Trial Outcomes & Findings for Combined Effects of Non-statin Treatments on Apolipoprotein A-I Up-Regulation (CENTAUR): A Feasibility Study (NCT NCT00728910)
NCT ID: NCT00728910
Last Updated: 2016-02-29
Results Overview
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.
COMPLETED
PHASE2
25 participants
4 weeks, 12 weeks and 22 weeks
2016-02-29
Participant Flow
Recruitment lasted from June 2008 until February 2009.
Subjects washed out of current lipid lowering medications
Participant milestones
| Measure |
Atorvastatin/ABT335/Niaspan
All participants received atorvastatin 10 mg/day for 4 weeks, followed by sequential addition of ABT335 135 mg/day for 8 weeks, and ER niacin 2000 mg/day for 10 weeks, for a total study duration of 22 weeks
|
|---|---|
|
Atorvastatin
STARTED
|
25
|
|
Atorvastatin
COMPLETED
|
22
|
|
Atorvastatin
NOT COMPLETED
|
3
|
|
Atorvastatin+ABT335
STARTED
|
22
|
|
Atorvastatin+ABT335
COMPLETED
|
22
|
|
Atorvastatin+ABT335
NOT COMPLETED
|
0
|
|
Atorvastatin+ABT335+ER Niacin
STARTED
|
22
|
|
Atorvastatin+ABT335+ER Niacin
COMPLETED
|
22
|
|
Atorvastatin+ABT335+ER Niacin
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Combined Effects of Non-statin Treatments on Apolipoprotein A-I Up-Regulation (CENTAUR): A Feasibility Study
Baseline characteristics by cohort
| Measure |
Group 1
n=25 Participants
All participants received atorvastatin 10 mg/day for 4 weeks, followed by sequential addition of ABT335 135 mg/day for 8 weeks, and ER niacin 2000 mg/day for 10 weeks.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
25 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
47 years
STANDARD_DEVIATION 10.74 • n=5 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
25 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 4 weeks, 12 weeks and 22 weeksPopulation: Patients who completed any of the three phases for whom the kinetic study data was available for any phase of treatment
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.
Outcome measures
| Measure |
Atorvastatin
n=21 Participants
Subjects received atorvastatin 10 mg daily by mouth for 4 weeks followed by apo-A1 kinetics
|
Atorvastatin+ABT335
n=21 Participants
Subjects received atorvastatin 10 mg daily and ABT335 135 mg daily by mouth for 8 weeks.
|
Atorvastatin+ABT335+Niaspan
n=20 Participants
Subjects received atorvastatin 10 mg daily, ABT335 135 mg and Niaspan 2000 mg daily by mouth for 10 weeks.
|
|---|---|---|---|
|
The Apolipoprotein A-I Fractional Catabolic Rate (FCR)
|
0.294 pools/day
Interval 0.27 to 0.32
|
0.294 pools/day
Interval 0.27 to 0.32
|
0.295 pools/day
Interval 0.25 to 0.34
|
PRIMARY outcome
Timeframe: 4 weeks, 12 weeks and 22 weeksPopulation: Patients who completed any phase of treatment for whom kinetic data were available
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.
Outcome measures
| Measure |
Atorvastatin
n=20 Participants
Subjects received atorvastatin 10 mg daily by mouth for 4 weeks followed by apo-A1 kinetics
|
Atorvastatin+ABT335
n=20 Participants
Subjects received atorvastatin 10 mg daily and ABT335 135 mg daily by mouth for 8 weeks.
|
Atorvastatin+ABT335+Niaspan
n=20 Participants
Subjects received atorvastatin 10 mg daily, ABT335 135 mg and Niaspan 2000 mg daily by mouth for 10 weeks.
|
|---|---|---|---|
|
Apo-A1 Production Rate
|
14.2 mg/kg/day
Interval 11.0 to 17.0
|
14.2 mg/kg/day
Interval 12.0 to 17.0
|
13.8 mg/kg/day
Interval 11.0 to 17.0
|
PRIMARY outcome
Timeframe: 4 weeks, 12 weeks, 22 weeksPopulation: subjects completing any phase of treatment for whom complete post-prandial data were available
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)
Outcome measures
| Measure |
Atorvastatin
n=22 Participants
Subjects received atorvastatin 10 mg daily by mouth for 4 weeks followed by apo-A1 kinetics
|
Atorvastatin+ABT335
n=22 Participants
Subjects received atorvastatin 10 mg daily and ABT335 135 mg daily by mouth for 8 weeks.
|
Atorvastatin+ABT335+Niaspan
n=22 Participants
Subjects received atorvastatin 10 mg daily, ABT335 135 mg and Niaspan 2000 mg daily by mouth for 10 weeks.
|
|---|---|---|---|
|
Post-prandial Triglyceride Incremental Area Under the Curve (iAUC)
|
770 mg/dl*h
Interval 618.0 to 921.0
|
515 mg/dl*h
Interval 361.0 to 670.0
|
381 mg/dl*h
Interval 214.0 to 547.0
|
Adverse Events
Atorvastatin/ABT335/Niaspan
Serious adverse events
| Measure |
Atorvastatin/ABT335/Niaspan
n=25 participants at risk
Subjects received atorvastatin 10 mg/day for 4 weeks, followed by addition of ABT335 135 mg/day for a further 8 weeks followed by the addition of Niaspan 2000 mg/day for a further 10 weeks.
|
|---|---|
|
Gastrointestinal disorders
ulcer
|
4.0%
1/25 • Number of events 1 • 22 weeks
|
Other adverse events
| Measure |
Atorvastatin/ABT335/Niaspan
n=25 participants at risk
Subjects received atorvastatin 10 mg/day for 4 weeks, followed by addition of ABT335 135 mg/day for a further 8 weeks followed by the addition of Niaspan 2000 mg/day for a further 10 weeks.
|
|---|---|
|
Nervous system disorders
headache
|
4.0%
1/25 • Number of events 1 • 22 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place