A Clinical Study to Determine Biomarkers of Response to a Gamma Secretase Inhibitor

NCT ID: NCT00803894

Last Updated: 2016-06-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-12-31
• Study Completion Date: 2009-01-31

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

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: DOUBLE

Study Groups

A

MK0752 1000 mg

Group Type: ACTIVE_COMPARATOR

MK0752

Intervention Type: DRUG

Single dose MK0752 capsules, 1000 mg: there will be a 7-day washout period between treatments.

B

MK0752 350 mg

Group Type: ACTIVE_COMPARATOR

Comparator: MK0752.

Intervention Type: DRUG

Single dose MK0752 capsules, 350 mg: there will be a 7-day washout period between treatments.

C

Placebo

Group Type: PLACEBO_COMPARATOR

Comparator: Placebo

Intervention Type: DRUG

Single dose placebo capsules: there will be a 7-day washout period between treatments.

Interventions

MK0752

Single dose MK0752 capsules, 1000 mg: there will be a 7-day washout period between treatments.

Intervention Type: DRUG

Comparator: MK0752.

Single dose MK0752 capsules, 350 mg: there will be a 7-day washout period between treatments.

Intervention Type: DRUG

Comparator: Placebo

Single dose placebo capsules: there will be a 7-day washout period between treatments.

Intervention Type: DRUG

Other Intervention Names

MK0752

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Monitor

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

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.

Reference Type: RESULT

PMID: 26765077 (View on PubMed)

Other Identifiers

2008_594

Identifier Type: -

Identifier Source: secondary_id

0752-022

Identifier Type: -

Identifier Source: org_study_id