A Dose-Finding Study of MK-1602 in the Treatment of Acute Migraine (MK-1602-006)

A Phase IIb, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Dose-Finding Study of MK-1602 in the Treatment of Acute Migraine

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01613248

Enrollment

834

Registered

2012-06-07

Start date

2012-07-01

Completion date

2012-12-01

Last updated

2019-01-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Migraine

Brief summary

The purpose of this study is to assess the effectiveness, safety and tolerability of a range of doses of MK-1602 versus placebo in the treatment of acute migraine.

Interventions

DRUGMK-1602

Single 1, 10, 25, 50 or 100 mg dose of MK-1602 taken at onset of migraine of moderate or severe intensity. Dosage form is film coated tablet for oral administration. Dose is provided to participants as a blinded bottle of tablets packaged to achieve the various MK-1602 dose levels to be studied. Participants will be instructed to take all study medication from the bottle when they treat their migraine headache.

DRUGPlacebo-matching MK-1602

Single administration of placebo-matching MK-1602 taken at onset of migraine of moderate or severe intensity. Dosage form is film coated tablet for oral administration. Dose is provided to participants as a blinded bottle of tablets packaged to achieve placebo study medication. Participants will be instructed to take all study medication from the bottle when they treat their migraine headache.

DRUGRescue medication

If moderate or severe migraine headache pain continues 2 hours after dose of study medication or if migraine headache comes back within 48 hours, Participants will be allowed to take their own rescue migraine medication, which may include analgesics (e.g., nonsteroidal anti-inflammatory drugs \[NSAIDs\]), anti-emetics, triptans or other medication not explicitly excluded.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

Inclusion criteria

* \> 1 year history of migraine with or without aura as defined by International Headache Society (IHS) criteria 1.1 and/or 1.2 * Migraines typically last between 4 to 72 hours, if untreated * ≥ 2 and ≤ 8 moderate or severe migraine attacks per month in each of the two months prior to screening * Male, female who is not of reproductive potential, or female of reproductive potential with a screening serum β-human chorionic gonadotropin (β-hCG) level consistent with a not-pregnant state, and who agrees to use acceptable contraception

Exclusion criteria

* Pregnant or breast-feeding, or is a female expecting to conceive within the projected duration of study participation * Participant has difficulty distinguishing his/her migraine attacks from tension-type headaches * History of predominantly mild migraine attacks or migraines that usually resolve spontaneously in less than two hours * 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 three months prior to screening * Basilar-type or hemiplegic migraine headache * \> 50 years old at age of migraine onset * Taking migraine prophylactic medication where the prescribed daily dose has changed during the 3 months prior to screening and will not be changed during the study * Taking a proton pump inhibitor (PPI) or a histamine receptor 2 (H2) blocker on a daily or near daily basis (\> 3 days per week) * Taking the following medications from 1 month prior to screening through study period: potent cytochrome P450 (CYP) 3A4 inhibitors (e.g., cyclosporine, itraconazole, ketoconazole, fluconazole, erythromycin, clarithromycin, nefazodone, telithromycin, cimetidine, quinine, diltiazem, verapamil, and human immunodeficiency virus \[HIV\] protease inhibitors), moderate or marked CYP3A4 inducers (e.g., rifampicin, rifabutin, barbiturates \[e.g., phenobarbital and primidone\], systemic glucocorticoids, nevirapine, efavirenz, pioglitazone, carbamazepine, phenytoin, and St. Johns wort), or drugs with narrow therapeutic margins and potential for drug interactions in the CYP2C family (e.g., warfarin) * Participant is unable to refrain from consumption of grapefruit or grapefruit juice during study * History of hypersensitivity to, or has experienced a serious adverse event in response to 3 or more classes of drugs (prescription and over-the-counter) * Clinical or laboratory evidence of uncontrolled diabetes, human immunodeficiency virus (HIV) disease, or significant pulmonary, renal, hepatic, endocrine, or other systemic disease * Other confounding pain syndromes, psychiatric conditions such as uncontrolled major depression, dementia or significant neurological disorders other than migraine. Patients who are currently being treated with non-prohibited medication for depression and symptoms are well controlled are eligible to participate * Participant is at imminent risk of self-harm * History of malignancy ≤ 5 years prior to study, except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer * History of gastric or small intestinal surgery (including gastric bypass surgery or banding), or presence of a disease that causes malabsorption * Participant has recent history (within the last year) of drug or alcohol abuse or dependence or is a user of recreational or illicit drugs * Participant is legally or mentally incapacitated * Donation of blood products or phlebotomy of \> 300 ml within 8 weeks of study, or intent to donate blood products or receive blood products within 30 days of screening and throughout study * Intent to donate eggs or sperm within the projected duration of the study * Current participation in or participation within 30 days of screening in a study with an investigational compound or device * Previous exposure to MK-0974 and/or MK-3207 * Use within the past 2 months of an opioid- or barbiturate-containing analgesic for migraine relief * Inpatient or emergency department treatment of an acute migraine attack within the past 2 months

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants Reporting Pain Freedom (PF) at 2 Hours Post-Dose	2 hours post-dose	PF was defined as a reduction in headache severity from Grade 2 or 3 at Baseline to Grade 0. Headache severity was reported by the participant using a 4-point scale where: 0=no pain, 1=mild pain, 2=moderate pain and 3=severe pain.
Percentage of Participants Reporting Pain Relief (PR) at 2 Hours Post-Dose	2 hours post-dose	PR was defined as a reduction of a moderate or severe migraine headache (Grade 2 or 3) at Baseline to a mild headache or no headache (Grade 1 or 0) 2 hours post-dose. Headache severity was reported by the participant using a 4-point scale where: 0=no pain, 1=mild pain, 2=moderate pain and 3=severe pain.
Number of Participants With One or More Adverse Events Within 48 Hours Post-Dose	Up to 48 hours post-dose	An AE is any unfavorable and unintended change in the structure (signs), function (symptoms), or chemistry (laboratory data) of the body temporally associated with any use of a sponsor product, whether or not considered related to the use of the product.
Number of Participants With One or More Adverse Events Within 14 Days Post-Dose	Up to 14 days post-dose	An AE is any unfavorable and unintended change in the structure (signs), function (symptoms), or chemistry (laboratory data) of the body temporally associated with any use of a sponsor product, whether or not considered related to the use of the product.
Number of Participants Who Discontinued From Study Due to Adverse Events	Up to 5 weeks post-dose	—

Secondary

Measure	Time frame	Description
Percentage of Participants Reporting Sustained Pain Relief (SPR) 2-24 Hours Post-Dose	2-24 hours post-dose	SPR was defined as PR at 2 hours post-dose, with no administration of any rescue medication and with no occurrence of a moderate/severe headache during the 24 hour period after dosing with study medication.
Percentage of Participants Reporting SPR 2-48 Hours Post-Dose	2-48 hours post-dose	SPR was defined as PR at 2 hours post-dose, with no administration of any rescue medication and with no occurrence of a moderate/severe headache during the 48 hour period after dosing with study medication.
Percentage of Participants Reporting Absence of Phonophobia at 2 Hours Post-Dose	2 hours post-dose	Phonophobia is sensitivity to loud sounds.
Percentage of Participants Reporting TMF at 2-24 Hours Post-Dose	2-24 hours post-dose	TMF at 2-24 hours post-dose was defined as SPF with no photophobia, phonophobia, nausea, or vomiting during the 2 to 24 hour period after dosing with study medication.
Percentage of Participants Reporting TMF at 2-48 Hours Post-Dose	2-48 hours post-dose	TMF at 2-48 hours post-dose was defined as SPF with no photophobia, phonophobia, nausea, or vomiting during the 2 to 48 hour period after dosing with study medication.
Percentage of Participants Reporting Total Migraine Freedom (TMF) at 2 Hours Post-Dose	2 hours post-dose	TMF at 2 hours post dose was defined as PF with no photophobia, phonophobia, nausea, or vomiting at 2 hours post-dose.
Percentage of Participant Reporting Absence of Photophobia at 2 Hours Post-Dose	2 hours post-dose	Photophobia is sensitivity to bright light.
Percentage of Participants Reporting Absence of Nausea at 2 Hours Post-Dose	2 hours post-dose	—
Percentage of Participants Reporting Sustained Pain Freedom (SPF) 2-24 Hours Post-Dose	2-24 hours post-dose	SPF was defined as PF at 2 hours post-dose, with no administration of any rescue medication and with no occurrence of a mild/moderate/severe headache during the 24 hour period after dosing with study medication.
Percentage of Participants Reporting SPF 2-48 Hours Post-Dose	2-48 hours post-dose	SPF was defined as PF at 2 hours post-dose, with no administration of any rescue medication and with no occurrence of a mild/moderate/severe headache during the 48 hour period after dosing with study medication.

Participant flow

Participants by arm

Arm	Count
Placebo Placebo-matching MK-1602 single dose as treatment for a moderate or severe migraine headache. After 2 hours participants were able to take rescue medication if necessary.	113
MK-1602 1 mg MK-1602 1 mg single dose as treatment for a moderate or severe migraine headache. After 2 hours participants were able to take rescue medication if necessary.	107
MK-1602 10 mg MK-1602 10 mg single dose as treatment for a moderate or severe migraine headache. After 2 hours participants were able to take rescue medication if necessary.	108
MK-1602 25 mg MK-1602 25 mg single dose as treatment for a moderate or severe migraine headache. After 2 hours participants were able to take rescue medication if necessary.	104
MK-1602 50 mg MK-1602 50 mg single dose as treatment for a moderate or severe migraine headache. After 2 hours participants were able to take rescue medication if necessary.	106
MK-1602 100 mg MK-1602 100 mg single dose as treatment for a moderate or severe migraine headache. After 2 hours participants were able to take rescue medication if necessary.	102
Total	640

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004	FG005
Overall Study	Adverse Event	0	0	0	1	0	0
Overall Study	Lack of Qualifying Event	9	11	10	11	15	18
Overall Study	Lost to Follow-up	5	7	4	8	4	2
Overall Study	Physician Decision	8	8	9	4	7	6
Overall Study	Pregnancy	0	0	0	1	0	0
Overall Study	Study Terminated by Sponsor	4	6	8	8	9	11
Overall Study	Withdrawal by Subject	3	2	2	5	0	1

Baseline characteristics

Characteristic	Placebo	MK-1602 1 mg	MK-1602 10 mg	MK-1602 25 mg	MK-1602 50 mg	MK-1602 100 mg	Total
Age, Continuous	40.5 years STANDARD_DEVIATION 11.7	39.6 years STANDARD_DEVIATION 10.7	41.1 years STANDARD_DEVIATION 10.9	41.4 years STANDARD_DEVIATION 11.5	40.7 years STANDARD_DEVIATION 12.3	41.9 years STANDARD_DEVIATION 11	40.8 years STANDARD_DEVIATION 11.4
Age, Customized 20 to 29 years	18 participants	21 participants	19 participants	13 participants	19 participants	16 participants	106 participants
Age, Customized < 20 years	1 participants	1 participants	0 participants	2 participants	2 participants	0 participants	6 participants
Age, Customized 30 to 39 years	42 participants	29 participants	28 participants	32 participants	32 participants	26 participants	189 participants
Age, Customized 40 to 49 years	22 participants	36 participants	42 participants	33 participants	23 participants	33 participants	189 participants
Age, Customized 50 to 59 years	19 participants	17 participants	14 participants	16 participants	21 participants	23 participants	110 participants
Age, Customized 60 to 64 years	10 participants	2 participants	5 participants	8 participants	9 participants	3 participants	37 participants
Age, Customized >= 65 years	1 participants	1 participants	0 participants	0 participants	0 participants	1 participants	3 participants
Sex: Female, Male Female	99 Participants	95 Participants	92 Participants	91 Participants	92 Participants	90 Participants	559 Participants
Sex: Female, Male Male	14 Participants	12 Participants	16 Participants	13 Participants	14 Participants	12 Participants	81 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —	— / —	— / —
other Total, other adverse events	15 / 113	22 / 107	13 / 108	15 / 104	14 / 106	17 / 102
serious Total, serious adverse events	0 / 113	0 / 107	0 / 108	0 / 104	1 / 106	0 / 102

Outcome results

Primary

Number of Participants Who Discontinued From Study Due to Adverse Events

Time frame: Up to 5 weeks post-dose

Population: ASaT population included all randomized participants who received at least one dose of study treatment.

Arm	Measure	Value (NUMBER)
Placebo	Number of Participants Who Discontinued From Study Due to Adverse Events	0 participants
MK-1602 1 mg	Number of Participants Who Discontinued From Study Due to Adverse Events	0 participants
MK-1602 10 mg	Number of Participants Who Discontinued From Study Due to Adverse Events	0 participants
MK-1602 25 mg	Number of Participants Who Discontinued From Study Due to Adverse Events	0 participants
MK-1602 50 mg	Number of Participants Who Discontinued From Study Due to Adverse Events	0 participants
MK-1602 100 mg	Number of Participants Who Discontinued From Study Due to Adverse Events	0 participants

Primary

Number of Participants With One or More Adverse Events Within 14 Days Post-Dose

An AE is any unfavorable and unintended change in the structure (signs), function (symptoms), or chemistry (laboratory data) of the body temporally associated with any use of a sponsor product, whether or not considered related to the use of the product.

Time frame: Up to 14 days post-dose

Population: ASaT population included all randomized participants who received at least one dose of study treatment.

Arm	Measure	Value (NUMBER)
Placebo	Number of Participants With One or More Adverse Events Within 14 Days Post-Dose	33 participants
MK-1602 1 mg	Number of Participants With One or More Adverse Events Within 14 Days Post-Dose	37 participants
MK-1602 10 mg	Number of Participants With One or More Adverse Events Within 14 Days Post-Dose	32 participants
MK-1602 25 mg	Number of Participants With One or More Adverse Events Within 14 Days Post-Dose	24 participants
MK-1602 50 mg	Number of Participants With One or More Adverse Events Within 14 Days Post-Dose	30 participants
MK-1602 100 mg	Number of Participants With One or More Adverse Events Within 14 Days Post-Dose	32 participants

Primary

Number of Participants With One or More Adverse Events Within 48 Hours Post-Dose

Time frame: Up to 48 hours post-dose

Population: All Subjects as Treated (ASaT) population included all randomized participants who received at least one dose of study treatment.

Arm	Measure	Value (NUMBER)
Placebo	Number of Participants With One or More Adverse Events Within 48 Hours Post-Dose	28 participants
MK-1602 1 mg	Number of Participants With One or More Adverse Events Within 48 Hours Post-Dose	33 participants
MK-1602 10 mg	Number of Participants With One or More Adverse Events Within 48 Hours Post-Dose	29 participants
MK-1602 25 mg	Number of Participants With One or More Adverse Events Within 48 Hours Post-Dose	21 participants
MK-1602 50 mg	Number of Participants With One or More Adverse Events Within 48 Hours Post-Dose	23 participants
MK-1602 100 mg	Number of Participants With One or More Adverse Events Within 48 Hours Post-Dose	30 participants

Primary

Percentage of Participants Reporting Pain Freedom (PF) at 2 Hours Post-Dose

PF was defined as a reduction in headache severity from Grade 2 or 3 at Baseline to Grade 0. Headache severity was reported by the participant using a 4-point scale where: 0=no pain, 1=mild pain, 2=moderate pain and 3=severe pain.

Time frame: 2 hours post-dose