Clinical trial NCT00803894: A Clinical Study to Determine Biomarkers of Response to a Gamma Secretase Inhibitor
Official title: A Randomized Clinical Trial to Study the Effects of MK0752 Versus Placebo on Biomarkers in Healthy Young Adult Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Biomarkers of Notch inhibition
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2008-12-08
Enrollment: 30
Sex: MALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: DIAGNOSTIC

Brief summary: The purpose of this study is to determine the transcriptional signature of Notch Inhibition by testing hair and blood samples on healthy male volunteers who have received MK0752 vs placebo for possible future biomarkers in the treatment of cancer or Alzheimers Disease


Eligibility criteria: Inclusion Criteria:

* Patient is a male
* Patient has no clinically significant abnormality on electrocardiogram performed
* Patient agrees to not to consume apple juice, grapefruit or grapefruit products beginning 2 weeks prior to first dose of study drug and for the duration of the study
* Patient has been a nonsmoker and/or has not used nicotine or nicotine-containing products for approximately 6 months.
* Patient is willing to not use any hair enhancement product or procedures for the duration of the study (for example, permanents, hair straightening techniques)
* Patient has a full head of hair
* Patient has at least 90% non-gray hair

Exclusion Criteria:

* Patient has had treatment with any investigational therapy during the prior 21 days
* Patient has any history of significant gastrointestinal abnormalities within the last 10 years
* Patient has a history of any long-term or active liver disease including elevated liver blood tests. Any patient with a history of Hepatitis B or C (and/or treated previously) will be excluded
* Patient has a known history or family history of aortic valve disease, congenital (from birth) heart disease or deafness, hearing loss or early onset Alzheimer's disease (onset at age \< 55)
* Patient has a known sensitivity to the ingredients in the drug
* Patient has had active and uncontrolled infection within the past month
* Patient is HIV positive
* Patient has a history of stomach, intestine, heart, blood, liver, brain, kidney, lung, bladder or endocrine abnormalities or diseases
* Patient has a history of cancer except for certain skin cancer (basal cell)
* Patient has a history of multiple and/or severe allergies or has had an allergic reaction to food or prescription/non-prescription drugs
* Patient has had major surgery, donated or lost 1 unit of blood (about 500 mL) within the past month
* Patient has premature graying hair (\> 10% gray hair)
* Patient has male pattern hair loss
* Patient has a prior history of high blood pressure
* Patient uses any medication, including prescription and non-prescription drugs or herbal remedies (such as St. John's Wort) beginning approximately 2 weeks prior to the first dose of study drug, throughout the study until the post study visit
* Patient consumes excessive amounts of alcohol (greater than 3 glasses of alcoholic beverages)
* Patient consumes excessive amounts (greater than 6 servings) of coffee, tea, cola or other caffeinated beverages per day
* Patient is a regular use (including "recreational use") of any illicit drugs, has a positive urine drug screen before randomization or has a history of drug (including alcohol) abuse within approximately the past 2 years
* Patient has prior exposure to MK 0752 with the past 21 days

Primary outcomes:
measure: To evaluate the existing Notch response signature using plucked hair follicle profiling data from health young male volunteers given 1000 mg MK0752 and 350 mg MK0752.
timeFrame: 8.5 hours post dose.
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Monitor
role: STUDY_DIRECTOR
References:
citation: Tanis KQ, Podtelezhnikov AA, Blackman SC, Hing J, Railkar RA, Lunceford J, Klappenbach JA, Wei B, Harman A, Camargo LM, Shah S, Finney EM, Hardwick JS, Loboda A, Watters J, Bergstrom DA, Demuth T, Herman GA, Strack PR, Iannone R. An accessible pharmacodynamic transcriptional biomarker for notch target engagement. Clin Pharmacol Ther. 2016 Apr;99(4):370-80. doi: 10.1002/cpt.335. Epub 2016 Feb 17.