A Pharmacokinetic Study of MK-1602 in the Treatment of Acute Migraine (MK-1602-007)

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

The purpose of this study is to characterize the pharmacokinetics of MK-1602 in the treatment of acute migraine, including the influence of demographic and other variables on MK-1602 pharmacokinetics, and to evaluate the relationship between MK-1602 concentrations and efficacy of the drug.

Study Overview

• Status: Completed
• Conditions: Migraine
• Intervention / Treatment: Drug: Placebo; Drug: Rescue medication; Drug: MK-1602

• Study Type: Interventional
• Enrollment (Actual): 195
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 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, modafinil 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, 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

• History or current evidence of any condition, therapy, lab abnormality or

other circumstance that might confound the results of the study, or interfere with subject's participation for the full duration of the study

• 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, with the exception of MK-1602 Protocol 006

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; MK-1602 placebo-matching tablet orally for 3 doses: Dose 1 at the onset of a moderate or severe migraine (Day 1), Dose 2 in the evening of Day 3 and Dose 3 on Day 4. After 2 hours participants were able to take rescue medication if necessary.	Drug: Placebo; Three administrations of placebo for MK-1602 on separate days. Dose 1: Taken at onset of migraine of moderate or severe intensity. Dose 2: Taken the evening before Visit 2. Dose 3: Taken at Visit 2, which is Day 4 post migraine treatment (Dose 1). Dosage form is film coated tablet for oral administration.; Drug: Rescue 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, opiates or other medication not explicitly excluded.
Experimental: MK-1602 1 mg; MK-1602 1 mg tablet orally for 3 doses: Dose 1 at the onset of a moderate or severe migraine (Day 1), Dose 2 in the evening of Day 3 and Dose 3 on Day 4. After 2 hours participants were able to take rescue medication if necessary.	Drug: Rescue 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, opiates or other medication not explicitly excluded.; Drug: MK-1602; Three administrations of the same dose of MK-1602 on separate days. All 3 doses are either 1, 10, 25, 50 or 100 mg of MK-1602. Dose 1: Taken at onset of migraine of moderate or severe intensity. Dose 2: Taken the evening before Visit 2. Dose 3: Taken at Visit 2, which is Day 4 post migraine treatment (Dose 1). Dosage form is film coated tablet for oral administration.
Experimental: MK-1602 10 mg; MK-1602 10 mg tablet orally for 3 doses: Dose 1 at the onset of a moderate or severe migraine (Day 1), Dose 2 in the evening of Day 3 and Dose 3 on Day 4. After 2 hours participants were able to take rescue medication if necessary.	Drug: Rescue 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, opiates or other medication not explicitly excluded.; Drug: MK-1602; Three administrations of the same dose of MK-1602 on separate days. All 3 doses are either 1, 10, 25, 50 or 100 mg of MK-1602. Dose 1: Taken at onset of migraine of moderate or severe intensity. Dose 2: Taken the evening before Visit 2. Dose 3: Taken at Visit 2, which is Day 4 post migraine treatment (Dose 1). Dosage form is film coated tablet for oral administration.
Experimental: MK-1602 25 mg; MK-1602 25 mg tablet orally for 3 doses: Dose 1 at the onset of a moderate or severe migraine (Day 1), Dose 2 in the evening of Day 3 and Dose 3 on Day 4. After 2 hours participants were able to take rescue medication if necessary.	Drug: Rescue 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, opiates or other medication not explicitly excluded.; Drug: MK-1602; Three administrations of the same dose of MK-1602 on separate days. All 3 doses are either 1, 10, 25, 50 or 100 mg of MK-1602. Dose 1: Taken at onset of migraine of moderate or severe intensity. Dose 2: Taken the evening before Visit 2. Dose 3: Taken at Visit 2, which is Day 4 post migraine treatment (Dose 1). Dosage form is film coated tablet for oral administration.
Experimental: MK-1602 50 mg; MK-1602 50 mg tablet orally for 3 doses: Dose 1 at the onset of a moderate or severe migraine (Day 1), Dose 2 in the evening of Day 3 and Dose 3 on Day 4. After 2 hours participants were able to take rescue medication if necessary.	Drug: Rescue 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, opiates or other medication not explicitly excluded.; Drug: MK-1602; Three administrations of the same dose of MK-1602 on separate days. All 3 doses are either 1, 10, 25, 50 or 100 mg of MK-1602. Dose 1: Taken at onset of migraine of moderate or severe intensity. Dose 2: Taken the evening before Visit 2. Dose 3: Taken at Visit 2, which is Day 4 post migraine treatment (Dose 1). Dosage form is film coated tablet for oral administration.
Experimental: MK-1602 100 mg; MK-1602 100 mg tablet orally for 3 doses: Dose 1 at the onset of a moderate or severe migraine (Day 1), Dose 2 in the evening of Day 3 and Dose 3 on Day 4. After 2 hours participants were able to take rescue medication if necessary.	Drug: Rescue 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, opiates or other medication not explicitly excluded.; Drug: MK-1602; Three administrations of the same dose of MK-1602 on separate days. All 3 doses are either 1, 10, 25, 50 or 100 mg of MK-1602. Dose 1: Taken at onset of migraine of moderate or severe intensity. Dose 2: Taken the evening before Visit 2. Dose 3: Taken at Visit 2, which is Day 4 post migraine treatment (Dose 1). Dosage form is film coated tablet for oral administration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dry Blood Spot (DBS) MK-1602 Concentration at 2 Hours Post-Dose on Migraine Treatment Day	The participant collected blood by fingerstick on a card. The card was sent to a laboratory and the concentration of MK-1602 determined using the dried blood spot (DBS) assay.	2 hours post dose 1
Percentage of Participants Reporting Pain Freedom (PF) at 2 Hours Post-Dose on Migraine Treatment Day	PF was defined as a decrease from a moderate or severe migraine headache (Grade 2 or 3) at Baseline to no pain (Grade 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 1
Percentage of Participants With Pain Relief (PR) at 2 Hours Post-Dose on Migraine Treatment Day	PR was defined as a decrease from 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 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Reporting Absence of Phonophobia at 2 Hours Post-Dose on Migraine Treatment Day	Phonophobia is sensitivity to sound.	2 hours post dose 1
Percentage of Participants Reporting Absence of Photophobia at 2 Hours Post-Dose on Migraine Treatment Day	Photophobia is sensitivity to light.	2 hours post dose 1
Percentage of Participants Reporting Absence of Nausea at 2 Hours Post-Dose on Migraine Treatment Day		2 hours post dose 1
Percentage of Participants With Sustained Pain Freedom (SPF) From 2-24 Hours Post-Dose on Migraine Treatment Day	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 2-24 hour period after dosing with study medication.	2-24 hours post dose 1
Percentage of Participants With Sustained Pain Relief (SPR) From 2-24 Hours Post-Dose on Migraine Treatment Day	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 2-24 hour period after dosing with study medication.	2-24 hours post dose 1
Percentage of Participants With Total Migraine Freedom (TMF) at 2 Hours Post-Dose on Migraine Treatment Day	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 1
Percentage of Participants With TMF From 2-24 Hours Post-Dose on Migraine Treatment Day	TMF from 2-24 hours post-dose was defined as SPF with no photophobia, phonophobia, nausea, or vomiting during the 2-24 hour period after dosing with study medication.	2-24 hours post dose 1

Other Outcome Measures

Outcome Measure	Time Frame
Dry Blood Spot (DBS) MK-1602 Concentrations on Migraine Treatment Day	Up to 24 hours post dose 1
Dry Blood Spot MK-1602 Concentration at 3.5 Hours Post-Dose at Visit 2 (Day 4)	3.5 hours post dose 3
Plasma MK-1602 Concentrations at Visit 2 (Day 4)	Up to 3.5 hours post dose 3

Collaborators and Investigators

• Sponsor: Allergan

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Actual): November 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: August 2, 2012
• First Submitted That Met QC Criteria: August 2, 2012
• First Posted (Estimate): August 6, 2012

Study Record Updates

• Last Update Posted (Estimate): December 9, 2016
• Last Update Submitted That Met QC Criteria: October 18, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders
• Other Study ID Numbers: 1602-007