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

A Long-Term, Open-Label Study to Evaluate the Safety of M207 (Zolmitriptan Intracutaneous Microneedle System) in the Acute Treatment of Migraine

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03282227

Acronym

ADAM

Enrollment

342

Registered

2017-09-13

Start date

2017-11-07

Completion date

2019-05-17

Last updated

2020-08-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Migraine

Keywords

migraine, migraine headache, acute migraine, acute migraine headache

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.

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.

Interventions

DRUGM207 Microneedle System

M207 Microneedle System 3.8 mg

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Masking description

Open-label

Intervention model description

Single dose, open-label treatment

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

Inclusion criteria

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: 1. at least 2 migraines per month 2. no more than 8 migraines per month 3. no more than 15 headache days per month 4. 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. 5. 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 7. History or current abuse or dependence on alcohol or drugs

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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.
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.
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.
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.
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.
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.

Countries

United States

Participant flow

Participants by arm

Arm	Count
M207 Microneedle System 3.8 mg M207 Microneedle System 3.8 mg (1.9 mg/patch x 2 patches) M207 Microneedle System: M207 Microneedle System 3.8 mg	335
Total	335

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	15
Overall Study	Exposure Goals Achieved	60
Overall Study	Lack of Efficacy	12
Overall Study	Lost to Follow-up	21
Overall Study	Non-compliance w/ protocol requirements	79
Overall Study	Other	1
Overall Study	Physician Decision	2
Overall Study	Pregnancy	2
Overall Study	Sponsor decision	3
Overall Study	Withdrawal by Subject	20

Baseline characteristics

Characteristic	M207 Microneedle System 3.8 mg
Age, Continuous	42.9 years STANDARD_DEVIATION 12.07
BMI	29.19 kg/m^2 STANDARD_DEVIATION 7.185
Ethnicity (NIH/OMB) Hispanic or Latino	60 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	275 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Height	165.20 cm STANDARD_DEVIATION 8.602
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	7 Participants
Race (NIH/OMB) Black or African American	55 Participants
Race (NIH/OMB) More than one race	4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants
Race (NIH/OMB) White	265 Participants
Sex: Female, Male Female	297 Participants
Sex: Female, Male Male	38 Participants
Weight	79.76 kg STANDARD_DEVIATION 20.847

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 335
other Total, other adverse events	323 / 335
serious Total, serious adverse events	5 / 335

Outcome results

Primary

Number of Subjects With Any Treatment-emergent Adverse Events (TEAE) Over 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.

Time frame: 0 to 12 months

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

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
M207 Microneedle System 3.8 mg	Number of Subjects With Any Treatment-emergent Adverse Events (TEAE) Over 12 Months	323 Participants

Secondary

Percentage of Migraine Attacks for Which Most Bothersome Symptom Freedom Was Achieved at 2 Hours Post-dose

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.