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Oral ALLOD-2 vs. Its Components & Placebo in the Acute Treatment of Migraine (ANODYNE-1)

This study is currently recruiting participants.
Verified October 2017 by Allodynic Therapeutics, LLC
Sponsor:
ClinicalTrials.gov Identifier:
NCT03061734
First Posted: February 23, 2017
Last Update Posted: October 31, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Allodynic Therapeutics, LLC
  Purpose

The objective of this study is to compare ALLOD-2 (a two-component combination) to its individual components for headache pain and for the most bothersome migraine-associated symptom to provide data to comply with the requirements of the FDA's combination rule.

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 Intervention Phase
Migraine With or Without Aura Drug: ALLOD-2 Drug: ALLOD-2H Drug: Component A (regular dose) Drug: Component B Drug: Placebo Phase 2 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Single Center, Phase 2B, Randomized, Double-Blind, Placebo, Individual Components, and 2-Doses, Controlled Study to Assess the Efficacy and Safety of a Single Dose of ALLOD-2 in the Acute Treatment of Migraine (ANODYNE-1)

Resource links provided by NLM:


Further study details as provided by Allodynic Therapeutics, LLC:

Primary Outcome Measures:
  • The proportion of patients with headache pain free for ALLOD-2 vs. placebo at 2 hours. [ Time Frame: 2 hours ]
    Headache pain-free=headache pain score=0, on a 4-point scale (0=none; 1=mild; 2=moderate; 3=severe).

  • The proportion of patients with most bothersome migraine-associated symptom-free for ALLOD-2 vs. placebo at 2 hours. [ Time Frame: 2 hours ]
    Most bothersome migraine-associated symptom is prospectively identified at baseline.


Secondary Outcome Measures:
  • The proportion of patients with absence of photophobia, phonophobia, and neck/shoulder pain for ALLOD-2 vs. placebo at 2 hours. [ Time Frame: 2 hours ]
    Absence of migraine associated symptoms photophobia, phonophobia, and neck/shoulder pain.

  • The proportion of patients with absence of headache pain, nausea, photophobia, phonophobia, and neck/shoulder pain for ALLOD-2H versus placebo at 2 hours. [ Time Frame: 2 hours ]
  • The proportion of patients with headache pain-free and nausea-free for ALLOD-2 vs. Component A at 2 hours. [ Time Frame: 2 hours ]
    Absence=0 score.

  • The proportion of patients with headache pain-free and nausea-free for ALLOD-2 vs. Component B at 2 hours. [ Time Frame: 2 hours ]
    Absence=0 score.

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

  • The proportion of patients with nausea-free for ALLOD-2 versus placebo at 2 hours. [ Time Frame: 24 hours and 48 hours. ]
    Nausea-free is defined as nausea improvement from severe/moderate to none.

  • The proportion of patients with nausea relief for ALLOD-2 versus placebo at 2 hours. [ Time Frame: 2-48 hours ]
    Nausea-relief is defined as nausea improvement from severe/moderate to none/mild.

  • The proportion of patients who used rescue medications for ALLOD-2 vs. placebo within 24 hours and within 48 hours. [ Time Frame: 2-48 hours ]
    rescue medications use.


Other Outcome Measures:
  • The proportion of patients with sustained absence of pain for ALLOD-2 vs. placebo at 48-hour. [ Time Frame: 48 hours ]
    48-hour-sustained absence of pain is defined as having absence of headache pain at 2 hours, with no use of rescue medications and no relapse of headache pain within 48 hours.

  • The proportion of patients with headache pain relapse for ALLOD-2 versus placebo within 48 hours. [ Time Frame: 48 hours ]
    Defined as the return of headache of any severity within 48 hours, when the patient had absence of pain at 2 hours.

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

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

  • The change from screening to post treatment in blood count, hepatic, and renal function [ Time Frame: up to 8 weeks ]
    Safety outcome measure

  • Comparison of the change from screening to post treatment in systolic blood pressure, diastolic blood pressure, and pulse. [ Time Frame: up to 8 weeks ]
    Safety outcome measure


Estimated Enrollment: 120
Actual Study Start Date: February 18, 2017
Estimated Study Completion Date: April 2018
Estimated Primary Completion Date: February 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ALLOD-2 Capsules
Each patient receives one capsule containing component A (regular dose) and one capsule containing component B and uses both capsules together for treatment of a qualified Migraine attack
Drug: ALLOD-2
ALLOD-2: Component A (regular dose) plus Component B
Experimental: ALLOD-2H Capsules
Each patient receives one capsule containing component A (high dose) and one capsule containing component B and uses both capsules together for treatment of a qualified Migraine attack
Drug: ALLOD-2H
ALLOD-2H: Component A (high dose) plus Component B
Active Comparator: Active Comparator Component A Capsules
Each patient receives one capsule containing component A of ALLOD-2 and one capsule containing a placebo comparator for component B of ALLOD-2 and uses both capsules together for treatment of a qualified Migraine attack
Drug: Component A (regular dose)
Component A (regular dose) of ALLOD-2
Active Comparator: Active Comparator Component B Capsules
Each patient receives one capsule containing component B of ALLOD-2 and one capsule containing a placebo comparator for component A of ALLOD-2 and uses both capsules together for treatment of a qualified Migraine attack
Drug: Component B
Component B of ALLOD-2
Placebo Comparator: Placebo Capsules
Each patient receives one capsule containing a placebo comparator for component A of ALLOD-2 and one capsule containing a placebo comparator for component B of ALLOD-2 and uses both capsules together for treatment of a qualified Migraine attack
Drug: Placebo
Placebo for Component A plus Placebo for Component B

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 treatment of a moderate or severe migraine attack. The duration of patients' participation in the study is up to 9 weeks.
  Eligibility

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.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female 18 years of age or older.
  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 of 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 adequate and reliable contraception throughout the study (e.g., barrier with additional spermicidal, intra-uterine device, hormonal contraception). The male patient must be surgically sterile or commit to the use of 2 different methods of birth control during the study and for 28 days after taking the study drug.

Exclusion Criteria:

  1. The patient in the opinion of the investigator, may have medication-overuse headache pain (as defined by ICHD - 3 beta criteria for medication-overuse headache), (analgesic, opioid, ergotamine or triptan overuse) during the 3 months preceding screening.
  2. The patient in the opinion of the investigator has chronic migraine (as defined by ICHD - 3 beta criteria for chronic migraine).
  3. History of cluster headache or neurologically complicated migraine (hemiplegic, basilar, retinal, ophthalmoplegic migraine).
  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, selective serotonin re-uptake inhibitors (SSRIs), serotonin-norepinephrine re-uptake inhibitors (SNRIs), or Botox).
  5. Any concurrent medical or psychiatric condition, this includes, but is not limited to chronic unstable debilitating diseases, significant renal or hepatic impairment.
  6. A history within the previous 3 years of abuse of any drug, prescription, illicit, or alcohol.
  7. 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.
  8. Use of opiates or barbiturates more than 3 days per month.
  9. Known-hypersensitivity reaction to any of the components of the investigational drug.
  10. Consumption of analgesic medication for other conditions on a regular basis, (nonsteroidal anti-inflammatory drugs, or acetaminophen, or muscle relaxants).
  11. Use of emergency care treatment more than 3 times in the previous 6 months.
  12. Participation in another study with an investigational drug within 30 days prior to randomization and/or a plan to participate during the study.
  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): NCT03061734


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

Locations
United States, Florida
Annette C. Toledano MD Recruiting
North Miami, Florida, United States, 33181
Sponsors and Collaborators
Allodynic Therapeutics, LLC
Investigators
Study Director: Annette C Toledano, M.D. Allodynic Therapeutics, LLC
  More Information

Responsible Party: Allodynic Therapeutics, LLC
ClinicalTrials.gov Identifier: NCT03061734     History of Changes
Other Study ID Numbers: ANODYNE-1
First Submitted: February 17, 2017
First Posted: February 23, 2017
Last Update Posted: October 31, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Keywords provided by Allodynic Therapeutics, LLC:
Migraine Disorders
Headache Disorders
Migraine with Aura
Migraine without Aura

Additional relevant MeSH terms:
Migraine Disorders
Headache Disorders, Primary
Headache Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases