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

Migraine Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01657370
• Other study ID #: 1602-007
• Status: Completed
• Phase: Phase 2
• First received: August 2, 2012
• Last updated: January 23, 2015
• Start date: August 2012
• Est. completion date: December 2012

Study information

• Verified date: January 2015
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 195
• Est. completion date: December 2012
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 ß-human chorionic gonadotropin (ß-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 Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Migraine
• Migraine Disorders

Intervention

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.
• 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.
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dry Blood Spot MK-1602 concentration at 2 hours post dose on migraine treatment day		2 hours post dose 1	No
Primary	Pain freedom (PF) at 2 hours post dose on migraine treatment day		2 hours post dose 1	No
Primary	Pain relief (PR) at 2 hours post dose on migraine treatment day		2 hours post dose 1	No
Secondary	Dry Blood Spot MK-1602 concentrations on migraine treatment day		Up to 24 hours post dose 1	No
Secondary	Dry Blood Spot MK-1602 concentration at 3.5 hours post dose on Visit 2		3.5 hours post dose 3	No
Secondary	Plasma MK-1602 concentrations at Visit 2		Up to 3.5 hours post dose 3	No
Secondary	Absence of phonophobia at 2 hours post dose on migraine treatment day		2 hours post dose 1	No
Secondary	Absence of photophobia at 2 hours post dose on migraine treatment day		2 hours post dose 1	No
Secondary	Absence of nausea at 2 hours post dose on migraine treatment day		2 hours post dose 1	No
Secondary	Sustained pain freedom (SPF) from 2-24 hours post dose on migraine treatment day	SPF is 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	No
Secondary	Sustained pain relief (SPR) from 2-24 hours post dose on migraine treatment day	SPR is 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	No
Secondary	Total migraine freedom (TMF) at 2 hours post dose on migraine treatment day	TMF at 2 hours post dose is defined as PF with no photophobia, phonophobia, nausea, or vomiting at 2 hours post dose.	2 hours post dose 1	No
Secondary	TMF from 2-24 hours post dose on migraine treatment day	TMF from 2-24 hours post dose is 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	No