Pharmacokinetics & Safety of Cambia® in Migraine With or Without Aura in 12-17 Year Olds
Condition: Migraine
MeSH terms: Migraine Disorders
Intervention: Diclofenac Potassium for Oral Solution
Intervention description: NSAID
Intervention MeSH terms: Diclofenac
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 25.0
Sex: All
Minimum age: 12 Years
Maximum age: 17 Years
Healthy volunteers: No
Keywords: Migraine with and without aura

Summary:

      Study Objectives:

        1. The primary objective is to characterize the pharmacokinetics of a single oral
           administration of 50 mg Cambia in pediatric subjects, ages 12-17 years with a diagnosis
           of episodic migraine with or without aura.

        2. The secondary objectives are to determine:

             1. The safety and tolerability of Cambia from a single dose

             2. Three-month safety evaluation of Cambia in outpatient usage in this population
    

Eligibility criteria:

        Inclusion Criteria:

          1. Subject is ≥12 and ≤17 years of age at screening.

          2. Subject diagnosed with episodic migraine with or without aura for at least 3 months
             (migraine defined based on the International classification of headache disorders-II
             1.2.1 or 1.1).

          3. Subject has 14 or fewer headache days per month.

          4. Subject receiving prophylactic treatment for migraine may be included.

          5. If female, is not of childbearing potential (defined as premenarchal) or if of
             childbearing potential must have a negative serum pregnancy test at screening and a
             negative urine pregnancy test on Study Day 1, if the Screening visit and Day 1 are not
             on the same day, and must use medically acceptable methods of birth control as listed
             below and agrees to continue its use throughout the study:1) hormonal methods (e.g.,
             oral, implantable, injectable, or transdermal contraceptives for a minimum of 1 full
             menstrual cycle before study drug administration), 2) Total abstinence from sexual
             intercourse since the last menses before study drug administration, 3) intrauterine
             device, 4) double-barrier method (e.g., condoms, sponge, diaphragm, or vaginal ring
             with spermicidal jellies or cream).

          6. Subject's legally authorized representative (e.g., parent, guardian) must voluntarily
             sign and date an informed consent form (ICF) that is approved by an Institutional
             Review Board (IRB), and the subject must sign an assent (if appropriate), before the
             commencement of any study assessment.

          7. Subject's legally authorized representative (e.g., parent, guardian) and subject (if
             appropriate), is able to read and understand the study procedures and requirements and
             adhere to the protocol requirements and procedures.

        Exclusion Criteria:

          1. Subject has a known history of allergic reaction, hypersensitivity, or clinically
             significant intolerance to diclofenac, aspirin, or any nonsteroidal anti inflammatory
             drugs (NSAIDs); history of NSAID induced bronchospasm (subjects with the triad of
             asthma, nasal polyps, and chronic rhinitis are at greater risk for bronchospasm and
             should be considered carefully); or hypersensitivity, allergy, or significant reaction
             to the non-active ingredients of the study medication.

          2. Subject is pregnant or lactating or considered at risk of pregnancy.

          3. Subject has been under an inconsistent dosing regimen of prophylactic treatment for
             migraine.

          4. Subject has headache symptoms likely due to, or aggravated by, traumatic injury to the
             head or neck region, such as whiplash, within the last six months;

          5. Subject has or is suspected of having a secondary headache.

          6. Subject has significant abnormal findings during the neurological exam at screening.

          7. Subject has a history of any GI event (e.g., perforation, obstruction, bleed) before
             Screening that, in the opinion of the investigator, would make the subject unsuitable
             for study participation.

          8. Subject is receiving any medication that, in the opinion of the investigator, may
             cause a clinically significant condition when used concomitantly with diclofenac
             (e.g., aspirin, anticoagulants, ACE inhibitors, methotrexate, cyclosporine,
             furosemide, lithium).

          9. Subject is and has been receiving a medication that is known to strongly inhibit
             and/or induce cytochrome P450 2C9 such that it might unpredictably affect the
             pharmacokinetics of diclofenac (e.g., fluconazole, amiodarone, oxandrolone,
             sulfipyrazone as inhibitors and rifampin as an inducer).

         10. Subject has any condition or any laboratory abnormality that would, in the opinion of
             the investigator, contraindicate study participation.

         11. Subject has impaired liver function (e.g., alanine aminotransferase [ALT] ≥ 3 times
             the upper limit of normal [ULN] or bilirubin ≥ 3 times ULN), known active hepatic
             disease (e.g., hepatitis), or evidence of clinically significant liver disease or
             other condition affecting the liver that may suggest the potential for an increased
             susceptibility to hepatic toxicity with oral diclofenac exposure.

         12. Subject has any history of renal disease that, in the opinion of the investigator,
             would contraindicate study participation; or subject has significantly impaired renal
             function as evidenced by an estimated GFR of ≤60 ml/min/1.73m2.

         13. Subject is considered by the investigator, for any reason (including, but not limited
             to the risks described as precautions, warnings, and contraindications in the
             Prescribing Information for Cambia), to be an unsuitable candidate to receive the
             study medication.

         14. Subject has a history of laboratory test results obtained within 6 months before the
             Screening visit that show the presence of HIV, hepatitis B surface antigen, hepatitis
             C antibody, or active hepatitis A immunoglobulin M.

         15. Subject is currently receiving any medication that is contraindicated for use
             concomitantly with diclofenac (refer to the products' professional labeling) or the
             subject has not undergone a washout period of at least 5-6 half-lives of PK or PD,
             whichever is longer, for these medications.

         16. Subject has a known or suspected history of alcohol use and or drug/ substance abuse
             or misuse within 2 years before Screening; or evidence of tolerance or physical
             dependence before study medication administration.

         17. Subject has a documented history of a medical condition that, in the opinion of the
             investigator, would compromise the subject's ability to absorb, metabolize, or excrete
             diclofenac, including (but not limited to) intractable nausea and/or vomiting and/or
             severe GI narrowing (pathologic or iatrogenic).

         18. Subject has received any investigational product or device within 30 days before the
             Screening, or is scheduled to receive an investigational device or another
             investigational drug (other than Cambia) during the course of this study.

         19. Subject is a relative of a member of the study site staff or Sponsor directly involved
             in this study.