Migraine Headache
Conditions
Brief summary
This study consists of a 4-week screening period, a 24-week treatment period for all participants, followed by a 28-week treatment period extension (to 52 weeks in total) for a subset of at least 60 and up to 80 participants, and a 2-week post-treatment follow-up period.
Detailed description
This is an outpatient study in people who currently suffer a minimum of 2 migraines per month. During the study, participants will be instructed to use no more than 2 doses of the study drug INP104 within a 24-hour period, or 3 doses in a 7-day period. Participants will self-administer INP104 nasally and record their migraines in an eDiary.
Interventions
COMBINATION_PRODUCTINP104
No more than 2 doses within 24 hours, 3 doses within 7 days. 1.45 mg in a divided dose, one actuation per nostril.
Sponsors
Impel Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Documented diagnosis of migraine with or without aura, with at least 2 attacks per month for the previous 6 months. * Participants must be in good general health, with no significant medical history (excluding migraine). * Participants must have the ability and willingness to attend the necessary visits at the study center. * Participants must be able to provide the written informed consent prior to entry into the study. * Women of childbearing potential must agree to use adequate contraception (as defined in the protocol and by study personnel) during the study and for 30 days after the last dose fo the study drug. * Male participants and their partners must agree to use effective contraception (as defined in the protocol and by study personnel) during the study and for 30 days after the last dose of the study drug. Male participants should also refrain from sperm donation for 30 days after study completion.
Exclusion criteria
* Subjects with trigeminal autonomic cephalalgias (including cluster headache, hemicrania syndromes and short-lasting unilateral, neuralgiform headache attacks with conjunctival injection and tearing), hemiplegic migraine, or migraine with brainstem aura (previously referred to as basilar migraines). * Subjects with chronic migraines, medication overuse headache or other chronic headache syndromes. * Subjects with ischemic heart disease or subjects with clinical symptoms or findings consistent with coronary artery vasospasm, including Prinzmetal's variant angina. * Subjects with significant risk factors for coronary artery disease (CAD) including current use of nicotine-containing products, medical history of diabetes, uncontrolled hypertension (high blood pressure), known peripheral arterial disease, Raynaud's phenomenon, sepsis or vascular surgery (within 3 months prior to study start), or severely impaired hepatic or renal (kidney) function. * Subjects with recurrent sinusitis or epistaxis. * Subjects with a history or presence of alcoholism or drug abuse within 2 years prior to first study drug administration. * Women who are pregnant, or planning to get pregnant, or who are lactating while participating in the study. * Use of any medications prohibited by protocol. * Use of \>12 days per month of triptan or ergot-based medication in the 2 months prior to screening. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Serious Adverse Events (SAEs) | From study enrollment up to Week 26 (for the 24-Week Treatment Group) and up to Week 54 (for the 52-WeekTreatment Group) | Number of participants with Serious Adverse Events (SAEs) whether or not related to study drug. |
| Number of Participants With Non-serious Treatment Emergent Adverse Events (AEs) | From first use of INP104 up to Week 26 (for the 24-Week Treatment Group) and up to Week 54 (for the 52-WeekTreatment Group) | Number of participants with non-serious treatment emergent adverse events (AEs), whether or not related to study drug. |
| Change in Nasal Mucosa | Baseline up to Week 24 (for the 24-Week Treatment Group) and Baseline up to Week 52 (for the 52-WeekTreatment Group) | Mean change from baseline in Quantitative Scoring Scale for Evaluation of the Nasal Mucosa (QSS-NM) score, reported at designated intervals on study. This scale was scored by otolaryngologists during routine endoscopy of the upper nasal cavity of participants. A minimum score of 0 means no issues were detected. A maximum score of 34 indicates severe issues (worse outcome). |
| Change in Olfactory Function | Baseline up to Week 24 (for the 24-Week Treatment Group) and Baseline up to Week 52 (for the 52-WeekTreatment Group) | Mean change from baseline in olfactory function score, assessed using the University of Pennsylvania Smell Identification Test (UPSIT), and reported at designated intervals on study. The UPSIT is a 40 question scratch and sniff test of olfactory function. The minimum score of 0 indicates worst olfactory function, and the maximum score of 40 indicates the highest level of olfactory function detectable by the test. |
Countries
United States
Participant flow
Pre-assignment details
360 participants were enrolled and were dispensed INP104. Only those participants who dosed at least once with INP104 were included in the 24-Week Treatment Group, which was 354.
Participants by arm
| Arm | Count |
|---|---|
| 24-Week Treatment Group Participants in this group dosed at least once with INP104, and treated their migraine headaches as needed up to 2 times in 24 hours or up to 3 times per week with INP104, for up to 24-weeks. | 354 |
| Total | 354 |
Baseline characteristics
| Characteristic | 24-Week Treatment Group |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 353 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 29 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 324 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Mean duration of migraine history | 19.5 years STANDARD_DEVIATION 12.13 |
| Mean number of migraines in 28-day baseline period | 4.60 number of migraines STANDARD_DEVIATION 2.313 |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 79 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 266 Participants |
| Region of Enrollment United States | 354 Participants |
| Sex: Female, Male Female | 304 Participants |
| Sex: Female, Male Male | 50 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 354 | 0 / 73 |
| other Total, other adverse events | 241 / 354 | 61 / 73 |
| serious Total, serious adverse events | 5 / 354 | 3 / 73 |
Outcome results
Primary
Change in Nasal Mucosa
Mean change from baseline in Quantitative Scoring Scale for Evaluation of the Nasal Mucosa (QSS-NM) score, reported at designated intervals on study. This scale was scored by otolaryngologists during routine endoscopy of the upper nasal cavity of participants. A minimum score of 0 means no issues were detected. A maximum score of 34 indicates severe issues (worse outcome).
Time frame: Baseline up to Week 24 (for the 24-Week Treatment Group) and Baseline up to Week 52 (for the 52-WeekTreatment Group)
Population: Only those participants with assessments at baseline and at the indicated time point have data analyzed in that row.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 24-Week Treatment Group | Change in Nasal Mucosa | Week 4 | 0.2 mean change in score on a scale | Standard Deviation 1.26 |
| 24-Week Treatment Group | Change in Nasal Mucosa | Week 12 | 0.1 mean change in score on a scale | Standard Deviation 0.93 |
| 24-Week Treatment Group | Change in Nasal Mucosa | Week 24 | 0.1 mean change in score on a scale | Standard Deviation 0.88 |
| 24-Week Treatment Group | Change in Nasal Mucosa | Week 8 | 0.2 mean change in score on a scale | Standard Deviation 1.43 |
| 52-Week Treatment Group | Change in Nasal Mucosa | Week 12 | 0.1 mean change in score on a scale | Standard Deviation 0.78 |
| 52-Week Treatment Group | Change in Nasal Mucosa | Week 36 | -0.1 mean change in score on a scale | Standard Deviation 0.68 |
| 52-Week Treatment Group | Change in Nasal Mucosa | Week 24 | 0.0 mean change in score on a scale | Standard Deviation 0.79 |
| 52-Week Treatment Group | Change in Nasal Mucosa | Week 4 | 0.0 mean change in score on a scale | Standard Deviation 0.62 |
| 52-Week Treatment Group | Change in Nasal Mucosa | Week 8 | 0.1 mean change in score on a scale | Standard Deviation 0.91 |
| 52-Week Treatment Group | Change in Nasal Mucosa | Week 52 | -0.1 mean change in score on a scale | Standard Deviation 0.61 |
Primary
Change in Olfactory Function
Mean change from baseline in olfactory function score, assessed using the University of Pennsylvania Smell Identification Test (UPSIT), and reported at designated intervals on study. The UPSIT is a 40 question scratch and sniff test of olfactory function. The minimum score of 0 indicates worst olfactory function, and the maximum score of 40 indicates the highest level of olfactory function detectable by the test.
Time frame: Baseline up to Week 24 (for the 24-Week Treatment Group) and Baseline up to Week 52 (for the 52-WeekTreatment Group)
Population: Only those subjects with data at baseline and the indicated time point are included in the analysis for that row.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 24-Week Treatment Group | Change in Olfactory Function | Week 12 | -0.48 mean change in score | Standard Deviation 2.69 |
| 24-Week Treatment Group | Change in Olfactory Function | Week 24 | -0.22 mean change in score | Standard Deviation 2.27 |
| 52-Week Treatment Group | Change in Olfactory Function | Week 36 | -0.13 mean change in score | Standard Deviation 2.93 |
| 52-Week Treatment Group | Change in Olfactory Function | Week 52 | -0.80 mean change in score | Standard Deviation 2.71 |
| 52-Week Treatment Group | Change in Olfactory Function | Week 12 | -0.18 mean change in score | Standard Deviation 2.573 |
| 52-Week Treatment Group | Change in Olfactory Function | Week 24 | 0.03 mean change in score | Standard Deviation 2.373 |
Primary
Number of Participants With Non-serious Treatment Emergent Adverse Events (AEs)
Number of participants with non-serious treatment emergent adverse events (AEs), whether or not related to study drug.
Time frame: From first use of INP104 up to Week 26 (for the 24-Week Treatment Group) and up to Week 54 (for the 52-WeekTreatment Group)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 24-Week Treatment Group | Number of Participants With Non-serious Treatment Emergent Adverse Events (AEs) | 241 Participants |
| 52-Week Treatment Group | Number of Participants With Non-serious Treatment Emergent Adverse Events (AEs) | 61 Participants |
Primary
Number of Participants With Serious Adverse Events (SAEs)
Number of participants with Serious Adverse Events (SAEs) whether or not related to study drug.
Time frame: From study enrollment up to Week 26 (for the 24-Week Treatment Group) and up to Week 54 (for the 52-WeekTreatment Group)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 24-Week Treatment Group | Number of Participants With Serious Adverse Events (SAEs) | 5 Participants |
| 52-Week Treatment Group | Number of Participants With Serious Adverse Events (SAEs) | 3 Participants |