Positron Emission Tomography Study of Brain CGRP Receptors After MK-0974 Administration (MK-0974-067)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01315847
First received: February 22, 2011
Last updated: January 17, 2014
Last verified: January 2014
  Purpose

The purpose of this study is to determine the receptor occupancy (RO) associated with MK-0974 (telcagepant) administration based on displacement of [11C]MK-4232 from the calcitonin gene-related peptide (CGRP) receptors in the brain using Positron Emission Tomography (PET).The study started recruiting healthy subjects January 2010. It is planned to enroll patients February 2011.


Condition Intervention Phase
Migraine
Drug: telcagepant
Drug: [11C]MK-4232
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Three-Part Positron Emission Tomography Study of Brain CGRP Receptor Occupancy Levels Following Administration of MK-0974, Using [11C]MK-4232 as an Imaging Agent

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Number of participants with adverse experiences after a single oral doses of telcagepant [ Time Frame: Part I: Predose and up 10 to 14 days post dose ] [ Designated as safety issue: Yes ]
  • Number of participants with adverse experiences after a single oral doses of telcagepant [ Time Frame: Part III: predose up to 2 months post treatment ] [ Designated as safety issue: Yes ]
  • CGRP RO at the maximum dose of telcagepant in healthy subject [ Time Frame: Part I (Period 1): 3 to 5 hours post dose ] [ Designated as safety issue: No ]
  • CGRP RO at the maximum dose of telcagepant in healthy subject [ Time Frame: Part I (Period 2): 2 to 4 hours post dose ] [ Designated as safety issue: No ]
  • CGRP RO at the maximum dose of telcagepant in migraine patients during and between migraine attacks [ Time Frame: Baseline and 2 to 4 hours post dose ] [ Designated as safety issue: No ]
  • CGRP-RO and plasma concentration relationship after administration of telcagepant in healthy subjects and migraine patients [ Time Frame: Part I (Period 1): baseline and 2 to 5 hours post dose ] [ Designated as safety issue: No ]
  • CGRP-RO and plasma concentration relationship after administration of telcagepant in healthy subjects and migraine patients [ Time Frame: Part I (Period 2): baseline and 1 to 4 hours postdose ] [ Designated as safety issue: No ]
  • CGRP-RO and plasma concentration relationship after administration of telcagepant in healthy subjects and migraine patients [ Time Frame: Part III: baseline and 1 to 4 hours post dose ] [ Designated as safety issue: No ]

Enrollment: 10
Study Start Date: January 2010
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Healthy Subjects Drug: telcagepant
Single oral dose of telcagepant 1120 mg Part I (Period 1) and 140 mg Part I (Period 2) and Part III (Period 1 and 2)
Other Name: MK-0974
Drug: [11C]MK-4232
Single intravenous dose of [11C]MK-4232 administered as a 5 minute infusion
Experimental: Migraine Patients Drug: telcagepant
Single oral dose of telcagepant 1120 mg Part I (Period 1) and 140 mg Part I (Period 2) and Part III (Period 1 and 2)
Other Name: MK-0974
Drug: [11C]MK-4232
Single intravenous dose of [11C]MK-4232 administered as a 5 minute infusion

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  • 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 (situational depression in the past 6 to 12 months

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 adequately treated non-melanomatous skin carcinoma or carcinoma in situ of the cervix may participate in the study; has 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 (except those cancers identified at the beginning of exclusion criterion

- 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
  • 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 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.
  Contacts and Locations
No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01315847     History of Changes
Other Study ID Numbers: 0974-067
Study First Received: February 22, 2011
Last Updated: January 17, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Migraine Disorders
Headache Disorders, Primary
Headache Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases

ClinicalTrials.gov processed this record on April 16, 2014