Migraine
Conditions
Brief summary
This is a double-blind, randomized, multicenter, outpatient evaluation of the safety and efficacy of elismetrep as compared to placebo in the acute treatment of migraine.
Interventions
DRUGElismetrep (K-304) 2 mg
Administered orally
DRUGElismetrep (K-304) 5 mg
Administered orally
DRUGElismetrep (K-304) 10 mg
Administered orally
DRUGElismetrep (K-304) 20 mg
Administered orally
DRUGPlacebo
Administered orally
Sponsors
Kallyope Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Be a male or female, age 18 to 70 years, inclusive, at the time of signing informed consent. 2. Participant has greater than a one-year history of migraine with or without aura as defined by International Conference on Harmonization (IHS) criteria 1.1 and 1.2 and his/her migraines typically last between 4 to 72 hours, if untreated as documented in the participant's medical records from his/her treating physician and confirmed by the investigator. 3. Participant has had ≥2 and ≤10 moderate or severe migraine attacks per month in each of the two months prior to screening (Visit 1). 4. Meet the following requirements: 1. Is a male OR 2. Is a female who is of non-childbearing potential defined by at least 1 of the following criteria: 3. Postmenopausal (aged \>45 years and with a minimum of 12 months of spontaneous amenorrhea with a screening serum follicle-stimulating hormone (FSH) level in the menopausal range established for the central laboratory. 4. Post hysterectomy, bilateral oophorectomy or bilateral salpingectomy, based on the participant's recall of their medical history. OR 5. Is a female of reproductive potential and: 6. agrees to remain abstinent from heterosexual activity\* \*Abstinence can be used as the sole method of contraception if it is in line with the participant's preferred and usual lifestyle and if considered acceptable by local regulatory agencies and ethics committees. Periodic abstinence (e.g., calendar, ovulation, sympto-thermal, post-ovulation methods, etc.) and withdrawal are not acceptable methods of contraception. 7. or agrees to use (or have their partner use) a birth control method that is acceptable from the first dose of study drug until the end of trial (EoT) visit. Acceptable methods of birth control are: * combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: * oral * intravaginal * transdermal * progestogen-only hormonal contraception associated with inhibition of ovulation: * oral * injectable * implantable * intrauterine device (IUD) * intrauterine hormone-releasing system (IUS) * bilateral tubal occlusion * vasectomised partner * sexual abstinence * progestogen-only oral hormonal contraception, where inhibition of ovulation is not the primary mode of action * male or female condom with or without spermicide * cap, diaphragm or sponge with spermicide * A combination of male condom with either cap, diaphragm or sponge with spermicide (double barrier methods) This condition is waived if the participant is proven to have no child-bearing potential (eg, hysterectomy). 5. Participant voluntarily agrees to participate in the study by giving written informed consent. 6. Participant is able to read, understand and complete the study questionnaires and diary. 7. Be willing and able to comply with the study schedule of visits, all trial procedures and restrictions. 8. Be willing to use their own personal, qualified smartphone to download study specific eDiary applications for use during the study.
Exclusion criteria
1. Is a female who is pregnant, breast-feeding or intends to become pregnant during the planned course of the study. Note: Participants must have a negative serum pregnancy test (β-human chorionic gonadotropin (β-hCG)) performed by the central laboratory prior to enrollment in the study and negative urine pregnancy result at the randomization visit. Migraine history related 2. Participant has difficulty distinguishing his/her migraine attacks from tension-type headaches. 3. Participant has a history of predominantly mild migraine attacks or migraines that usually resolve spontaneously in less than two hours. 4. Participant has more than 15 headache-days per month or has taken medication for acute headache on more than 10 days per month in any of the three months prior to screening (Visit 1). 5. Participant has brainstem (a.k.a. basilar-type) or hemiplegic migraine headache, or retinal migraine. 6. Participant was \>50 years old at age of first migraine onset. 7. Participant is taking migraine prophylactic medication where the prescribed daily dose has changed during the 3 months prior to screening (Visit 1) or anticipates any change during the study. Any withdrawal of preventive medications for the treatment of migraine should be completed at least 30 days prior to screening. Medical history related 8. Participant has, in the opinion of the investigator, other confounding pain syndromes, psychiatric conditions such as uncontrolled major depression, history of psychosis, dementia or significant neurological disorders other than migraine \[participants who are currently being treated with non-prohibited medication for depression and symptoms are well controlled, in the opinion of the investigator, are eligible to participate in this study\]. 9. Participant is at imminent risk of self-harm, based on clinical interview and responses on the Columbia Suicidality Severity Rating Scale (C-SSRS), or of harm to others in the opinion of the investigator. Participants must be excluded if they report suicidal ideation with intent, with or without a plan (i.e., Type 4 or 5 on the C-SSRS) in the past 2 months or suicidal behavior in the past 6 months. 10. Has a recent history (within the past 3 years of the Screening Visit) or current diagnosis or evidence of endocrine, hematological, immunological, renal, respiratory, neurologic, gastrointestinal, biliary, or genitourinary abnormalities or diseases that, per the investigator's judgement, may jeopardize the participant's safety or compliance with the protocol, or otherwise interfere with interpretation of efficacy and/or safety results. 11. Has a history of malignant neoplasms within the past 5 years prior to screening. Basal and squamous cell skin cancer and any carcinoma in-situ are allowed if they have received treatment and follow-up consistent with local standard of care. 12. Participant history with current evidence of uncontrolled, unstable or recently diagnosed cardiovascular disease, such as ischemic heart disease, coronary artery vasospasm, and cerebral ischemia. Participants with Myocardial Infarction (MI), Acute Coronary Syndrome (ACS), percutaneous Coronary Intervention (PCI), cardiac surgery, stroke or transient ischemic attack (TIA) during the 6 months prior to screening. 13. Has a history of human immunodeficiency virus disease. 14. Participant has a history of gastric or small intestinal surgery (including gastric bypass surgery or banding but not including cholecystectomy or appendectomy) or has a disease that causes malabsorption. Laboratory, vital sign, and electrocardiogram (ECG) related 15. Has a positive test result at screening for hepatitis B surface antigen (Ag), hepatitis C virus antibody. 16. Has a screening estimated Glomerular Filtration Rate (eGFR) estimated with the Modification of Diet in Renal Disease (MDRD) equation of \<45 ml/min/1.73 m\^2. 17. Has a screening result for alanine aminotransferase or aspartate aminotransferase (ALT or AST) of \>2.0X upper limit of normal (ULN) or total bilirubin \>1.5X ULN at the Screening Visit. Note: An isolated bilirubin \>1.5X ULN is acceptable if bilirubin is fractionated, and direct bilirubin is within the laboratory normal range. 18. Has a corrected QT interval to Fridericia's formula (QTcF) \>450 milliseconds (msec) for males and \>470 msec for females at screening. 19. Has a mean value for triplicate seated systolic blood pressure \>160 mmHg and/or diastolic blood pressure (BP) \>95 mmHg measured after at least 5 minutes at rest at the Screening Visit. Note: If a participant's BP is exclusionary on the first triplicate assessment at the Screening Visit, they may have 1 repeat triplicate BP assessment at that visit after another rest of at least 10 minutes. Medication use and substance abuse related 20. Has known history of or suspected abuse of alcohol or recreational drugs at screening. 21. Has use of soft drugs (such as marijuana or any substances containing tetrahydrocannabinol (THC) or cannabidiol (CBD)) within 3 months prior to screening, or hard drugs (such as cocaine, illicit narcotics/opiates) within 6 months prior to screening. 22. Has a positive drug screen at screening. Note: If benzodiazepines are detected on the drug screen, this is not exclusionary if they are prescribed a benzodiazepine for a therapeutic purpose (e.g. for insomnia) and confirmatory documentation is obtained from the prescribing physician. 23. Is currently in violation of study requirements for prohibited and permissible concomitant medications (not already specified in other criteria) or is anticipated to violate these requirements during study participation. 24. Has any use of prescription opiate medications within 14 days of screening or any anticipated/potential use of opiates during study participation. 25. History of use of ergotamine medications on greater than/equal 10 days per month on a regular basis for greater than/equal 3 months prior to screening. 26. History of non-narcotic analgesic intake on greater than/equal 15 days per month for greater than/equal 3 months prior to screening. Other 27. Has known or suspected hypersensitivity to trial product(s) or related products. 28. Has a history of multiple significant and/or any severe allergies (e.g., food, drug, latex allergy) or has had an anaphylactic reaction or significant intolerance to prescription or nonprescription drugs or food. 29. Has any surgery scheduled for the duration of the trial. 30. Had major surgery or donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the Screening Visit; has a screening hemoglobin \<11.0 g/dL (males) or \<10.0 g/dL (females), or has a known hemoglobinopathy (e.g. sickle cell anemia, hemolytic anemia). 31. Has previous participation in this trial. Participation is defined as signed informed consent. 32. Has participated in any clinical trial of an approved or non-approved investigational biological medicinal product (e.g. antibody therapy) within 90 days of screening or has participated in any clinical trial of an approved or non-approved investigational small molecule medicinal product within 30 days or 5 half-lives (whichever is longer) of screening. 33. Has any other disorder, unwillingness or inability, not covered by any of the other
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pain Freedom | 2 hours post-dose | Assessed using the number of evaluable participants that reported no pain at 2 hours post-dose. Pain was measured on a 4-point Likert scale (0 = none, 1 = mild, 2 = moderate, 3 = severe) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Freedom From the Most Bothersome Symptom (MBS) (Nausea, Phonophobia or Photophobia) | 2 hours post-dose | Assessed using the number of evaluable participants that reported the absence of their MBS |
| Pain Relief | 2 hours post-dose | Assessed using the number of evaluable participants that reported a pain level of moderate or severe (responses of 2 or 3 on the 4-point Likert scale) at baseline and then reported a pain level of none or mild (response of 0 or 1). |
| Freedom From Photophobia | 2 hours post-dose | Assessed by tabulating the number of participants that reported the absence of photophobia at 2 hours post-dose in the subset of participants that reported the presence of photophobia at baseline. |
| Freedom From Phonophobia | 2 hours post-dose | Assessed by tabulating the number of participants that reported the absence of phonophobia at 2 hours post-dose in the subset of participants that reported the presence of phonophobia at baseline. |
| Freedom From Nausea | 2 hours post-dose | Assessed by tabulating the number of participants that reported the absence of nausea at 2 hours post-dose in the subset of participants that reported the presence of nausea at baseline. |
| The Probability of Requiring Rescue Medication | 24 hours post-dose | Assessed using the number of participants that took rescue medication within 24 hours after administration of study therapy |
| Sustained Pain Freedom | From 2 to 24 hours | Assessed using the number of participants that did not experience any headache pain through the time period of interest |
| Sustained Pain Relief | From 2 to 24 hours | Assessed using the number of participants that did not experience any moderate or severe headache pain through the time period of interest. |
| Proportion of Participants Who Experienced 1 or More Treatment-emergent Adverse Events (AEs) | up to 7 days after administration of study therapy | — |
| Proportion of Participants Who Experienced 1 or More Treatment-emergent Serious Adverse Events (SAEs) | Up to 7 days after administration of study therapy | Serious adverse events were assessed in the Safety Analysis Set. |
Countries
United States
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 44.5 years STANDARD_DEVIATION 10.13 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 46 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 67 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) White | 40 Participants |
| Sex: Female, Male Female | 89 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 51 | 0 / 101 | 0 / 97 | 0 / 51 | 0 / 104 |
| other Total, other adverse events | 2 / 51 | 1 / 101 | 10 / 97 | 19 / 51 | 0 / 104 |
| serious Total, serious adverse events | 0 / 51 | 0 / 101 | 0 / 97 | 0 / 51 | 0 / 104 |
Outcome results
None listed