Study to Determine the Effect of Repeated Administration of Diltiazem on the Pharmacokinetics of Darapladib (Sb-480848).
|ClinicalTrials.gov Identifier: NCT01852565|
Recruitment Status : Completed
First Posted : May 13, 2013
Last Update Posted : July 13, 2017
Darapladib (SB-480848) is a novel, selective, orally active inhibitor of lipoprotein associated phospholipase A2 (Lp-PLA2) currently under clinical development by GlaxoSmithKline as a potential anti-atherosclerosis agent for reduction of major adverse cardiovascular (CV) events in patient populations with chronic coronary heart disease and after an acute coronary syndrome.
This study will determine the effect of repeated administration of diltiazem on the pharmacokinetics of a repeated administration of darapladib. A drug interaction study with a moderate CYP3A4 inhibitor is warranted to provide guidance to prescribing physicians.
|Condition or disease||Intervention/treatment||Phase|
|Atherosclerosis||Drug: Darapladib Drug: Diltiazem||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||36 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||An Open-Label, Three Period, Single Sequence Study To Determine The Effect Of Repeat Oral Dosing Of Diltiazem On The Pharmacokinetics Of Repeat Oral Dosing Of Darapladib (SB-480848).|
|Actual Study Start Date :||May 14, 2013|
|Actual Primary Completion Date :||September 30, 2013|
|Actual Study Completion Date :||September 30, 2013|
Experimental: Darapladib+Diltizem Arm
Each subject will receive darapladib EC tablet 160 mg once daily for 10 days followed by darapladib EC tablet 160 mg once daily + diltiazem 240mg once daily for 14 days and then diltiazem 240mg once daily alone for three days
Enteric coated, free base (micronized) white round tablet, 160mg, Oral/repeat dose/10 days (Treatment Period 1), 14 days (Treatment Period 2)Drug: Diltiazem
Extended release, Blue capsule imprinted with cardizem CD and 240mg on one end, 240 mg, Oral/repeat dose/17 days
- AUC(0-24h) of darapladib [ Time Frame: Up to 32 days. (PK samples will be collected on Days 8, 9, 26 and 27 at predose. Day 10 and Day 28 predose and at 0.5, 1, 2, 3, 4, 6, 9, 12, 18, 24, 32, 48, 72, and 96 hours post-dose) ]The area under the concentrations-time curve (AUC0-24) from the time of administration of darapladib up to 24 h after administration.
- Cmax of darapladib [ Time Frame: Up to 32 days. (PK samples will be collected on Days 8, 9, 26 and 27 at predose. Day 10 and Day 28 predose and at 0.5, 1, 2, 3, 4, 6, 9, 12, 18, 24, 32, 48, 72, and 96 hours post-dose) ]The maximum concentration (Cmax) was obtained directly from the measured concentration-time curves.
- Number of subjects with adverse event (AE). [ Time Frame: Up to 70 days. ]AE's will be collected from the start of study treatment to the last follow up.
- 12-Lead electrocardiogram (ECG) assessment as a measure of safety and tolerability [ Time Frame: Up to 42 days. (Screening Day 32 and Follow up [Day 38 to 42]). ]Single 12-lead ECGs will be obtained after the subject has been in a supine position for at least 10 minutes at each timepoint during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTcF intervals.
- Vital signs assessment as a measure of safety and tolerability [ Time Frame: Up to 42 days (Screening, Day -1, 15, 16, 22, 28, 32 and Follow up [Day 38 to 42]). ]Systolic and diastolic blood pressure and pulse rate measurements will be recorded after the subject has been resting in a semi-supine or supine position for at least 10 minutes.
- Safety laboratory tests assessment as a measure of safety and tolerability [ Time Frame: Up to 42 days (Screening, Day -1, 15, 32 and Follow up [Day 38 to 42]). ]Hematology, clinical chemistry, urinalysis were assessed.
- Tmax and t1/2 of darapladib. [ Time Frame: Up to 32 days (PK samples will be collected on Days 8, 9, 26 and 27 at predose. Day 10 and Day 28 predose and at 0.5, 1, 2, 3, 4, 6, 9, 12, 18, 24, 32, 48, 72, and 96 hours post-dose. ]Tmax is defined as the time required reaching the maximum concentration of the drug in the plasma after its administration. t1/2 is defined as the time taken to reach half the concentration of the drug after administration.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01852565
|United States, Maryland|
|GSK Investigational Site|
|Baltimore, Maryland, United States, 21225|
|Study Director:||GSK Clinical Trials||GlaxoSmithKline|