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
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Tonix Pharmaceuticals, Inc.
- Enrollment
- 165
- Locations
- 10
- Primary Endpoint
- Number of Subjects Pain Free
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
- •Body mass index (BMI) ≥ 18.5 and ≤ 45.
- •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
- •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
- •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
- •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.
Arms & Interventions
TNX-201
4 X 35 mg capsules to be taken when qualifying tension-type headache occurs
Intervention: TNX-201 (Drug)
Placebo
4 X placebo capsules to be taken when qualifying tension-type headache occurs
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
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 Outcomes
- 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)
- Number of Subjects With at Least a Two-category Improvement From Baseline at 2 Hours Post-dose in VAS Severity Category (Carvalho Responders)(2 hours)