The Apolipoprotein A-I Fractional Catabolic Rate (FCR)
4 weeks, 12 weeks and 22 weeks

After receiving total daily caloric intake over 20 hrs as 20 identical small meals, starting at 0600 hrs, subjects took study medications at 0800 hrs. Five hours after the first meal, i.v. 5,5,5-2H3-L-leucine was administered, followed by a primed-constant infusion at 10 mol/kg body weight per hr for 15 hrs during which 14 blood samples were collected. Isotopic enrichment of leucine in apoA1 band excised from polyacrylamide gel was calculated. Assuming steady state apo A-I metabolism, we used a compartment model to fit data, consisting a precursor compartment (Compartment 1), the plasma leucine pool, an intracellular compartment accounting for apoA1 synthesis and lipoprotein assembly (Compartment 2), and compartments to account for dispositional kinetics of the subfractions including a plasma pool compartment (Compartment 3). The apoA1 FCR corresponds to the rate of irreversible loss of leucine pools from Compartment 3.

Apo-A1 Production Rate
4 weeks, 12 weeks and 22 weeks

The apolipoprotein A-I production rate using (5,5,5-2H3-L-leucine) was measured following each of the three study periods i.e following 4 weeks of atorvastatin 10 mg/day, following 8 further weeks of ABT335 135 mg/day added to atorvastatin and following 10 further weeks of ER niacin 2000 mg/day and aspirin 325 mg/day added to atorvastatin+ABT335.

Post-prandial Triglyceride Incremental Area Under the Curve (iAUC)
4 weeks, 12 weeks, 22 weeks

Triglyceride iAUC was measured during an oral fat tolerance test administered after 4 weeks of atorvastatin 10 mg/day , a further 8 weeks of atorvastatin 10mg /day+ABT335 135mg/day and then after a further 10 weeks of atorvastatin 10 mg/day+ABT335 135 mg/day+Niaspan 2000 mg/day. The standardized oral fat load was administered one hour post medication dosing and blood was collected prior to drug dosing, prior to the oral fat load and hourly thereafter for 10 hours (0,1,2,3,4,5,6,7,8,9,10,12 hrs post drug dosing)

Secondary Endpoints
Median Percent Change in Triglycerides From Baseline to Week 52 of the Open-label Study
Baseline to Week 52 of the open-label study
Mean Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 52 of the Open-label Study
Baseline to Week 52 of the open-label study
Mean Percent Change in Direct Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 52 of the Open-label Study
Baseline to Week 52 of the open-label study
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Study Design & Arms
AllocationRANDOMIZED
MaskingNONE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
AACTIVE_COMPARATOR20 mg drug and ABT-335
BACTIVE_COMPARATOR40 mg drug and ABT 335
CACTIVE_COMPARATOR40 mg drug and ABT-335
DPLACEBO_COMPARATOR20 mg simvastatin monotherapy
EPLACEBO_COMPARATOR40 mg simvastatin monotherapy
FPLACEBO_COMPARATOR80 mg simvastatin monotherapy
AtorvastatinACTIVE_COMPARATORatorvastatin 10 mg/day by mouth for a total duration of 4 weeks
ABT335ACTIVE_COMPARATORABT335 135 mg/day by mouth added to atorvastatin for a total duration of at least 8
ER niacinACTIVE_COMPARATORER niacin titrated up to 2 g/day with aspirin 325 mg/day by mouth added to atorvastatin and ABT335 for 10 weeks
Interventions
NameTypeDescription
ABT-335 and rosuvastatin calciumDRUGABT-335 135 mg plus rosuvastatin calcium daily, 52 weeks
ABT-335 and atorvastatin calciumDRUGABT-335 135 mg plus atorvastatin calcium daily, 52 weeks
ABT-335 and simvastatinDRUGABT-335 135 mg plus simvastatin daily, 52 weeks
ABT-335DRUG135 mg, daily, 12 weeks
SimvastatinDRUGdaily, 12 weeks, see Arm Description for dosage information
PlaceboDRUGDaily, 12 weeks, see Arm Description for placebo information
Rosuvastatin CalciumDRUGDaily, 12 weeks, see Arm Description for dosage information
AtorvastatinDRUG10 mg QD for 4 weeks
ABT335DRUG135 mg QD added to atorvastatin for 8 weeks
ER NiacinDRUG2000 mg QD added to atorvastatin and ABT335 for 10 weeks
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Eligibility Criteria
Age Range18 Years — N/A
SexALL
Healthy VolunteersNo
Study Sites1

Inclusion Criteria: * Adult male and female subjects who voluntarily sign the informed consent. * Subject has successfully completed one of the three ABT-335, rosuvastatin, simvastatin and atorvastatin combination therapy studies. Exclusion Criteria: * Subject is using or will use investigational...

Countries:United States
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