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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00652431
First received: March 31, 2008
Last updated: May 15, 2014
Last verified: May 2014
  Purpose

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


Condition Intervention Phase
Hypercholesterolemia
Hyperlipidemia
Drug: Vytorin + Niaspan
Drug: Vytorin
Drug: Niaspan
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: SCH 465981: Assessment of Bi-Directional Interaction Between Components of Vytorin® (Ezetimibe and Simvastatin) and Niaspan® (Niacin Extended-Release Tablets) in Healthy Subjects

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Evaluate the potential for a PK interaction between NIASPAN and components of VYTORIN, using Tmax, Cmax, and AUC. [ Time Frame: Day 7 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Evaluate safety and tolerability: laboratory test results, ECGs, adverse events, vital signs. [ Time Frame: throughout study ] [ Designated as safety issue: Yes ]

Enrollment: 18
Study Start Date: May 2007
Study Completion Date: July 2007
Primary Completion Date: July 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vytorin + Niaspan
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 (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
Other Names:
  • SCH 465981
  • ezetimibe
  • simvastatin
  • niacin
  • nicotinic acid
Active Comparator: Vytorin
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
Vytorin (1 tablet containing ezetimibe 10 mg and simvastatin 20 mg) once daily in the morning for 7 days
Other Names:
  • SCH 465981
  • ezetimibe
  • simvastatin
Active Comparator: Niaspan
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
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
Other Names:
  • niacin
  • nicotinic acid

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

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
    • Medically prescribed IUD with spermicide, and
    • Surgical sterilization (eg. hysterectomy or tubal ligation). Vasectomy of the partner should be considered a single barrier and one additional contraceptive methods listed above must be used. Females who are not currently sexually active must agree and consent to use one of the above-mentioned methods should they become sexually active while participating in the study.
  • Female subjects must be surgically sterilized (eg, documented hysterectomy or tubal ligation) or be postmenopausal. (Defined as 12 months with no menses and with an estradiol level of <30 pg/mL.)
  • Men must agree to use a medically accepted method of contraception prior to Screening, while receiving protocol-specified medication, and for 30 days after stopping the medication.

Exclusion Criteria:

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.
  • Subjects who have donated blood in the past 60 days.
  • Subjects who have previously received and demonstrated intolerance to NIASPAN® (niacin extended-release tablets), VYTORIN® (ezetimibe/simvastatin), ZETIA® (ezetimibe), ZOCOR® (simvastatin) or products containing niacin/nicotinic acid.
  • Subjects who are currently participating in another clinical study or have participated in a clinical study within 30 days.
  • Subjects who are part of the study staff personnel or family members of the study staff personnel.
  • Subjects who have demonstrated allergic reactions (eg, food, drug, atopic reactions or asthmatic episodes).
  • Subjects who smoke more than 10 cigarettes or equivalent tobacco use per day.
  • Subjects who have received any treatment listed in Table 2 of protocol P04955 (Doc ID: 3498819) more recently than the indicated washout period prior to Baseline in each period.
  • Subjects who received vaccination(s) within 30 days prior to screening.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

Publications:
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00652431     History of Changes
Other Study ID Numbers: P04955, Doc ID: 3498819
Study First Received: March 31, 2008
Last Updated: May 15, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hypercholesterolemia
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Niacin
Simvastatin
Ezetimibe
Nicotinic Acids
Niacinamide
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Vasodilator Agents
Cardiovascular Agents
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Anticholesteremic Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 31, 2014