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

Phase 3

Completed

Conditions: Migraine
Headaches

Interventions: Drug: OPTINOSE SUMATRIPTAN delivered nasally and placebo tablet
Drug: 100 mg Sumatriptan Tablet and OPTINOSE Placebo delivered nasally

Registration Number: NCT01667679

Lead Sponsor: Avanir Pharmaceuticals

Brief Summary: 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: 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

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 275

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
OPTINOSE SUMATRIPTAN and Placebo	OPTINOSE SUMATRIPTAN delivered nasally and placebo tablet	20 mg OPTINOSE SUMATRIPTAN Powder Delivered Intranasally With the Bi-directional Device nasally and Placebo Tablet
100mg Sumatriptan and OPTINOSE Placebo	100 mg Sumatriptan Tablet and OPTINOSE Placebo delivered nasally	100 mg Sumatriptan Tablet and OPTINOSE Placebo delivered nasally

Primary Outcome Measures

Name	Time	Method
Mean Sum of Migraine Pain Intensity Differences (SPID)-30	Baseline and 30 minutes post-dose (up to 24 weeks)	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.

Secondary Outcome Measures

Name	Time	Method
Mean Sum of Migraine Pain Intensity Differences (SPID)-30 for Headaches With a Baseline Intensity of Mild and Moderate/Severe	Baseline and 30 minutes post-dose (up to 24 weeks)	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.
Percentage of Attacks in Which Pain Reduction Was Achieved	10, 15, 30, 45, 60, 90, and 120 minutes	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.
Percentage of Attacks in Which Pain Freedom Was Achieved	Baseline and 10, 15, 30, 45, 60, 90, and 120 minutes post-dose (up to 24 weeks)	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.
Percentage of Attacks in Which Pain Relief Was Achieved	Baseline and 10, 15, 30, 45, 60, 90, and 120 minutes post-dose (up to 24 weeks)	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.
Median Time to Pain Freedom	120 minutes post-dose (up to 24 weeks)	Pain freedom is defined as a pain level reduced to none (Grade 0).
Mean Change in Headache Severity From Baseline to 10, 15, 30, 45, 60, 90, and 120 Minutes Post-dose	Baseline and 10, 15, 30, 45, 60, 90, and 120 minutes post-dose (up to 24 weeks)	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.
Mean Change From Baseline in Clinical Disability Score at 10, 15, 30, 45, 60, 90, and 120 Minutes Post-dose	Baseline and 10, 15, 30, 45, 60, 90, and 120 minutes post-dose (up to 24 weeks)	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.
Number of Participants With Any Treatment-emergent Non-serious and Serious Adverse Event	Baseline compared to Vist 2, 3 and 4	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.
Change From Baseline in Hemoglobin at Visit 3 (up to 12 Weeks) and Visit 4 (up to 24 Weeks)	Baseline and Visits 3 (up to 12 weeks) and 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.
Change From Baseline in Hematocrit at Visit 3 (up to 12 Weeks) and Visit 4 (up to 24 Weeks)	Baseline and Visits 3 (up to 12 weeks) and 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.
Change From Baseline in Red Blood Cell Count at Visit 3 (up to Week 12) and Visit 4 (up to Week 24)	Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks)	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.
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)	Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks)	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.
Change From Baseline in Urea at Visit 3 (up to Week 12) and Visit 4 (up to Week 24)	Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks)	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.
Change From Baseline in Creatinine at Visit 3 (up to Week 12) and Visit 4 (up to Week 24)	Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks)	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.
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)	Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks)	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.
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)	Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks)	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.
Change From Baseline in Total Bilirubin at Visit 3 (up to Week 12) and Visit 4 (up to Week 24)	Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks)	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.
Change From Baseline in Albumin and Total Protein at Visit 3 (up to Week 12) and Visit 4 (up to Week 24)	Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks)	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.
Change From Baseline in Sodium, Potassium, Chloride, Calcium, and Glucose at Visit 3 (up to Week 12) and Visit 4 (up to Week 24)	Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks)	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.
Change From Baseline in Urinalysis Values by Dipstick Method at Visit 3 (up to Week 12) and Visit 4 (up to Week 24)	Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks)	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.
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)	Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks)	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.
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)	Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks)	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.
Change From Baseline in Pulse at Visit 3 (up to Week 12) and Visit 4 (up to Week 24)	Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks)	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.
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)	Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks)	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.
Number of Participants With the Indicated Physical Examination Abnormalities at Baseline, Visit 3 (up to Week 12), and Visit 4 (up to Week 24)	Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks)	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.
Number of Participants With the Indicated Concomitant Medications	up to 24 weeks	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.

Trial Locations

Locations (13): ClinVest
🇺🇸
Springfield, Missouri, United States
San Francisco Clinical Research Center
🇺🇸
San Francisco, California, United States
Michigan Head and Pain Institute
🇺🇸
Ann Arbor, Michigan, United States
California Medical Clinic for Headache
🇺🇸
Santa Monica, California, United States
MedVadis
🇺🇸
Watertown, Massachusetts, United States
Associated Neurologists of Southern CT, P.C.
🇺🇸
Fairfied, Connecticut, United States
Premiere Research Institute
🇺🇸
West Palm Beach, Florida, United States
Mercy Health Research
🇺🇸
St. Louis, Missouri, United States
PMG Research of Winston Salem, LLC
🇺🇸
Winston Salem, North Carolina, United States
Headache Welness Center
🇺🇸
Greensboro, North Carolina, United States
Coastal Carolina Research Center
🇺🇸
Mt. Pleasant, South Carolina, United States
DENT Neurologic Institute
🇺🇸
Amherst, New York, United States
Jefferson Headache Center
🇺🇸
Philadelphia, Pennsylvania, United States