An Efficacy and Safety Study of DFN-02 (Sumatriptan Nasal Spray 10 mg)

• Sponsor: Upsher-Smith Laboratories (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02856802
• Collaborator: (none)
• Enrollment: 107
• Locations: 9
• Arms: 2
• Actual Duration (Months): 7
• Patients Per Site: 11.9
• Patients Per Site Per Month: 1.7

Study Details

Study Description

Brief Summary

A safety and efficacy study of DFN-02 (Sumatriptan Nasal Spray 10 mg), being conducted at multiple centers in the United States.

Condition or Disease	Intervention/Treatment	Phase
Migraine Headaches	Drug: Sumatriptan 10 mg Nasal Spray; Other: Sumatriptan Placebo Nasal Spray	Phase 2

Detailed Description

This was a randomized, two double-blind (DB) treatment period dosing study.

Previously diagnosed subjects with a history of episodic migraine (as defined by International Classification of Headache Disorders (ICHD), 3rd edition [beta version] [ICHD 3]) who experienced an average of 2 to 8 migraine attacks per month for at least the prior 12 months, with no more than 14 headache days per month, and with 48 hours of headache free time between migraine, were randomized in a 1:1 ratio in both DB periods to receive either DFN-02 (sumatriptan nasal spray 10 mg) or a matching placebo.

Subjects treated one moderate to severe migraine attack in the first double-blind treatment period (DB1) and, if eligible, were re-randomized into the second double-blind treatment period (DB2) to treat another migraine attack at any pain level.

There was a screening period of up to 21 days to evaluate whether subjects fit the migraine inclusion criteria pursuant to ICHD-3, and did not have medication overuse. Subjects with at least a 12 month medical history of acute migraine were eligible for enrollment in the treatment period. Subjects continued to take their normal migraine medication during this screening period.

If eligible and randomized, subjects in the DB1 treatment period were instructed to use the study medication in one migraine attack as soon as (and no more than within one hour after) experiencing moderate to severe migraine pain (defined as headache pain rating of Grade 2 [moderate] or Grade 3 [severe] on a pain severity scale of 0 to 3). If the subject was not able to use study medication for the first migraine after randomization, they were instructed to use the study medication for the next attack. Those subjects who did not experience a migraine attack, and/or did not treat any migraine attack with study medication or record diary data, were not allowed to continue into the DB2 treatment period, and were discontinued.

After treating a migraine attack with study medication, subjects were instructed to contact the site within 24 hours of the treated migraine (or the next working day) to schedule their next visit.

Subjects returned to the study site within 2 to 7 days in the DB1 treatment period and, if continuing to be eligible, were re-randomized into a DB2 treatment period to treat one migraine attack at any pain level, and return to the study site within 2 to 7 days of the second treatment.

Once randomized, the total duration of each subject's participation in the study was up to 10 weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 107 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study of DFN-02 in Episodic Migraine With or Without Aura
• Actual Study Start Date: Jul 11, 2016
• Actual Primary Completion Date: Feb 10, 2017
• Actual Study Completion Date: Feb 10, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: DFN-02 Participants self-administered a single-dose of DFN-02 (sumatriptan 10-mg/100 μL nasal spray) intranasally within one hour of an acute migraine pain episode.	Drug: Sumatriptan 10 mg Nasal Spray; 100 μL nasal spray once; Other Names: Sumatriptan
Other: Placebo Participants self-administered a single-dose of DFN-02 placebo nasal spray matching DFN-02 intranasally within one hour of an acute migraine pain episode.	Other: Sumatriptan Placebo Nasal Spray; 100 μL nasal spray once

Outcome Measures

Primary Outcome Measures

1. Number of Participants Free From Headache Pain at 2 Hours After the First Dose of Study Medication Taken for a Migraine Attack With Moderate to Severe Headache Pain During the Double-blind Treatment Period 1 (DB1). [2 hours after study medication administration]

   Freedom from headache pain at 2 hours after the first dose of study medication taken within one hour after experiencing a migraine attack of moderate to severe headache pain during the DB1 treatment period, e.g., headache pain rating of moderate [Grade 2] or severe [Grade 3] predose and reduced to none [Grade 0] postdose). Mild headache pain was recorded as Grade 1. If the subject was not able to use study medication for the first migraine after randomization, they were instructed to use the study medication for the next attack. If the subject experienced insufficient relief from the first dose of study medication, they were permitted to take a second dose of study medication or rescue medication 2 or more hours after the first dose, and only after completing the 2 hours' postdose assessments. If no relief was experienced from the first dose of study medication after 2 hours only rescue medication could be administered. Maximum 2 doses of study medication per 24 hours.

Secondary Outcome Measures

1. Number of Participants With Absence of Most Bothersome Symptom (MBS) Among Nausea, Photophobia and Phonophobia at 2 Hours (DB1) [2 hours after study medication administration]

   Number of participants with their MBS among nausea, photophobia and phonophobia absent at 10, 15, 20, 30, 60, 90, and 120 minutes after the first dose of study medication taken for a migraine attack during DB1 treatment period are summarized by treatment group and time point for the full analysis set (FAS1). The corresponding p-values from Fisher's exact test were computed for the comparison between treatment groups. Subjects who reported a MBS predose and reported the status of the MBS at the particular postdose time point were analyzed.

2. Number of Participants With Headache Pain Freedom at 2 Hours Postdose in the Double-blind Treatment Period 2 (DB2) [2 hours after study medication administration]

   In Double-blind Treatment Period 2 (DB2), freedom from headache pain 2 hours after the first dose of study medication taken within one hour of experiencing a migraine attack for any headache pain level, e.g., mild [Grade 1], moderate [Grade 2], or severe [Grade 3] and reduced to none [Grade 0] after study medication administration. If the subject was not able to use study medication for the first migraine after randomization, they were instructed to use the study medication for the next attack.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. A history of episodic migraine who experience an average of 2 to 8 migraine attacks per month for at least the past 12 months, with no more than 14 headache days per month, and with 48 hours of headache free time between migraine headaches

2. Patients who have migraine with or without aura. If migraine with aura, the aura cannot last longer than 60 minutes.

3. Patients who are willing and able to:

4. Evaluate and record pain, migraine symptoms, and study medication effectiveness information in real-time using a diary for the duration of the study;

5. Record each instance of the use of study medication and rescue medication in a patient diary in real-time for the duration of the study;

6. Comply with all other study procedures and scheduling requirements.

Exclusion Criteria:

1. Minors, even if they are in the specified study age range

2. Medication overuse:

3. Opioids ≥ 10 days during the 90 days prior to screening

4. Combination medications (e.g., Fiorinal®) ≥ 10 days during the 90 days prior to screening (only applies if combination medication contains an opioid and/or barbiturate)

5. Nonsteroidal Anti-inflammatory Drugs or other simple medications ˃ 14 days a month during the 90 days prior to screening

6. Triptans or ergots ≥ 10 days a month during the 90 days prior to screening

7. Treated with onabotulinumtoxinA (Botox®) or other botulinum toxin treatment within 4 months prior to screening for migraine prophylaxis (patients who were treated with same for cosmetic purposes may be allowed on a case-by-case basis after approval from the Medical Monitor)

8. A history of or current neurological or psychiatric impairment, or cognitive dysfunction that, in the opinion of the Investigator, would compromise data collection

9. Use of antipsychotics at least 15 days prior to randomization

10. Patients who received treatment with an investigational drug or device within 30 days prior to randomization, or within 3 months if associated with central nervous system

11. Patients who participated in a central nervous system clinical trial within 3 months prior to randomization

12. Patients who test positive for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibody serology testing

13. Patients who are employees or immediate relatives of the employees of the Sponsor, any of its affiliates or partners, or of the clinical study research site

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Site 30	San Diego	California	United States	92108
2	Site 11	Santa Monica	California	United States	90404
3	Site 31	Boston	Massachusetts	United States	02131
4	Site 18	Ann Arbor	Michigan	United States	48104
5	Site 02	Albuquerque	New Mexico	United States	87102
6	Site 29	Rochester	New York	United States	14609
7	Site 25	Williamsville	New York	United States	14221
8	Site 33	Mount Pleasant	South Carolina	United States	29464
9	Site 28	West Jordan	Utah	United States	84088

Sponsors and Collaborators

• Upsher-Smith Laboratories

Investigators

• Study Director: Sagar Munjal, MD, Dr. Reddy's Laboratories, LLC

Study Documents (Full-Text)

• Study Protocol - Jun 1, 2016
• Statistical Analysis Plan - Sep 16, 2016

More Information

Publications

None provided.

• Responsible Party: Upsher-Smith Laboratories
• ClinicalTrials.gov Identifier: NCT02856802
• Other Study ID Numbers: DFN-02-CD-012
• First Posted: Aug 5, 2016
• Last Update Posted: Mar 30, 2021
• Last Verified: Dec 1, 2020

• Keywords provided by Upsher-Smith Laboratories: Aura
• Additional relevant MeSH terms: Migraine Disorders; Headache; Sumatriptan

Study Results

Participant Flow

Recruitment Details	The study was conducted in the United States. At least 1 subject was enrolled at 9 study centers.
Pre-assignment Detail	Subjects had to have an average of 2 to 8 migraine attacks per month for at least the prior 12 months, with no more than 14 headache days per month, and with 48 hours of headache free time between migraine.

Arm/Group Title	DFN-02	Placebo
Arm/Group Description	DFN-02 Active Nasal Sumatriptan 10mg spray upon onset of acute migraine pain during each acute migraine episode DFN-02	DFN-02 Placebo spray upon onset of acute migraine pain during each acute migraine episode DFN-02 Placebo
Period Title: Double-Blind Treatment Period 1
STARTED	50	43
COMPLETED	48	38
NOT COMPLETED	2	5
Period Title: Double-Blind Treatment Period 1
STARTED	37	38
COMPLETED	36	38
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	DFN-02 (Double-Blind Treatment Period 1)	Placebo (Double-Blind Treatment Period 1)	Total
Arm/Group Description	50 of 54 randomized subjects started and were dosed; 2 subjects had no migraine attack, 1 subject withdrew and 1 subject was lost to follow-up. Per protocol these 4 subjects are excluded from analysis.	43 of 53 randomized subjects started and were dosed; 6 subjects had no migraine attack, 3 subjects withdrew and 1 subject was terminated by the sponsor. Per protocol these 10 subjects are excluded from analysis.	Total of all reporting groups
Overall Participants	50	43	93
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	43.4	41.0	42.3
Sex: Female, Male (Count of Participants)
Female	38 76%	37 86%	75 80.6%
Male	12 24%	6 14%	18 19.4%
Race/Ethnicity, Customized (participants) [Number]
Asian	0 0%	1 2.3%	1 1.1%
Black or African American	5 10%	2 4.7%	7 7.5%
Native Hawaiian or Other Pacific Islander	1 2%	0 0%	1 1.1%
White	42 84%	40 93%	82 88.2%
Other	2 4%	0 0%	2 2.2%
Region of Enrollment (participants) [Number]
United States	50 100%	43 100%	93 100%
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	27.70 (6.441)	28.80 (7.500)	28.21 (6.933)

Outcome Measures

1. Primary Outcome

Title	Number of Participants Free From Headache Pain at 2 Hours After the First Dose of Study Medication Taken for a Migraine Attack With Moderate to Severe Headache Pain During the Double-blind Treatment Period 1 (DB1).
Description	Freedom from headache pain at 2 hours after the first dose of study medication taken within one hour after experiencing a migraine attack of moderate to severe headache pain during the DB1 treatment period, e.g., headache pain rating of moderate [Grade 2] or severe [Grade 3] predose and reduced to none [Grade 0] postdose). Mild headache pain was recorded as Grade 1. If the subject was not able to use study medication for the first migraine after randomization, they were instructed to use the study medication for the next attack. If the subject experienced insufficient relief from the first dose of study medication, they were permitted to take a second dose of study medication or rescue medication 2 or more hours after the first dose, and only after completing the 2 hours' postdose assessments. If no relief was experienced from the first dose of study medication after 2 hours only rescue medication could be administered. Maximum 2 doses of study medication per 24 hours.
Time Frame	2 hours after study medication administration

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) population. Last observation carried forward (LOCF) imputation method. The FAS included all randomized subjects who took at least one dose of study medication during the DB treatment period (1) and had at least one post-baseline efficacy time point assessment in DB treatment period (1).

Arm/Group Title	DFN-02 (DB1)	Placebo (DB1)
Arm/Group Description	DFN-02 Active Nasal Sumatriptan 10mg spray upon onset of acute migraine pain during each acute migraine episode DFN-02	DFN-02 Placebo spray upon onset of acute migraine pain during each acute migraine episode DFN-02 Placebo
Measure Participants	48	40
Count of Participants [Participants]	21 42%	9 20.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DFN-02 (DB1), Placebo (DB1)
	Comments	Statistical testing and confidence intervals (CIs) were 2 sided and performed using a significance (alpha) level of 0.05. All statistical analyses were conducted with the statistical analysis system (SAS)® software package (version 9.3).
	Type of Statistical Test	Non-Inferiority
	Comments	Assumption that 15% of placebo and 42% of DFN 02 10 mg (treated) subjects would be pain-free at 2 hours. A sample size of 50 subjects in each DB1 dosing arm provided 86% power to detect this assumed difference between placebo and DFN-02 10 mg at a 5% (2-sided) level of significance.
Statistical Test of Hypothesis	p-Value	0.044
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.68
	Confidence Interval	(2-Sided) 95%; 1.05 to 6.83
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Number of Participants With Absence of Most Bothersome Symptom (MBS) Among Nausea, Photophobia and Phonophobia at 2 Hours (DB1)
Description	Number of participants with their MBS among nausea, photophobia and phonophobia absent at 10, 15, 20, 30, 60, 90, and 120 minutes after the first dose of study medication taken for a migraine attack during DB1 treatment period are summarized by treatment group and time point for the full analysis set (FAS1). The corresponding p-values from Fisher's exact test were computed for the comparison between treatment groups. Subjects who reported a MBS predose and reported the status of the MBS at the particular postdose time point were analyzed.
Time Frame	2 hours after study medication administration

Outcome Measure Data

Analysis Population Description

Subjects who reported a MBS predose and reported the status of the MBS at the particular postdose time point were analyzed.

Arm/Group Title	DFN-02 (DB1)	Placebo (DB1)
Arm/Group Description	DFN-02 Active Nasal Sumatriptan 10mg spray upon onset of acute migraine pain during each acute migraine episode DFN-02	DFN-02 Placebo spray upon onset of acute migraine pain during each acute migraine episode DFN-02 Placebo
Measure Participants	41	38
Count of Participants [Participants]	29 58%	15 34.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DFN-02 (DB1), Placebo (DB1)
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority conducted as specified in the statistical analysis plan (SAP).
Statistical Test of Hypothesis	p-Value	0.007
	Comments	The corresponding p-values from Fisher's exact test were computed for the comparison between treatment groups.
	Method	Fisher Exact
	Comments

3. Secondary Outcome

Title	Number of Participants With Headache Pain Freedom at 2 Hours Postdose in the Double-blind Treatment Period 2 (DB2)
Description	In Double-blind Treatment Period 2 (DB2), freedom from headache pain 2 hours after the first dose of study medication taken within one hour of experiencing a migraine attack for any headache pain level, e.g., mild [Grade 1], moderate [Grade 2], or severe [Grade 3] and reduced to none [Grade 0] after study medication administration. If the subject was not able to use study medication for the first migraine after randomization, they were instructed to use the study medication for the next attack.
Time Frame	2 hours after study medication administration

Outcome Measure Data

Analysis Population Description

Last observation carried forward (LOCF) imputation method. Analysis included all randomized subjects who took at least one dose of study medication during the second DB treatment period (2) and had at least one post-baseline efficacy time point assessment in DB treatment period (2).

Arm/Group Title	DFN-02 (DB2)	Placebo (DB2)
Arm/Group Description	Participants self-administered a single-dose of DFN-02 (sumatriptan 10-mg/100 μL nasal spray) intranasally within one hour of an acute migraine pain episode. Sumatriptan 10 MG Nasal Spray: 100 μL nasal spray once	Participants self-administered a single-dose of DFN-02 placebo nasal spray matching DFN-02 intranasally within one hour of an acute migraine pain episode. Sumatriptan Placebo Nasal Spray: 100 μL nasal spray once
Measure Participants	36	37
Count of Participants [Participants]	19 38%	17 39.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DFN-02 (DB1), Placebo (DB1)
	Comments	Statistical testing and confidence intervals (CIs) were 2 sided and performed using a significance (alpha) level of 0.05. All statistical analyses were conducted with the SAS® software package (version 9.3).
	Type of Statistical Test	Non-Inferiority
	Comments	No assumptions made.
Statistical Test of Hypothesis	p-Value	0.642
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.31
	Confidence Interval	(2-Sided) 95%; 0.52 to 3.30
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Adverse Events were assessed from the initial dose of study medication up to 5 days after the last dose of study medication.
Arm/Group Title	DFN-02 (DB1)		Placebo (DB1)		DFN-02 (DB2)		Placebo (DB2)
Arm/Group Description	DFN-02 Active Nasal Sumatriptan 10-mg spray upon onset of acute migraine pain during each acute migraine episode DFN-02 Active in Double-blind Treatment Period 1		DFN-02 Placebo spray upon onset of acute migraine pain during each acute migraine episode DFN-02 Placebo in Double-blind Treatment Period 1		DFN-02 Active Nasal Sumatriptan 10-mg spray upon onset of acute migraine pain during each acute migraine episode DFN-02 Active in Double-blind Treatment Period 2		DFN-02 Placebo spray upon onset of acute migraine pain during each acute migraine episode DFN-02 Placebo in Double-blind Treatment Period 2
All Cause Mortality
	DFN-02 (DB1)		Placebo (DB1)		DFN-02 (DB2)		Placebo (DB2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/50 (0%)		0/43 (0%)		0/37 (0%)		0/38 (0%)
Serious Adverse Events
	DFN-02 (DB1)		Placebo (DB1)		DFN-02 (DB2)		Placebo (DB2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/50 (0%)		0/43 (0%)		0/37 (0%)		0/38 (0%)
Other (Not Including Serious) Adverse Events
	DFN-02 (DB1)		Placebo (DB1)		DFN-02 (DB2)		Placebo (DB2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/50 (10%)		0/43 (0%)		5/37 (13.5%)		0/38 (0%)
General disorders
Application site pain	1/50 (2%)	1	0/43 (0%)	0	1/37 (2.7%)	1	0/38 (0%)	0
Chest Discomfort	1/50 (2%)	1	0/43 (0%)	0	0/37 (0%)	0	0/38 (0%)	0
Malaise	0/50 (0%)	0	0/43 (0%)	0	1/37 (2.7%)	1	0/38 (0%)	0
Infections and infestations
Ear Infection	0/50 (0%)	0	0/43 (0%)	0	1/37 (2.7%)	1	0/38 (0%)	0
Injury, poisoning and procedural complications
Laceration	1/50 (2%)	1	0/43 (0%)	0	0/37 (0%)	0	0/38 (0%)	0
Nervous system disorders
Burning sensation	1/50 (2%)	1	0/43 (0%)	0	0/37 (0%)	0	0/38 (0%)	0
Dysgeusia	1/50 (2%)	1	0/43 (0%)	0	3/37 (8.1%)	3	0/38 (0%)	0
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea	1/50 (2%)	1	0/43 (0%)	0	0/37 (0%)	0	0/38 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.