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

Multi-Center, Double-Blind, Placebo Controlled 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.