E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Heterozygous Familial Hypercholesterolaemia |
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E.1.1.1 | Medical condition in easily understood language |
Heterozygous Familial Hypercholesterolaemia - High cholesterol |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10058108 |
E.1.2 | Term | Dyslipidaemia |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10020603 |
E.1.2 | Term | Hypercholesterolaemia |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10057099 |
E.1.2 | Term | Heterozygous familial hypercholesterolaemia |
E.1.2 | System Organ Class | 100000004850 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare the pharmacokinetics of laropiprant following administration of a single dose of 1 (Panel A) and 2 (Panel B) combination tablets of MK-0524A (1000mg ER niacin/20mg laropiprant) between adolescents with heterozygous familial hypercholesterolemia and healthy adults (historical data from MK-0524A P057 and P059). |
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E.2.2 | Secondary objectives of the trial |
To compare the total urinary excretion of niacin and niacin metabolites following administration of a single dose of 1 (Panel A) and 2 (Panel B) combination tablets of MK0524A (1000 mg ER niacin/20 mg laropiprant) in adolescents with heterozygous familial hypercholesterolemia with healthy adults (historical data from MK0524A P057 and P059). To compare the pharmacokinetics of nicotinuric acid (NUA) following administration of a single dose of 1 (Panel A) and 2 (Panel B) combination tablets of MK0524A (1000 mg ER niacin/20 mg laropiprant) in adolescents with heterozygous familial hypercholesterolemia with healthy adults (historical data from MK0524A P057 and P059). To evaluate the safety and tolerability following administration of a single dose of 1(Panel A) and 2 (Panel B) combination tablets of MK0524A (1000 mg ER niacin/20 mg laropiprant) in adolescents with heterozygous familial hypercholesterolemia |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Demographics1. Patient is a male or female post-pubertal adolescent subject of age 10-16 with heterozygous familial hypercholesterolemia Males: Tanner stage II or higher Females: Post-menarche (defined as at least 1 year after the first menstrual period and having had at least 3 menstrual periods) 2. Patients height and weight fall between the 10th and 95th percentile for age with a minimum body weight of 23Kg at the screening visit Protocol-specific Inclusion Criteria 3. The patient has LDL-C values ≥ 110mg/dL (2.85mmol/L) and ≤400mg/dL (10.3mmol/L) 4. Patient trigleride (TG) values ≤400mg/dL (4.52mmol/L) 5. Patient has heterozygous familial hypercholesterolemia Medical history, physical examinations, laboratory safety tests and ECG measurements 6. Patient receives appropriate medical care for their hypercholesterolemia, such as a statin or other lipid modifying therapy. Patients on a statin or any other lipid modifying therpay must be on a stable regimen for 6 weeks prior to the screening visit. 7. Glycemic status of the patient has been determined prior to randomisation 8. Patient is judged to be in good health based on medical history, physical examination, vital sign measurements, and laboratory safety tests performed at the prestudy and/or prior to administration of the initial dose of study drug 9. Patient has no clinically significant abnormality on ECG performed at the prestudy visit and/or prior to administration of the initial dose of study drug Diet/Activity/Other 10. Parent/legal guardian and patient understand the study procedures and agree to participate in the study as indicated by parental/legal guardian signature on the subject consent 11. Patient is willing to comply with the study restrictions |
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E.4 | Principal exclusion criteria |
Medical history, physical examinations, laboratory safety tests and ECG measurements 1. Patient with a history of psychiatric or personality disorders that in the opinion of the investigator and sponsor, affects the patient's ability to participate in the trial 2. Patient has a history of any illness that in the opinion of the study investigator, might confound the results of the study or poses an additional risk to the patient by their participation in the study. 3. Patient has an estimated creatinine clearance of ≤80ml/min based on the Schwartz equation, the Schwartz equation is: CrCl (ml/min) = length(cm) X K/Scr(mg/dL) where K = 0.55 for all children 1 to 12 years, K=0.55 for females age 13 to 18 years and K=0.7 for males age 13 to 18 years. 4. Patient has a history of stroke, chronic seizures or major neurological disorder 5. Patient has a history of clinically significant endocrine, gastrointestinal cardiovascular, hematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases (excluding lipid abnormalities). Patients with a history of uncomplicated kidney stones or childhood asthma may be enrolled in the study at the discretion of the investigator. 6. Patient has Type 1 or Type 2 diabetes mellitus and: - is poorly controlled (HbA1C at Visit 1 >8%) or is newly diagnosed (within 3 months of Visit 1) - has recently experienced repeated hypoglycemia or unstable glycemic control. - is taking new or recently adjusted anti-diabetic pharmacotherapy (with the exception of ± 10 units of insulin) within 3 months of Visit 1. 7. Patient has a history of neoplastic disease within 5 years from screening Exceptions: (1) Patients with adequately treated non-melanomatous skin carcinoma or carcinoma in situ of the cervix may participate in the study; (2) Patients with other malignancies which have been successfully treated 10 years prior to the prestudy (screening) visit where, in the judgment of both the investigator and treating physician, appropriate follow-up has revealed no evidence of recurrence from the time of treatment through the time of the prestudy (screening) visit (except those cancers identified at the beginning of exclusion criterion f); or, (3) Patients, who, in the opinion of the study investigator, are highly unlikely to sustain a recurrence for the duration of the study. Diet/Activity/Other 8. Patient has LDL-C < 160 mg/dL ( 4.1 mmol/L) after dietary treatment 9. Patient consumes alcohol. 10. Patient consumes excessive amounts, defined as greater than 4 servings (1 serving is approximately equivalent to 120 mg of caffeine) of cola, coffee, tea, or other caffeinated beverages per day. 11. Patient has had major surgery, donated and/or received blood as follows: - Donated blood products or lost >300 mL within 8 weeks prior to signing the consent form - Intends to give or receive blood products during the study - Intends to donate more than 250 mL of blood products within 8 weeks following the follow-up visit 12. Patient has participated in another investigational study within 4 weeks prior to the prestudy (screening) visit. The 4 week window will be derived from the date of the last study procedure (i.e. poststudy, AE follow-up, etc.) in the previous study to the prestudy/screening visit of the current study. 13. Patient has a 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. 14. Patients who are positive for hepatitis B surface antigen, hepatitis C antibodies or HIV cannot be enrolled. 15. The patient cannot swallow large tablets. 16. There is any concern by the investigator regarding the safe participation of the patient in the study or for any other reason, the investigator considers the patient inappropriate for participation in the study. 17. Patient has the following age-specific exclusionary central laboratory values at screening: ALT (SGPT) >1.5 x upper limit of normal (ULN) AST (SGOT) >1.5 x ULN CK > 50% ULN TSH >20% ULN Platelet count <100,000/mm3 18. Patient is a nursing mother. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Pharmacokinetics of laropiprant, niacin and its metabolites and nicotinuric acid following administration of a single dose of 1 tablet of MK0524A and 2 tablets of MK0524A. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
For laropiprant: Day 1 predose through 48 hours postdose. For Niacin/NUA: Day 1 predose through 24 hours postdose, For Nicotinic acid/metabolites: Day 1 predose through 72 hours postdose (urine only) |
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E.5.2 | Secondary end point(s) |
Safety and tolerability following a single dose of 1 tablet of MK0524A and 2 tablets of MK0524A in adolescents with heterozygous familial hypercholesterolemia |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Prestudy through poststudy |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
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E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
New Zealand |
Norway |
South Africa |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 6 |