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Efficacy, Safety, and Tolerability of Twice Daily Oral ALLOD-2 vs. Placebo in Episodic Migraine Prevention (ANODYNE-3)

This study is currently recruiting participants.
Verified November 2017 by Allodynic Therapeutics, LLC
Sponsor:
ClinicalTrials.gov Identifier:
NCT03194555
First Posted: June 21, 2017
Last Update Posted: November 28, 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

While many individuals are able to limit therapy to the treatment of migraine attacks, others need medication to reduce the frequency and severity of the attacks. Patients with prolonged or severe attacks leading to substantial disability or patients who are refractory to abortive treatments can benefit from migraine prevention.

The primary aim of this study is to demonstrate the migraine prevention properties of ALLOD-2. The secondary aims are to demonstrate ALLOD-2, may potentially address two migraine unmet medical need conditions, namely, reduce nausea and not cause precipitation of Medication Overuse Headache (MOH).

Our early studies suggest, ALLOD-2, reduces nausea, which other approve migraine treatments do not. Also, ALLOD-2 does not induce MOH when used on a daily basis. MOH represents a significant unmet medical need and is now considered the third-most prevalent type of headache. This study aims to demonstrate, ALLOD-2, unlike the other approved medications for the acute treatment of migraine can be used on an ongoing basis in migraineurs without the risk of precipitating MOH.

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. 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.


Condition Intervention Phase
Migraine With or Without Aura Drug: ALLOD-2 Capsules Drug: Placebo Capsules Phase 2 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Official Title: A Single Center, Proof of Concept, Phase 2B, Randomized, Double-Blind, Study to Assess the Efficacy, Safety, and Tolerability of ALLOD-2 vs. Placebo in the Prevention of Episodic Migraine With Associated Nausea in Adults (ANODYNE-3)

Resource links provided by NLM:


Further study details as provided by Allodynic Therapeutics, LLC:

Primary Outcome Measures:
  • Change from baseline in the mean number of migraine/probable migraine headache days. [ Time Frame: From the 28-day baseline period to the last 28 days of the 12-week treatment period. ]

    (Migraine with or without aura is defined according to the International Classification of Headache Disorders (ICHD)-3rd edition (beta version).

    Probable migraine, is defined according to the ICHD - 3 (beta version) criteria, as attacks fulfilling all but one of criteria A-D for migraine with or without aura, where criteria B is headache attacks lasting 4-72 hours (untreated or unsuccessfully treated).

    Migraine/probable migraine headaches must be moderate or severe and lasting ≥30 minutes. When the patient falls asleep during migraine and wakes up without it, duration of the attack is reckoned until the time of awakening).



Secondary Outcome Measures:
  • Change from baseline in the mean number of headache days. [ Time Frame: From the 28-day baseline period to the last 28 days of the 12-week treatment period. ]
    (Headache days are defined as none-migraine headache days plus migraine headache days).

  • Proportion of patients with 50% or more reduction in migraine/probable migraine headache days. [ Time Frame: From the28-day baseline period to the last 28 days of the12-week treatment period. ]
  • Change from baseline in the mean migraine severity. [ Time Frame: From the 28-day baseline period to the last 28 days of the 12-week treatment period. ]
    (Measured on the 4-point (0-3) rating scale, (0=none, 1=mild, 2=moderate, 3=severe)).

  • Change from baseline in the mean migraine duration. [ Time Frame: From the 28-day baseline period to the last 28 days of the12-week treatment period. ]
  • Change from baseline in the mean nausea severity. [ Time Frame: From the 28-day baseline period to the last 28 days of the12-week treatment period. ]
    (Measured on the 4-point (0-3) rating scale, (0=none, 1=mild, 2=moderate, 3=severe)).

  • Change from baseline in the mean number of acute migraine medications intake days. [ Time Frame: From the 28-day baseline period to the last 28 days of the 12-week treatment period. ]
  • Proportion of patients "satisfied" or "extremely satisfied" with migraine prevention. [ Time Frame: Week 12. ]
  • Change from baseline in the mean migraine disability assessment scale (MIDAS) [ Time Frame: From baseline to week 12 of the treatment period. ]
  • Change from baseline in the mean headache impact test (HIT-6). [ Time Frame: From the 28-day baseline period to the last 28 days of the 12-week treatment period. ]
  • Change from baseline in the mean Pittsburgh Insomnia Rating Scale-20 (PIRS-20). [ Time Frame: From baseline to week 12 of the treatment period. ]
  • Comparison of the proportion of patients who experienced adverse events, defined as any untoward medical occurrences, regardless of their suspected cause. [ Time Frame: A 12-week treatment period. ]
  • Comparison of the proportion of patients who experienced treatment related adverse events. [ Time Frame: A 12-week treatment period. ]

Estimated Enrollment: 12
Actual Study Start Date: August 1, 2017
Estimated Study Completion Date: October 2018
Estimated Primary Completion Date: August 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ALLOD-2 capsules
Component A and Component B
Drug: ALLOD-2 Capsules
One capsule contains component A and one capsule contains component B taken together twice daily for 12 weeks.
Placebo Comparator: Placebo capsules
Placebo for Component A and Placebo for Component B
Drug: Placebo Capsules
One capsule contains placebo for component A and one capsule contains placebo for component B taken together twice daily for 12 weeks.

Detailed Description:
The study consists of three study periods: a 4-week baseline period, a 12-week double blind treatment period, and 4-week post-treatment follow-up period.
  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. The patient is a male or a 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 onset of migraine prior to 50 years of age.
  3. Migraine-associated nausea with ≥half of migraine attacks.
  4. 5-8 migraine/probable migraine headache days on average per month in the three months prior to Visit 1 and during the Baseline Period.
  5. The patient agrees to refrain from taking opiate medications from Visit 1 to 7 days after the last dose of the study drug.
  6. 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.
  7. The patient has been taking a stable dose of a medication with migraine prevention potential for at least 3 month prior to the screening visit and agrees to not start, stop, or change dosage of any medication with migraine prevention potential during the study period. (E.g., beta-blockers, calcium channel blockers, tricyclic antidepressants, anticonvulsants, selective serotonin re-uptake inhibitors (SSRIs), serotonin-norepinephrine re-uptake inhibitors (SNRIs), magnesium or riboflavin supplements at high doses, herbal preparations (e.g. feverfew or St. john's wort)), Botulinum toxin must be discontinued one year prior to Visit 1.
  8. The patient agrees to forgo any elective surgery for the duration of the study.
  9. 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.

Exclusion Criteria:

  1. Usage of acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs) ≥15 days/month, or ergotamine and triptans >10 days/month, or opioids and barbiturates >2 days/month in the 3 months prior to Visit 1 or during the Baseline Period.
  2. Tension-type-like, and/or migraine-like headache on ≥15 days per month in the 3 months prior to Visit 1 or during the Baseline Period. Diagnosis of chronic migraine, cluster headache or neurologically complicated migraine (hemiplegic, basilar, retinal, ophthalmoplegic migraine).
  3. Regular use of the following medications for any reason: acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), antipsychotic drugs, monoamine oxidase inhibitors, benzodiazepines, sleep medications, muscle relaxants, anti-emetic medications, blood thinning medications (e.g., warfarin or heparin), cannabinoids, or botulinum toxin to head and neck regions. Low-dose aspirin for cardiovascular disease prophylaxis is permitted.
  4. Confounding painful conditions, (e.g. fibromyalgia, chronic low back pain, complex regional pain syndrome, etc.).
  5. Diagnosis of any concurrent medical or psychiatric condition; this includes, chronic unstable debilitating diseases such as Parkinson's disease, multiple sclerosis, cancer, significant renal impairment, significant hepatic impairment, etc.
  6. The patient has a history or diagnosis of moderate-to-severe hepatic or renal impairment (>2 × the upper limit of normal [ULN] for alanine transaminase or aspartate transaminase. ≥1.5 × ULN for alkaline Phosphatase, bilirubin, BUN, or creatinine). (Patients with elevated bilirubin level due to Gilbert's syndrome are allowed).
  7. The patient has a history within the previous 5 years of abuse of any drug, prescription, illicit, or alcohol.
  8. The Female patient is pregnant, actively trying to become 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-allergy to any of the components of the investigational drug.
  10. Participation in another study with an investigational drug within 30 days before Visit 1 or during the study.
  11. Use of emergency care treatment more than 3 times in the previous 6 months.
  12. The patient is in the opinion of the investigator, is unsuitable to participate in this study for any other reason.
  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): NCT03194555


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

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

Responsible Party: Allodynic Therapeutics, LLC
ClinicalTrials.gov Identifier: NCT03194555     History of Changes
Other Study ID Numbers: ANODYNE-3
First Submitted: June 16, 2017
First Posted: June 21, 2017
Last Update Posted: November 28, 2017
Last Verified: November 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
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Allodynic Therapeutics, LLC:
Innate Immune System
Cytokines
Cox-2
Headache
Migraine
Migraine Prevention

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