The primary objective of this study is to demonstrate non-inferiority by pharmacodynamic (PD) analysis of the prasugrel 5-mg maintenance dose (MD) in aspirin-treated subjects =60 kg with stable CAD, as assessed by maximum platelet aggregation (MPA)…
ID
Source
Brief title
Condition
- Coronary artery disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Criteria for Evaluation:
Efficacy: No efficacy measures will be collected in this study.
Safety: Laboratory measures, adverse events.
Pharmacokinetic: Blood samples will be collected for the determination of
plasma concentrations of the prasugrel active metabolite (R-138727), prasugrel
inactive metabolites (R-95913, R-106583, and R-119251), and the clopidogrel
active metabolite (R-130964). Inactive metabolites of clopidogrel will not be
analysed in this study.
Pharmacodynamic: LTA (ADP); VerifyNow® P2Y12; Vasodilator-associated stimulated
phosphoprotein (VASP).
Secondary outcome
-
Background summary
The TRITON-TIMI 38 Phase 3 clinical study (Study TAAL) revealed significantly
reduced rates of ischaemic events on prasugrel therapy compared to clopidogrel
for the composite endpoint of CV death, MI, or stroke in subjects with acute
coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI);
however, with prasugrel there was a greater risk of bleeding identified in
subjects with low body weight (<60 kg). Reducing the prasugrel maintenance dose
(MD) to 5 mg in subjects <60 kg in weight is expected to reduce exposure to
prasugrel*s active metabolite to a range that will lower the risk of bleeding
while providing efficacy comparable to that of 10-mg prasugrel MD in subjects
>=60 kg (there are no direct efficacy outcomes for this study). The use of
prasugrel for patients <60 kg is recommended at the lower MD of 5 mg in the
European Summary of Product Characteristics (EU SPC) and in the United States
Package Insert (USPI).
There is currently a lack of clinical data on the prasugrel 5-mg MD in subjects
who are <60 kg. This study, which is a post-marketing commitment based on the
Committee for Medicinal Products for Human Use (CHMP) review of the prasugrel
marketing authorisation application, will test the hypothesis that a prasugrel
5-mg MD in subjects with low body weight will achieve a non-inferior
pharmacodynamic (PD) effect to a 10-mg MD in subjects with higher body weight.
This study will provide further support for the prasugrel 5-mg MD
recommendation in subjects <60 kg in weight. In addition the approved
clopidogrel 75-mg MD will be compared with the 5-mg and 10-mg MD of prasugrel.
Study objective
The primary objective of this study is to demonstrate non-inferiority by
pharmacodynamic (PD) analysis of the prasugrel 5-mg maintenance dose (MD) in
aspirin-treated subjects <60 kg with stable coronary artery disease (CAD)
versus the prasugrel 10-mg MD in aspirin-treated subjects >=60 kg with stable
CAD, as assessed by maximum platelet aggregation (MPA) to 20 µM ADP measured
with light transmission aggregometry (LTA) at the pre-dose trough on day 12 ± 2
of the MD period (Study Period 1).
Study design
This Phase 1b study will be a multi-center, partially-blinded (single-blind for
subjects Period 1; double-blind in Periods 2 and 3), double-dummy (5 mg
prasugrel, 10 mg prasugrel, 75 mg clopidogrel with matching placebo), parallel
group (two population arms), active comparator, multiple dose (30-42 days
total), randomised sequence, 3 period (first period fixed, remaining two
periods crossover within each population arm) study design (3 periods of 12 ± 2
days without intervening or terminal washout periods) in aspirin-treated
subjects with stable coronary artery disease.
Intervention
Physical examination (1x during the study), ECG (1x), vital signs (5x).
The subjects of this study will not be subjected to a behavior change. No
questionnaires will be taken, Diaries do not have to be kept.
Lichamelijk onderzoek (1 x gedurende dit onderzoek), ECG (1x), meten van
lengte, gewicht (1x) en pols/ hartsag (5x)
De proefpersonen aan dit onderzoek worden niet onderworpen aan een
gedragswijze. Er worden geen vragenlijsten afgenomen. Dagboeken worden ook niet
bijgehouden.
Study burden and risks
Risks associated with study drug Prasugrel
Prasugrel has been taken by around 10,500 patients in clinical trials and is
already approved in Europe as medication for patients with Acute Coronary
Syndrome, however it has been tested as a treatment for stable Coronary Artery
Disease only by a limited number of people. This medication is not yet approved
on the market in the Netherlands.
The most common side effect is bleeding. The following examples may be signs of
bleeding: Blood in the Urine; Blood in the Stool; Uncontrollable bleeding
Additional common side effects: Bleeding in the stomach or bowels, bleeding
from a needle puncture site, Nose bleeds, Small red bruises on the skin
(ecchymoses), Blood in urine
Hematoma (bleeding under the skin at the site of an injection, or into a
muscle, causing swelling)
There are additional uncommon side effects of which your study doctor can tell
you more if you would like to.
Risks associated with comparator drug Clopidogrel
The most common side effect is bleeding. Bleeding may occur for example as
bleeding in the stomach or bowels, bruising, haematoma, nose bleed, blood in
the urine, bleeding in the eye or prolonged bleeding. Common side effects are:
Diarrhoea, abdominal pain, indigestion or heartburn.
There are additional uncommon side effects of which study doctor can tell you
more if would like to.
Risks and Discomforts associated with Aspirin
Aspirin may have undesirable side effects. People who are allergic to
acetylsalicylic acid, or have asthma, persisting or recurring stomach problems
(such as heartburn, upset stomach or stomach pain), ulcers, or bleeding
problems should not take aspirin unless directed by a doctor.
Do not use aspirin if you are taking a prescription drug for thinning the
blood, diabetes, gout, or arthritis, unless directed by a doctor. Combining
aspirin or similar drugs with oral anti-diabetes drugs can decrease blood sugar
levels more than expected.
Possible side effects of aspirin include stomach pain or discomfort,
indigestion, heartburn, nausea, or vomiting. Less common side effects include
unusual bleeding or bruising, black stools, severe diarrhea, ringing in the
ears, severe headache, dizziness, drowsiness, confusion, changes in vision,
changes in behavior, excessive sweating, and increased thirst.
The combination of study drug with other drugs prescribed for your condition
may have other unknown risks or possible harmful interaction.
Risks associated with study procedures
Blood Sampling
As a result of blood sampling you might feel pain or be light-headed. You may
experience some temporary discomfort, bleeding, bruising, or rarely, infection,
at the site of a needle puncture you receive during the drawing of blood
samples. The study blood draws might also increase the risk of anaemia caused
by study medications.
ECG
The ECG is a painless procedure that requires you to lie still for a few
minutes while electrodes are attached to your chest to record the activity of
your heart. The ECG leads placed on your skin may cause slight discomfort
during placement and removal. Some individuals are sensitive to the sticky
patches used during an ECG, which may result in redness and sore skin in those
areas.
In addition to the risks already described, prasugrel and clopidogrel, alone or
in combination with Aspirin®, and the study procedures may have other unknown
risks.
There may also be unknown risks to an embryo, fetus, or nursing infant.
Lilly Corporate Center DC 6076
IN 46285, Indianapolis, Indiana
US
Lilly Corporate Center DC 6076
IN 46285, Indianapolis, Indiana
US
Listed location countries
Age
Inclusion criteria
Participants will include both male and female subjects with stable coronary artery disease (CAD) who are at least 18 years of age and less than 75 years of age (with subjects grouped by body weight, either <60 kg or >=60 kg), and who are not currently indicated for treatment with a thienopyridine. Stable coronary artery disease is defined as any of the following: Subjects diagnosed with chronic stable angina; prior history of unstable angina (including non-ST-segment elevation myocardial infarction) or acute myocardial infarction (AMI); previous coronary revascularisation including percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), or CAD in at least one coronary vessel on previous angiography or noninvasive imaging procedure.;The following inclusion criterion is applicable only to patients enrolled at sites in the
Netherlands:
Subjects previously treated with clopidogrel and aspirin for at least 1
year and who did not have a bleeding event requiring medical attention
during treatment.
Exclusion criteria
• Unstable coronary artery disease.
• PCI or CABG within the previous 90 days.
• History of refractory ventricular arrhythmias within the last 6 months; an implanted defibrillator device; congestive heart failure within 6 months prior to screening; major surgery, or severe trauma, fracture or organ biopsy within 90 days prior to randomisation.
• Any planned surgical procedure or any coronary revascularisation (surgical or percutaneous) planned within 60 days following randomisation.
• Any known contraindication to treatment with an antiplatelet agent.
• Significant hypertension at the time of screening or randomisation.
• Clinically significant out-of-range values for platelet count or haemoglobin at screening, in the investigator*s opinion, or results of clinical laboratory tests at the time of screening that are judged to be clinically significant for the study population, as determined by the investigator.
• Prior history or presence of significant bleeding disorders, abnormal bleeding tendency, or personal history of coagulation or bleeding disorders.
• Prior history or clinical suspicion of cerebral vascular malformations, intracranial neoplasm, transient ischaemic attack (TIA), or stroke.
• Prior history or presence of thrombocytopaenia or thrombocytosis.
• Use of antiplatelet agents (excluding aspirin) *10 days prior to screening; the use (or planned use) of heparin, oral anticoagulants, or fibrinolytic agents within 30 days of screening; or subjects receiving daily treatment with nonsteroidal anti-inflammatory drugs (NSAIDS) or cyclooxygenase-2 (COX-2) inhibitors that cannot be discontinued for the duration of the study.;The following exclusion criteria are applicable only to patients enrolled at sites in the
Netherlands:
- Prior history or presence of decreased kidney function (as defined by
creatinine clearance <30 mL/min) and/or a diagnosis of end stage renal
disease [ESRD].
- Any bleeding requiring medical attention within the last 2 years prior
to screening.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2009-012739-13-NL |
| CCMO | NL32935.100.10 |