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

NCT00803894 | Completed Phase 1

• 2 other identifiers: 0752-0222008_594
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

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

Keywords

Biomarkers of Notch inhibition

Outcome Measures

Primary Outcomes (1)

• 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.

  8.5 hours post dose.

Study Arms (3)

A

ACTIVE COMPARATOR

MK0752 1000 mg

Drug: MK0752

B

ACTIVE COMPARATOR

MK0752 350 mg

Drug: Comparator: MK0752.

C

PLACEBO COMPARATOR

Placebo

Drug: Comparator: Placebo

Interventions

MK0752 DRUG

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

A

Comparator: MK0752. DRUG

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

Also known as: MK0752

B

Comparator: Placebo DRUG

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

C

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• 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.

  PMID: 26765077 RESULT

MeSH Terms

Interventions

3-(4-((4-chlorophenyl)sulfonyl)-4-(2,5-difluorophenyl)cyclohexyl)propanoic acid

Study Officials

• Medical Monitor

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2008
• First Posted: December 8, 2008
• Study Start: December 1, 2008
• Primary Completion: January 1, 2009
• Study Completion: January 1, 2009
• Last Updated: June 17, 2016

Record last verified: 2016-06