NP101-008: An Open-Label Study to Evaluate the Safety of NP101 in the Treatment of Acute Migraine Over 12 Months

• Sponsor: NuPathe Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00792103
• Collaborator: (none)
• Enrollment: 198
• Locations: 34
• Arm: 1
• Duration (Months): 20
• Patients Per Site: 5.8
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The primary objective is to evaluate the safety of long-term treatment with NP101 as assessed by:

• Subject self-examination skin irritation scores

• Adverse events

• Changes in vital signs and ECG parameters

The secondary objective is to evaluate the long term efficacy of NP101 as assessed by:

• Headache pain free at two hours after patch activation for all initial acute migraine attacks treated with NP101

• Headache pain relief at two hours after patch activation for all initial acute migraine attacks treated with NP101

• Nausea free at two hours after patch activation for all initial acute migraine attacks treated with NP101

• Phonophobia free at two hours after patch activation for all initial acute migraine attacks treated with NP101

• Photophobia free at two hours after patch activation for all initial acute migraine attacks treated with NP101

• Migraine free at two hours after patch activation for all initial acute migraine attacks treated with NP101

This study will use an open-label design to assess the long term safety of NP101 (sumatriptan iontophoretic transdermal patch).

Subjects who continue to be in good health (use of a triptan or use of an NP101 patch is not contraindicated) and received treatment (patch activation) with the study patch for a qualifying migraine under study NP101-007 will be considered eligible for enrollment into the open-label study. Subjects will be expected to remain in the study for up to 12 months.

Condition or Disease	Intervention/Treatment	Phase
Migraine Disorders	Drug: NP101	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 198 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label Study to Evaluate the Safety of NP101, a Sumatriptan Iontophoretic Transdermal Patch, in the Treatment of Acute Migraine Over 12 Months
• Study Start Date: Jan 1, 2009
• Actual Primary Completion Date: Sep 1, 2010
• Actual Study Completion Date: Sep 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: NP101 sumatriptan iontophoretic transdermal patch	Drug: NP101; NP101 study patch 4 hour application

Outcome Measures

Primary Outcome Measures

1. Subject Self-examination of Skin Irritation [24 hours post patch activation]

   For each patch application, subjects performed a self-examination of skin irritation using a 5-point scale (0=no redness; 1=minimal skin redness; 2=moderate skin redness with sharp borders; 3=intense skin redness with or without swelling; 4=intense skin redness with blisters or broken skin).

Secondary Outcome Measures

1. Pain Relief [2 hours]

   Headache pain relief (no pain or mild headache pain) at two hours post activation of NP101.

2. Nausea Free [2 hours]

   Nausea free at two hours after patch activation.

3. Phonophobia Free [2 hours]

   Phonophobia free at two hours after patch activation.

4. Photophobia Free [2 hours]

   Photophobia free at two hours after patch activation.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subject was previously enrolled in study NP101-007 and treated (patch activation) a qualifying migraine.

• Subject will be judged to be in good health, based upon the results of a medical history, physical examination, vital signs, and ECG. Subjects will not have any clinically significant abnormal vital signs or ECG parameters in order to qualify for enrollment. ECG must be done at enrollment for NP101-008 unless ECG for the Final Visit of study NP101-007 was conducted within 30 days.

• Female subjects of childbearing potential (not surgically sterile or 2 years post menopausal) must have a negative pregnancy test at enrollment.

Exclusion Criteria:

• Subject has less than two potential skin application sites.

• Subject has clinically significant abnormal vital signs or ECG parameters or had an adverse event while participating in NP101-007 that would preclude the continued treatment with the NP101 patch.

• Subject has had changes in their medical history or medication use that would preclude their use of sumatriptan as per the approved Imitrex® product Prescribing Information (PI) or their safe use of NP101 as per the NP101 Investigator's Brochure.

• Subject has or plans to start, stop, change treatment or dose of any of the following within 3 months prior to the subject's study Enrollment date and through the Final Visit: anxiolytics, lithium and other mood stabilizers such as valproate, carbamazepine or lamotrigine, hypnotics or antipsychotics.

• Subject has taken non-triptan serotonergic drugs including selective serotonin reuptake inhibitor (SSRI), serotonin and norepinephrine reuptake inhibitor (SNRI), tricyclic antidepressants (TCAs), monoamine oxidase inhibitor (MAOI) or preparations containing St. John's Wort within 1 month prior to enrollment and/or is planning to start any of these medications during the study (through Final Visit).

• Female subjects who are pregnant, breast feeding, or of childbearing potential, and are not using or are unwilling to use an effective form of contraception during the study and for a period of 30 days following Final Visit. Acceptable methods of contraception include barrier method with spermicide, intrauterine device (IUD), steroidal contraceptive (oral, transdermal, implanted or injected) or abstinence. If the exclusive male partner is surgically sterile, this will be acceptable.

• Subject has participated in a clinical study within 30 days of enrollment (excluding NP101-007) or is planning to participate in another clinical study for the duration of NP101-008.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Phoenix	Arizona	United States
2		Little Rock	Arkansas	United States
3		Newport Beach	California	United States
4		San Francisco	California	United States
5		Santa Monica	California	United States
6		Fairfield	Connecticut	United States
7		Ocala	Florida	United States
8		Palm Beach Gardens	Florida	United States
9		Sunrise	Florida	United States
10		Atlanta	Georgia	United States
11		Columbus	Georgia	United States
12		Decatur	Georgia	United States
13		Savannah	Georgia	United States
14		Chicago	Illinois	United States
15		Ann Arbor	Michigan	United States
16		Kalamazoo	Michigan	United States
17		Springfield	Missouri	United States
18		St. Louis	Missouri	United States
19		Mount Vernon	New York	United States
20		Plainview	New York	United States
21		Greensboro	North Carolina	United States
22		West Chester	Ohio	United States
23		Oklahoma City	Oklahoma	United States
24		Philadelphia	Pennsylvania	United States
25		Pittsburgh	Pennsylvania	United States
26		Wynnewood	Pennsylvania	United States
27		Memphis	Tennessee	United States
28		Nashville	Tennessee	United States
29		Dallas	Texas	United States
30		Houston	Texas	United States
31		San Antonio	Texas	United States
32		Alexandria	Virginia	United States
33		Virginia Beach	Virginia	United States
34		Seattle	Washington	United States

Sponsors and Collaborators

• NuPathe Inc.

Investigators

• Study Chair: Mark Pierce, MD PhD, NuPathe Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: NuPathe Inc.
• ClinicalTrials.gov Identifier: NCT00792103
• Other Study ID Numbers: PROT-15-NP101-008
• First Posted: Nov 17, 2008
• Last Update Posted: Feb 4, 2016
• Last Verified: Feb 1, 2016

• Additional relevant MeSH terms: Migraine Disorders

Study Results

Participant Flow

Recruitment Details	The study was initiated January 2009 and completed in September 2010. Patients were enrolled from 34 investigative sites across the United States.
Pre-assignment Detail	This was an open-label study to assess the long-term safety of NP101. Subjects who continued to be in good health and received treatment with an NP101 patch for a qualifying migraine in the pivotal NP101-007 study were considered eligible for enrollment.

Arm/Group Title	NP101
Arm/Group Description	The NP101 patch contained 86 mg of sumatriptan and was designed to deliver approximately 6.5 mg of sumatriptan over 4 hours. Patients were asked to use study patches to treat migraine episodes with moderate or severe headache pain for up to 12 months, during which they were permitted to apply (to the upper arms or thighs) a maximum of 6 patches within a 30-day period.
Period Title: Overall Study
STARTED	198
COMPLETED	65
NOT COMPLETED	133

Baseline Characteristics

Arm/Group Title	NP101
Arm/Group Description	The NP101 patch contained 86 mg of sumatriptan and was designed to deliver approximately 6.5 mg of sumatriptan over 4 hours. Patients were asked to use study patches to treat migraine episodes with moderate or severe headache pain for up to 12 months, during which they were permitted to apply (to the upper arms or thighs) a maximum of 6 patches within a 30-day period.
Overall Participants	183
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	183 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42.0 (10.28)
Sex: Female, Male (Count of Participants)
Female	152 83.1%
Male	31 16.9%
Region of Enrollment (participants) [Number]
United States	183 100%

Outcome Measures

1. Secondary Outcome

Title	Pain Relief
Description	Headache pain relief (no pain or mild headache pain) at two hours post activation of NP101.
Time Frame	2 hours

Outcome Measure Data

Analysis Population Description

Per protocol, the intent-to-treat population was defined as all subjects who applied and activated at least one NP101 study patch and had at least one post baseline assessment for each migraine symptom (pain, photophobia, phonophobia, and nausea). Two treated subjects in the safety population did not meet this criteria.

Arm/Group Title	NP101
Arm/Group Description	The NP101 patch contained 86 mg of sumatriptan and was designed to deliver approximately 6.5 mg of sumatriptan over 4 hours. Patients were asked to use study patches to treat migraine episodes with moderate or severe headache pain for up to 12 months, during which they were permitted to apply (to the upper arms or thighs) a maximum of 6 patches within a 30-day period.
Measure Participants	181
Number [participants]	105 (0.341) 57.4%

2. Primary Outcome

Title	Subject Self-examination of Skin Irritation
Description	For each patch application, subjects performed a self-examination of skin irritation using a 5-point scale (0=no redness; 1=minimal skin redness; 2=moderate skin redness with sharp borders; 3=intense skin redness with or without swelling; 4=intense skin redness with blisters or broken skin).
Time Frame	24 hours post patch activation

Outcome Measure Data

Analysis Population Description

Per protocol, the intent-to-treat population was defined as all subjects who applied and activated at least one NP101 study patch and had at least one post baseline assessment for each migraine symptom (pain, photophobia, phonophobia, and nausea).

Arm/Group Title	NP101
Arm/Group Description	The NP101 patch contained 86 mg of sumatriptan and was designed to deliver approximately 6.5 mg of sumatriptan over 4 hours. Patients were asked to use study patches to treat migraine episodes with moderate or severe headache pain for up to 12 months, during which they were permitted to apply (to the upper arms or thighs) a maximum of 6 patches within a 30-day period.
Measure Participants	183
Measure NP101 Patches	1917
Mean (Standard Deviation) [scores on a scale]	1.0 (0.96)

3. Secondary Outcome

Title	Nausea Free
Description	Nausea free at two hours after patch activation.
Time Frame	2 hours

Outcome Measure Data

Analysis Population Description

Per protocol, the intent-to-treat population was defined as all subjects who applied and activated at least one NP101 study patch and had at least one post baseline assessment for each migraine symptom (pain, photophobia, phonophobia, and nausea). Two treated subjects in the safety population did not meet this criteria.

Arm/Group Title	NP101
Arm/Group Description	The NP101 patch contained 86 mg of sumatriptan and was designed to deliver approximately 6.5 mg of sumatriptan over 4 hours. Patients were asked to use study patches to treat migraine episodes with moderate or severe headache pain for up to 12 months, during which they were permitted to apply (to the upper arms or thighs) a maximum of 6 patches within a 30-day period.
Measure Participants	181
Number [participants]	143 78.1%

4. Secondary Outcome

Title	Phonophobia Free
Description	Phonophobia free at two hours after patch activation.
Time Frame	2 hours

Outcome Measure Data

Analysis Population Description

Per protocol, the intent-to-treat population was defined as all subjects who applied and activated at least one NP101 study patch and had at least one post baseline assessment for each migraine symptom (pain, photophobia, phonophobia, and nausea). Two treated subjects in the safety population did not meet this criteria.

Arm/Group Title	NP101
Arm/Group Description	The NP101 patch contained 86 mg of sumatriptan and was designed to deliver approximately 6.5 mg of sumatriptan over 4 hours. Patients were asked to use study patches to treat migraine episodes with moderate or severe headache pain for up to 12 months, during which they were permitted to apply (to the upper arms or thighs) a maximum of 6 patches within a 30-day period.
Measure Participants	181
Number [participants]	109 59.6%

5. Secondary Outcome

Title	Photophobia Free
Description	Photophobia free at two hours after patch activation.
Time Frame	2 hours

Outcome Measure Data

Analysis Population Description

Per protocol, the intent-to-treat population was defined as all subjects who applied and activated at least one NP101 study patch and had at least one post baseline assessment for each migraine symptom (pain, photophobia, phonophobia, and nausea). Two treated subjects in the safety population did not meet this criteria.

Arm/Group Title	NP101
Arm/Group Description	The NP101 patch contained 86 mg of sumatriptan and was designed to deliver approximately 6.5 mg of sumatriptan over 4 hours. Patients were asked to use study patches to treat migraine episodes with moderate or severe headache pain for up to 12 months, during which they were permitted to apply (to the upper arms or thighs) a maximum of 6 patches within a 30-day period.
Measure Participants	181
Number [participant]	97

Adverse Events

Time Frame	All adverse events were collected from study enrollment until 30 days after the last patch application.
Arm/Group Title	NP101
Arm/Group Description	The NP101 patch contained 86 mg of sumatriptan and was designed to deliver approximately 6.5 mg of sumatriptan over 4 hours. Patients were asked to use study patches to treat migraine episodes with moderate or severe headache pain for up to 12 months, during which they were permitted to apply (to the upper arms or thighs) a maximum of 6 patches within a 30-day period.
All Cause Mortality
	NP101
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	NP101
	Affected / at Risk (%)	# Events
Total	2/183 (1.1%)
Ear and labyrinth disorders
Vertigo	1/183 (0.5%)	1
Metabolism and nutrition disorders
Dehydration	1/183 (0.5%)	1
Other (Not Including Serious) Adverse Events
	NP101
	Affected / at Risk (%)	# Events
Total	66/183 (36.1%)
General disorders
Application site hypersensitivity	11/183 (6%)	11
Application Site Pain	39/183 (21.3%)	39
Application site pruritus	40/183 (21.9%)	40

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Per the study agreement, Investigators have the right to publish or present information and/or data arising from the study, provided the text of any such publication or presentation is submitted for review at least thirty days prior to submission for publication or other disclosure and NuPathe shall have the right to request the removal of any confidential information.