Pilot Study of VVD-101 for the Treatment of Delayed Alcohol-Induced Headaches

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.