Primary Hypercholesterolemia, Mixed Hyperlipidemia
Conditions
Brief summary
This is a 3-period study. Periods 1 and 2 will evaluate the effects of multiple doses of laropiprant on the antiplatelet effects of clopidogrel and aspirin administered in combination in participants with primary hypercholesterolemia or mixed dyslipidemia. Period 3 will be open-label and will evaluate single dose pharmacokinetics of nicotinic acid and laropiprant components of Tredaptive.
Interventions
open-label, single dose Tredaptive (1000mg ER niacin/ 20mg laropiprant) 2 oral tablets
DRUGComparator: aspirin
81 mg oral tablet once daily for 7 days
DRUGComparator: clopidogrel
75 mg oral tablet once daily for 7 days
40 mg oral tablet once daily for 7 days
DRUGComparator: placebo
placebo oral tablet once daily for 7 days
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Participant has primary hypercholesterolemia or mixed dyslipidemia (high cholesterol) * Participant is a non-smoker
Exclusion criteria
* Participant has a history of chronic seizures * Participant has a history of cancer * Participant has a history of stomach or intestinal ulcers or any history of GI bleeding * Participant has had major surgery, donated blood or participated in another investigational study in the past 4 weeks
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cutaneous Bleeding Time (BT) | Day 8 | Cutaneous bleeding Time (BT) on Day 8 after daily administration of laropiprant with aspirin and clopidogrel for 7 days versus BT on Day 8 after daily administration of placebo with aspirin and clopidogrel for 7 days. The model used included treatment, period and sequence as fixed effect variables and subjects as the random effect variable. Period 3 was not analyzed as bleeding time was not an objective for this part of the study. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Participants Periods 1 and 2 evaluated the effects of multiple doses of laropiprant on the antiplatelet effects of clopidogrel and aspirin administered in combination in participants with primary hypercholesterolemia or mixed dyslipidemia. Period 3 was open-label and evaluated single dose pharmacokinetics of nicotinic acid and laropiprant components of Tredaptive. | 36 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Period 1 | Withdrawal by Subject | 1 |
| Period 2 | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 55.0 years |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 24 / 36 | 23 / 36 | 20 / 20 |
| serious Total, serious adverse events | 0 / 36 | 0 / 36 | 0 / 20 |
Outcome results
Primary
Cutaneous Bleeding Time (BT)
Cutaneous bleeding Time (BT) on Day 8 after daily administration of laropiprant with aspirin and clopidogrel for 7 days versus BT on Day 8 after daily administration of placebo with aspirin and clopidogrel for 7 days. The model used included treatment, period and sequence as fixed effect variables and subjects as the random effect variable. Period 3 was not analyzed as bleeding time was not an objective for this part of the study.
Time frame: Day 8
Population: Due to technical reasons, bleeding time was zero for some participants; they were considered to be missing data. Therefore, these observations were excluded from the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Clopidogrel + Aspirin +Laropiprant | Cutaneous Bleeding Time (BT) | 478 Seconds |
| Clopidogrel + Aspirin | Cutaneous Bleeding Time (BT) | 389 Seconds |
90% CI: [0.96, 1.56]