Safety and Tolerability Study of Ezetimibe (SCH 058235/MK-0653) Plus Atorvastatin or Simvastatin in Homozygous Familial Hypercholesterolemia (P01417/MK-0653-019)

• Register: ClinicalTrials.gov
• Last refreshed on: 21 February 2022
• Main ID: NCT03885921
• Date of registration: 20/03/2019
• Prospective Registration: No
• Primary sponsor: Organon and Co
• Public title: Safety and Tolerability Study of Ezetimibe (SCH 058235/MK-0653) Plus Atorvastatin or Simvastatin in Homozygous Familial Hypercholesterolemia (P01417/MK-0653-019)
• Scientific title: Long-Term, Open-Label, Safety and Tolerability Study of SCH 58235 in Addition to Atorvastatin or Simvastatin in the Therapy of Homozygous Familial Hypercholesterolemia
• Date of first enrolment: October 25, 2000
• Target sample size: 44
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03885921
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 3

Contacts

• Name: Medical Director
• Affiliation: Merck Sharp & Dohme Corp.

Key inclusion & exclusion criteria

Inclusion Criteria:

- Has successfully completed the 12-week double-blind, efficacy and safety study of
ezetimibe (Study P01030/MK-0653-018). Entry into this protocol must occur at the time
of completion of Study P01030/MK-0653-018.

- All women must have a negative pregnancy test prior to study entry. Women of child
bearing potential must agree to practice an effective barrier method of birth control
for the duration of the study. In addition, participants administered a statin must
agree to practice an effective barrier method of birth control for 30 days following
the last dose of statin administered.

- Postmenopausal women who are receiving postmenopausal hormonal therapy or raloxifene
must be maintained on a stable estrogen (ERT), estrogen/progestin (HRT) or raloxifene
regimen during study period.

- Is willing to observe the National Cholesterol Education Program (NCEP) Step I diet
for the duration of the study.

- Is willing to participate in the study and to complete all assessments.

- Patients or in the case of children, their parents or legal guardians, must agree to
give written informed consent.

Exclusion Criteria:

- Participants who discontinued prematurely from Study P01030/MK-0653-018.

- Participants who are in a situation or have any condition which, in the opinion of the
Investigator, may interfere with optimal participation in the study.

- Pregnant or lactating women.

- Participants who are known to be human immunodeficiency virus (HIV) positive.

- Participants who are taking any prohibited concomitant medications. Prohibited
medications include:

- Fibric Acid Derivatives;

- Oral corticosteroids;

- (Cardiovascular drugs such as beta blockers, calcium channel blockers,
angiotensin-converting enzyme [ACE] inhibitors, nitrates or alpha-adrenergic blockers
or thiazide diuretics will be allowed, provided the dose will remain constant
throughout the duration of the study. Acetylsalicylic acid administered as a platelet
aggregation inhibitor or analgesic is permitted.);

- Treatment with psyllium or other fiber-based laxatives unless treated with a stable
regimen treatment throughout the duration of the study period;

- Treatment with cyclosporine;

- Treatment with orlistat;

- Treatment with troglitazone (Rezulin®) or other thiazolidinedione antidiabetic agents,
unless treated with a stable regimen throughout the duration of the study period;

- Treatment with agents with known drug interactions with simvastatin or atorvastatin
including antifungal azoles (e.g. itraconazole and ketoconazole), macrolide
antibiotics (e.g. erythromycin and clarithromycin) and nefazodone; In addition,
treatment with other agents that may interfere with or induce the CYP3A4 isoenzyme of
the cytochrome P450 system should be avoided, although they are not necessarily
prohibited medications.;

- Treatment with medications which interact with simvastatin through uncertain
mechanisms, including amiodarone and verapamil, are prohibited in participants
administered simvastatin in this protocol.

- (Participants receiving LDL-C apheresis may continue on this therapy provided that
they are on a stable regimen throughout the duration of the study and lipid levels for
study visits are drawn just prior to an apheresis treatment session.);

- Participants on a stable regimen of resin therapy (as defined by the dose taken during
the P01030/MK-0653-018 study) may continue that therapy provided that the daily dose
of study treatment is taken =4 hours prior to the administration of the resin or =4
hours following any resin dose. In addition, the dose of resin should be taken no less
than 4 hours before and no less than 4 hours after administration of study treatment.



Age minimum: 12 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Hypercholesterolemia

Intervention(s)

Drug: Atorvastatin

Drug: Ezetimibe

Drug: Simvastatin

Primary Outcome(s)

Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) [Time Frame: Up to 24 Months]

Number of Participants Who Experience an Adverse Event (AE) [Time Frame: Up to 24 Months]

Secondary Outcome(s)

Mean Percent Change from Baseline in Triglycerides (TG) [Time Frame: Baseline and Month 24]

Mean Percent Change from Baseline in Low-density-lipoprotein Cholesterol (LDL-C) [Time Frame: Baseline and Month 24]

Mean Percent Change from Baseline in Total Cholesterol (TC) [Time Frame: Baseline and Month 24]

Mean Percent Change from Baseline in High-density-lipoprotein Cholesterol (HDL-C) [Time Frame: Baseline and Month 24]

Secondary ID(s)

MK-0653-019

P01417

Source(s) of Monetary Support

Please refer to primary and secondary sponsors