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

Study Overview
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Brief Summary
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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.

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

Conditions
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Migraine

Intervention / Treatment
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* Drug: MK-1602
* Drug: Placebo-matching MK-1602
* Drug: Rescue medication


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MK-1602 1 mg<br>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. | Drug: MK-1602<br>* 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.<br>Drug: Rescue medication<br>* 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.<br>|
| Experimental: MK-1602 10 mg<br>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. | Drug: MK-1602<br>* 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.<br>Drug: Rescue medication<br>* 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.<br>|
| Experimental: MK-1602 25 mg<br>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. | Drug: MK-1602<br>* 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.<br>Drug: Rescue medication<br>* 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.<br>|
| Experimental: MK-1602 50 mg<br>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. | Drug: MK-1602<br>* 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.<br>Drug: Rescue medication<br>* 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.<br>|
| Experimental: MK-1602 100 mg<br>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. | Drug: MK-1602<br>* 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.<br>Drug: Rescue medication<br>* 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.<br>|
| Placebo Comparator: Placebo<br>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. | Drug: Placebo-matching MK-1602<br>* 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.<br>Drug: Rescue medication<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 2 hours post-dose | 
| Percentage of Participants Reporting Pain Relief (PR) at 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. | 2 hours post-dose | 
| Number of Participants With One or More Adverse Events Within 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. | Up to 48 hours post-dose | 
| 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. | Up to 14 days post-dose | 
| Number of Participants Who Discontinued From Study Due to Adverse Events |  | Up to 5 weeks post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Reporting Absence of Phonophobia at 2 Hours Post-Dose | Phonophobia is sensitivity to loud sounds. | 2 hours post-dose | 
| Percentage of Participant Reporting Absence of Photophobia at 2 Hours Post-Dose | Photophobia is sensitivity to bright light. | 2 hours post-dose | 
| 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 | 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. | 2-24 hours post-dose | 
| Percentage of Participants Reporting SPF 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. | 2-48 hours post-dose | 
| Percentage of Participants Reporting Sustained Pain Relief (SPR) 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. | 2-24 hours post-dose | 
| Percentage of Participants Reporting SPR 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. | 2-48 hours post-dose | 
| Percentage of Participants Reporting Total Migraine Freedom (TMF) at 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. | 2 hours post-dose | 
| Percentage of Participants Reporting TMF at 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. | 2-24 hours post-dose | 
| Percentage of Participants Reporting TMF at 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. | 2-48 hours post-dose |