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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01657370
First received: August 2, 2012
Last updated: February 21, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Migraine
Drug: MK-1602
Drug: Placebo
Drug: Rescue medication
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase IIb, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Pharmacokinetic Study of MK-1602 in the Treatment of Acute Migraine

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Dry Blood Spot MK-1602 concentration at 2 hours post dose on migraine treatment day [ Time Frame: 2 hours post dose 1 ] [ Designated as safety issue: No ]
  • Pain freedom (PF) at 2 hours post dose on migraine treatment day [ Time Frame: 2 hours post dose 1 ] [ Designated as safety issue: No ]
  • Pain relief (PR) at 2 hours post dose on migraine treatment day [ Time Frame: 2 hours post dose 1 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Dry Blood Spot MK-1602 concentrations on migraine treatment day [ Time Frame: Up to 24 hours post dose 1 ] [ Designated as safety issue: No ]
  • Dry Blood Spot MK-1602 concentration at 3.5 hours post dose on Visit 2 [ Time Frame: 3.5 hours post dose 3 ] [ Designated as safety issue: No ]
  • Plasma MK-1602 concentrations at Visit 2 [ Time Frame: Up to 3.5 hours post dose 3 ] [ Designated as safety issue: No ]
  • Absence of phonophobia at 2 hours post dose on migraine treatment day [ Time Frame: 2 hours post dose 1 ] [ Designated as safety issue: No ]
  • Absence of photophobia at 2 hours post dose on migraine treatment day [ Time Frame: 2 hours post dose 1 ] [ Designated as safety issue: No ]
  • Absence of nausea at 2 hours post dose on migraine treatment day [ Time Frame: 2 hours post dose 1 ] [ Designated as safety issue: No ]
  • Sustained pain freedom (SPF) from 2-24 hours post dose on migraine treatment day [ Time Frame: 2-24 hours post dose 1 ] [ Designated as safety issue: No ]

    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.


  • Sustained pain relief (SPR) from 2-24 hours post dose on migraine treatment day [ Time Frame: 2-24 hours post dose 1 ] [ Designated as safety issue: No ]
    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.

  • Total migraine freedom (TMF) at 2 hours post dose on migraine treatment day [ Time Frame: 2 hours post dose 1 ] [ Designated as safety issue: No ]
    TMF at 2 hours post dose is defined as PF with no photophobia, phonophobia, nausea, or vomiting at 2 hours post dose.

  • TMF from 2-24 hours post dose on migraine treatment day [ Time Frame: 2-24 hours post dose 1 ] [ Designated as safety issue: No ]
    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.


Enrollment: 195
Study Start Date: August 2012
Study Completion Date: December 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MK-1602 1 mg 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.

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 10 mg 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.

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 25 mg 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.

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 50 mg 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.

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 100 mg 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.

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.

Placebo Comparator: Placebo 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.


  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01657370     History of Changes
Other Study ID Numbers: 1602-007
Study First Received: August 2, 2012
Last Updated: February 21, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Migraine Disorders
Brain Diseases
Central Nervous System Diseases
Headache Disorders
Headache Disorders, Primary
Nervous System Diseases

ClinicalTrials.gov processed this record on October 30, 2014