Safety and Efficacy Study of TNX-201 Capsules for Treatment of Single Tension-Type Headache
- Conditions
- Tension-Type Headache
- Interventions
- Drug: TNX-201Drug: Placebo
- Registration Number
- NCT02423408
- Lead Sponsor
- Tonix Pharmaceuticals, Inc.
- Brief Summary
This is a randomized, multicenter, double-blind, placebo-controlled, parallel-group study to evaluate the safety and efficacy of a single dose of TNX-201 (140 mg) for the treatment of a single qualifying Tension-Type-Headache (TTH).
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 165
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description TNX-201 TNX-201 4 X 35 mg capsules to be taken when qualifying tension-type headache occurs Placebo Placebo 4 X placebo capsules to be taken when qualifying tension-type headache occurs
- Primary Outcome Measures
Name Time Method Number of Subjects Pain Free 2 hours Number of subjects pain free at 2 hours post-dose (Pain assessed by 4-point NRS, VAS, and binary yes/no question).
4-point NRS grades: 0=none, 1=mild, 2=moderate, 3=severe; "pain-free" defined as score = 0.
VAS: 0-100 scale, anchored by verbal anchors of No Pain (0) vs. Worst Imaginable Headache Pain (100). "Pain-free" was defined as a score \<= 5
- Secondary Outcome Measures
Name Time Method Number of Subjects Using Rescue Medication During the 24-hour Post-dose Period 24-hour post-dose period Number of Subjects Pain Free at 15, 30, 60, 90 Minutes and 4 Hours Post-dose (Pain Will be Assessed by 4-point NRS, VAS, and Binary Yes/no Question) 15, 30, 60, 90 minutes and 4 hours post-dose 4-point NRS grades: 0=none, 1=mild, 2=moderate, 3=severe.
VAS: 0-100 scale, No Pain vs. Worst Imaginable Headache PainNumber of Subjects With at Least a Two-category Improvement From Baseline at 2 Hours Post-dose in VAS Severity Category (Carvalho Responders) 2 hours The Carvalho Responder analysis refers to subjects with at least 2 categories of improvement in their VAS severity category (0-100 scale). VAS severity categories were defined as "severe" if between 52-100 inclusive, "moderate" between 31-51 inclusive, "mild" between 6-30 inclusive, and pain-free if less than 6. Therefore, a Carvalho responder was either a subject who had a VAS response classified as 'severe' at baseline and 'mild' or pain-free at the post-dose assessment time point, or a subject who had a VAS response classified as 'moderate' at baseline and pain-free at the post-dose assessment time point.
Trial Locations
- Locations (10)
Rapid Medical Research, Inc.
🇺🇸Cleveland, Ohio, United States
Avail Clinical Research LLC.
🇺🇸DeLand, Florida, United States
Duane G. Wombolt, MD
🇺🇸Norfolk, Virginia, United States
John Rubino, MD
🇺🇸Raleigh, North Carolina, United States
Nathan Segall, MD, CPI
🇺🇸Stockbridge, Georgia, United States
James D. Wolfe, MD
🇺🇸San Jose, California, United States
Michigan Head-Pain Neurological Institute
🇺🇸Ann Arbor, Michigan, United States
Gary D. Berman, MD
🇺🇸Minneapolis, Minnesota, United States
Stephan C. Sharp, MD
🇺🇸Nashville, Tennessee, United States
PMG Research of Winston-Salem, LLC.
🇺🇸Winston-Salem, North Carolina, United States