Assessment of Interaction Between Vytorin and Niaspan in Healthy Subjects (P04955AM2)

NCT00652431 | Completed Phase 1

• 2 other identifiers: P04955Doc ID: 3498819
• Study Type: interventional
• Target: 18
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a single-center, randomized, open-label, 3-period, 3-treatment multiple-dose crossover study designed to assess the interaction between VYTORIN® (Ezetimibe and Simvastatin) and NIASPAN® (Niacin Extended-Release Tablets) in healthy subjects. Treatment spans 7 days

Conditions

Hypercholesterolemia; Hyperlipidemia

Outcome Measures

Primary Outcomes (1)

• Evaluate the potential for a PK interaction between NIASPAN and components of VYTORIN, using Tmax, Cmax, and AUC.

  Day 7

Secondary Outcomes (1)

• Evaluate safety and tolerability: laboratory test results, ECGs, adverse events, vital signs.

  throughout study

Study Arms (3)

Vytorin + Niaspan

EXPERIMENTAL

NIASPAN 1000 mg (1 x 1000 mg tablet) once-daily in the morning on Days 1 to 2, followed by NIASPAN 2000 mg (2 x 1000 mg tablets) once-daily in the morning on Days 3 to 7 + VYTORIN 10/20 mg (1 x 10/20 mg tablet containing ezetimibe 10 mg and simvastatin 20 mg) once-daily in the morning for 7 days

Drug: Vytorin + Niaspan

Vytorin

ACTIVE COMPARATOR

VYTORIN 10/20 mg (1 x 10/20 mg tablet containing ezetimibe 10 mg and simvastatin 20 mg) once-daily in the morning for 7 days

Drug: Vytorin

Niaspan

ACTIVE COMPARATOR

NIASPAN 1000 mg (1 x 1000 mg tablet) once-daily in the morning on Days 1 to 2, followed by NIASPAN 2000 mg (2 x 1000 mg tablets) once-daily in the morning on Days 3 to 7 for a total of 7 days of treatment

Drug: Niaspan

Interventions

Vytorin + Niaspan DRUG

Vytorin (1 tablet containing ezetimibe 10 mg and simvastatin 20 mg) once daily in the morning for 7 days + Niaspan 1000 mg (1 x 1000-mg tablet) once daily in the morning on Days 1 and 2, followed by Niaspan 2000 mg (2 x 1000-mg tablets) once daily in the morning on Days 3 to 7

Also known as: SCH 465981, ezetimibe, simvastatin, niacin, nicotinic acid

Vytorin + Niaspan

Vytorin DRUG

Vytorin (1 tablet containing ezetimibe 10 mg and simvastatin 20 mg) once daily in the morning for 7 days

Also known as: SCH 465981, ezetimibe, simvastatin

Vytorin

Niaspan DRUG

Niaspan 1000 mg (1 x 1000-mg tablet) once daily in the morning on Days 1 and 2, followed by Niaspan 2000 mg (2 x 1000-mg tablets) once daily in the morning on Days 3 to 7

Also known as: niacin, nicotinic acid

Niaspan

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• The subject must meet ALL the criteria listed below for entry:
• Subjects must be willing to give written informed consent and able to adhere to dose and visit schedules.
• Subjects of either sex and of any race between the ages of 18 and 55 years, inclusive, having a Body Mass Index (BMI) between 19 to 32, inclusive. BMI = weight (kg)/height (m\^2).
• Subjects' clinical laboratory tests (CBC, blood chemistry, and urinalysis) must be within normal limits or clinically acceptable to the investigator/sponsor. Subject's liver function test results (AST, ALT, and GGT) must not be elevated above normal limits at Screening and on Day-1. Subjects' CPK test results must not be elevated more than 1.25 times the upper limit of normal, at Screening and on Day -1.
• Subjects must be free of any clinically significant disease that would interfere with the study evaluations.
• Screening ECG conduction intervals must be within gender specific normal range (QTc males \<=430 msec and females \<=450 msec).
• Vital sign measurements (taken after \~3 minutes in a seated position) must be within the following ranges:
• oral body temperature between 35.0°C to 37.5°C
• systolic blood pressure, 90 to 140 mm Hg
• diastolic blood pressure, 45 to 90 mm Hg
• pulse rate, 40 to 100 bpm
• Female subjects of childbearing potential must have a negative serum pregnancy test (beta-hCG) at Screening and have a negative urine pregnancy test upon each admission to the study center.
• Women of child-bearing potential must agree to use medically accepted methods of contraception prior to screening, while receiving protocol-specified medication, and for 30 days after stopping the medication. Acceptable methods of contraception include:
• Condoms (male or female) with spermicide,
• Diaphragm or cervical cap with spermicide

You may not qualify if:

• The subject will be excluded from entry if ANY of the criteria listed below are met:
• Female subjects who are pregnant, intend to become pregnant (within 3 months of ending the study), or are breastfeeding.
• Subjects who, in the opinion of the investigator, will not be able to participate optimally in the study.
• Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of any drug. The investigator should be guided by evidence of any of the following and be discussed with the sponsor prior to enrollment into the trial:
• history or presence of inflammatory bowel disease, ulcers, gastrointestinal or rectal bleeding;
• history of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection;
• history of pancreatic injury or pancreatitis;
• history or presence of liver disease or liver injury;
• history or presence of impaired renal function as indicated by abnormal creatinine, urinary albumin, BUN/urea or clinical significant urinary cellular constituents (eg, cast); or
• history of urinary obstruction or difficulty in voiding.
• Subject who has a history of any infectious disease within 4 weeks prior to drug administration.
• Subjects who are positive for hepatitis B surface antigen, hepatitis C antibodies or HIV.
• Subjects who have a positive screen for drugs with a high potential for abuse.
• Subjects with a history of mental instability or who have been treated for mood disorders.
• Subjects with a history of alcohol or drug abuse in the past 2 years.

Sponsors & Collaborators

• Organon and Co: lead
• Merck Sharp & Dohme LLC: collaborator

Related Publications (1)

• Kosoglou T, Zhu Y, Statkevich P, Triantafyllou I, Taggart W, Xuan F, Kim KT, Cutler DL. Assessment of potential pharmacokinetic interactions of ezetimibe/simvastatin and extended-release niacin tablets in healthy subjects. Eur J Clin Pharmacol. 2011 May;67(5):483-92. doi: 10.1007/s00228-010-0955-6. Epub 2010 Dec 1.

  PMID: 21120461 RESULT

MeSH Terms

Conditions

Hypercholesterolemia; Hyperlipidemias

Interventions

Ezetimibe, Simvastatin Drug Combination; Niacin; Ezetimibe; Simvastatin

Condition Hierarchy (Ancestors)

Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Azetidines; Azetines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations; Nicotinic Acids; Acids, Heterocyclic; Pyridines

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 31, 2008
• First Posted: April 3, 2008
• Study Start: May 1, 2007
• Primary Completion: July 1, 2007
• Study Completion: July 1, 2007
• Last Updated: February 16, 2022

Record last verified: 2022-02