ADAM: A Study to Evaluate the Long-Term Safety of M207 in the Acute Treatment of Migraine

• Sponsor: Zosano Pharma Corporation (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03282227
• Collaborator: (none)
• Enrollment: 342
• Locations: 31
• Arm: 1
• Actual Duration (Months): 18.3
• Patients Per Site: 11
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

This is an open-label, twelve-month safety study. There is a screening period followed by a run-in period to record migraine activity. Qualified subjects will receive study medication for up to twelve months for the treatment of multiple migraine attacks. Using the electronic diary (eDiary) to confirm they are experiencing a qualified migraine, subjects will self-administer the patches and respond to questions in the eDiary post treatment administration.

Condition or Disease	Intervention/Treatment	Phase
Migraine	Drug: M207 Microneedle System	Phase 3

Detailed Description

This is an open-label, twelve-month safety study. There is a screening period followed by a run-in period (14 to 21 days) to determine eligibility for treatment with study medication based on daily eDiary data collection. Qualified subjects will receive study medication on Day 1 for up to twelve months for the treatment of migraine headaches. Migraines will be treated with a single dose, consisting of two patches, but subjects can treat multiple migraine attacks throughout the 12 months. Using the eDiary to confirm they are experiencing a qualified migraine, subjects will self-administer the patches and continue to respond to questions in the eDiary for 48 hours post treatment administration.

Study Design

• Study Type: Interventional
• Actual Enrollment: 342 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Single dose, open-label treatmentSingle dose, open-label treatment
• Masking: None (Open Label)
• Masking Description: Open-label
• Primary Purpose: Treatment
• Official Title: A Long-Term, Open-Label Study to Evaluate the Safety of M207 (Zolmitriptan Intracutaneous Microneedle System) in the Acute Treatment of Migraine
• Actual Study Start Date: Nov 7, 2017
• Actual Primary Completion Date: May 17, 2019
• Actual Study Completion Date: May 17, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: M207 Microneedle System 3.8 mg M207 Microneedle System 3.8 mg (1.9 mg/patch x 2 patches)	Drug: M207 Microneedle System; M207 Microneedle System 3.8 mg; Other Names: ZP-Zolmitriptan Intracutaneous Microneedle System ADAM-Zolmitriptan

Outcome Measures

Primary Outcome Measures

1. Number of Subjects With Any Treatment-emergent Adverse Events (TEAE) Over 12 Months [0 to 12 months]

   Number and % of subjects in safety population with any treatment-emergent adverse event(s) during the study. TEAE is defined as any new adverse event (AE) that started after first patch application. This was an open-label study with no control group. No statistical analyses were performed. Application site skin reactions including erythema, swelling, haemorrhage, bruise, pain, and pruritus were collected systematically via subject e-diary and/or investigator skin assessment at study visits. All other AEs were spontaneously reported by subject or observed upon examination.

Secondary Outcome Measures

1. Percentage of Migraine Attacks for Which Pain Freedom Was Achieved at 2 Hours Post-dose [2 hours for each Migraine, up to 12 months for each subject]

   Percentage of migraine attacks for which pain freedom defined as a pain level of 'None' (Grade 0 on pain severity scale where 0: None, 1: Mild, 2: Moderate, 3: Severe, and lower values represent a better outcome) was achieved at 2 hours post-dose without the use of rescue medication. This was an open-label study with no control group. No statistical analyses were performed.

2. Percentage of Migraine Attacks for Which Most Bothersome Symptom Freedom Was Achieved at 2 Hours Post-dose [2 hours for each Migraine, up to 12 months for each subject]

   Percentage of migraine attacks for which freedom from most bothersome symptom other than pain defined as an absence of the most bothersome symptom was achieved at 2 hours post-dose without the use of rescue medication. This was an open-label study with no control group. No statistical analyses were performed.

3. Percentage of Migraine Attacks for Which Pain Relief Was Achieved at 2 Hours Post-dose [2 hours for each Migraine, up to 12 months for each subject]

   Percentage of migraine attacks for which pain relief defined as an improvement of pain severity (1) to mild (Grade 1) or none (Grade 0) from moderate (Grade 2) or severe (Grade 3) at baseline, or (2) an improvement of pain severity to none (Grade 0) from mild (Grade 1) at baseline, without rescue medication was achieved. Pain severity scale has grades: 0: None, 1: Mild, 2: Moderate, 3: Severe, where lower values represent a better outcome. This was an open-label study with no control group. No statistical analyses were performed.

4. Percentage of Migraine Attacks for Which Nausea Freedom Was Achieved at 2 Hours Post-dose [2 hours for each Migraine, up to 12 months for each subject]

   Percentage of subjects for which nausea freedom defined as absence of nausea and/or vomiting without the use of rescue medication was achieved at 2 hours post-dose. This was an open-label study with no control group. No statistical analyses were performed.

5. Percentage of Migraine Attacks for Which Photophobia Freedom Was Achieved at 2 Hours Post-dose [2 hours for each Migraine, up to 12 months for each subject]

   Percentage of migraine attacks for which photophobia freedom defined as an absence of photophobia without the use of rescue medication was achieved at 2 hours post-dose. This was an open-label study with no control group. No statistical analyses were performed.

6. Percentage of Migraine Attacks for Which Phonophobia Freedom Was Achieved at 2 Hours Post-dose [2 hours for each Migraine, up to 12 months for each subject]

   Percentage of migraine attacks for which phonophobia freedom defined as an absence of phonophobia without the use of rescue medication was achieved at 2 hours post-dose. This was an open-label study with no control group. No statistical analyses were performed.

Eligibility Criteria

Criteria

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

Main Inclusion Criteria:

1. Women or men 18 to 75 years of age

2. Greater than 1 year history of episodic, migraine (with or without aura) with onset prior to 50 years of age.

3. Migraine history during the prior 6 months must include:

4. at least 2 migraines per month

5. no more than 8 migraines per month

6. no more than 15 headache days per month

7. Women of child-bearing potential must not be pregnant, must agree to avoid pregnancy and use an acceptable double-barrier method of birth control during the trial.

8. Willing and able to treat a minimum of 2 migraines per month with study medication and consistently complete eDiary for up to 12 months.

Main Exclusion Criteria:

1. Contraindication to triptans

2. Use of selective serotonin reuptake inhibitors (drugs like Prozac®) or serotonin or norepinephrine reuptake inhibitors (drugs like Effexor®) or anti-coagulants (drugs like Coumadin®)

3. Known allergy or sensitivity to zolmitriptan or its derivatives or formulations

4. Known allergy or sensitivity to adhesives and/or titanium

5. Women who are pregnant, breast-feeding or plan a pregnancy during this study

6. Three or more of the following cardiovascular risk factors:

• Current tobacco use

• Hypertension or receiving anti-hypertensive medication for hypertension

• Hyperlipidemia or on prescribed anti-cholesterol treatment

• Family history of premature coronary artery disease

• Diabetes mellitus

1. History or current abuse or dependence on alcohol or drugs

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Achieve Clinical Research	Birmingham	Alabama	United States	35216
2	Elite Clinical Studies	Phoenix	Arizona	United States	85018
3	Downtown L.A. Research Center	Los Angeles	California	United States	90017
4	Stanford University Medical Center	Palo Alto	California	United States	94304
5	Allergy Asthma Associates of Santa Clara Valley Research Center	San Jose	California	United States	95117
6	California Medical Clinic for Headache	Santa Monica	California	United States	90404
7	Empire Clinical Research	Upland	California	United States	91786
8	Colorado Allergy Asthma Centers	Denver	Colorado	United States	80230
9	Harmony Medical Research Institute	Hialeah	Florida	United States	33016
10	Advanced Clinical Research	Meridian	Idaho	United States	83642
11	DelRicht Research	New Orleans	Louisiana	United States	70124
12	Boston Clinical Trials	Boston	Massachusetts	United States	02131
13	MedVadis Research Corporation	Watertown	Massachusetts	United States	02472
14	Michigan Headache and Neurological Institute	Ann Arbor	Michigan	United States	48104
15	Clinical Research Institute	Minneapolis	Minnesota	United States	55402
16	Clinical Research Institute	Plymouth	Minnesota	United States	55441
17	StudyMetrix Research LLC	Saint Peters	Missouri	United States	63303-3041
18	Clinvest Research	Springfield	Missouri	United States	65810
19	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
20	Albuquerque Clinical Trials	Albuquerque	New Mexico	United States	87102
21	Rochester Clinical Research	Rochester	New York	United States	14609
22	Peters Medical Research	High Point	North Carolina	United States	27262
23	North Carolina Clinical Research	Raleigh	North Carolina	United States	27607
24	Raleigh Medical Group PMG Research	Raleigh	North Carolina	United States	27609
25	Lillestol Research	Fargo	North Dakota	United States	58103
26	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
27	Primary Care Associates/Radiant Research	Anderson	South Carolina	United States	29621
28	Coastal Carolina Research Center	Mount Pleasant	South Carolina	United States	29464
29	FutureSearch Trials of Neurology	Austin	Texas	United States	78731
30	University of Texas Southwestern Medical Center - Neurology Clinic	Dallas	Texas	United States	75390
31	Central Texas Health Research	New Braunfels	Texas	United States	78130

Sponsors and Collaborators

• Zosano Pharma Corporation

Investigators

• Study Director: Don Kellerman, Pharm.D., Zosano Pharma Corporation

Study Documents (Full-Text)

• Statistical Analysis Plan - Nov 30, 2018
• Study Protocol - Apr 6, 2018

More Information

Publications

None provided.

• Responsible Party: Zosano Pharma Corporation
• ClinicalTrials.gov Identifier: NCT03282227
• Other Study ID Numbers: CP-2017-001
• First Posted: Sep 13, 2017
• Last Update Posted: Aug 19, 2020
• Last Verified: Aug 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Zosano Pharma Corporation: migraine; migraine headache; acute migraine; acute migraine headache
• Additional relevant MeSH terms: Migraine Disorders; Oxazolidinones; Zolmitriptan

Study Results

Participant Flow

Arm/Group Title	M207 Microneedle System 3.8 mg
Arm/Group Description	M207 Microneedle System 3.8 mg (1.9 mg/patch x 2 patches) M207 Microneedle System: M207 Microneedle System 3.8 mg
Period Title: Overall Study
STARTED	342
Completed at Least 6 Months	257
COMPLETED	127
NOT COMPLETED	215

Baseline Characteristics

Arm/Group Title	M207 Microneedle System 3.8 mg
Arm/Group Description	M207 Microneedle System 3.8 mg (1.9 mg/patch x 2 patches) M207 Microneedle System: M207 Microneedle System 3.8 mg
Overall Participants	335
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42.9 (12.07)
Sex: Female, Male (Count of Participants)
Female	297 88.7%
Male	38 11.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	60 17.9%
Not Hispanic or Latino	275 82.1%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	7 2.1%
Native Hawaiian or Other Pacific Islander	1 0.3%
Black or African American	55 16.4%
White	265 79.1%
More than one race	4 1.2%
Unknown or Not Reported	3 0.9%
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	165.20 (8.602)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	79.76 (20.847)
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	29.19 (7.185)

Outcome Measures

1. Primary Outcome

Title	Number of Subjects With Any Treatment-emergent Adverse Events (TEAE) Over 12 Months
Description	Number and % of subjects in safety population with any treatment-emergent adverse event(s) during the study. TEAE is defined as any new adverse event (AE) that started after first patch application. This was an open-label study with no control group. No statistical analyses were performed. Application site skin reactions including erythema, swelling, haemorrhage, bruise, pain, and pruritus were collected systematically via subject e-diary and/or investigator skin assessment at study visits. All other AEs were spontaneously reported by subject or observed upon examination.
Time Frame	0 to 12 months

Outcome Measure Data

Analysis Population Description

Safety Population included 335 subjects (98.0%) who received any amount of study drug (applied at least 1 patch).

Arm/Group Title	M207 Microneedle System 3.8 mg
Arm/Group Description	M207 Microneedle System 3.8 mg (1.9 mg/patch x 2 patches) M207 Microneedle System: M207 Microneedle System 3.8 mg
Measure Participants	335
Count of Participants [Participants]	323 96.4%

2. Secondary Outcome

Title	Percentage of Migraine Attacks for Which Pain Freedom Was Achieved at 2 Hours Post-dose
Description	Percentage of migraine attacks for which pain freedom defined as a pain level of 'None' (Grade 0 on pain severity scale where 0: None, 1: Mild, 2: Moderate, 3: Severe, and lower values represent a better outcome) was achieved at 2 hours post-dose without the use of rescue medication. This was an open-label study with no control group. No statistical analyses were performed.
Time Frame	2 hours for each Migraine, up to 12 months for each subject

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat (mITT) Population included all subjects who received any amount of study drug to treat a qualifying migraine, and who had efficacy data.

Arm/Group Title	M207 Microneedle System 3.8 mg
Arm/Group Description	M207 Microneedle System 3.8 mg (1.9 mg/patch x 2 patches) M207 Microneedle System: M207 Microneedle System 3.8 mg
Measure Participants	335
Measure Qualifying migraines with 2 hour data	5617
Count of Units [Qualifying migraines with 2 hour data]	2477

3. Secondary Outcome

Title	Percentage of Migraine Attacks for Which Most Bothersome Symptom Freedom Was Achieved at 2 Hours Post-dose
Description	Percentage of migraine attacks for which freedom from most bothersome symptom other than pain defined as an absence of the most bothersome symptom was achieved at 2 hours post-dose without the use of rescue medication. This was an open-label study with no control group. No statistical analyses were performed.
Time Frame	2 hours for each Migraine, up to 12 months for each subject

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat Population included all subjects who received

Arm/Group Title	M207 Microneedle System 3.8 mg
Arm/Group Description	M207 Microneedle System 3.8 mg (1.9 mg/patch x 2 patches) M207 Microneedle System: M207 Microneedle System 3.8 mg
Measure Participants	335
Measure Qualifying migraines with 2 hr data	5330
Count of Units [Qualifying migraines with 2 hr data]	3315

4. Secondary Outcome

Title	Percentage of Migraine Attacks for Which Pain Relief Was Achieved at 2 Hours Post-dose
Description	Percentage of migraine attacks for which pain relief defined as an improvement of pain severity (1) to mild (Grade 1) or none (Grade 0) from moderate (Grade 2) or severe (Grade 3) at baseline, or (2) an improvement of pain severity to none (Grade 0) from mild (Grade 1) at baseline, without rescue medication was achieved. Pain severity scale has grades: 0: None, 1: Mild, 2: Moderate, 3: Severe, where lower values represent a better outcome. This was an open-label study with no control group. No statistical analyses were performed.
Time Frame	2 hours for each Migraine, up to 12 months for each subject

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat (mITT) Population included all subjects who received any amount of study drug to treat a qualifying migraine, and who had efficacy data.

Arm/Group Title	M207 Microneedle System 3.8 mg
Arm/Group Description	M207 Microneedle System 3.8 mg (1.9 mg/patch x 2 patches) M207 Microneedle System: M207 Microneedle System 3.8 mg
Measure Participants	335
Measure Qualifying migraines with 2 hr data	5617
Count of Units [Qualifying migraines with 2 hr data]	4552

5. Secondary Outcome

Title	Percentage of Migraine Attacks for Which Nausea Freedom Was Achieved at 2 Hours Post-dose
Description	Percentage of subjects for which nausea freedom defined as absence of nausea and/or vomiting without the use of rescue medication was achieved at 2 hours post-dose. This was an open-label study with no control group. No statistical analyses were performed.
Time Frame	2 hours for each Migraine, up to 12 months for each subject

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat (mITT) Population included all subjects who received any amount of study drug to treat a qualifying migraine, and who had efficacy data.

Arm/Group Title	M207 Microneedle System 3.8 mg
Arm/Group Description	M207 Microneedle System 3.8 mg (1.9 mg/patch x 2 patches) M207 Microneedle System: M207 Microneedle System 3.8 mg
Measure Participants	335
Measure Qualifying migraines with 2 hr data	5617
Count of Units [Qualifying migraines with 2 hr data]	4628

6. Secondary Outcome

Title	Percentage of Migraine Attacks for Which Photophobia Freedom Was Achieved at 2 Hours Post-dose
Description	Percentage of migraine attacks for which photophobia freedom defined as an absence of photophobia without the use of rescue medication was achieved at 2 hours post-dose. This was an open-label study with no control group. No statistical analyses were performed.
Time Frame	2 hours for each Migraine, up to 12 months for each subject

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat (mITT) Population included all subjects who received any amount of study drug to treat a qualifying migraine, and who had efficacy data.

Arm/Group Title	M207 Microneedle System 3.8 mg
Arm/Group Description	M207 Microneedle System 3.8 mg (1.9 mg/patch x 2 patches) M207 Microneedle System: M207 Microneedle System 3.8 mg
Measure Participants	335
Measure Qualifying migraines with 2 hour data	5617
Count of Units [Qualifying migraines with 2 hour data]	3410

7. Secondary Outcome

Title	Percentage of Migraine Attacks for Which Phonophobia Freedom Was Achieved at 2 Hours Post-dose
Description	Percentage of migraine attacks for which phonophobia freedom defined as an absence of phonophobia without the use of rescue medication was achieved at 2 hours post-dose. This was an open-label study with no control group. No statistical analyses were performed.
Time Frame	2 hours for each Migraine, up to 12 months for each subject

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat (mITT) Population included all subjects who received any amount of study drug to treat a qualifying migraine, and who had efficacy data.

Arm/Group Title	M207 Microneedle System 3.8 mg
Arm/Group Description	M207 Microneedle System 3.8 mg (1.9 mg/patch x 2 patches) M207 Microneedle System: M207 Microneedle System 3.8 mg
Measure Participants	335
Measure Qualifying migraines with 2 hour data	5617
Count of Units [Qualifying migraines with 2 hour data]	3563

Adverse Events

Time Frame	0-12 months
Adverse Event Reporting Description	Application site skin reactions including erythema, swelling, haemorrhage, bruise, pain, and pruritus were collected systematically via subject e-diary and/or investigator skin assessment at study visits. All other AEs were spontaneously reported by subject or observed upon examination.
Arm/Group Title	M207 Microneedle System 3.8 mg
Arm/Group Description	M207 Microneedle System 3.8 mg (1.9 mg/patch x 2 patches) M207 Microneedle System: M207 Microneedle System 3.8 mg
All Cause Mortality
	M207 Microneedle System 3.8 mg
	Affected / at Risk (%)	# Events
Total	0/335 (0%)
Serious Adverse Events
	M207 Microneedle System 3.8 mg
	Affected / at Risk (%)	# Events
Total	5/335 (1.5%)
Congenital, familial and genetic disorders
Foetal disorder	1/335 (0.3%)
Infections and infestations
Pneumonia	1/335 (0.3%)
Metabolism and nutrition disorders
Hypokalaemia	1/335 (0.3%)
Nervous system disorders
Procedural pain	1/335 (0.3%)
Reproductive system and breast disorders
Breast cancer stage II	1/335 (0.3%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/335 (0.3%)
Hypoxia	1/335 (0.3%)
Other (Not Including Serious) Adverse Events
	M207 Microneedle System 3.8 mg
	Affected / at Risk (%)	# Events
Total	323/335 (96.4%)
Gastrointestinal disorders
Nausea	9/335 (2.7%)
Infections and infestations
Upper respiratory tract infection	28/335 (8.4%)
Sinusitis	13/335 (3.9%)
Viral upper respiratory tract infection	7/335 (2.1%)
Skin and subcutaneous tissue disorders
Application site erythema	316/335 (94.3%)
Application site swelling	296/335 (88.4%)
Application site haemorrhage	225/335 (67.2%)
Application site bruise	194/335 (57.9%)
Application site pain	81/335 (24.2%)
Application site discolouration	53/335 (15.8%)
Application site pruritus	52/335 (15.5%)
Application site oedema	8/335 (2.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.