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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02423408
Recruitment Status : Completed
First Posted : April 22, 2015
Results First Posted : February 17, 2017
Last Update Posted : April 11, 2017
Information provided by (Responsible Party):
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).

Condition or disease Intervention/treatment Phase
Tension-Type Headache Drug: TNX-201 Drug: Placebo Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 165 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Proof-of-Concept Phase 2, Double-Blind, Randomized, Multicenter, Placebo-Controlled Study to Evaluate the Efficacy and Safety of TNX-201 for the Treatment of A Single Tension-Type Headache
Study Start Date : June 2015
Actual Primary Completion Date : February 2016
Actual Study Completion Date : February 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Headache

Arm Intervention/treatment
Experimental: TNX-201
4 X 35 mg capsules to be taken when qualifying tension-type headache occurs
Drug: TNX-201
TNX-201 capsule
Other Name: (R)-isometheptene mucate

Placebo Comparator: Placebo
4 X placebo capsules to be taken when qualifying tension-type headache occurs
Drug: Placebo
Placebo capsule
Other Name: TNX-201 Placebo

Primary Outcome Measures :
  1. Number of Subjects Pain Free [ Time Frame: 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 :
  1. 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) [ Time Frame: 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 Pain

  2. Number of Subjects Using Rescue Medication During the 24-hour Post-dose Period [ Time Frame: 24-hour post-dose period ]
  3. Number of Subjects With at Least a Two-category Improvement From Baseline at 2 Hours Post-dose in VAS Severity Category (Carvalho Responders) [ Time Frame: 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.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Capable of reading and understanding English and able to provide written informed consent to participate.
  2. Male or female adults ≥ 18 and < 65 years of age at the time of Visit 1.
  3. Body mass index (BMI) ≥ 18.5 and ≤ 45.0.
  4. Greater than 1 year history of episodic tension-type headache with onset prior to 50 years of age.
  5. History of tension-type headaches that typically last ≥ 4 hours if untreated.
  6. History of 2-14 tension-type headaches per month for the last 3 months prior to Visit 1.
  7. Diagnosis must comply with the International Headache Society (IHS) diagnostic criteria.
  8. No significant ECG findings at Screening
  9. 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.
  10. Willing and able to comply with all protocol-specified requirements.

Exclusion Criteria:

  1. Known or suspected hypersensitivity to isometheptene mucate or any excipients used in the formulation.
  2. Use of any excluded concomitant medications.
  3. Current use of opiate analgesics.
  4. 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.
  5. History of medication use for acute headache on ≥ 10 days per month on average during the 3 months prior to Visit 1.
  6. Positive results for addictive substances (e.g., cocaine, phencyclidine (PCP), amphetamines, opiates) at Screening.
  7. History of migraine that exceeds a mean of four attacks per month during the preceding calendar year.
  8. Lifetime history of schizophrenia, schizoaffective disorder, bipolar I/II disorder, delusional disorder, or psychotic disorder not otherwise specified.
  9. Chronic pain disorders requiring medical treatment with opioids, chronic daily use of NSAIDs at the time of screening
  10. 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).
  11. Inadequately controlled hypertension or persistently elevated systolic blood pressure or diastolic blood pressure upon repeat assessment at screening or on the day of randomization.
  12. 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)
  13. History cerebral vascular accident, transient ischemic attack, seizure disorders.
  14. Other clinically significant cardiac disease.
  15. History of concurrent illness that requires hospitalization within 30 days prior to Visit 1.
  16. Current evidence of human immunodeficiency virus infection or clinically significant hepatitis B or C infection.
  17. Clinically significant laboratory abnormalities based on screening laboratory tests and/or medical history.
  18. 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.
  19. Women who are pregnant, breast-feeding, or planning to become pregnant during this trial.
  20. Any other household member currently participating in a Tonix-sponsored study or family member or relative of investigative staff.
  21. Any condition and/or medical history that would make the subject unsuitable for study participation and completion.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02423408

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United States, California
James D. Wolfe, MD
San Jose, California, United States, 95117
United States, Florida
Avail Clinical Research LLC.
DeLand, Florida, United States, 32720
United States, Georgia
Nathan Segall, MD, CPI
Stockbridge, Georgia, United States, 30281
United States, Michigan
Michigan Head-Pain Neurological Institute
Ann Arbor, Michigan, United States, 48104
United States, Minnesota
Gary D. Berman, MD
Minneapolis, Minnesota, United States, 55402
United States, North Carolina
John Rubino, MD
Raleigh, North Carolina, United States, 27609
PMG Research of Winston-Salem, LLC.
Winston-Salem, North Carolina, United States, 27103
United States, Ohio
Rapid Medical Research, Inc.
Cleveland, Ohio, United States, 44122
United States, Tennessee
Stephan C. Sharp, MD
Nashville, Tennessee, United States, 37203
United States, Virginia
Duane G. Wombolt, MD
Norfolk, Virginia, United States, 23507
Sponsors and Collaborators
Tonix Pharmaceuticals, Inc.
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Study Director: Tracie Ruther, M.S 1 513 579 9911 ext 2214
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Responsible Party: Tonix Pharmaceuticals, Inc. Identifier: NCT02423408    
Other Study ID Numbers: TNX-IS-T201
First Posted: April 22, 2015    Key Record Dates
Results First Posted: February 17, 2017
Last Update Posted: April 11, 2017
Last Verified: December 2016
Additional relevant MeSH terms:
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Tension-Type Headache
Neurologic Manifestations
Headache Disorders, Primary
Headache Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases