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Oral ALLOD-2 vs. Oral Sumatriptan and vs. Placebo in the Acute Treatment of Migraine With Associated Nausea (ANODYNE-2)

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ClinicalTrials.gov Identifier: NCT03185143
Recruitment Status : Recruiting
First Posted : June 14, 2017
Last Update Posted : October 31, 2017
Sponsor:
Information provided by (Responsible Party):

Study Description
Brief Summary:

The objective of this study is to compare side-by-side ALLOD-2 to sumatriptan, (a current acute migraine standard of care treatment), in the acute treatment of migraine.

The investigational product (ALLOD-2), is a combination of two marketed drugs used for the acute treatment of migraine due to the discovery of biologically and clinically relevant affinities for a new target for pain. Both drugs are used at a significantly lower dosage compared to the dosage that has already been approved for the marketed indications.

The combination is a First-in-Class drug due to its new and unique mechanism of action.

The investigators propose that in predisposed individuals, migraine attacks occur due to exuberant innate immune system activation nearby the trigeminal nerve and other cranial nerves. The innate immunity activation leads to the release of pro-inflammatory cytokines [nitric oxide (NO), tumor necrosis factor-α (TNF-α), and reactive oxygen species (ROS)], and to the activation of cyclooxygenase-2 (COX-2), which produces neuro-inflammation, causing headache and various migraine-associated symptoms.

The investigation will focus on the comparison of migraine-associated nausea, which has been shown none-responsive to other known migraine treatments and is considered an unmet treatment need.

ALLOD-2 reverses the neuro-inflammation through dual action, inhibition of the release of pro-inflammatory cytokines and inhibition of the activation of COX-2. Efficacy of this product for migraine headache pain and for migraine-associated symptoms, especially nausea, may suggest the product addresses the root cause of migraine.


Condition or disease Intervention/treatment Phase
Migraine With and Without Aura Drug: ALLOD-2 Capsules Drug: Sumatriptan 100 mg Capsules Drug: Placebo capsules Phase 2 Phase 3

Detailed Description:
The study consists of a screening visit, at home treatment of a migraine attack with a single dose of the study drug within 8 weeks, and End-of-Study Visit 2-7 days after the treatment of a moderate or severe migraine attack. The duration of patients' participation in the study is up to 9 weeks.

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Single Site, Phase 2B, Randomized, Double-Blind, and Placebo-Controlled Study to Assess the Efficacy and Safety of a Single Dose of ALLOD-2 Versus Sumatriptan in the Acute Treatment of Migraine With Associated Nausea in Adults (ANODYNE-2)
Actual Study Start Date : June 27, 2017
Estimated Primary Completion Date : June 2018
Estimated Study Completion Date : October 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Sumatriptan
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: ALLOD-2 Capsules
One capsule contains component A and one capsule contains component B
Drug: ALLOD-2 Capsules
One capsule contains component A and one capsule contains component B taken together to treat a single Qualified Migraine attack.
Active Comparator: Sumatriptan 100 mg Capsules
One capsule contains Sumatriptan 100 mg and one capsule contains a sham comparator for component B.
Drug: Sumatriptan 100 mg Capsules
One capsule contains Sumatriptan 100 mg and one capsule contains a sham for component B taken together to treat a single Qualified Migraine attack.
Placebo Comparator: Placebo Capsules
One capsule contains a sham comparator for component A and one capsule contains a sham comparator for component B .
Drug: Placebo capsules
One capsule contains a sham for component A and one capsule contains a sham for component B taken together to treat a single Qualified Migraine attack.


Outcome Measures

Primary Outcome Measures :
  1. The proportion of patients with headache pain-free at 2 hours. [ Time Frame: 2 hours ]
    Headache pain-free is defined as headache pain improvement from severe/moderate to none. Headache will be measured on a 4-point scale (0=none, 1=mild, 2=moderate, 3=severe).

  2. The proportion of patients with nausea-free at 2 hours. [ Time Frame: 2 hours ]
    Nausea-free is defined as nausea improvement from severe/moderate to none. Nausea will be measured on a 4-point scale (0=none, 1=mild, 2=moderate, 3=severe).

  3. The proportion of patients with nausea-relief at 2 hours. [ Time Frame: 2 hours ]
    Nausea-relief is defined as nausea improvement from severe/moderate to none/mild. Nausea will be measured on a 4-point scale (0=none, 1=mild, 2=moderate, 3=severe).

  4. The proportion of patients with Most Bothersome Migraine Associated Symptom-free at 2 hours. [ Time Frame: 2 hours ]
    Most Bothersome Migraine Associated Symptom will be prospectively identified at baseline.


Secondary Outcome Measures :
  1. The proportion of patients with photophobia-free, phonophobia-free, and neck/shoulder pain-free fat 2 hours. [ Time Frame: 2 hours ]
    Absence of migraine associated symptoms photophobia, phonophobia and neck/shoulder pain

  2. The proportion of patients with headache pain-relief at 2 hours. [ Time Frame: 2 hours ]
    Headache pain-relief is defined as headache pain improvement from severe/moderate to none/mild.

  3. The proportion of patients who used rescue medications within 24 hours and within 48 hours. [ Time Frame: 24 and 48 hours ]
    Rescue medication use.

  4. The proportion of patients with sustained pain-free at 48-hour. [ Time Frame: 48 hours. ]
    48-hour-sustained pain-free is defined as having headache pain-free at 2 hours, with no use of rescue medications and no relapse of headache pain within 48 hours.

  5. The proportion of patients with headache pain relapse within 48 hours. [ Time Frame: 48 hours ]
    Headache pain relapse within 48 hours is defined as the return of headache of any severity within 48 hours, when the patient was pain-free at 2 hours.

  6. The proportion of patients who experienced adverse events within 48 hours after taking the study drug. [ Time Frame: 48 hours ]
    Defined as any untoward medical occurrences, regardless of their suspected cause.

  7. The proportion of patients who experienced treatment related adverse events within 48 hours after taking the study drug. [ Time Frame: 48 hours ]
    Treatment related AEs

  8. Comparison of the change from screening to post treatment in blood counts, hepatic, and renal function. [ Time Frame: Up to 8 weeks ]
    Pre-treatment and Post-treatment laboratory parameters.


Eligibility Criteria

Information from the National Library of Medicine

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

Inclusion Criteria:

  1. Male or female 18 to 65 years of age.
  2. History of migraine with or without aura according to the International Classification of Headache Disorders (ICHD)-3rd edition (beta version) for at least one-year with first migraine prior to age 50.
  3. Migraine-associated nausea with ≥half the migraine attacks.
  4. 2 - 8 migraines per month in each of the previous 3 months.
  5. The patient is able to complete study questionnaires, comply with the study requirements and restrictions, and willing to provide written informed consent and authorize HIPAA.
  6. The female patient who is premenopausal or postmenopausal less than 1 year, or have not had surgical sterilization (i.e., tubal ligation, partial or complete hysterectomy) must have a negative urine pregnancy test, be non-lactating, and commit to using 2 methods of adequate and reliable contraception throughout the study and for 28 days after taking the last dose of the study drug (e.g., barrier with additional spermicidal, intra-uterine device, hormonal contraception). Male patients must be surgically sterile or commit to the use of 2 different methods of birth control during the study and for 28 days after the study.ice, hormonal contraception).

Exclusion Criteria:

  1. The patient in the opinion of the investigator may have medication-overuse headaches (as defined by ICHD - 3 beta criteria for medication-overuse headache) during the preceding 3 months.
  2. The patient in the opinion of the investigator has chronic migraine (as defined by ICHD - 3 beta criteria for chronic migraine) during the preceding 3 months.
  3. History of cluster headaches or neurologically complicated migraine (hemiplegic, basilar, retinal, ophthalmoplegic).
  4. Initiation or change in medications with possible migraine prophylactic effects during 3 months before inclusion into the trial (E.g., calcium channel blockers, tricyclic antidepressants, beta-blockers, or Botox).
  5. Use of opiates or barbiturates more than 3 days per month.
  6. Any concurrent medical or psychiatric condition, this includes, but is not limited to chronic unstable debilitating diseases, significant renal or hepatic impairment.
  7. The patient has a history within the previous 3 years of abuse of any drug, prescription, illicit, or alcohol.
  8. The Female patient is pregnant or breast-feeding. The Male patient is not practicing 2 different methods of birth control with their partner during the study, and for 28 days after the investigational drug last dose or will not remain abstinent during the study, and for 28 days after the last dose.
  9. The patient has known-hypersensitivity reaction to any of the components of the investigational drug.
  10. Consumption of analgesic medication or muscle relaxants (including all benzodiazepines) for other conditions on a regular basis.
  11. The patient has used emergency care treatment more than 3 times in the previous 6 months.
  12. The patient has participated in another study with an investigational drug within 30 days prior to randomization and/or plan to participate during the study.
  13. The patient has a history of congenital heart disease, cardiac arrhythmias, or cardiovascular disease, e.g., ischemic heart disease (e.g., stable angina pectoris, unstable angina, vasospastic angina, myocardial infarction or silent myocardial ischemia), cerebrovascular syndromes (e.g., strokes of any type or transient ischemic attacks), peripheral vascular disease, ischemic bowel disease, or Raynaud syndrome.
  14. Uncontrolled hypertension (sitting >160 mmHg systolic pressure or >95mmHg diastolic pressure).
  15. The patient, in the investigator's opinion, is likely to have unrecognized cardiovascular or cerebrovascular disease.
  16. History of epilepsy. Allergy to sulfonamides.
  17. Consumption of monoamine oxidase inhibitor (MAOI) drug, tricyclic antidepressant, selective serotonin reuptake inhibitor (SSRI) or Serotonin Noradrenaline Reuptake Inhibitor (SNRI).
Contacts and Locations

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 ClinicalTrials.gov identifier (NCT number): NCT03185143


Contacts
Contact: Annette C. Toledano, M.D. 305-895-6808 Info@allodynic.com

Locations
United States, Florida
Annette C. Toledano, M.D. Recruiting
North Miami, Florida, United States, 33181
Contact: Annette C. Toledano, M.D.    305-895-6808    Info@allodynic.com   
Sponsors and Collaborators
Allodynic Therapeutics, LLC
Investigators
Principal Investigator: Annette C. Toledano, M.D. Allodynic Therapeutics, LLC
More Information

Responsible Party: Allodynic Therapeutics, LLC
ClinicalTrials.gov Identifier: NCT03185143     History of Changes
Other Study ID Numbers: ANODYNE-2
First Posted: June 14, 2017    Key Record Dates
Last Update Posted: October 31, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Migraine Disorders
Headache Disorders, Primary
Headache Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Sumatriptan
Vasoconstrictor Agents
Serotonin 5-HT1 Receptor Agonists
Serotonin Receptor Agonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs