Safety and Efficacy Study of TNX-201 Capsules for Treatment of Single Tension-Type Headache

The study will be conducted in 4 periods (the Screening Period, the Run-In Period, the Double-Blind Treatment Period and the Follow-up Period) and 4 visits (the Screening Visit, Enrollment Visit, Randomization Visit and End-of-Study Visit).

Screening Period- Eligible subjects who provide written informed consent to participate will have study assessments performed at the Screening.

Run-In Period- The Run-In Period will last for at least 28 days. During the Run-In period, subjects will be assessed for frequency of headache, study compliance and to ensure they meet all required study criteria for randomization.

Double-Blind Treatment Period- The Double-Blind Treatment Period (Treatment Period) will last up to 4 weeks or until a qualifying headache episode has occurred and been treated using the study drug, whichever occurs first.

Follow-up Period- All subjects will return to the investigational site for this visit, regardless of whether they have treated a qualifying TTH with study medication. Subjects who have not treated a qualifying TTH with study drug during the Treatment Period will be asked to return study materials and undergo safety evaluations at the End-of-Study Visit and will be discharged from the study. Subjects who have treated a qualifying TTH with study drug during the Treatment Period will ingest a 140 mg dose of open-label TNX-201 at this visit and undergo urine and blood sample collection for 3 hours post-dose to characterize each subject's genetic metabolism and PK profile.

Inclusion criteria

• Capable of reading and understanding English and able to provide written informed consent to participate.
• Male or female adults ≥ 18 and < 65 years of age at the time of Visit 1.
• Body mass index (BMI) ≥ 18.5 and ≤ 45.0.
• Greater than 1 year history of episodic tension-type headache with onset prior to 50 years of age.
• History of tension-type headaches that typically last ≥ 4 hours if untreated.
• History of 2-14 tension-type headaches per month for the last 3 months prior to Visit 1.
• Diagnosis must comply with the International Headache Society (IHS) diagnostic criteria.
• No significant ECG findings at Screening
• If female, is either not of childbearing potential or is practicing a predefined medically acceptable method of birth control (hormonal methods, intrauterine device, double-barrier method, sexually-exclusive vasectomized male partner, same-sex relationship) throughout the study.
• Willing and able to comply with all protocol-specified requirements.

Exclusion criteria

• Known or suspected hypersensitivity to isometheptene mucate or any excipients used in the formulation.
• Use of any excluded concomitant medications.
• Current use of opiate analgesics.
• Use of any prophylactic drug therapy for headache control within 4 weeks of screening (e.g., anticonvulsants, mood stabilizers, beta-blocker, antidepressants, muscle relaxants, botulinum toxin). Subjects taking any of these medications for an indication other than headache (e.g., a beta-blocker for hypertension) will require medical monitor's approval prior to initiation of the Run-In Period.
• History of medication use for acute headache on ≥ 10 days per month on average during the 3 months prior to Visit 1.
• Positive results for addictive substances (e.g., cocaine, phencyclidine (PCP), amphetamines, opiates) at Screening.
• History of migraine that exceeds a mean of four attacks per month during the preceding calendar year.
• Lifetime history of schizophrenia, schizoaffective disorder, bipolar I/II disorder, delusional disorder, or psychotic disorder not otherwise specified.
• Chronic pain disorders requiring medical treatment with opioids, chronic daily use of NSAIDs at the time of screening
• History of coronary artery disease, coronary vasospasm, aortic aneurysm, peripheral vascular disease or other ischemic diseases (e.g., ischemic bowel syndrome or Raynaud's syndrome).
• Inadequately controlled hypertension or persistently elevated systolic blood pressure or diastolic blood pressure upon repeat assessment at screening or on the day of randomization.
• Current history of two or more CAD risk factors at Screening (tobacco use, receiving anti-hypertensive medication for hypertension, high LDL cholesterol or low HDL cholesterol levels, family history of premature CAD, diabetes mellitus)
• History cerebral vascular accident, transient ischemic attack, seizure disorders.
• Other clinically significant cardiac disease.
• History of concurrent illness that requires hospitalization within 30 days prior to Visit 1.
• Current evidence of human immunodeficiency virus infection or clinically significant hepatitis B or C infection.
• Clinically significant laboratory abnormalities based on screening laboratory tests and/or medical history.
• Participation in another investigational trial during the 30 days prior to Visit 1 or during this trial. Subjects who have participated in non-interventional trials may be permitted to participate on a case-by-case basis after review with the Medical Monitor.
• Women who are pregnant, breast-feeding, or planning to become pregnant during this trial.
• Any other household member currently participating in a Tonix-sponsored study or family member or relative of investigative staff.
• Any condition and/or medical history that would make the subject unsuitable for study participation and completion.