Trial Outcomes & Findings for 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 (NCT NCT01667679)

NCT ID: NCT01667679

Last Updated: 2017-04-12

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 275 participants
• Primary outcome timeframe: Baseline and 30 minutes post-dose (up to 24 weeks)
• Results posted on: 2017-04-12

Participant Flow

A total of 334 participants were assessed for eligibility; of these, 275 participants were randomized.

Participant milestones

Measure	20 mg Sumatriptan+PBO (TP1)/100 mg Sumatriptan+PBO (TP2) In Treatment Period (TP) 1 (\<=12 weeks), participants received 20 milligrams (mg) sumatriptan nasal powder delivered intranasally with a bi-directional device and a placebo (PBO) tablet taken orally. After completing Treatment Period 1 (upon reaching 12 weeks or treating the fifth qualifying migraine headache in the treatment period, whichever came first), participants entered Treatment Period 2 (\<=12 weeks), during which they received a 100 mg sumatriptan tablet taken orally and placebo (lactose) as a nasal powder administered into the nostril on the side of the migraine, followed by another administration into the other nostril. Participants were to treat \<=5 qualifying migraine headaches during Treatment Period 2.	100 mg Sumatriptan+PBO (TP1)/20 mg Sumatriptan+PBO (TP2) In Treatment Period 1 (\<=12 weeks), participants received a 100 mg sumatriptan tablet taken orally and placebo (lactose) as a nasal powder administered into the nostril on the side of the migraine, followed by another administration into the other nostril. After completing Treatment Period 1 (upon reaching 12 weeks or treating the fifth qualifying migraine headache in the treatment period, whichever came first), participants entered Treatment Period 2 (\<=12 weeks), during which they received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device and a placebo tablet taken orally. Participants were to treat \<=5 qualifying migraine headaches during Treatment Period 2.
Treatment Period 1 (<=12 Weeks) STARTED	138	137
Treatment Period 1 (<=12 Weeks) COMPLETED	122	107
Treatment Period 1 (<=12 Weeks) NOT COMPLETED	16	30
Treatment Period 2 (<=12 Weeks) STARTED	122	107
Treatment Period 2 (<=12 Weeks) COMPLETED	100	85
Treatment Period 2 (<=12 Weeks) NOT COMPLETED	22	22

Reasons for withdrawal

Measure	20 mg Sumatriptan+PBO (TP1)/100 mg Sumatriptan+PBO (TP2) In Treatment Period (TP) 1 (\<=12 weeks), participants received 20 milligrams (mg) sumatriptan nasal powder delivered intranasally with a bi-directional device and a placebo (PBO) tablet taken orally. After completing Treatment Period 1 (upon reaching 12 weeks or treating the fifth qualifying migraine headache in the treatment period, whichever came first), participants entered Treatment Period 2 (\<=12 weeks), during which they received a 100 mg sumatriptan tablet taken orally and placebo (lactose) as a nasal powder administered into the nostril on the side of the migraine, followed by another administration into the other nostril. Participants were to treat \<=5 qualifying migraine headaches during Treatment Period 2.	100 mg Sumatriptan+PBO (TP1)/20 mg Sumatriptan+PBO (TP2) In Treatment Period 1 (\<=12 weeks), participants received a 100 mg sumatriptan tablet taken orally and placebo (lactose) as a nasal powder administered into the nostril on the side of the migraine, followed by another administration into the other nostril. After completing Treatment Period 1 (upon reaching 12 weeks or treating the fifth qualifying migraine headache in the treatment period, whichever came first), participants entered Treatment Period 2 (\<=12 weeks), during which they received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device and a placebo tablet taken orally. Participants were to treat \<=5 qualifying migraine headaches during Treatment Period 2.
Treatment Period 1 (<=12 Weeks) Failure to Treat Migraine Headache	2	6
Treatment Period 1 (<=12 Weeks) Dosed Incorrectly	2	0
Treatment Period 1 (<=12 Weeks) Lack of Efficacy	2	0
Treatment Period 1 (<=12 Weeks) Could Not Tolerate Diary	1	0
Treatment Period 1 (<=12 Weeks) Withdrawal by Subject	6	13
Treatment Period 1 (<=12 Weeks) Adverse Event	3	3
Treatment Period 1 (<=12 Weeks) Lost to Follow-up	0	2
Treatment Period 1 (<=12 Weeks) Protocol Violation	0	2
Treatment Period 1 (<=12 Weeks) Non-compliance	0	3
Treatment Period 1 (<=12 Weeks) Moved Out of State	0	1
Treatment Period 2 (<=12 Weeks) Withdrawal by Subject	6	4
Treatment Period 2 (<=12 Weeks) Non-compliance with Electronic Diary	2	0
Treatment Period 2 (<=12 Weeks) Lost to Follow-up	8	10
Treatment Period 2 (<=12 Weeks) Non-compliance	3	4
Treatment Period 2 (<=12 Weeks) Sponsor Decision	1	0
Treatment Period 2 (<=12 Weeks) Failure to Treat Migraine Headache	1	0
Treatment Period 2 (<=12 Weeks) Adverse Event	1	0
Treatment Period 2 (<=12 Weeks) Significant Improvement in Migraine	0	1
Treatment Period 2 (<=12 Weeks) Partially Dosed	0	1
Treatment Period 2 (<=12 Weeks) Brought in before 12 Weeks/5 Migraines	0	1
Treatment Period 2 (<=12 Weeks) Refused Last Day of Visit 4 Procedures	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	20 mg Sumatriptan+PBO (TP1)/100 mg Sumatriptan+PBO (TP2) n=133 Participants In Treatment Period 1 (\<=12 weeks), participants received 20 milligrams (mg) sumatriptan nasal powder delivered intranasally with a bi-directional device and a placebo (PBO) tablet taken orally. After completing Treatment Period 1, participants entered Treatment Period 2 (\<=12 weeks), during which they received a 100 mg sumatriptan tablet taken orally and placebo (lactose) as a nasal powder administered into the nostril on the side of the migraine, followed by another administration into the other nostril.	100 mg Sumatriptan+PBO (TP1)/20 mg Sumatriptan+PBO (TP2) n=129 Participants In Treatment Period 1 (\<=12 weeks), participants received a 100 mg sumatriptan tablet taken orally and placebo (lactose) as a nasal powder administered into the nostril on the side of the migraine, followed by another administration into the other nostril. After completing Treatment Period 1, participants entered Treatment Period 2 (\<=12 weeks), during which they received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device and a placebo tablet taken orally.	Total n=262 Participants Total of all reporting groups
Age, Continuous	39.5 Years STANDARD_DEVIATION 12.55 • n=5 Participants	40.7 Years STANDARD_DEVIATION 11.93 • n=7 Participants	40.1 Years STANDARD_DEVIATION 12.24 • n=5 Participants
Sex: Female, Male Female	107 Participants n=5 Participants	115 Participants n=7 Participants	222 Participants n=5 Participants
Sex: Female, Male Male	26 Participants n=5 Participants	14 Participants n=7 Participants	40 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	24 Participants n=5 Participants	26 Participants n=7 Participants	50 Participants n=5 Participants
Race (NIH/OMB) White	104 Participants n=5 Participants	100 Participants n=7 Participants	204 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 30 minutes post-dose (up to 24 weeks)

Population: Full Analysis Set (FAS): all participants who experienced at least 1 headache attack per treatment period, received at least 1 dose of study medication (sumatriptan nasal powder or tablet) in each treatment period, and had at least 1 post-Baseline assessment for a treated attack in each treatment period.

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.

Outcome measures

Measure	20 mg Sumatriptan Nasal Powder n=185 Participants Participants received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device in Treatment Period 1 or Treatment Period 2.	100 mg Sumatriptan Tablet n=185 Participants Participants received a 100 mg sumatriptan tablet taken orally in Treatment Period 1 or Treatment Period 2.
Mean Sum of Migraine Pain Intensity Differences (SPID)-30	10.80 scores on a scale Standard Error 0.880	7.41 scores on a scale Standard Error 0.880

SECONDARY outcome

Timeframe: Baseline and 30 minutes post-dose (up to 24 weeks)

Population: FAS. Only those participants with the type of attack specified were analyzed (specified by n=X, X in the corresponding category title). A single participant could have had both a mild and a moderate/severe attack.

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.

Outcome measures

Measure	20 mg Sumatriptan Nasal Powder n=185 Participants Participants received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device in Treatment Period 1 or Treatment Period 2.	100 mg Sumatriptan Tablet n=185 Participants Participants received a 100 mg sumatriptan tablet taken orally in Treatment Period 1 or Treatment Period 2.
Mean Sum of Migraine Pain Intensity Differences (SPID)-30 for Headaches With a Baseline Intensity of Mild and Moderate/Severe mild attacks, n=113, 109	3.90 scores on a scale Standard Error 0.921	0.24 scores on a scale Standard Error 0.931
Mean Sum of Migraine Pain Intensity Differences (SPID)-30 for Headaches With a Baseline Intensity of Mild and Moderate/Severe moderate/severe attacks, n=158, 168	13.83 scores on a scale Standard Error 1.022	10.07 scores on a scale Standard Error 0.997

SECONDARY outcome

Timeframe: 10, 15, 30, 45, 60, 90, and 120 minutes

Population: FAS. The LOCF imputation method was used in this analysis.

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.

Outcome measures

Measure	20 mg Sumatriptan Nasal Powder n=765 number of attacks Participants received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device in Treatment Period 1 or Treatment Period 2.	100 mg Sumatriptan Tablet n=766 number of attacks Participants received a 100 mg sumatriptan tablet taken orally in Treatment Period 1 or Treatment Period 2.
Percentage of Attacks in Which Pain Reduction Was Achieved 10 minutes post-dose	11.5 percentage of attacks	10.2 percentage of attacks
Percentage of Attacks in Which Pain Reduction Was Achieved 15 minutes post-dose	26.4 percentage of attacks	19.6 percentage of attacks
Percentage of Attacks in Which Pain Reduction Was Achieved 30 minutes post-dose	49.0 percentage of attacks	35.2 percentage of attacks
Percentage of Attacks in Which Pain Reduction Was Achieved 45 minutes post-dose	60.7 percentage of attacks	49.9 percentage of attacks
Percentage of Attacks in Which Pain Reduction Was Achieved 60 minutes post-dose	67.2 percentage of attacks	59.8 percentage of attacks
Percentage of Attacks in Which Pain Reduction Was Achieved 90 minutes post-dose	74.6 percentage of attacks	69.8 percentage of attacks
Percentage of Attacks in Which Pain Reduction Was Achieved 120 minutes post-dose	78.0 percentage of attacks	75.2 percentage of attacks

SECONDARY outcome

Timeframe: Baseline and 10, 15, 30, 45, 60, 90, and 120 minutes post-dose (up to 24 weeks)

Population: FAS. The LOCF imputation method was used for this analysis.

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.

Outcome measures

Measure	20 mg Sumatriptan Nasal Powder n=765 number of attacks Participants received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device in Treatment Period 1 or Treatment Period 2.	100 mg Sumatriptan Tablet n=766 number of attacks Participants received a 100 mg sumatriptan tablet taken orally in Treatment Period 1 or Treatment Period 2.
Percentage of Attacks in Which Pain Freedom Was Achieved 10 minutes post-dose	2.5 percentage of attacks	1.3 percentage of attacks
Percentage of Attacks in Which Pain Freedom Was Achieved 15 minutes post-dose	7.2 percentage of attacks	3.7 percentage of attacks
Percentage of Attacks in Which Pain Freedom Was Achieved 30 minutes post-dose	18.2 percentage of attacks	10.8 percentage of attacks
Percentage of Attacks in Which Pain Freedom Was Achieved 45 minutes post-dose	31.0 percentage of attacks	21.3 percentage of attacks
Percentage of Attacks in Which Pain Freedom Was Achieved 60 minutes post-dose	41.2 percentage of attacks	32.9 percentage of attacks
Percentage of Attacks in Which Pain Freedom Was Achieved 90 minutes post-dose	52.8 percentage of attacks	44.9 percentage of attacks
Percentage of Attacks in Which Pain Freedom Was Achieved 120 minutes post-dose	60.4 percentage of attacks	56.3 percentage of attacks

SECONDARY outcome

Timeframe: Baseline and 10, 15, 30, 45, 60, 90, and 120 minutes post-dose (up to 24 weeks)

Population: FAS. The LOCF imputation method was used in this analysis.

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.

Outcome measures

Measure	20 mg Sumatriptan Nasal Powder n=509 number of moderate or severe attacks Participants received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device in Treatment Period 1 or Treatment Period 2.	100 mg Sumatriptan Tablet n=532 number of moderate or severe attacks Participants received a 100 mg sumatriptan tablet taken orally in Treatment Period 1 or Treatment Period 2.
Percentage of Attacks in Which Pain Relief Was Achieved 60 minutes post-dose	72.1 percentage of attacks	62.6 percentage of attacks
Percentage of Attacks in Which Pain Relief Was Achieved 90 minutes post-dose	77.4 percentage of attacks	72.0 percentage of attacks
Percentage of Attacks in Which Pain Relief Was Achieved 120 minutes post-dose	79.6 percentage of attacks	76.9 percentage of attacks
Percentage of Attacks in Which Pain Relief Was Achieved 10 minutes post-dose	13.8 percentage of attacks	11.5 percentage of attacks
Percentage of Attacks in Which Pain Relief Was Achieved 15 minutes post-dose	27.9 percentage of attacks	20.9 percentage of attacks
Percentage of Attacks in Which Pain Relief Was Achieved 30 minutes post-dose	53.8 percentage of attacks	38.7 percentage of attacks
Percentage of Attacks in Which Pain Relief Was Achieved 45 minutes post-dose	65.0 percentage of attacks	53.9 percentage of attacks

SECONDARY outcome

Timeframe: 120 minutes post-dose (up to 24 weeks)

Population: FAS. If the participant did not report pain freedom within 120 minutes post-dose, he/she was considered to be censored at the last non-missing result prior to the 120-minute time point.

Pain freedom is defined as a pain level reduced to none (Grade 0).

Outcome measures

Measure	20 mg Sumatriptan Nasal Powder n=185 Participants Participants received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device in Treatment Period 1 or Treatment Period 2.	100 mg Sumatriptan Tablet n=185 Participants Participants received a 100 mg sumatriptan tablet taken orally in Treatment Period 1 or Treatment Period 2.
Median Time to Pain Freedom	91 minutes The confidence interval is un-estimable due to the number of participants who were observed pain free at the post-dose time points.	121 minutes Interval 91.0 to 121.0

SECONDARY outcome

Timeframe: Baseline and 10, 15, 30, 45, 60, 90, and 120 minutes post-dose (up to 24 weeks)

Population: FAS. The LOCF imputation method was used for this analysis. Results are from an ANCOVA model with treatment, period, and treatment sequence as fixed effects and participant as a random effect.

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.

Outcome measures

Measure	20 mg Sumatriptan Nasal Powder n=185 Participants Participants received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device in Treatment Period 1 or Treatment Period 2.	100 mg Sumatriptan Tablet n=185 Participants Participants received a 100 mg sumatriptan tablet taken orally in Treatment Period 1 or Treatment Period 2.
Mean Change in Headache Severity From Baseline to 10, 15, 30, 45, 60, 90, and 120 Minutes Post-dose 10 minutes post-dose	-0.11 scores on a scale Standard Error 0.018	-0.09 scores on a scale Standard Error 0.018
Mean Change in Headache Severity From Baseline to 10, 15, 30, 45, 60, 90, and 120 Minutes Post-dose 15 minutes post-dose	-0.26 scores on a scale Standard Error 0.029	-0.18 scores on a scale Standard Error 0.029
Mean Change in Headache Severity From Baseline to 10, 15, 30, 45, 60, 90, and 120 Minutes Post-dose 30 minutes post-dose	-0.56 scores on a scale Standard Error 0.042	-0.38 scores on a scale Standard Error 0.042
Mean Change in Headache Severity From Baseline to 10, 15, 30, 45, 60, 90, and 120 Minutes Post-dose 45 minutes post-dose	-0.77 scores on a scale Standard Error 0.049	-0.60 scores on a scale Standard Error 0.049
Mean Change in Headache Severity From Baseline to 10, 15, 30, 45, 60, 90, and 120 Minutes Post-dose 60 minutes post-dose	-0.93 scores on a scale Standard Error 0.051	-0.79 scores on a scale Standard Error 0.051
Mean Change in Headache Severity From Baseline to 10, 15, 30, 45, 60, 90, and 120 Minutes Post-dose 90 minutes post-dose	-1.09 scores on a scale Standard Error 0.052	-0.98 scores on a scale Standard Error 0.052
Mean Change in Headache Severity From Baseline to 10, 15, 30, 45, 60, 90, and 120 Minutes Post-dose 120 minutes post-dose	-1.19 scores on a scale Standard Error 0.053	-1.15 scores on a scale Standard Error 0.053

SECONDARY outcome

Timeframe: Baseline and 10, 15, 30, 45, 60, 90, and 120 minutes post-dose (up to 24 weeks)

Population: FAS. The LOCF imputation method was used for this analysis. Results are from an ANCOVA model with treatment, period, and treatment sequence as fixed effects and participant as a random effect.

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.

Outcome measures

Measure	20 mg Sumatriptan Nasal Powder n=185 Participants Participants received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device in Treatment Period 1 or Treatment Period 2.	100 mg Sumatriptan Tablet n=185 Participants Participants received a 100 mg sumatriptan tablet taken orally in Treatment Period 1 or Treatment Period 2.
Mean Change From Baseline in Clinical Disability Score at 10, 15, 30, 45, 60, 90, and 120 Minutes Post-dose 10 minutes post-dose	-0.08 scores on a scale Standard Error 0.017	-0.03 scores on a scale Standard Error 0.017
Mean Change From Baseline in Clinical Disability Score at 10, 15, 30, 45, 60, 90, and 120 Minutes Post-dose 15 minutes post-dose	-0.18 scores on a scale Standard Error 0.025	-0.09 scores on a scale Standard Error 0.025
Mean Change From Baseline in Clinical Disability Score at 10, 15, 30, 45, 60, 90, and 120 Minutes Post-dose 30 minutes post-dose	-0.42 scores on a scale Standard Error 0.038	-0.26 scores on a scale Standard Error 0.038
Mean Change From Baseline in Clinical Disability Score at 10, 15, 30, 45, 60, 90, and 120 Minutes Post-dose 45 minutes post-dose	-0.60 scores on a scale Standard Error 0.046	-0.43 scores on a scale Standard Error 0.046
Mean Change From Baseline in Clinical Disability Score at 10, 15, 30, 45, 60, 90, and 120 Minutes Post-dose 60 minutes post-dose	-0.73 scores on a scale Standard Error 0.049	-0.56 scores on a scale Standard Error 0.049
Mean Change From Baseline in Clinical Disability Score at 10, 15, 30, 45, 60, 90, and 120 Minutes Post-dose 90 minutes post-dose	-0.83 scores on a scale Standard Error 0.052	-0.72 scores on a scale Standard Error 0.052
Mean Change From Baseline in Clinical Disability Score at 10, 15, 30, 45, 60, 90, and 120 Minutes Post-dose 120 minutes post-dose	-0.92 scores on a scale Standard Error 0.054	-0.85 scores on a scale Standard Error 0.054

SECONDARY outcome

Timeframe: Baseline compared to Vist 2, 3 and 4

Population: Safety Analysis Set: all randomized participants who received at least 1 dose of either 20 mg sumatriptan nasal powder or 100 mg sumatriptan tablet

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.

Outcome measures

Measure	20 mg Sumatriptan Nasal Powder n=219 Participants Participants received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device in Treatment Period 1 or Treatment Period 2.	100 mg Sumatriptan Tablet n=228 Participants Participants received a 100 mg sumatriptan tablet taken orally in Treatment Period 1 or Treatment Period 2.
Number of Participants With Any Treatment-emergent Non-serious and Serious Adverse Event Treatment-emergent Adverse Event	118 participants	73 participants
Number of Participants With Any Treatment-emergent Non-serious and Serious Adverse Event Treatment-emergent Serious Adverse Event	0 participants	0 participants

SECONDARY outcome

Timeframe: Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks)

Population: Safety Analysis Set. Only those participants with data available at Visit 3 and Visit 4 were assessed at that respective visit (indicated by n=X, X in the category titles).

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.

Outcome measures

Measure	20 mg Sumatriptan Nasal Powder n=124 Participants Participants received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device in Treatment Period 1 or Treatment Period 2.	100 mg Sumatriptan Tablet n=110 Participants Participants received a 100 mg sumatriptan tablet taken orally in Treatment Period 1 or Treatment Period 2.
Change From Baseline in Hemoglobin at Visit 3 (up to 12 Weeks) and Visit 4 (up to 24 Weeks) Visit 3	-1.3 grams per Liter (g/L) Standard Deviation 6.07	-1.3 grams per Liter (g/L) Standard Deviation 6.66
Change From Baseline in Hemoglobin at Visit 3 (up to 12 Weeks) and Visit 4 (up to 24 Weeks) Visit 4	-2.7 grams per Liter (g/L) Standard Deviation 6.58	-0.8 grams per Liter (g/L) Standard Deviation 6.63

SECONDARY outcome

Timeframe: Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks)

Population: Safety Analysis Set. Only those participants with data available at Visit 3 and Visit 4 were assessed at that respective visit (indicated by n=X, X in the category titles).

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.

Outcome measures

Measure	20 mg Sumatriptan Nasal Powder n=124 Participants Participants received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device in Treatment Period 1 or Treatment Period 2.	100 mg Sumatriptan Tablet n=110 Participants Participants received a 100 mg sumatriptan tablet taken orally in Treatment Period 1 or Treatment Period 2.
Change From Baseline in Hematocrit at Visit 3 (up to 12 Weeks) and Visit 4 (up to 24 Weeks) Visit 3, n=108, 94	-0.002 proportion Standard Deviation 0.0204	-0.005 proportion Standard Deviation 0.0222
Change From Baseline in Hematocrit at Visit 3 (up to 12 Weeks) and Visit 4 (up to 24 Weeks) Visit 4, n=124, 110	-0.005 proportion Standard Deviation 0.0222	-0.002 proportion Standard Deviation 0.0198

SECONDARY outcome

Timeframe: Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks)

Population: Safety Analysis Set. Only those participants with data available at Visit 3 and Visit 4 were assessed at that respective visit (indicated by n=X, X in the category titles).

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.

Outcome measures

Measure	20 mg Sumatriptan Nasal Powder n=124 Participants Participants received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device in Treatment Period 1 or Treatment Period 2.	100 mg Sumatriptan Tablet n=110 Participants Participants received a 100 mg sumatriptan tablet taken orally in Treatment Period 1 or Treatment Period 2.
Change From Baseline in Red Blood Cell Count at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) Visit 4, n=124, 110	-0.05 10^12 cells per Liter Standard Deviation 0.228	-0.02 10^12 cells per Liter Standard Deviation 0.209
Change From Baseline in Red Blood Cell Count at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) Visit 3, n=109, 95	-0.02 10^12 cells per Liter Standard Deviation 0.227	-0.04 10^12 cells per Liter Standard Deviation 0.280

SECONDARY outcome

Timeframe: Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks)

Population: Safety Analysis Set. Only those participants with data available at Visit 3 and Visit 4 were assessed at that respective visit (indicated by n=X, X in the category titles).

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.

Outcome measures

Measure	20 mg Sumatriptan Nasal Powder n=124 Participants Participants received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device in Treatment Period 1 or Treatment Period 2.	100 mg Sumatriptan Tablet n=110 Participants Participants received a 100 mg sumatriptan tablet taken orally in Treatment Period 1 or Treatment Period 2.
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) WBC Count, Visit 3, n=109, 95	-0.10 10^9 cells per Liter Standard Deviation 1.398	-0.19 10^9 cells per Liter Standard Deviation 1.381
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) WBC Count, Visit 4, n=124, 110	-0.05 10^9 cells per Liter Standard Deviation 1.477	-0.09 10^9 cells per Liter Standard Deviation 1.464
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) Basophils, Visit 3, n=108, 95	0.000 10^9 cells per Liter Standard Deviation 0.0301	0.000 10^9 cells per Liter Standard Deviation 0.0297
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) Basophils, Visit 4, n=124, 110	0.000 10^9 cells per Liter Standard Deviation 0.0283	-0.001 10^9 cells per Liter Standard Deviation 0.0235
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) Monocytes, Visit 3, n=108, 95	-0.030 10^9 cells per Liter Standard Deviation 0.1356	-0.022 10^9 cells per Liter Standard Deviation 0.1160
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) Monocytes, Visit 4, n=124, 110	-0.014 10^9 cells per Liter Standard Deviation 0.1504	-0.026 10^9 cells per Liter Standard Deviation 0.1281
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) Neutrophils, Visit 3, n=108, 95	-0.052 10^9 cells per Liter Standard Deviation 1.2553	-0.134 10^9 cells per Liter Standard Deviation 1.1600
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) Neutrophils, Visit 4, n=124, 110	-0.059 10^9 cells per Liter Standard Deviation 1.4270	-0.057 10^9 cells per Liter Standard Deviation 1.2885
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) Lymphocytes, Visit 3, n=108, 95	-0.049 10^9 cells per Liter Standard Deviation 0.4702	-0.038 10^9 cells per Liter Standard Deviation 0.3892
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) Lymphocytes, Visit 4, n=124, 110	0.012 10^9 cells per Liter Standard Deviation 0.4252	-0.020 10^9 cells per Liter Standard Deviation 0.3925
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) Eosinophils, Visit 3, n=108, 95	-0.001 10^9 cells per Liter Standard Deviation 0.0766	0.006 10^9 cells per Liter Standard Deviation 0.0493
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) Eosinophils, Visit 4, n=124, 110	0.012 10^9 cells per Liter Standard Deviation 0.1068	0.013 10^9 cells per Liter Standard Deviation 0.0824
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) Platelets, Visit 3, n=109, 93	-1.9 10^9 cells per Liter Standard Deviation 29.14	-8.2 10^9 cells per Liter Standard Deviation 46.92
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) Platelets, Visit 4, n=123, 110	-4.0 10^9 cells per Liter Standard Deviation 27.92	-7.5 10^9 cells per Liter Standard Deviation 43.40

SECONDARY outcome

Timeframe: Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks)

Population: Safety Analysis Set. Only those participants with data available at Visit 3 and Visit 4 were assessed at that respective visit (indicated by n=X, X in the category titles).

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.

Outcome measures

Measure	20 mg Sumatriptan Nasal Powder n=123 Participants Participants received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device in Treatment Period 1 or Treatment Period 2.	100 mg Sumatriptan Tablet n=110 Participants Participants received a 100 mg sumatriptan tablet taken orally in Treatment Period 1 or Treatment Period 2.
Change From Baseline in Urea at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) Visit 3, n=108, 94	0.070 millimoles per Liter (mmol/L) Standard Deviation 1.2118	0.079 millimoles per Liter (mmol/L) Standard Deviation 1.2227
Change From Baseline in Urea at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) Visit 4, n=123, 110	0.156 millimoles per Liter (mmol/L) Standard Deviation 1.2840	0.308 millimoles per Liter (mmol/L) Standard Deviation 1.3674

SECONDARY outcome

Timeframe: Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks)

Population: Safety Analysis Set. Only those participants with data available at Visit 3 and Visit 4 were assessed at that respective visit (indicated by n=X, X in the category titles).

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.

Outcome measures

Measure	20 mg Sumatriptan Nasal Powder n=123 Participants Participants received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device in Treatment Period 1 or Treatment Period 2.	100 mg Sumatriptan Tablet n=110 Participants Participants received a 100 mg sumatriptan tablet taken orally in Treatment Period 1 or Treatment Period 2.
Change From Baseline in Creatinine at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) Visit 3, n=108, 94	-1.9 micromoles per Liter (µmol/L) Standard Deviation 10.73	-0.7 micromoles per Liter (µmol/L) Standard Deviation 6.59
Change From Baseline in Creatinine at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) Visit 4, n=123, 110	-1.3 micromoles per Liter (µmol/L) Standard Deviation 11.77	-0.6 micromoles per Liter (µmol/L) Standard Deviation 8.24

SECONDARY outcome

Timeframe: Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks)

Population: Safety Analysis Set. Only those participants with data available at Visit 3 and Visit 4 were assessed at that respective visit (indicated by n=X, X in the category titles).

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.

Outcome measures

Measure	20 mg Sumatriptan Nasal Powder n=123 Participants Participants received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device in Treatment Period 1 or Treatment Period 2.	100 mg Sumatriptan Tablet n=110 Participants Participants received a 100 mg sumatriptan tablet taken orally in Treatment Period 1 or Treatment Period 2.
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) ALP, Visit 3, n=108, 94	-0.5 International Units per Liter (IU/L) Standard Deviation 8.92	0.0 International Units per Liter (IU/L) Standard Deviation 6.78
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) ALP, Visit 4, n=123, 110	-1.7 International Units per Liter (IU/L) Standard Deviation 9.92	-1.0 International Units per Liter (IU/L) Standard Deviation 9.45
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) ALT, Visit 3, n=108, 94	0.4 International Units per Liter (IU/L) Standard Deviation 7.08	0.0 International Units per Liter (IU/L) Standard Deviation 8.86
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) ALT, Visit 4, n=123, 110	0.4 International Units per Liter (IU/L) Standard Deviation 6.83	-0.9 International Units per Liter (IU/L) Standard Deviation 7.16

SECONDARY outcome

Timeframe: Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks)

Population: Safety Analysis Set. Only those participants with data available at Visit 3 and Visit 4 were assessed at that respective visit (indicated by n=X, X in the category titles).

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.

Outcome measures

Measure	20 mg Sumatriptan Nasal Powder n=123 Participants Participants received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device in Treatment Period 1 or Treatment Period 2.	100 mg Sumatriptan Tablet n=110 Participants Participants received a 100 mg sumatriptan tablet taken orally in Treatment Period 1 or Treatment Period 2.
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) AST, Visit 3, n=108, 92	-0.2 International Units per Liter (IU/L) Standard Deviation 5.26	0.5 International Units per Liter (IU/L) Standard Deviation 14.39
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) AST, Visit 4, n=123, 110	0.6 International Units per Liter (IU/L) Standard Deviation 7.88	-1.2 International Units per Liter (IU/L) Standard Deviation 5.84
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) GGT, Visit 3, n=108, 94	0.8 International Units per Liter (IU/L) Standard Deviation 10.09	0.0 International Units per Liter (IU/L) Standard Deviation 7.05
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) GGT, Visit 4, n=123, 110	0.4 International Units per Liter (IU/L) Standard Deviation 10.31	-0.7 International Units per Liter (IU/L) Standard Deviation 7.35

SECONDARY outcome

Timeframe: Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks)

Population: Safety Analysis Set. Only those participants with data available at Visit 3 and Visit 4 were assessed at that respective visit (indicated by n=X, X in the category titles).

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.

Outcome measures

Measure	20 mg Sumatriptan Nasal Powder n=123 Participants Participants received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device in Treatment Period 1 or Treatment Period 2.	100 mg Sumatriptan Tablet n=110 Participants Participants received a 100 mg sumatriptan tablet taken orally in Treatment Period 1 or Treatment Period 2.
Change From Baseline in Total Bilirubin at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) Visit 3, n=108, 94	0.2 Units per Liter (U/L) Standard Deviation 4.26	-0.2 Units per Liter (U/L) Standard Deviation 2.96
Change From Baseline in Total Bilirubin at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) Visit 4, n=123, 110	-0.6 Units per Liter (U/L) Standard Deviation 4.09	0.2 Units per Liter (U/L) Standard Deviation 4.01

SECONDARY outcome

Timeframe: Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks)

Population: Safety Analysis Set. Only those participants with data available at Visit 3 and Visit 4 were assessed at that respective visit (indicated by n=X, X in the category titles).

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.

Outcome measures

Measure	20 mg Sumatriptan Nasal Powder n=123 Participants Participants received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device in Treatment Period 1 or Treatment Period 2.	100 mg Sumatriptan Tablet n=110 Participants Participants received a 100 mg sumatriptan tablet taken orally in Treatment Period 1 or Treatment Period 2.
Change From Baseline in Albumin and Total Protein at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) albumin, Visit 3, n=108, 94	-0.8 grams per Liter (grams/L) Standard Deviation 2.82	-0.9 grams per Liter (grams/L) Standard Deviation 2.84
Change From Baseline in Albumin and Total Protein at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) albumin, Visit 4, n=123, 110	-0.9 grams per Liter (grams/L) Standard Deviation 2.98	-0.5 grams per Liter (grams/L) Standard Deviation 2.62
Change From Baseline in Albumin and Total Protein at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) total protein, Visit 3, n=108, 94	-1.0 grams per Liter (grams/L) Standard Deviation 3.75	-1.2 grams per Liter (grams/L) Standard Deviation 3.61
Change From Baseline in Albumin and Total Protein at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) total protein, Visit 4, n=122, 110	-1.2 grams per Liter (grams/L) Standard Deviation 4.20	-1.0 grams per Liter (grams/L) Standard Deviation 3.35

SECONDARY outcome

Timeframe: Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks)

Population: Safety Analysis Set. Only those participants with data available at Visit 3 and Visit 4 were assessed at that respective visit (indicated by n=X, X in the category titles).

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.

Outcome measures

Measure	20 mg Sumatriptan Nasal Powder n=123 Participants Participants received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device in Treatment Period 1 or Treatment Period 2.	100 mg Sumatriptan Tablet n=110 Participants Participants received a 100 mg sumatriptan tablet taken orally in Treatment Period 1 or Treatment Period 2.
Change From Baseline in Sodium, Potassium, Chloride, Calcium, and Glucose at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) sodium, Visit 3, n=108, 94	-0.3 mmoles/L Standard Deviation 2.62	-0.5 mmoles/L Standard Deviation 2.24
Change From Baseline in Sodium, Potassium, Chloride, Calcium, and Glucose at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) sodium, Visit 4, n=122, 110	-0.3 mmoles/L Standard Deviation 2.76	-0.2 mmoles/L Standard Deviation 2.25
Change From Baseline in Sodium, Potassium, Chloride, Calcium, and Glucose at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) potassium, Visit 3, n=108, 94	-0.08 mmoles/L Standard Deviation 0.440	-0.04 mmoles/L Standard Deviation 0.404
Change From Baseline in Sodium, Potassium, Chloride, Calcium, and Glucose at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) potassium, Visit 4, n=122, 110	-0.10 mmoles/L Standard Deviation 0.411	-0.00 mmoles/L Standard Deviation 0.406
Change From Baseline in Sodium, Potassium, Chloride, Calcium, and Glucose at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) chloride, Visit 3, n=108, 94	-0.1 mmoles/L Standard Deviation 2.95	0.0 mmoles/L Standard Deviation 2.39
Change From Baseline in Sodium, Potassium, Chloride, Calcium, and Glucose at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) chloride, Visit 4, n=122, 110	0.2 mmoles/L Standard Deviation 2.62	0.2 mmoles/L Standard Deviation 2.51
Change From Baseline in Sodium, Potassium, Chloride, Calcium, and Glucose at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) calcium, Visit 3, n=108, 94	-0.019 mmoles/L Standard Deviation 0.1017	-0.016 mmoles/L Standard Deviation 0.1043
Change From Baseline in Sodium, Potassium, Chloride, Calcium, and Glucose at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) calcium, Visit 4, n=123, 110	-0.011 mmoles/L Standard Deviation 0.1058	-0.006 mmoles/L Standard Deviation 0.0886
Change From Baseline in Sodium, Potassium, Chloride, Calcium, and Glucose at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) glucose, Visit 3, n=108, 94	0.34 mmoles/L Standard Deviation 1.316	0.05 mmoles/L Standard Deviation 0.930
Change From Baseline in Sodium, Potassium, Chloride, Calcium, and Glucose at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) glucose, Visit 4, n=123, 110	0.20 mmoles/L Standard Deviation 1.063	0.24 mmoles/L Standard Deviation 1.135

SECONDARY outcome

Timeframe: Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks)

Population: Safety Analysis Set. Only those participants with data available at Visit 3 and Visit 4 were assessed at that respective visit (indicated by n=X, X in the category titles).

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.

Outcome measures

Measure	20 mg Sumatriptan Nasal Powder n=124 Participants Participants received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device in Treatment Period 1 or Treatment Period 2.	100 mg Sumatriptan Tablet n=109 Participants Participants received a 100 mg sumatriptan tablet taken orally in Treatment Period 1 or Treatment Period 2.
Change From Baseline in Urinalysis Values by Dipstick Method at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) Visit 3, n=108, 95	-0.04 pH Standard Deviation 0.603	-0.03 pH Standard Deviation 0.720
Change From Baseline in Urinalysis Values by Dipstick Method at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) Visit 4, n=124, 109	0.01 pH Standard Deviation 0.664	-0.07 pH Standard Deviation 0.658

SECONDARY outcome

Timeframe: Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks)

Population: Safety Analysis Set

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.

Outcome measures

Measure	20 mg Sumatriptan Nasal Powder n=133 Participants Participants received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device in Treatment Period 1 or Treatment Period 2.	100 mg Sumatriptan Tablet n=129 Participants Participants received a 100 mg sumatriptan tablet taken orally in Treatment Period 1 or Treatment Period 2.
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) Protein, Baseline, negative	112 participants	105 participants
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) Protein, Baseline, trace	16 participants	19 participants
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) Protein, Baseline, 1+	5 participants	3 participants
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) Protein, Baseline, 2+	0 participants	2 participants
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) Protein, Visit 3, negative	92 participants	75 participants
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) Protein, Visit 3, trace	11 participants	15 participants
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) Protein, Visit 3, 1+	4 participants	5 participants
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) Protein, Visit 3, 2+	1 participants	0 participants
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) Protein, Visit 4, negative	104 participants	90 participants
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) Protein, Visit 4, trace	17 participants	12 participants
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) Protein, Visit 4, 1+	3 participants	6 participants
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) Protein, Visit 4, 2+	0 participants	1 participants
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) Glucose, Baseline, negative	132 participants	126 participants
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) Glucose, Baseline, trace	1 participants	2 participants
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) Glucose, Baseline, 3+	0 participants	1 participants
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) Glucose, Visit 3, negative	107 participants	94 participants
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) Glucose, Visit 3, trace	0 participants	1 participants
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) Glucose, Visit 3, 3+	1 participants	0 participants
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) Glucose, Visit 4, negative	122 participants	108 participants
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) Glucose, Visit 4, trace	0 participants	1 participants
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) Glucose, Visit 4, 1+	1 participants	0 participants
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) Glucose, Visit 4, 3+	1 participants	0 participants
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) Ketones, Baseline, negative	124 participants	121 participants
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) Ketones, Baseline, trace	7 participants	7 participants
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) Ketones, Baseline, 1+	0 participants	1 participants
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) Ketones, Baseline, 2+	2 participants	0 participants
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) Ketones, Visit 3, negative	102 participants	88 participants
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) Ketones, Visit 3, trace	5 participants	6 participants
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) Ketones, Visit 3, 1+	1 participants	0 participants
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) Ketones, Visit 3, 2+	0 participants	1 participants
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) Ketones, Visit 4, negative	119 participants	101 participants
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) Ketones, Visit 4, trace	3 participants	8 participants
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) Ketones, Visit 4, 1+	2 participants	0 participants
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) Blood, Baseline, negative	116 participants	116 participants
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) Blood, Baseline, trace	7 participants	4 participants
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) Blood, Baseline, 1+	2 participants	3 participants
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) Blood, Baseline, 2+	5 participants	1 participants
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) Blood, Baseline, 3+	3 participants	5 participants
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) Blood, Visit 3, negative	94 participants	78 participants
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) Blood, Visit 3, trace	4 participants	6 participants
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) Blood, Visit 3, 1+	5 participants	4 participants
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) Blood, Visit 3, 2+	2 participants	2 participants
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) Blood, Visit 3, 3+	3 participants	5 participants
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) Blood, Visit 4, negative	111 participants	94 participants
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) Blood, Visit 4, trace	3 participants	6 participants
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) Blood, Visit 4, 1+	1 participants	5 participants
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) Blood, Visit 4, 2+	4 participants	3 participants
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) Blood, Visit 4, 3+	5 participants	1 participants
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) WBCs, Baseline, negative	99 participants	101 participants
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) WBCs, Baseline, trace	12 participants	8 participants
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) WBCs, Baseline, 1+	12 participants	11 participants
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) WBCs, Baseline, 2+	7 participants	5 participants
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) WBCs, Baseline, 3+	3 participants	4 participants
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) WBCs, Visit 3, negative	90 participants	75 participants
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) WBCs, Visit 3, trace	8 participants	7 participants
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) WBCs, Visit 3, 1+	4 participants	4 participants
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) WBCs, Visit 3, 2+	5 participants	6 participants
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) WBCs, Visit 3, 3+	1 participants	3 participants
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) WBCs, Visit 4, negative	105 participants	85 participants
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) WBCs, Visit 4, trace	5 participants	7 participants
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) WBCs, Visit 4, 1+	4 participants	5 participants
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) WBCs, Visit 4, 2+	8 participants	8 participants
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) WBCs, Visit 4, 3+	2 participants	4 participants

SECONDARY outcome

Timeframe: Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks)

Population: Safety Analysis Set. Only those participants with data available at Visit 3 and Visit 4 were assessed at that respective visit (indicated by n=X, X in the category titles).

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.

Outcome measures

Measure	20 mg Sumatriptan Nasal Powder n=124 Participants Participants received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device in Treatment Period 1 or Treatment Period 2.	100 mg Sumatriptan Tablet n=111 Participants Participants received a 100 mg sumatriptan tablet taken orally in Treatment Period 1 or Treatment Period 2.
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) SBP, Visit 3, n=110, 95	0.1 millimeters of mercury (mmHg) Standard Deviation 11.58	1.5 millimeters of mercury (mmHg) Standard Deviation 11.46
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) SBP, Visit 4, n=124, 111	1.6 millimeters of mercury (mmHg) Standard Deviation 11.52	2.0 millimeters of mercury (mmHg) Standard Deviation 11.94
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) DBP, Visit 3, n=110, 95	-0.2 millimeters of mercury (mmHg) Standard Deviation 7.17	1.0 millimeters of mercury (mmHg) Standard Deviation 8.89
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) DBP, Visit 4, n=124, 111	0.2 millimeters of mercury (mmHg) Standard Deviation 7.42	-0.2 millimeters of mercury (mmHg) Standard Deviation 7.90

SECONDARY outcome

Timeframe: Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks)

Population: Safety Analysis Set. Only those participants with data available at Visit 3 and Visit 4 were assessed at that respective visit (indicated by n=X, X in the category titles).

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.

Outcome measures

Measure	20 mg Sumatriptan Nasal Powder n=124 Participants Participants received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device in Treatment Period 1 or Treatment Period 2.	100 mg Sumatriptan Tablet n=111 Participants Participants received a 100 mg sumatriptan tablet taken orally in Treatment Period 1 or Treatment Period 2.
Change From Baseline in Pulse at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) Visit 3, n=110, 95	0.1 beats per minute Standard Deviation 8.63	0.1 beats per minute Standard Deviation 9.24
Change From Baseline in Pulse at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) Visit 4, n=124, 111	-2.2 beats per minute Standard Deviation 9.07	-0.2 beats per minute Standard Deviation 10.96

SECONDARY outcome

Timeframe: Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks)

Population: Safety Analysis Set

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.

Outcome measures

Measure	20 mg Sumatriptan Nasal Powder n=133 Participants Participants received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device in Treatment Period 1 or Treatment Period 2.	100 mg Sumatriptan Tablet n=129 Participants Participants received a 100 mg sumatriptan tablet taken orally in Treatment Period 1 or Treatment Period 2.
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, normal; n=133, 129	96 participants	99 participants
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, abnormal, CS; n=133, 129	1 participants	0 participants
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, abnormal, CNS; n=133, 129	36 participants	30 participants
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) Visit 3, normal; n=110, 95	79 participants	70 participants
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) Visit 3, abnormal, CS; n=110, 95	0 participants	0 participants
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) Visit 3, abnormal, CNS; n=110, 95	31 participants	25 participants
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) Visit 4, normal; n=124, 111	90 participants	73 participants
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) Visit 4, abnormal, CS; n=124, 111	0 participants	1 participants
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) Visit 4, abnormal, CNS; n=123, 111	34 participants	37 participants

SECONDARY outcome

Timeframe: Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks)

Population: Safety Analysis Set

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.

Outcome measures

Measure	20 mg Sumatriptan Nasal Powder n=133 Participants Participants received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device in Treatment Period 1 or Treatment Period 2.	100 mg Sumatriptan Tablet n=129 Participants Participants received a 100 mg sumatriptan tablet taken orally in Treatment Period 1 or Treatment Period 2.
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, CS; n=133, 129	1 participants	0 participants
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, CNS; n=133, 129	132 participants	129 participants
Number of Participants With the Indicated Physical Examination Abnormalities at Baseline, Visit 3 (up to Week 12), and Visit 4 (up to Week 24) Visit 3, CS; n=110, 95	1 participants	2 participants
Number of Participants With the Indicated Physical Examination Abnormalities at Baseline, Visit 3 (up to Week 12), and Visit 4 (up to Week 24) Visit 3, CNS; n=110, 95	109 participants	93 participants
Number of Participants With the Indicated Physical Examination Abnormalities at Baseline, Visit 3 (up to Week 12), and Visit 4 (up to Week 24) Visit 4, CS; n=124, 111	0 participants	0 participants
Number of Participants With the Indicated Physical Examination Abnormalities at Baseline, Visit 3 (up to Week 12), and Visit 4 (up to Week 24) Visit 4, CNS; n=124, 111	124 participants	111 participants

SECONDARY outcome

Timeframe: up to 24 weeks

Population: Safety Analysis Set

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.

Outcome measures

Measure	20 mg Sumatriptan Nasal Powder n=219 Participants Participants received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device in Treatment Period 1 or Treatment Period 2.	100 mg Sumatriptan Tablet n=228 Participants Participants received a 100 mg sumatriptan tablet taken orally in Treatment Period 1 or Treatment Period 2.
Number of Participants With the Indicated Concomitant Medications Any concomitant medication	218 participants	226 participants
Number of Participants With the Indicated Concomitant Medications Agents acting on the renin-angiotensin system	12 participants	14 participants
Number of Participants With the Indicated Concomitant Medications Other therapeutic products	2 participants	2 participants
Number of Participants With the Indicated Concomitant Medications Allergens	3 participants	4 participants
Number of Participants With the Indicated Concomitant Medications Anabolic agents for systemic use	1 participants	1 participants
Number of Participants With the Indicated Concomitant Medications Analgesics	143 participants	148 participants
Number of Participants With the Indicated Concomitant Medications Anesthetics	6 participants	6 participants
Number of Participants With the Indicated Concomitant Medications Anti-acne preparations	2 participants	2 participants
Number of Participants With the Indicated Concomitant Medications Anti-Parkinson drugs	3 participants	3 participants
Number of Participants With the Indicated Concomitant Medications Antianemic preparations	18 participants	20 participants
Number of Participants With the Indicated Concomitant Medications Antibacterials for systemic use	13 participants	17 participants
Number of Participants With the Indicated Concomitant Medications Antibiotics and chemotherapeutics for derm. use	0 participants	2 participants
Number of Participants With the Indicated Concomitant Medications Antidiarrrheals, intestinal antiinflammatories	7 participants	6 participants
Number of Participants With the Indicated Concomitant Medications Antiemetics and antinauseants	11 participants	12 participants
Number of Participants With the Indicated Concomitant Medications Antiepileptics	5 participants	4 participants
Number of Participants With the Indicated Concomitant Medications Antigout preparations	1 participants	1 participants
Number of Participants With the Indicated Concomitant Medications Antihistamines for systemic use	38 participants	39 participants
Number of Participants With the Indicated Concomitant Medications Antiinflammatory and antirheumatic products	135 participants	143 participants
Number of Participants With the Indicated Concomitant Medications Antimyotics for systemic use	1 participants	3 participants
Number of Participants With the Indicated Concomitant Medications Antiobesity preparations, exluding diet products	3 participants	3 participants
Number of Participants With the Indicated Concomitant Medications Antiprotozoals	0 participants	1 participants
Number of Participants With the Indicated Concomitant Medications Antiseptics and disinfectants	1 participants	0 participants
Number of Participants With the Indicated Concomitant Medications Antithrombotic agents	8 participants	8 participants
Number of Participants With the Indicated Concomitant Medications Antivirals for systemic use	2 participants	3 participants
Number of Participants With the Indicated Concomitant Medications Beta blocking agents	18 participants	15 participants
Number of Participants With the Indicated Concomitant Medications Calcium channel blockers	9 participants	8 participants
Number of Participants With the Indicated Concomitant Medications Cardiac therapy	1 participants	1 participants
Number of Participants With the Indicated Concomitant Medications Corticosteroids for systemic use	7 participants	8 participants
Number of Participants With the Indicated Concomitant Medications Corticosteroids, dermatologic preparations	1 participants	1 participants
Number of Participants With the Indicated Concomitant Medications Cough and cold preparations	8 participants	9 participants
Number of Participants With the Indicated Concomitant Medications Diuretics	6 participants	7 participants
Number of Participants With the Indicated Concomitant Medications Drugs for acid related disorders	22 participants	23 participants
Number of Participants With the Indicated Concomitant Medications Drugs for functional gastrointestinal disorders	5 participants	3 participants
Number of Participants With the Indicated Concomitant Medications Drugs for obstructive airways diseases	20 participants	26 participants
Number of Participants With the Indicated Concomitant Medications Drugs for treatment of bone diseases	1 participants	1 participants
Number of Participants With the Indicated Concomitant Medications Drugs used in diabetes	7 participants	9 participants
Number of Participants With the Indicated Concomitant Medications Ectoparasiticides, incl. scabacides, insecticides	1 participants	0 participants
Number of Participants With the Indicated Concomitant Medications Gynecological antiinfectives and antiseptics	1 participants	2 participants
Number of Participants With the Indicated Concomitant Medications Immune sera and immunoglobulins	1 participants	1 participants
Number of Participants With the Indicated Concomitant Medications Laxatives	4 participants	3 participants
Number of Participants With the Indicated Concomitant Medications Lipid modifying agents	23 participants	20 participants
Number of Participants With the Indicated Concomitant Medications Mineral supplements	20 participants	22 participants
Number of Participants With the Indicated Concomitant Medications Muscle relaxants	12 participants	16 participants
Number of Participants With the Indicated Concomitant Medications Nasal preparations	25 participants	27 participants
Number of Participants With the Indicated Concomitant Medications Opthalmologicals	7 participants	6 participants
Number of Participants With the Indicated Concomitant Medications Other alimentary tract and metabolism products	5 participants	5 participants
Number of Participants With the Indicated Concomitant Medications Other dermatological preparations	1 participants	1 participants
Number of Participants With the Indicated Concomitant Medications Other gynecologicals	21 participants	21 participants
Number of Participants With the Indicated Concomitant Medications Other nervous system drugs	3 participants	3 participants
Number of Participants With the Indicated Concomitant Medications Otologicals	1 participants	0 participants
Number of Participants With the Indicated Concomitant Medications Psychoanaleptics	57 participants	60 participants
Number of Participants With the Indicated Concomitant Medications Psycholeptics	31 participants	31 participants
Number of Participants With the Indicated Concomitant Medications Sex hormones and modulators of the genital system	62 participants	59 participants
Number of Participants With the Indicated Concomitant Medications Thyroid therapy	18 participants	16 participants
Number of Participants With the Indicated Concomitant Medications Unspecified herbal and traditional medicine	11 participants	12 participants
Number of Participants With the Indicated Concomitant Medications Urologicals	3 participants	4 participants
Number of Participants With the Indicated Concomitant Medications Vaccines	1 participants	2 participants
Number of Participants With the Indicated Concomitant Medications Vitamins	57 participants	56 participants

Adverse Events

20 mg Sumatriptan Nasal Powder

Serious events: 0 serious events

Other events: 98 other events

Deaths: 0 deaths

100 mg Sumatriptan Tablet

Serious events: 0 serious events

Other events: 35 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	20 mg Sumatriptan Nasal Powder n=219 participants at risk Participants received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device in Treatment Period 1 or Treatment Period 2.	100 mg Sumatriptan Tablet n=228 participants at risk Participants received a 100 mg sumatriptan tablet taken orally in Treatment Period 1 or Treatment Period 2.
Gastrointestinal disorders Nausea	4.1% 9/219 • Treatment-emergent adverse events were collected from the first dose of investigational product through up to 24 weeks. Adverse events were collected in members of the Safety Analysis Set, comprised of all randomized participants who received at least 1 dose of either 20 mg sumatriptan nasal powder or 100 mg sumatriptan tablet.	3.1% 7/228 • Treatment-emergent adverse events were collected from the first dose of investigational product through up to 24 weeks. Adverse events were collected in members of the Safety Analysis Set, comprised of all randomized participants who received at least 1 dose of either 20 mg sumatriptan nasal powder or 100 mg sumatriptan tablet.
General disorders Product taste abnormal	26.0% 57/219 • Treatment-emergent adverse events were collected from the first dose of investigational product through up to 24 weeks. Adverse events were collected in members of the Safety Analysis Set, comprised of all randomized participants who received at least 1 dose of either 20 mg sumatriptan nasal powder or 100 mg sumatriptan tablet.	3.9% 9/228 • Treatment-emergent adverse events were collected from the first dose of investigational product through up to 24 weeks. Adverse events were collected in members of the Safety Analysis Set, comprised of all randomized participants who received at least 1 dose of either 20 mg sumatriptan nasal powder or 100 mg sumatriptan tablet.
Infections and infestations Ear infection	0.46% 1/219 • Treatment-emergent adverse events were collected from the first dose of investigational product through up to 24 weeks. Adverse events were collected in members of the Safety Analysis Set, comprised of all randomized participants who received at least 1 dose of either 20 mg sumatriptan nasal powder or 100 mg sumatriptan tablet.	1.3% 3/228 • Treatment-emergent adverse events were collected from the first dose of investigational product through up to 24 weeks. Adverse events were collected in members of the Safety Analysis Set, comprised of all randomized participants who received at least 1 dose of either 20 mg sumatriptan nasal powder or 100 mg sumatriptan tablet.
Infections and infestations Gastroenteritis viral	0.46% 1/219 • Treatment-emergent adverse events were collected from the first dose of investigational product through up to 24 weeks. Adverse events were collected in members of the Safety Analysis Set, comprised of all randomized participants who received at least 1 dose of either 20 mg sumatriptan nasal powder or 100 mg sumatriptan tablet.	1.3% 3/228 • Treatment-emergent adverse events were collected from the first dose of investigational product through up to 24 weeks. Adverse events were collected in members of the Safety Analysis Set, comprised of all randomized participants who received at least 1 dose of either 20 mg sumatriptan nasal powder or 100 mg sumatriptan tablet.
Infections and infestations Sinusitis	1.4% 3/219 • Treatment-emergent adverse events were collected from the first dose of investigational product through up to 24 weeks. Adverse events were collected in members of the Safety Analysis Set, comprised of all randomized participants who received at least 1 dose of either 20 mg sumatriptan nasal powder or 100 mg sumatriptan tablet.	1.8% 4/228 • Treatment-emergent adverse events were collected from the first dose of investigational product through up to 24 weeks. Adverse events were collected in members of the Safety Analysis Set, comprised of all randomized participants who received at least 1 dose of either 20 mg sumatriptan nasal powder or 100 mg sumatriptan tablet.
Infections and infestations Upper respiratory tract infection	4.1% 9/219 • Treatment-emergent adverse events were collected from the first dose of investigational product through up to 24 weeks. Adverse events were collected in members of the Safety Analysis Set, comprised of all randomized participants who received at least 1 dose of either 20 mg sumatriptan nasal powder or 100 mg sumatriptan tablet.	3.5% 8/228 • Treatment-emergent adverse events were collected from the first dose of investigational product through up to 24 weeks. Adverse events were collected in members of the Safety Analysis Set, comprised of all randomized participants who received at least 1 dose of either 20 mg sumatriptan nasal powder or 100 mg sumatriptan tablet.
Musculoskeletal and connective tissue disorders Neck pain	0.46% 1/219 • Treatment-emergent adverse events were collected from the first dose of investigational product through up to 24 weeks. Adverse events were collected in members of the Safety Analysis Set, comprised of all randomized participants who received at least 1 dose of either 20 mg sumatriptan nasal powder or 100 mg sumatriptan tablet.	1.3% 3/228 • Treatment-emergent adverse events were collected from the first dose of investigational product through up to 24 weeks. Adverse events were collected in members of the Safety Analysis Set, comprised of all randomized participants who received at least 1 dose of either 20 mg sumatriptan nasal powder or 100 mg sumatriptan tablet.
Nervous system disorders Headache	0.91% 2/219 • Treatment-emergent adverse events were collected from the first dose of investigational product through up to 24 weeks. Adverse events were collected in members of the Safety Analysis Set, comprised of all randomized participants who received at least 1 dose of either 20 mg sumatriptan nasal powder or 100 mg sumatriptan tablet.	1.3% 3/228 • Treatment-emergent adverse events were collected from the first dose of investigational product through up to 24 weeks. Adverse events were collected in members of the Safety Analysis Set, comprised of all randomized participants who received at least 1 dose of either 20 mg sumatriptan nasal powder or 100 mg sumatriptan tablet.
Respiratory, thoracic and mediastinal disorders Nasal discomfort	15.5% 34/219 • Treatment-emergent adverse events were collected from the first dose of investigational product through up to 24 weeks. Adverse events were collected in members of the Safety Analysis Set, comprised of all randomized participants who received at least 1 dose of either 20 mg sumatriptan nasal powder or 100 mg sumatriptan tablet.	1.3% 3/228 • Treatment-emergent adverse events were collected from the first dose of investigational product through up to 24 weeks. Adverse events were collected in members of the Safety Analysis Set, comprised of all randomized participants who received at least 1 dose of either 20 mg sumatriptan nasal powder or 100 mg sumatriptan tablet.
Respiratory, thoracic and mediastinal disorders Rhinalgia	1.4% 3/219 • Treatment-emergent adverse events were collected from the first dose of investigational product through up to 24 weeks. Adverse events were collected in members of the Safety Analysis Set, comprised of all randomized participants who received at least 1 dose of either 20 mg sumatriptan nasal powder or 100 mg sumatriptan tablet.	0.00% 0/228 • Treatment-emergent adverse events were collected from the first dose of investigational product through up to 24 weeks. Adverse events were collected in members of the Safety Analysis Set, comprised of all randomized participants who received at least 1 dose of either 20 mg sumatriptan nasal powder or 100 mg sumatriptan tablet.
Respiratory, thoracic and mediastinal disorders Throat irritation	1.8% 4/219 • Treatment-emergent adverse events were collected from the first dose of investigational product through up to 24 weeks. Adverse events were collected in members of the Safety Analysis Set, comprised of all randomized participants who received at least 1 dose of either 20 mg sumatriptan nasal powder or 100 mg sumatriptan tablet.	0.00% 0/228 • Treatment-emergent adverse events were collected from the first dose of investigational product through up to 24 weeks. Adverse events were collected in members of the Safety Analysis Set, comprised of all randomized participants who received at least 1 dose of either 20 mg sumatriptan nasal powder or 100 mg sumatriptan tablet.
Respiratory, thoracic and mediastinal disorders Upper-airway cough syndrome	2.7% 6/219 • Treatment-emergent adverse events were collected from the first dose of investigational product through up to 24 weeks. Adverse events were collected in members of the Safety Analysis Set, comprised of all randomized participants who received at least 1 dose of either 20 mg sumatriptan nasal powder or 100 mg sumatriptan tablet.	0.88% 2/228 • Treatment-emergent adverse events were collected from the first dose of investigational product through up to 24 weeks. Adverse events were collected in members of the Safety Analysis Set, comprised of all randomized participants who received at least 1 dose of either 20 mg sumatriptan nasal powder or 100 mg sumatriptan tablet.

Additional Information

Nadine Knowles; Executive Director, Research & Development Operations

Avanir Pharmaceuticals

Phone: 1-949-268-8972

Email: nknowles@avanir.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: OTHER