Efficacy and Safety of 20 mg Sumatriptan Powder Delivered Intranasally With the Bi-directional Device Compared With 100 mg Sumatriptan Tablets in Adults With Acute Migraine With or Without Aura

Study Overview
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Brief Summary
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This study is being conducted to determine if OPTINOSE SUMATRIPTAN delivered nasally (through the nose) using the OPTINOSE SUMATRIPTAN DEVICE can reduce the pain associated with migraine headaches in 30 minutes after use.

Detailed Description
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The primary objective for this study is to compare the proportion of attacks in which pain reduction (defined as a decrease in pain intensity of at least 1 point) is achieved at 30 minutes following 20 mg OPTINOSE SUMATRIPTAN treatment with 100 mg Sumatriptan Tablets

Official Title
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A Randomized, Double-Blind, Double-Dummy, Active-Controlled, Cross-Over Study Evaluating the Efficacy and Safety of 20 mg Sumatriptan Powder Delivered Intranasally With the Bi-directional Device Compared With 100 mg Sumatriptan Tablets in Adults With Acute Migraine With or Without Aura

Conditions
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Migraine, Headaches

Intervention / Treatment
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* Drug: 100 mg Sumatriptan Tablet and OPTINOSE Placebo delivered nasally
* Drug: OPTINOSE SUMATRIPTAN delivered nasally and placebo tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Man or woman, between the ages of 18 to 65 years, inclusive at screening Have a diagnosis of episodic migraine, with or without aura according to InternationalClassification of Headache Disorders (2nd Edition) (ICHD-2) for at least 1 year prior to screening Experiences between 2 and 8 migraine attacks per month for the past 12 months Women of child bearing potential must be practicing an effective method of birth control Women of child-bearing potential must have a negative urine pregnancy test at the screening visit and a negative urine pregnancy test at the randomization visit Demonstrate the ability to use the bi-directional delivery device correctly Able and willing to read and comprehend written instructions and complete the electronic diary information required by the protocol Must be capable, in the opinion of the Investigator, of providing informed consent to participate in the study. Subjects (and their legally acceptable representatives, if applicable) must sign an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study Exclusion Criteria: Inability to distinguish other headaches from migraine Experiences headache of any kind at a frequency greater than or equal to 15 days per month History of resistance to sumatriptan, or non-response to 2 or more other triptans, defined as subjects who have not responded to an adequate dose and duration of treatment Current use of medication for migraine prophylaxis that has not been stable (no dose adjustment) for 30 days prior to screening Chronic opioid therapy (>3 consecutive days in the 30 days prior to screening) Current treatment with monoamine oxidase A (MAO-A) inhibitors or use within 4 weeks before randomization Have hemiplegic or basilar migraine History, symptoms or signs of ischemic cardiac, cerebrovascular or peripheral vascular syndromes. Ischemic cardiac syndromes include, but are not limited to, angina pectoris of any type (e.g., stable angina of effort, vasospastic forms of angina such as the Prinzmetal variant), all forms of myocardial infarction and silent myocardial ischemia. Cerebrovascular syndromes include, but are not limited to, strokes of any type as well as transient ischemic attacks. Peripheral vascular disease includes, but is not limited to, ischemic bowel disease, Raynaud syndrome Uncontrolled hypertension (screening systolic/diastolic blood pressure >140/95 mmHg) Have severe hepatic impairment Have history of epilepsy or conditions associated with a lowered seizure threshold History (within 2 years) of drug or alcohol abuse as defined by Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV) criteria

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OPTINOSE SUMATRIPTAN and Placebo<br>20 mg OPTINOSE SUMATRIPTAN Powder Delivered Intranasally With the Bi-directional Device nasally and Placebo Tablet | Drug: OPTINOSE SUMATRIPTAN delivered nasally and placebo tablet<br> <br> |
| Active Comparator: 100mg Sumatriptan and OPTINOSE Placebo<br>100 mg Sumatriptan Tablet and OPTINOSE Placebo delivered nasally | Drug: 100 mg Sumatriptan Tablet and OPTINOSE Placebo delivered nasally<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Sum of Migraine Pain Intensity Differences (SPID)-30 | SPID-30 is defined as the sum of the pain intensity differences (measured as area under the curve) from dosing (Baseline) through 30 minutes post-dose for headaches with a Baseline intensity of mild, moderate, or severe. The range of possible scores is -60 to +90. A higher number indicates a greater reduction in pain intensity. Negative values indicate worsening pain. A value of 0 indicates that there was no change in pain intensity from Baseline through 30 minutes. Results are from an analysis of covariance (ANCOVA) model with treatment, period, and treatment sequence as fixed effects and participant as a random effect. The Last Observation Carried Forward (LOCF) imputation method (missing values were replaced by carrying forward the preceding value) was used for this analysis. | Baseline and 30 minutes post-dose (up to 24 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Sum of Migraine Pain Intensity Differences (SPID)-30 for Headaches With a Baseline Intensity of Mild and Moderate/Severe | SPID-30 is defined as the sum of the pain intensity differences (measured as area under the curve) from dosing (Baseline) through 30 minutes post-dose for headaches with a Baseline intensity of mild and moderate/severe (rated on a 4-point scale: 0=none, 1=mild, 2=moderate, and 3=severe). The range of possible scores for all participants is -60 to +90. For participants with a mild headache at Baseline, the SPID range is -60 to +30. For participants with a moderate/severe headache at Baseline, the SPID range is -30 to +90. A higher number indicates a greater reduction in pain intensity. Negative values indicate worsening pain. A value of 0 indicates that there was no change in pain intensity from Baseline through 30 minutes. Results are from an ANCOVA model with treatment, period, and treatment sequence as fixed effects and participant as a random effect. The LOCF imputation method (missing values were replaced by carrying forward the preceding value) was used for this analysis. | Baseline and 30 minutes post-dose (up to 24 weeks) | 
| Percentage of Attacks in Which Pain Reduction Was Achieved | Percentage of attacks in which pain reduction (defined as a decrease in pain intensity of at least one point on the following scale: 0, none; 1, mild; 2, moderate; 3, severe) was achieved at 10, 15, 30, 45, 60, 90, and 120 minutes after the initial dose for all attacks. | 10, 15, 30, 45, 60, 90, and 120 minutes | 
| Percentage of Attacks in Which Pain Freedom Was Achieved | Percentage of attacks in which pain freedom (defined as pain level reduced to none [Grade 0]) was achieved at 10, 15, 30, 45, 60, 90, and 120 minutes after the initial dose for all attacks. | Baseline and 10, 15, 30, 45, 60, 90, and 120 minutes post-dose (up to 24 weeks) | 
| Percentage of Attacks in Which Pain Relief Was Achieved | Percentage of attacks treated at a severity of moderate (Grade 2) or severe (Grade 3) in which pain relief (defined as pain level reduced to none [Grade 0] or mild [Grade 1]) was achieved at 10, 15, 30, 45, 60, 90, and 120 minutes after the initial dose for all attacks. | Baseline and 10, 15, 30, 45, 60, 90, and 120 minutes post-dose (up to 24 weeks) | 
| Median Time to Pain Freedom | Pain freedom is defined as a pain level reduced to none (Grade 0). | 120 minutes post-dose (up to 24 weeks) | 
| Mean Change in Headache Severity From Baseline to 10, 15, 30, 45, 60, 90, and 120 Minutes Post-dose | Participants were required to record their headache severity score in their e-diaries immediately before intake of study medication (Baseline) and at 10, 15, 30, 45, 60, 90, and 120 minutes post-dose. Participants graded their headaches on the following severity scale: 0, none; 1, mild; 2, moderate; 3, severe. Mean change from Baseline was calculated as the post-Baseline value minus the Baseline value. | Baseline and 10, 15, 30, 45, 60, 90, and 120 minutes post-dose (up to 24 weeks) | 
| Mean Change From Baseline in Clinical Disability Score at 10, 15, 30, 45, 60, 90, and 120 Minutes Post-dose | Participants were required to record their clinical disability score in their e-diaries immediately before intake of study medication (Baseline) and at 10, 15, 30, 45, 60, 90, and 120 minutes post-dose. Participants graded their disability on the following scale: 0, no disability, able to function normally; 1, performance of daily activities mildly impaired, can still do everything but with difficulty; 2, performance of daily activities moderately impaired, unable to do some things; 3, performance of daily activities severely impaired, cannot do all or most things, bed rest may be necessary. Mean change from Baseline was calculated as the post-Baseline value minus the Baseline value. | Baseline and 10, 15, 30, 45, 60, 90, and 120 minutes post-dose (up to 24 weeks) | 
| Number of Participants With Any Treatment-emergent Non-serious and Serious Adverse Event | An adverse event is defined as any untoward medical occurrence associated with the use of an investigational product in humans, whether or not it is considered related to the investigational product. This includes any occurrence that was new in onset or aggravated in severity or frequency from the Baseline condition. | Baseline compared to Vist 2, 3 and 4 | 
| Change From Baseline in Hemoglobin at Visit 3 (up to 12 Weeks) and Visit 4 (up to 24 Weeks) | Change from Baseline in hemoglobin was assessed at Visit 3 (the start of Treatment Period 2) and Visit 4 (the end-of-study visit). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value is the last non-missing value prior to or on the start date of Treatment Period 1. | Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks) | 
| Change From Baseline in Hematocrit at Visit 3 (up to 12 Weeks) and Visit 4 (up to 24 Weeks) | Change from Baseline in hematocrit (proportion of total blood volume that is composed of red blood cells) was assessed at Visit 3 (the start of Treatment Period 2) and Visit 4 (the end-of-study visit). Change from Baseline was calculated as the post-Baseline value minus the Baseline value.The Baseline value is the last non-missing value prior to or on the start date of Treatment Period 1. | Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks) | 
| Change From Baseline in Red Blood Cell Count at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) | Change from Baseline in red blood cell count was assessed at Visit 3 (the start of Treatment Period 2) and Visit 4 (the end-of-study visit). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value is the last non-missing value prior to or on the start date of Treatment Period 1. | Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks) | 
| Change From Baseline in White Blood Cell Count, Basinophils, Monocytes, Neutrophils, Lymphocytes, Eosinophils, and Platelets at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) | Change from Baseline in white blood cell (WBC) count, basinophils, monocytes, neutrophils, lymphocytes, eosinophils, and platelets was assessed at Visit 3 (the start of Treatment Period 2) and Visit 4 (the end-of-study visit). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value is the last non-missing value prior to or on the start date of Treatment Period 1. | Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks) | 
| Change From Baseline in Urea at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) | Change from Baseline in urea was assessed at Visit 3 (the start of Treatment Period 2) and Visit 4 (the end-of-study visit). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value is the last non-missing value prior to or on the start date of Treatment Period 1. | Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks) | 
| Change From Baseline in Creatinine at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) | Change from Baseline in creatinine was assessed at Visit 3 (the start of Treatment Period 2) and Visit 4 (the end-of-study visit). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value is the last non-missing value prior to or on the start date of Treatment Period 1. | Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks) | 
| Change From Baseline in Alkaline Phosphatase (ALP) and Alanine Aminotransferase (ALT) at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) | Change from Baseline in ALP and ALT was assessed at Visit 3 (the start of Treatment Period 2) and Visit 4 (the end-of-study visit). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value is the last non-missing value prior to or on the start date of Treatment Period 1. | Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks) | 
| Change From Baseline in Aspartate Aminotransferase (AST) and Gamma Glutamyl Transferase (GGT) at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) | Change from Baseline in AST and GGT was assessed at Visit 3 (the start of Treatment Period 2) and Visit 4 (the end-of-study visit). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value is the last non-missing value prior to or on the start date of Treatment Period 1. | Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks) | 
| Change From Baseline in Total Bilirubin at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) | Change from Baseline in total bilirubin was assessed at Visit 3 (the start of Treatment Period 2) and Visit 4 (the end-of-study visit). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value is the last non-missing value prior to or on the start date of Treatment Period 1. | Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks) | 
| Change From Baseline in Albumin and Total Protein at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) | Change from Baseline in albumin and total protein was assessed at Visit 3 (the start of Treatment Period 2) and Visit 4 (the end-of-study visit). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value is the last non-missing value prior to or on the start date of Treatment Period 1. | Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks) | 
| Change From Baseline in Sodium, Potassium, Chloride, Calcium, and Glucose at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) | Change from Baseline in sodium, potassium, chloride, calcium, and glucose was assessed at Visit 3 (the start of Treatment Period 2) and Visit 4 (the end-of-study visit). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value is the last non-missing value prior to or on the start date of Treatment Period 1. | Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks) | 
| Change From Baseline in Urinalysis Values by Dipstick Method at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) | Change from Baseline in urinalysis values was assessed at Visit 3 (the start of Treatment Period 2) and Visit 4 (the end-of-study visit). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value is the last non-missing value prior to or on the start date of Treatment Period 1. | Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks) | 
| Number of Participants With the Indicated Amounts of Protein, Glucose, Ketones, Blood, and White Blood Cells (WBCs) in Urine at Baseline, Visit 3 (up to Week 12), and Visit 4 (up to Week 24) | The Baseline value is the last non-missing value prior to or on the start date of Treatment Period 1. Data are based on standard reads, with 1+, 2+, and 3+ indicating increasing amounts of metabolites in urine. | Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks) | 
| Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) | Change from Baseline in SBP and DBP was assessed at Visit 3 (the start of Treatment Period 2) and Visit 4 (the end-of-study visit). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value is the last non-missing value prior to or on the start date of Treatment Period 1. | Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks) | 
| Change From Baseline in Pulse at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) | Change from Baseline in pulse was assessed at Visit 3 (the start of Treatment Period 2) and Visit 4 (the end-of-study visit). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value is the last non-missing value prior to or on the start date of Treatment Period 1. | Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks) | 
| Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Findings at Baseline, Visit 3 (up to Week 12), and Visit 4 (up to Week 24) | The Baseline value is the last non-missing value prior to or on the start date of Treatment Period 1. Clinical significance was determined by the Investigator (per clinical judgement). A categorization of normal or abnormal was made per the investigators' clinical judgment of the ECG, taking the participants' demographic characteristics and other medical conditions into account. CS = clinically significant. CNS = clinically not significant. | Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks) | 
| Number of Participants With the Indicated Physical Examination Abnormalities at Baseline, Visit 3 (up to Week 12), and Visit 4 (up to Week 24) | The Baseline value is the last non-missing value prior to or on the start date of Treatment Period 1. Clinical significance was determined by the Investigator (per clinical judgement). CS = clinically significant. CNS = clinically not significant. | Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks) | 
| Number of Participants With the Indicated Concomitant Medications | Concomitant medications are defined as non-study medications with a start or stop date between the first dose of study medication and the end of safety follow-up, inclusive. Derm. = dermatologic; incl. - including. | up to 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Migraine, Headaches, Sumatriptan