Hypercholesterolemia, Familial, Heterozygous Familial Hypercholesterolemia
Conditions
Brief summary
The purpose of this study is to determine the pharmacokinetics of laropiprant following administration of a single dose of 1 (Panel A) and 2 (Panel B) combination tablets of MK-0524A in adolescents with heterozygous familial hypercholesterolemia.
Interventions
DRUGMK-0524A
1 tablet of MK-0524A (1g ER niacin/20mg laropripant) orally
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
10 Years to 16 Years
Healthy volunteers
No
Inclusion criteria
* Post-pubescent adolescent age 10 to 16 with heterozygous familial hypercholesterolemia * Agree to use (and/or have their partner use) acceptable methods of birth control beginning at the prestudy visit until at least 2 weeks after dosing of study drug * Height and weight fall between the 10th and 95th percentile for age with a minimum body weight of 23 kg * Receiving appropriate medical care for hypercholesterolemia, such as a statin or other lipid-modifying therapy.
Exclusion criteria
* History of psychiatric or personality disorders that may affect the patient's ability to participate * History of stroke, chronic seizures, or major neurological disorder * History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases (excluding lipid abnormalities) * Poorly controlled or recently diagnosed Type 1 or Type 2 diabetes mellitus * History of neoplastic disease within previous 5 years * Consumes alcohol or excessive amounts of products that contain caffeine (e.g. cola) * Has had major surgery, donated and/or received blood within previous 8 weeks * Participated in another investigational study within previous 4 weeks * History of significant multiple and/or severe allergies (including latex allergy), or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food * Positive for hepatitis B surface antigen, hepatitis C antibodies or human immunodeficiency virus (HIV) * Cannot swallow large tablets * Pregnant or breastfeeding
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Plasma Maximum Concentration (Cmax) of Laropiprant | Predose on Day 1 up to 48 hours postdose |
| Total Urinary Excretion of Niacin and Niacin Metabolites | Predose on Day 1 up to 72 hours postdose |
| Plasma Area Under the Concentration Curve From 0 to Infinity (AUC0-∞) of Laropiprant | Predose Day 1 up to 24 hours postdose |
| Plasma Cmax of Nicotinuric Acid (NUA) | Predose on Day 1 up to 48 hours postdose |
Participant flow
Pre-assignment details
MK-0524A-158 was terminated after the Phase 3 study HPS2-THRIVE (MK-0524A-042;NCT00461630) didn't meet its primary endpoint of reduction of major vascular events; there was also a significant increase in some types of non-fatal serious adverse events. MK-0524A-158 was terminated after 10 participants completed Panel A. Panel B was not conducted.
Participants by arm
| Arm | Count |
|---|---|
| MK-0524A 1 g/20 mg (Panel A) Single oral dose of 1 tablet of MK-0524A. Each tablet contained Extended Release (ER) Niacin 1g and laropiprant 20 mg | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | MK-0524A 1 g/20 mg (Panel A) |
|---|---|
| Age, Continuous | 15.4 Years STANDARD_DEVIATION 0.8 |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 10 | 0 / 0 |
| serious Total, serious adverse events | 0 / 10 | 0 / 0 |
Outcome results
Primary
Plasma Area Under the Concentration Curve From 0 to Infinity (AUC0-∞) of Laropiprant
Time frame: Predose Day 1 up to 24 hours postdose
Population: The study was terminated during Panel A and the decision was made to not analyze the blood and urine pharmacokinetic samples collected during Panel A; Panel B was not conducted.
Primary
Plasma Cmax of Nicotinuric Acid (NUA)
Time frame: Predose on Day 1 up to 48 hours postdose
Population: The study was terminated during Panel A and the decision was made to not analyze the blood and urine pharmacokinetic samples collected during Panel A; Panel B was not conducted.
Primary
Plasma Maximum Concentration (Cmax) of Laropiprant
Time frame: Predose on Day 1 up to 48 hours postdose
Population: The study was terminated during Panel A and the decision was made to not analyze the blood and urine pharmacokinetic samples collected during Panel A; Panel B was not conducted.
Primary
Total Urinary Excretion of Niacin and Niacin Metabolites
Time frame: Predose on Day 1 up to 72 hours postdose
Population: The study was terminated during Panel A and the decision was made to not analyze the blood and urine pharmacokinetic samples collected during Panel A; Panel B was not conducted.