Trial Outcomes & Findings for Positron Emission Tomography (PET) Study of Brain Calcitonin Gene-Related Peptide (CGRP) Receptor Occupancy After Telcagepant Administration (MK-0974-067) (NCT NCT01315847)

Last Updated: 2019-04-02

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

10 participants

Primary outcome timeframe

Up 14 days after the last dose of telcagepant and/or [11C]MK-4232 in Part I of study (Up to approximately 14 weeks)

Results posted on

2019-04-02

Participant Flow

Due to protocol amendment study Part II was not conducted. One subject who started in Part I, Period 2 had not participated in Part I, Period 1. Therefore, the cumulative total number who started Part I (including those starting in Period 1 and 2) is 6. Study participants were included in either Part I or Part III; none were included in both parts.

Participant milestones

Participant milestones
Measure	Telcagepant and [11C]MK-4232 (Part I): Healthy Participants Baseline positron emission tomography (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.	Telcagepant and [11C]MK-4232 (Part III): Migraineurs 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.
Part I, Period 1 STARTED	5	0
Part I, Period 1 Received Telcagepant	5	0
Part I, Period 1 Received [11C]MK-4232	5	0
Part I, Period 1 COMPLETED	2	0
Part I, Period 1 NOT COMPLETED	3	0
Part I, Period 2 STARTED	3	0
Part I, Period 2 Received Telcagepant	3	0
Part I, Period 2 Received [11C]MK-4232	3	0
Part I, Period 2 COMPLETED	3	0
Part I, Period 2 NOT COMPLETED	0	0
Part III, Period 1 STARTED	0	4
Part III, Period 1 Received Telcagepant	0	4
Part III, Period 1 Received [11C]MK-4232	0	4
Part III, Period 1 COMPLETED	0	3
Part III, Period 1 NOT COMPLETED	0	1
Part III, Period 2 STARTED	0	3
Part III, Period 2 Received Telcagepant	0	3
Part III, Period 2 Received [11C]MK-4232	0	3
Part III, Period 2 COMPLETED	0	3
Part III, Period 2 NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Telcagepant and [11C]MK-4232 (Part I): Healthy Participants Baseline positron emission tomography (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.	Telcagepant and [11C]MK-4232 (Part III): Migraineurs 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.
Part I, Period 1 Reached maximum number of arterial lines	3	0
Part III, Period 1 [11C]MK-4232 synthesis failure	0	1

Baseline Characteristics

Positron Emission Tomography (PET) Study of Brain Calcitonin Gene-Related Peptide (CGRP) Receptor Occupancy After Telcagepant Administration (MK-0974-067)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Telcagepant and [11C]MK-4232 (Part I): Healthy Participants n=6 Participants Baseline PET imaging of the brain using \[11C\]MK-4232 tracer (\~300 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.	Telcagepant and [11C]MK-4232 (Part III): Migraineurs n=4 Participants 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.	Total n=10 Participants Total of all reporting groups
Age, Continuous	32.50 years STANDARD_DEVIATION 10.63 • n=5 Participants	37.75 years STANDARD_DEVIATION 13.20 • n=7 Participants	34.60 years STANDARD_DEVIATION 11.33 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	0 Participants n=7 Participants	6 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up 14 days after the last dose of telcagepant and/or [11C]MK-4232 in Part I of study (Up to approximately 14 weeks)

Population: All participants who received at least one dose of study medication (telcagepant and/or \[11C\]MK-4232) in Part I of study.

Outcome measures

Outcome measures
Measure	Telcagepant and [11C]MK-4232 (Part I): Healthy Participants n=6 Participants Baseline PET imaging of the brain using \[11C\]MK-4232 tracer (\~300 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.
Number of Participants With Adverse Events (AEs) (Part I)	4 participants

PRIMARY outcome

Timeframe: Up 14 days after the last dose of telcagepant and/or [11C]MK-4232 in Part III of study (Up to approximately 6 months)

Population: All participants who received at least one dose of study medication (telcagepant and/or \[11C\]MK-4232) in Part III of study.

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.

Outcome measures

Outcome measures
Measure	Telcagepant and [11C]MK-4232 (Part I): Healthy Participants n=4 Participants Baseline PET imaging of the brain using \[11C\]MK-4232 tracer (\~300 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.
Number of Participants With AEs (Part III)	4 participants

PRIMARY outcome

Timeframe: 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

Population: Participants who received both telcagepant and \[11C\]MK-4232 during Part I, Period 1 of study, had evaluable data and were compliant with the the study protocol

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.

Outcome measures

Outcome measures
Measure	Telcagepant and [11C]MK-4232 (Part I): Healthy Participants n=3 Participants Baseline PET imaging of the brain using \[11C\]MK-4232 tracer (\~300 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.
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) Subject 04	43 percent CGRP RO
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) Subject 01	48 percent CGRP RO
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) Subject 103	58 percent CGRP RO

PRIMARY outcome

Timeframe: Part I, Period 1 post telcagepant, at ~0-90 minutes after [11C]MK-4232 dose

Population: Participants who received both telcagepant and \[11C\]MK-4232 during Part I, Period 1 of study, had evaluable data and were compliant with the the study protocol

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.

Outcome measures

Outcome measures
Measure	Telcagepant and [11C]MK-4232 (Part I): Healthy Participants n=3 Participants Baseline PET imaging of the brain using \[11C\]MK-4232 tracer (\~300 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.
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) Subject 04	16.3 μM Standard Deviation 1.84
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) Subject 01	20.2 μM Standard Deviation 3.93
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) Subject 103	22.2 μM Standard Deviation 4.43

PRIMARY outcome

Timeframe: 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

Population: Participants who received both telcagepant and \[11C\]MK-4232 during Part I, Period 2 of study, had evaluable data and were compliant with the the study protocol

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.

Outcome measures

Outcome measures
Measure	Telcagepant and [11C]MK-4232 (Part I): Healthy Participants n=3 Participants Baseline PET imaging of the brain using \[11C\]MK-4232 tracer (\~300 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.
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) Subject 02	5 percent 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 Healthy Participants (Part I, Period 2) Subject 04	10 percent 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 Healthy Participants (Part I, Period 2) Subject 101	4 percent CGRP RO

PRIMARY outcome

Timeframe: Part 1, Period 2 post telcagepant, at ~0-90 minutes after [11C]MK-4232 dose

Population: Participants who received both telcagepant and \[11C\]MK-4232 during Part I, Period 2 of study, had evaluable data and were compliant with the the study protocol

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.

Outcome measures

Outcome measures
Measure	Telcagepant and [11C]MK-4232 (Part I): Healthy Participants n=3 Participants Baseline PET imaging of the brain using \[11C\]MK-4232 tracer (\~300 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.
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) Subject 02	0.254 μM Standard Deviation 0.140
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) Subject 04	0.859 μM Standard Deviation 0.305
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) Subject 101	0.424 μM Standard Deviation 0.187

PRIMARY outcome

Timeframe: 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

Population: Results could not be obtained for this measure. For Part III data, the curve fits were unsatisfactory (model curves did not pass through the TAC data points) precluding the quantification of the VT and RO

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.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

Adverse Events

Telcagepant and [11C]MK-4232 (Part I): Healthy Participants

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Telcagepant and [11C]MK-4232 (Part III): Migraineurs

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission. Sponsor review can be expedited to meet publication timelines.
Publication restrictions are in place

Restriction type: OTHER

Measure	Telcagepant and [11C]MK-4232 (Part I): Healthy Participants n=6 participants at risk Baseline PET imaging of the brain using \[11C\]MK-4232 tracer (\~300 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.	Telcagepant and [11C]MK-4232 (Part III): Migraineurs n=4 participants at risk 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.
Cardiac disorders Sinus tachycardia	0.00% 0/6 • Up 14 days after the last dose of telcagepant and/or [11C]MK-4232 (Up to approximately 14 weeks for Part I, Up to approximately 6 months for Part III)	25.0% 1/4 • Number of events 1 • Up 14 days after the last dose of telcagepant and/or [11C]MK-4232 (Up to approximately 14 weeks for Part I, Up to approximately 6 months for Part III)
Eye disorders Eye pruritus	16.7% 1/6 • Number of events 1 • Up 14 days after the last dose of telcagepant and/or [11C]MK-4232 (Up to approximately 14 weeks for Part I, Up to approximately 6 months for Part III)	0.00% 0/4 • Up 14 days after the last dose of telcagepant and/or [11C]MK-4232 (Up to approximately 14 weeks for Part I, Up to approximately 6 months for Part III)
Eye disorders Ocular hyperaemia	16.7% 1/6 • Number of events 1 • Up 14 days after the last dose of telcagepant and/or [11C]MK-4232 (Up to approximately 14 weeks for Part I, Up to approximately 6 months for Part III)	0.00% 0/4 • Up 14 days after the last dose of telcagepant and/or [11C]MK-4232 (Up to approximately 14 weeks for Part I, Up to approximately 6 months for Part III)
Gastrointestinal disorders Abdominal pain upper	0.00% 0/6 • Up 14 days after the last dose of telcagepant and/or [11C]MK-4232 (Up to approximately 14 weeks for Part I, Up to approximately 6 months for Part III)	25.0% 1/4 • Number of events 1 • Up 14 days after the last dose of telcagepant and/or [11C]MK-4232 (Up to approximately 14 weeks for Part I, Up to approximately 6 months for Part III)
General disorders General physical health deterioration	16.7% 1/6 • Number of events 1 • Up 14 days after the last dose of telcagepant and/or [11C]MK-4232 (Up to approximately 14 weeks for Part I, Up to approximately 6 months for Part III)	0.00% 0/4 • Up 14 days after the last dose of telcagepant and/or [11C]MK-4232 (Up to approximately 14 weeks for Part I, Up to approximately 6 months for Part III)
Infections and infestations Cystitis	0.00% 0/6 • Up 14 days after the last dose of telcagepant and/or [11C]MK-4232 (Up to approximately 14 weeks for Part I, Up to approximately 6 months for Part III)	25.0% 1/4 • Number of events 2 • Up 14 days after the last dose of telcagepant and/or [11C]MK-4232 (Up to approximately 14 weeks for Part I, Up to approximately 6 months for Part III)
Infections and infestations Nasopharyngitis	0.00% 0/6 • Up 14 days after the last dose of telcagepant and/or [11C]MK-4232 (Up to approximately 14 weeks for Part I, Up to approximately 6 months for Part III)	25.0% 1/4 • Number of events 1 • Up 14 days after the last dose of telcagepant and/or [11C]MK-4232 (Up to approximately 14 weeks for Part I, Up to approximately 6 months for Part III)
Investigations Blood urine present	0.00% 0/6 • Up 14 days after the last dose of telcagepant and/or [11C]MK-4232 (Up to approximately 14 weeks for Part I, Up to approximately 6 months for Part III)	25.0% 1/4 • Number of events 1 • Up 14 days after the last dose of telcagepant and/or [11C]MK-4232 (Up to approximately 14 weeks for Part I, Up to approximately 6 months for Part III)
Investigations White blood cells urine positive	0.00% 0/6 • Up 14 days after the last dose of telcagepant and/or [11C]MK-4232 (Up to approximately 14 weeks for Part I, Up to approximately 6 months for Part III)	50.0% 2/4 • Number of events 3 • Up 14 days after the last dose of telcagepant and/or [11C]MK-4232 (Up to approximately 14 weeks for Part I, Up to approximately 6 months for Part III)
Musculoskeletal and connective tissue disorders Back pain	16.7% 1/6 • Number of events 2 • Up 14 days after the last dose of telcagepant and/or [11C]MK-4232 (Up to approximately 14 weeks for Part I, Up to approximately 6 months for Part III)	0.00% 0/4 • Up 14 days after the last dose of telcagepant and/or [11C]MK-4232 (Up to approximately 14 weeks for Part I, Up to approximately 6 months for Part III)
Nervous system disorders Headache	33.3% 2/6 • Number of events 2 • Up 14 days after the last dose of telcagepant and/or [11C]MK-4232 (Up to approximately 14 weeks for Part I, Up to approximately 6 months for Part III)	50.0% 2/4 • Number of events 3 • Up 14 days after the last dose of telcagepant and/or [11C]MK-4232 (Up to approximately 14 weeks for Part I, Up to approximately 6 months for Part III)
Nervous system disorders Migraine	0.00% 0/6 • Up 14 days after the last dose of telcagepant and/or [11C]MK-4232 (Up to approximately 14 weeks for Part I, Up to approximately 6 months for Part III)	100.0% 4/4 • Number of events 17 • Up 14 days after the last dose of telcagepant and/or [11C]MK-4232 (Up to approximately 14 weeks for Part I, Up to approximately 6 months for Part III)
Nervous system disorders Presyncope	0.00% 0/6 • Up 14 days after the last dose of telcagepant and/or [11C]MK-4232 (Up to approximately 14 weeks for Part I, Up to approximately 6 months for Part III)	25.0% 1/4 • Number of events 1 • Up 14 days after the last dose of telcagepant and/or [11C]MK-4232 (Up to approximately 14 weeks for Part I, Up to approximately 6 months for Part III)
Psychiatric disorders Insomnia	16.7% 1/6 • Number of events 1 • Up 14 days after the last dose of telcagepant and/or [11C]MK-4232 (Up to approximately 14 weeks for Part I, Up to approximately 6 months for Part III)	0.00% 0/4 • Up 14 days after the last dose of telcagepant and/or [11C]MK-4232 (Up to approximately 14 weeks for Part I, Up to approximately 6 months for Part III)
Respiratory, thoracic and mediastinal disorders Dysphonia	16.7% 1/6 • Number of events 1 • Up 14 days after the last dose of telcagepant and/or [11C]MK-4232 (Up to approximately 14 weeks for Part I, Up to approximately 6 months for Part III)	0.00% 0/4 • Up 14 days after the last dose of telcagepant and/or [11C]MK-4232 (Up to approximately 14 weeks for Part I, Up to approximately 6 months for Part III)
Skin and subcutaneous tissue disorders Ecchymosis	0.00% 0/6 • Up 14 days after the last dose of telcagepant and/or [11C]MK-4232 (Up to approximately 14 weeks for Part I, Up to approximately 6 months for Part III)	50.0% 2/4 • Number of events 2 • Up 14 days after the last dose of telcagepant and/or [11C]MK-4232 (Up to approximately 14 weeks for Part I, Up to approximately 6 months for Part III)