Pilot Study of VVD-101 for the Treatment of Delayed Alcohol-Induced Headaches
Pilot Study of VVD-101 for the Treatment of Delayed Alcohol-Induced Headaches
This study proposes to compare the efficacy of sumatriptan and aspirin to placebo as an acute
 abortive treatment for delayed alcohol induced headache in adult subjects.
The exploratory study will be conducted at 2 investigational sites. Approximately 26
 subjects, 21 years of age and older, with a history of delayed alcohol induced headache, as
 defined by International Classification of Headache Disorders (ICHD-3 beta) will be enrolled.
 The study will consist of two visits. Subject participation will last approximately 6 months.

 At the screening visit (Visit 1), and before any study procedures, an informed consent will
 be obtained from the subject. A physical, neurological exam, medication history, and
 pregnancy test (if appropriate) will be performed. Vital signs will be recorded for all
 subjects. Subjects will also complete the Simple Screening Instrument for Alcohol and Other
 Drugs (SSI-AOD).

 Subjects scoring greater than 4 (not including items 1 and 15) on the SSI-AOD, at Visit 1,
 will not be eligible for this study and will be referred to their primary care provider for
 follow up.

 Subjects meeting eligibility criteria will be randomized into 1 of 6 different groups. Each
 group will receive 3 doses of active drug and 3 doses of placebo in a different order to
 treat up to 6 delayed alcohol-induced headaches. Study product instructions will be reviewed.
 A copy of the instructions will be given to the subject. Subjects will be instructed they may
 take their investigator approved routine rescue medications for headaches 2 hours after
 taking the study medication if needed. Rescue medication usage and dosage will be recorded on
 the headache diary. Subjects may take acute headache medications as prescribed; however, this
 should be recorded on the headache diary. Therapy considered necessary for the subject's
 welfare may be given at the discretion of the investigator. Routine medications should be
 maintained on a stable dose and regimen for the duration of the study period.

 Subjects will be instructed regarding completion of the online Headache Diary to document
 treatment response of up to 6 delayed alcohol-induced headaches. Subjects will be provided
 instructions for completing the Headache Diary. The Headache Diary will be completed during
 each headache and will document the number of drinks consumed in the last sitting, time of
 last drink consumed, pain severity, headache symptoms, and hangover symptoms before
 treatment, time of treatment with study products, pain severity at 30 minutes, 1, 2, and 24
 hours following treatment, time of headache resolution, and time of meaningful headache
 relief. The Headache Diary will also include questions to evaluate subject satisfaction with
 study product. Subjects must be headache-free for 24 hours before recording the onset of and
 treating another headache. Subjects will be phoned monthly during the study to assess
 compliance, continued understanding, and to collect any adverse events.

 Visit 2 will occur within 1 week following treatment of a 6th attack or between 180-187 days
 following Visit 1, whichever occurs first. The medical and medication history will be updated
 and adverse events will be collected. A urine pregnancy test will be performed if appropriate
 and vital signs to include weight and height will be performed. Subjects will complete the
 SSI-AOD. Subjects scoring greater than 4 (not including items 1 and 15) on the SSI-AOD will
 be referred to their primary care provider for follow up. The Diary will be reviewed and any
 unused study product and used packaging will be collected. Drug accountability will be
 performed.
Inclusion Criteria:

 -  male or female 21 years or older.

 -  able to read, understand, and sign the informed consent.

 -  currently consume alcohol averaging at least four times per month.

 -  a negative urine pregnancy test at Visit 1, if female, and of childbearing potential.
 Note: If of childbearing potential, subject must agree to maintain true abstinence or
 use (or have their partner use) one of the listed methods of birth control for the
 duration of the study: hormonal contraceptive, intrauterine device (IUD), condoms,
 diaphragm, and/or vasectomy. The use of barrier contraceptive (condom or diaphragm)
 should always be supplemented with the use of a spermicide. Note: To be considered not
 of childbearing potential, subject must be 6 weeks post-surgical bilateral
 oophorectomy, hysterectomy, or bilateral tubal ligation, or postmenopausal for at
 least one year.

 -  at least a one year history of delayed alcohol-induced headache after light to
 moderate alcohol consumption.

 -  able to differentiate delayed alcohol-induced headache from any other headache they
 may experience (e.g., tension-type headache).

 -  able to stay awake for at least 2 hours after treatment following first dose of study
 product.

 -  willing to complete the online headache diary and questionnaires.

 -  concomitant medication dosages approved by the investigator.

 -  internet access and an email address for completion of online diary and
 questionnaires.

 Exclusion Criteria:

 -  > 6 migraine attacks per month during the 3 months previous to screening.

 -  history of receiving partial or complete relief of hangover headaches from 650 mg of
 aspirin.

 -  history of basilar, ophthalmoplegic, or hemiplegic migraine, cluster headache, or
 secondary headaches (such as due to trauma, infection, alterations of homeostasis,
 eye, nose, throat (ENT) disorders, or psychiatric disorders, cranial or cervical
 disorders or neuralgias) within the previous year.

 -  significant alcohol or drug use problems (score > 4 on the Simple Screening Instrument
 for Alcohol and Other Drugs (SSI-AOD)) or history of treatment or counseling for
 alcohol or drug abuse and or dependence.

 -  used acute headache medication including non-prescription medications, 15 or more days
 per month during the last 3 months.

 -  pregnant, actively trying to become pregnant, or breastfeeding.

 -  female of childbearing potential not using adequate contraceptive measures.

 -  has a history of serotonin syndrome or in the opinion of the investigator is at an
 increased risk for developing serotonin syndrome with the use of triptans.

 -  in the investigator's opinion, is likely to have unrecognized cardiovascular or
 cerebrovascular disease (based on history or the presence of risk factors including
 but not limited to hypertension, hypercholesterolemia, smoker, obesity, diabetes, or
 family history of coronary artery disease).

 -  if female, has migraine with aura, is a smoker, and currently taking estrogen
 containing birth control pill, and in the investigator's opinion, is at high risk for
 cerebrovascular disease.

 -  uncontrolled hypertension (≥140/90 mmHg in either systolic or diastolic in 2 out of 3
 blood pressure measurements at screening).

 -  history of any clinically significant medical or psychiatric condition, or evidence of
 substance abuse including binge drinking within the last year that, in the opinion of
 the investigator, will likely interfere with the study conduct, subject cooperation,
 or evaluation and interpretation of the study results, or which otherwise
 contraindicates participation in this study.

 -  has hypersensitivity, intolerance, or contraindication to the use of any triptan or
 aspirin (including all sumatriptan and aspirin preparations).

 -  has history of nasal polyps and/or asthma and in the investigator's opinion is at risk
 for hypersensitivity to aspirin.

 -  participated in an investigational drug trial within the past 30 days.

 -  planning or requiring surgery during the study.

 -  history of poor compliance with medical treatment.