MigrainePhase 1NCT01315847
Positron Emission Tomography (PET) Study of Brain Calcitonin Gene-Related Peptide (CGRP) Receptor Occupancy After Telcagepant Administration (MK-0974-067)
A Phase 1 study testing telcagepant and [11C]MK-4232 in people with Migraine, run by Merck Sharp & Dohme LLC.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Migraine
- What is being tested?
- telcagepant and [11C]MK-4232
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- No sites listed yet
- Study dates
- 14 Jan 2010to 26 Jul 2011
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
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- 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.
About this study
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
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.
Read the detailed description
For the 1120 mg (i.e., maximal) telcagepant dose, [11C]MK-4232 was administered and PET scan was started ~3 hours post telcagepant to coincide with the Tmax of the 1120 mg dose. For the 140 mg (i.e., therapeutic) telcagepant dose, [11C]MK-4232 was administered and PET scan was started ~2 hours post telcagepant to correspond with the timing of clinical efficacy measurements of telcagepant for migraine treatment in Phase III studies.
- Conditions
- Migraine
- Being tested
- telcagepant, [11C]MK-4232
- Medical subject headings
- Migraine Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
telcagepantDrug
Also called MK-0974
Single oral doses of telcagepant 1120 mg (Part I - Period 1) and 140 mg (Part I - Period 2; Part III - Period 1 and 2)
[11C]MK-4232Drug
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)
| Study group | Role | What they receive |
|---|---|---|
| Healthy Participants (Part I) | Experimental | Baseline PET imaging of the brain using [11C]MK-4232 tracer (~300 megabecquerel [MBq]) was performed in healthy participants; this PET data served as the baseline for both Period 1 and 2 of Part I. Subsequently in study Part I, Period 1 the healthy participants received a single 1120 mg dose of telcagepant followed by PET imaging of brain with [11C]MK-4232 tracer (~300 MBq) beginning ~3 hours post telcagepant dose. In Part I, Period 2 the healthy participants received a single 140 mg dose of telcagepant followed by PET imaging of brain with [11C]MK-4232 tracer (~300 MBq) beginning ~2 hours post telcagepant dose. Interval between Part I Period 1 and 2 was to be at least 1 week. Receives: Drug: telcagepant; Drug: [11C]MK-4232 |
| Participants with Migraine (Part III) | Experimental | In study Part III, Period 1 baseline PET imaging of the brain using [11C]MK-4232 tracer (~300 MBq) was performed in participants with migraine during a migraine attack (ictal phase). Later in Part III, Period 1 the participants with an ongoing migraine attack (ictal phase) received a single 140 mg dose of telcagepant followed by PET imaging of brain with [11C]MK-4232 tracer (~300 MBq) beginning ~2 hours post telcagepant dose. In Part III, Period 2 baseline PET imaging of the brain using [11C]MK-4232 tracer (~300 MBq) was performed in participants with migraine, however, without a migraine attack ongoing (interictal phase). Later in Part III, Period 2 participants with migraine without a migraine attack ongoing (interictal phase) received a single 140 mg dose of telcagepant followed by PET imaging of brain with [11C]MK-4232 tracer (~300 MBq) beginning ~2 hours post telcagepant dose. Interval between Part III Period 1 and 2 was to be at least 1 week. Receives: Drug: telcagepant; Drug: [11C]MK-4232 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adverse Events (AEs) (Part I)
Any AEs occurring among participants (all were healthy subjects) in Part I of study were recorded. An AE was defined as any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration, whether or not considered related to the study drug. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the administration of the study drug, was also an AE.
Measured: Up 14 days after the last dose of telcagepant and/or [11C]MK-4232 in Part I of study (Up to approximately 14 weeks)
Number of Participants With AEs (Part III)
Any AEs occurring among participants (all were migraine patients) in Part III of study were recorded. An AE was defined as any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration, whether or not considered related to the study drug. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the administration of the study drug, was also an AE.
Measured: Up 14 days after the last dose of telcagepant and/or [11C]MK-4232 in Part III of study (Up to approximately 6 months)
Brain Calcitonin Gene-related Peptide (CGRP) Receptor Occupancy (RO) Post Telcagepant Obtained by PET Imaging Using [11C]MK-4232 Tracer at Baseline and After a Maximum Dose of Telcagepant (1120 mg) in Healthy Participants (Part I, Period 1)
Brain CGRP RO post telcagepant was determined by change in [11C]MK-4232 PET tracer biokinetics at baseline and post telcagepant administration. Using PET brain images acquired over ~0-90 minutes after [11C]MK-4232 dose, regions of interest (ROIs) were drawn throughout cerebral cortex and white matter, striatum, thalamus, cerebellum and pons. The ROIs were projected onto all frames of the dynamic PET scans in order to generate [11C]MK-4232 tissue time-activity curves (TACs). Serial arterial blood samples for measurement of plasma radioactivity and [11C]MK-4232 concentrations were collected during the PET scans. These samples provided the arterial input function for a two-tissue compartmental model of [11C]MK-4232 tracer biokinetics. Total volume of distribution (VT), an index of receptor density, was estimated by fitting the two-tissue compartmental model to the PET [11C]MK-4232 TACs. Change in VT between baseline and post telcagepant PET studies was used to quantify the brain CGRP RO.
Measured: Part I Baseline, at ~0-90 minutes after [11C]MK-4232 dose; and Part I, Period 1 post telcagepant, at ~0-90 minutes after [11C]MK-4232 dose
Average Telcagepant Plasma Concentration During PET Imaging Using [11C]MK-4232 Tracer After a Maximum Dose of Telcagepant (1120 mg) in Healthy Participants (Part I, Period 1)
In Part I, Period 1 blood samples for determination of plasma telcagepant concentrations were obtained prior to the telcagepant dose (time 0) and at 2, 3, 4 and 5 hours post telcagepant dose. The average plasma telcagepant concentration during the PET scan was determined, calculated as the area under the plasma telcagepant concentration versus time curve during the PET scanning interval divided by the duration of the PET scanning interval.
Measured: Part I, Period 1 post telcagepant, at ~0-90 minutes after [11C]MK-4232 dose
Brain CGRP RO Post Telcagepant Obtained by PET Imaging Using [11C]MK-4232 Tracer at Baseline and After a Therapeutic Dose of Telcagepant (140 mg) in Healthy Participants (Part I, Period 2)
Brain CGRP RO post telcagepant was determined by change in [11C]MK-4232 PET tracer biokinetics at baseline and post telcagepant administration. Using PET brain images acquired over ~0-90 miniutes after [11C]MK-4232 dose, ROIs were drawn throughout the cerebral cortex and white matter, striatum, thalamus, cerebellum and pons. The ROIs were projected onto all frames of the dynamic PET scans in order to generate [11C]MK-4232 tissue TACs. Serial arterial blood samples for measurement of plasma radioactivity and [11C]MK-4232 concentrations were collected during the PET scans. These samples provided the arterial input function for a two-tissue compartmental model of [11C]MK-4232 tracer biokinetics. VT, an index of receptor density, was estimated by fitting the two-tissue compartmental model to the PET [11C]MK-4232 TACs. The change in VT between the baseline and post telcagepant PET studies was used to quantify the brain CGRP RO.
Measured: Part I Baseline, at ~0-90 minutes after [11C]MK-4232 dose; and Part I, Period 2 post telcagepant, at ~0-90 minutes after [11C]MK-4232 dose
Average Telcagepant Plasma Concentration During PET Imaging Using [11C]MK-4232 Tracer After a Therapeutic Dose of Telcagepant (140 mg) in Healthy Participants (Part I, Period 2)
In Part I, Period 2 blood samples for determination of plasma telcagepant concentrations were obtained prior to the telcagepant dose (time 0) and at 1, 2, 3 and 4 hours post telcagepant dose. The average plasma telcagepant concentration during the PET scan was determined, calculated as the area under the plasma telcagepant concentration versus time curve during the PET scanning interval divided by the duration of the PET scanning interval.
Measured: Part 1, Period 2 post telcagepant, at ~0-90 minutes after [11C]MK-4232 dose
Brain CGRP RO Post Telcagepant Obtained by PET Imaging Using [11C]MK-4232 Tracer at Baseline and After a Therapeutic Dose of Telcagepant (140 mg) in Participants With Migraine During a Migraine Attack (Ictal Phase)(Part III, Period 1)
Brain CGRP RO post telcagepant was determined by change in [11C]MK-4232 PET tracer biokinetics at baseline and post telcagepant administration. Using PET brain images acquired over ~0-90 minutes after [11C]MK-4232 dose, ROIs were drawn throughout the cerebral cortex and white matter, striatum, thalamus, cerebellum and pons. The ROIs were projected onto all frames of the dynamic PET scans in order to generate [11C]MK-4232 tissue TACs. Serial arterial blood samples for measurement of plasma radioactivity and [11C]MK-4232 concentrations were collected during the PET scans. These samples provided the arterial input function for a two-tissue compartmental model of [11C]MK-4232 tracer biokinetics. VT, an index of receptor density, was estimated by fitting the two-tissue compartmental model to the PET [11C]MK-4232 TACs. The change in VT between the baseline and post telcagepant PET studies was used to quantify the brain CGRP RO.
Measured: Part III, Period 1 Baseline, at ~0-90 minutes after [11C]MK-4232 dose; and Part III, Period 1 post telcagepant, at ~0-90 minutes after [11C]MK-4232 dose
Brain CGRP RO Post Telcagepant Obtained by PET Imaging Using [11C]MK-4232 Tracer at Baseline and After a Therapeutic Dose of Telcagepant (140 mg) in Participants With Migraine During Period When Migraine is Absent (Interictal Phase)(Part III, Period 2)
Brain CGRP RO post telcagepant was determined by change in [11C]MK-4232 PET tracer biokinetics at baseline and post telcagepant administration. Using PET brain images acquired over ~0-90 minutes after [11C]MK-4232 dose, ROIs were drawn throughout the cerebral cortex and white matter, striatum, thalamus, cerebellum and pons. The ROIs were projected onto all frames of the dynamic PET scans in order to generate [11C]MK-4232 tissue TACs. Serial arterial blood samples for measurement of plasma radioactivity and [11C]MK-4232 concentrations were collected during the PET scans. These samples provided the arterial input function for a two-tissue compartmental model of [11C]MK-4232 tracer biokinetics. VT, an index of receptor density, was estimated by fitting the two-tissue compartmental model to the PET [11C]MK-4232 TACs. The change in VT between the baseline and post telcagepant PET studies was used to quantify the brain CGRP RO.
Measured: Part III, Period 2 Baseline, at ~0-90 minutes after [11C]MK-4232 dose; and Part III, Period 2 post telcagepant, at ~0-90 minutes after [11C]MK-4232 dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2011 (estimated)
- Study start14 Jan 2010
- Primary completion26 Jul 2011
- Study completion26 Jul 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MigraineStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01315847
- Sponsor's protocol ID
- 0974-067
- Status last verified
- Mar 2019
- First submitted
- 22 Feb 2011
- Last updated
- 2 Apr 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Publications
Hostetler ED, Joshi AD, Sanabria-Bohorquez S, Fan H, Zeng Z, Purcell M, Gantert L, Riffel K, Williams M, O'Malley S, Miller P, Selnick HG, Gallicchio SN, Bell IM, Salvatore CA, Kane SA, Li CC, Hargreaves RJ, de Groot T, Bormans G, Van Hecken A, Derdelinckx I, de Hoon J, Reynders T, Declercq R, De Lepeleire I, Kennedy WP, Blanchard R, Marcantonio EE, Sur C, Cook JJ, Van Laere K, Evelhoch JL. In vivo quantification of calcitonin gene-related peptide receptor occupancy by telcagepant in rhesus monkey and human brain using the positron emission tomography tracer [11C]MK-4232. J Pharmacol Exp Ther. 2013 Nov;347(2):478-86. doi: 10.1124/jpet.113.206458. Epub 2013 Aug 23.
PubMed 23975906
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01315847
- Acronym / sponsor ID
- 0974-067
- Conditions
- Migraine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 14 Jan 2010 (actual)
- Primary completion
- 26 Jul 2011 (actual)
- Study completion
- 26 Jul 2011 (actual)
- First posted
- 15 Mar 2011 (estimated)
- Results
- Posted 24 Oct 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
For the 1120 mg (i.e., maximal) telcagepant dose, [11C]MK-4232 was administered and PET scan was started ~3 hours post telcagepant to coincide with the Tmax of the 1120 mg dose. For the 140 mg (i.e., therapeutic) telcagepant dose, [11C]MK-4232 was administered and PET scan was started ~2 hours post telcagepant to correspond with the timing of clinical efficacy measurements of telcagepant for migraine treatment in Phase III studies.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Healthy Participants (Part I) | Experimental | Drug: telcagepant, Drug: [11C]MK-4232Baseline PET imaging of the brain using [11C]MK-4232 tracer (~300 megabecquerel [MBq]) was performed in healthy participants; this PET data served as the baseline for both Period 1 and 2 of Part I. Subsequently in study Part I, Period 1 the healthy participants received a single 1120 mg dose of telcagepant followed by PET imaging of brain with [11C]MK-4232 tracer (~300 MBq) beginning ~3 hours post telcagepant dose. In Part I, Period 2 the healthy participants received a single 140 mg dose of telcagepant followed by PET imaging of brain with [11C]MK-4232 tracer (~300 MBq) beginning ~2 hours post telcagepant dose. Interval between Part I Period 1 and 2 was to be at least 1 week. |
| Participants with Migraine (Part III) | Experimental | Drug: telcagepant, Drug: [11C]MK-4232In study Part III, Period 1 baseline PET imaging of the brain using [11C]MK-4232 tracer (~300 MBq) was performed in participants with migraine during a migraine attack (ictal phase). Later in Part III, Period 1 the participants with an ongoing migraine attack (ictal phase) received a single 140 mg dose of telcagepant followed by PET imaging of brain with [11C]MK-4232 tracer (~300 MBq) beginning ~2 hours post telcagepant dose. In Part III, Period 2 baseline PET imaging of the brain using [11C]MK-4232 tracer (~300 MBq) was performed in participants with migraine, however, without a migraine attack ongoing (interictal phase). Later in Part III, Period 2 participants with migraine without a migraine attack ongoing (interictal phase) received a single 140 mg dose of telcagepant followed by PET imaging of brain with [11C]MK-4232 tracer (~300 MBq) beginning ~2 hours post telcagepant dose. Interval between Part III Period 1 and 2 was to be at least 1 week. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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)
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| telcagepantAlso: MK-0974Single oral doses of telcagepant 1120 mg (Part I - Period 1) and 140 mg (Part I - Period 2; Part III - Period 1 and 2) | Drug | Healthy Participants (Part I), Participants with Migraine (Part III) |
| [11C]MK-4232Single 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) | Drug | Healthy Participants (Part I), Participants with Migraine (Part III) |
Primary outcome
Number of Participants With Adverse Events (AEs) (Part I)
Time frame: Up 14 days after the last dose of telcagepant and/or [11C]MK-4232 in Part I of study (Up to approximately 14 weeks)
Any AEs occurring among participants (all were healthy subjects) in Part I of study were recorded. An AE was defined as any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration, whether or not considered related to the study drug. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the administration of the study drug, was also an AE.
Number of Participants With AEs (Part III)
Time frame: Up 14 days after the last dose of telcagepant and/or [11C]MK-4232 in Part III of study (Up to approximately 6 months)
Any AEs occurring among participants (all were migraine patients) in Part III of study were recorded. An AE was defined as any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration, whether or not considered related to the study drug. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the administration of the study drug, was also an AE.
Brain Calcitonin Gene-related Peptide (CGRP) Receptor Occupancy (RO) Post Telcagepant Obtained by PET Imaging Using [11C]MK-4232 Tracer at Baseline and After a Maximum Dose of Telcagepant (1120 mg) in Healthy Participants (Part I, Period 1)
Time frame: Part I Baseline, at ~0-90 minutes after [11C]MK-4232 dose; and Part I, Period 1 post telcagepant, at ~0-90 minutes after [11C]MK-4232 dose
Brain CGRP RO post telcagepant was determined by change in [11C]MK-4232 PET tracer biokinetics at baseline and post telcagepant administration. Using PET brain images acquired over ~0-90 minutes after [11C]MK-4232 dose, regions of interest (ROIs) were drawn throughout cerebral cortex and white matter, striatum, thalamus, cerebellum and pons. The ROIs were projected onto all frames of the dynamic PET scans in order to generate [11C]MK-4232 tissue time-activity curves (TACs). Serial arterial blood samples for measurement of plasma radioactivity and [11C]MK-4232 concentrations were collected during the PET scans. These samples provided the arterial input function for a two-tissue compartmental model of [11C]MK-4232 tracer biokinetics. Total volume of distribution (VT), an index of receptor density, was estimated by fitting the two-tissue compartmental model to the PET [11C]MK-4232 TACs. Change in VT between baseline and post telcagepant PET studies was used to quantify the brain CGRP RO.
Average Telcagepant Plasma Concentration During PET Imaging Using [11C]MK-4232 Tracer After a Maximum Dose of Telcagepant (1120 mg) in Healthy Participants (Part I, Period 1)
Time frame: Part I, Period 1 post telcagepant, at ~0-90 minutes after [11C]MK-4232 dose
In Part I, Period 1 blood samples for determination of plasma telcagepant concentrations were obtained prior to the telcagepant dose (time 0) and at 2, 3, 4 and 5 hours post telcagepant dose. The average plasma telcagepant concentration during the PET scan was determined, calculated as the area under the plasma telcagepant concentration versus time curve during the PET scanning interval divided by the duration of the PET scanning interval.
Brain CGRP RO Post Telcagepant Obtained by PET Imaging Using [11C]MK-4232 Tracer at Baseline and After a Therapeutic Dose of Telcagepant (140 mg) in Healthy Participants (Part I, Period 2)
Time frame: Part I Baseline, at ~0-90 minutes after [11C]MK-4232 dose; and Part I, Period 2 post telcagepant, at ~0-90 minutes after [11C]MK-4232 dose
Brain CGRP RO post telcagepant was determined by change in [11C]MK-4232 PET tracer biokinetics at baseline and post telcagepant administration. Using PET brain images acquired over ~0-90 miniutes after [11C]MK-4232 dose, ROIs were drawn throughout the cerebral cortex and white matter, striatum, thalamus, cerebellum and pons. The ROIs were projected onto all frames of the dynamic PET scans in order to generate [11C]MK-4232 tissue TACs. Serial arterial blood samples for measurement of plasma radioactivity and [11C]MK-4232 concentrations were collected during the PET scans. These samples provided the arterial input function for a two-tissue compartmental model of [11C]MK-4232 tracer biokinetics. VT, an index of receptor density, was estimated by fitting the two-tissue compartmental model to the PET [11C]MK-4232 TACs. The change in VT between the baseline and post telcagepant PET studies was used to quantify the brain CGRP RO.
Average Telcagepant Plasma Concentration During PET Imaging Using [11C]MK-4232 Tracer After a Therapeutic Dose of Telcagepant (140 mg) in Healthy Participants (Part I, Period 2)
Time frame: Part 1, Period 2 post telcagepant, at ~0-90 minutes after [11C]MK-4232 dose
In Part I, Period 2 blood samples for determination of plasma telcagepant concentrations were obtained prior to the telcagepant dose (time 0) and at 1, 2, 3 and 4 hours post telcagepant dose. The average plasma telcagepant concentration during the PET scan was determined, calculated as the area under the plasma telcagepant concentration versus time curve during the PET scanning interval divided by the duration of the PET scanning interval.
Brain CGRP RO Post Telcagepant Obtained by PET Imaging Using [11C]MK-4232 Tracer at Baseline and After a Therapeutic Dose of Telcagepant (140 mg) in Participants With Migraine During a Migraine Attack (Ictal Phase)(Part III, Period 1)
Time frame: Part III, Period 1 Baseline, at ~0-90 minutes after [11C]MK-4232 dose; and Part III, Period 1 post telcagepant, at ~0-90 minutes after [11C]MK-4232 dose
Brain CGRP RO post telcagepant was determined by change in [11C]MK-4232 PET tracer biokinetics at baseline and post telcagepant administration. Using PET brain images acquired over ~0-90 minutes after [11C]MK-4232 dose, ROIs were drawn throughout the cerebral cortex and white matter, striatum, thalamus, cerebellum and pons. The ROIs were projected onto all frames of the dynamic PET scans in order to generate [11C]MK-4232 tissue TACs. Serial arterial blood samples for measurement of plasma radioactivity and [11C]MK-4232 concentrations were collected during the PET scans. These samples provided the arterial input function for a two-tissue compartmental model of [11C]MK-4232 tracer biokinetics. VT, an index of receptor density, was estimated by fitting the two-tissue compartmental model to the PET [11C]MK-4232 TACs. The change in VT between the baseline and post telcagepant PET studies was used to quantify the brain CGRP RO.
Brain CGRP RO Post Telcagepant Obtained by PET Imaging Using [11C]MK-4232 Tracer at Baseline and After a Therapeutic Dose of Telcagepant (140 mg) in Participants With Migraine During Period When Migraine is Absent (Interictal Phase)(Part III, Period 2)
Time frame: Part III, Period 2 Baseline, at ~0-90 minutes after [11C]MK-4232 dose; and Part III, Period 2 post telcagepant, at ~0-90 minutes after [11C]MK-4232 dose
Brain CGRP RO post telcagepant was determined by change in [11C]MK-4232 PET tracer biokinetics at baseline and post telcagepant administration. Using PET brain images acquired over ~0-90 minutes after [11C]MK-4232 dose, ROIs were drawn throughout the cerebral cortex and white matter, striatum, thalamus, cerebellum and pons. The ROIs were projected onto all frames of the dynamic PET scans in order to generate [11C]MK-4232 tissue TACs. Serial arterial blood samples for measurement of plasma radioactivity and [11C]MK-4232 concentrations were collected during the PET scans. These samples provided the arterial input function for a two-tissue compartmental model of [11C]MK-4232 tracer biokinetics. VT, an index of receptor density, was estimated by fitting the two-tissue compartmental model to the PET [11C]MK-4232 TACs. The change in VT between the baseline and post telcagepant PET studies was used to quantify the brain CGRP RO.
Results and safety
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Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 23975906Hostetler ED, Joshi AD, Sanabria-Bohorquez S, Fan H, Zeng Z, Purcell M, Gantert L, Riffel K, Williams M, O'Malley S, Miller P, Selnick HG, Gallicchio SN, Bell IM, Salvatore CA, Kane SA, Li CC, Hargreaves RJ, de Groot T, Bormans G, Van Hecken A, Derdelinckx I, de Hoon J, Reynders T, Declercq R, De Lepeleire I, Kennedy WP, Blanchard R, Marcantonio EE, Sur C, Cook JJ, Van Laere K, Evelhoch JL. In vivo quantification of calcitonin gene-related peptide receptor occupancy by telcagepant in rhesus monkey and human brain using the positron emission tomography tracer [11C]MK-4232. J Pharmacol Exp Ther. 2013 Nov;347(2):478-86. doi: 10.1124/jpet.113.206458. Epub 2013 Aug 23.
- Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Merck Sharp & Dohme LLC
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing telcagepant and [11C]MK-4232 in people with Migraine, run by Merck Sharp & Dohme LLC.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Oct 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Adverse Events (AEs) (Part I) (time frame: Up 14 days after the last dose of telcagepant and/or [11C]MK-4232 in Part I of study (Up to approximately 14 weeks)). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01315847, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Apr 2019.