Positron Emission Tomography (PET) Study of Brain Calcitonin Gene-Related Peptide (CGRP) Receptor Occupancy After Telcagepant Administration (MK-0974-067)
Condition: Migraine
Intervention: telcagepant; [11C]MK-4232
Intervention description: Single oral doses of telcagepant 1120 mg (Part I - Period 1) and 140 mg (Part I - Period 2; Part III - Period 1 and 2); Single intravenous doses of ~300 MBq [11C]MK-4232 administered as a 5 minute infusion (Part I - Baseline, Period 1 and 2; Part III - Period 1 Baseline and Period 1, and Period 2 Baseline and Period 2)
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      The purpose of this study is to determine the receptor occupancy (RO) associated with
      telcagepant (MK-0974) administration based on displacement of [11C]MK-4232 from the CGRP
      receptors in the brain using PET. The study enrolled healthy participants (Part I) and
      migraine patients (Part III). Due to a protocol amendment, study Part II was not conducted.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participant (Part III only) agrees to use (or have their partner use) a highly
             effective method of birth control within the projected duration of the study

          -  Participant has a Body Mass Index (BMI) ≤32 kg/m2 at the prestudy visit

          -  Participant (Part III only) has had a history of migraine with or without aura >1 year
             with at least 1 and ≤8 moderate or severe migraine attacks per month in the last 3
             months prior to screening

          -  Participant is judged to be in good health (apart from migraine) based on medical
             history, physical examination, vital sign measurements, and laboratory safety tests

          -  Participant has no clinically significant abnormality on electrocardiogram (ECG)

          -  Participant has been a nonsmoker and/or has not used nicotine or nicotine containing
             products for at least approximately 6 months

          -  Participant is willing to comply with the study restrictions and willing to allow the
             investigators to place an arterial catheter in the radial artery.

        Exclusion Criteria:

          -  Participant is mentally or legally incapacitated, has significant emotional problems
             at the time of prestudy (screening) visit or expected during the conduct of the study
             or has a history of a clinically significant psychiatric disorder over the last 5
             years (participant with situational depression in the past 6 to 12 months, but not
             currently, may be enrolled at the discretion of the investigator)

          -  Participant has a history of any illness that, in the opinion of the study
             investigator, might confound the results of the study or poses an additional risk to
             the subject by their participation in the study

          -  Participant has an estimated creatinine clearance of ≤80 mL/min

          -  Participant has a history of stroke, chronic seizures, or major neurological disorder

          -  Participant has a history of clinically significant endocrine, gastrointestinal,
             cardiovascular, hematological, hepatic, immunological, renal, respiratory, or
             genitourinary abnormalities or diseases

          -  Participant has a history of neoplastic disease except 1) adequately treated
             non-melanomatous skin carcinoma or carcinoma in situ of the cervix 2) other
             malignancies which have been successfully treated ≥10 years prior to the prestudy
             (screening) visit where, in the judgment of both the investigator and treating
             physician, appropriate follow-up has revealed no evidence of recurrence from the time
             of treatment through the time of the prestudy (screening) visit

          -  For Part III only: Participant is a nursing mother, has difficulty distinguishing
             his/her migraine attacks from tension or interval headaches, has a history of
             predominantly mild migraine attacks or migraines usually resolved spontaneously in
             less than 4 hours, has basilar or hemiplegic migraine headache, has more than 15
             headache-days per month or has taken medication for acute headache on more than 10
             days per month in any of the 3 months prior to screening, is taking migraine
             prophylactic medication, was >50 years of at age of migraine onset, has, in the
             opinion of the investigator, other confounding pain syndromes, psychiatric conditions
             such as uncontrolled major depression, dementia or significant neurological disorders
             other than migraine, has liver function tests, specifically alanine aminotransferase
             (ALT)/aspartate aminotransferase (AST) and Alkaline Phosphatase are above the upper
             limit of normal at the prestudy (screening) visit or at recheck within 4 weeks prior
             to Day 1, is taking strong or moderate Cytochrome P450 3A4 (CYP3A4) inhibitors such as
             Ketoconazole, Diltiazem or Verapamil

          -  Participant is unable to refrain from or anticipates the use of any medication,
             including prescription and non-prescription drugs or herbal remedies

          -  Participant consumes excessive amounts of alcohol

          -  Participant consumes excessive amounts, defined as greater than 6 servings of
             caffeinated beverages per day

          -  Participant has had major surgery, donated or lost 1 unit of blood (approximately 500
             mL) or participated in another investigational study within 4 weeks prior to the
             prestudy visit

          -  Participant has a history of significant multiple and/or severe allergies (including
             latex allergy), or has had an anaphylactic reaction or significant intolerability to
             prescription or non-prescription drugs or food

          -  Participant is currently a regular user (including "recreational use") of any illicit
             drugs or has a history of drug (including alcohol) abuse within approximately 2 years

          -  Participant has participated in a PET study or other study involving administration of
             a radioactive substance or ionizing radiation within 12 months prior to the prestudy
             visit

          -  Participant has implanted or embedded metal objects or fragments in the head or body
             that would present a risk during the magnetic resonance imaging (MRI) scanning

          -  Participant suffers from claustrophobia and would be unable to undergo MRI or PET
             scanning

          -  Any concern by the investigator regarding the safe participation of the participant in
             the study, and the ability of the subject to tolerate the procedures.