SpringTMS

K162797 · Eneura, Inc. · OKP · Jun 26, 2017 · Neurology

Device Facts

• Record ID: K162797
• Device Name: SpringTMS
• Applicant: Eneura, Inc.
• Product Code: OKP · Neurology
• Decision Date: Jun 26, 2017
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 882.5808
• Device Class: Class 2
• Attributes: Therapeutic

Indications for Use

The eNeura Inc. SpringTMS® is indicated for the acute and prophylactic treatment of migraine headache.

Device Story

SpringTMS is a portable, hand-held device for single pulse transcranial magnetic stimulation (sTMS). It delivers a brief, 0.9 Tesla magnetic pulse to the occipital cortex to induce electrical currents, aiming to stop or reduce migraine effects. Designed for patient self-administration in home or office settings. Treatment regimen involves daily prophylactic pulses (4 pulses morning/evening) and acute treatment (3 pulses at onset, repeatable). Device is prescription-only. Healthcare providers use clinical outcomes to monitor treatment efficacy. Benefits include reduction in migraine headache days and decreased reliance on acute medications.

Clinical Evidence

Prospective, multicenter, non-randomized, single-arm observational study (ESPOUSE) with 217 subjects (Safety Data Set). Primary endpoint: mean reduction in migraine headache days over 28 days at 12 weeks. Results showed statistically significant reduction of 2.8 days (FAS, p<0.0001) and 3.0 days (PP, p<0.0001) from baseline. No serious adverse events reported; common AEs included lightheadedness, dizziness, tinnitus, and scalp discomfort.

Technological Characteristics

Portable, hand-held transcranial magnetic stimulator. Delivers 0.9 Tesla single magnetic pulse. Operates via electromagnetic induction to stimulate the occipital cortex. Class II device, Product Code OKP. Contraindicated for patients with metal-containing implants in the head, neck, or upper body (e.g., aneurysm clips, cochlear implants, shunts, stents, metal plates/screws).

Indications for Use

Indicated for acute and prophylactic treatment of migraine headache in patients 18 to 65 years of age with migraine with or without aura.

Regulatory Classification

Identification

A transcranial magnetic stimulator device for headache is a device that delivers brief duration, rapidly alternating, or pulsed, magnetic fields that are externally directed at spatially discrete regions of the brain to induce electrical currents for the treatment of headache.

Special Controls

*Classification.* Class II (special controls). The special controls for this device are:(1) Appropriate analysis/testing must demonstrate electromagnetic compatibility, electrical safety, and thermal safety. (2) Appropriate verification, validation, and hazard analysis must be performed on the device software and firmware. (3) The elements of the device that contact the patient must be assessed to be biocompatible. (4) Non-clinical testing data must demonstrate that the device performs as intended under anticipated conditions of use. This includes full characterization of the magnetic pulse output and resulting magnetic field map. This also includes characterization of the sound level of the device during use. (5) Clinical testing must demonstrate that the device is safe and effective for treating headache in the indicated patient population. (6) The physician and patient labeling must include the following: (i) A summary of the clinical performance testing, including any adverse events and complications. (ii) The intended use population in terms of the types of headaches appropriate for use with the device. (iii) Information on how to report adverse events and device malfunctions. (iv) A diagram or picture depicting the proper placement of the device on the user.

1. Appropriate analysis/testing must demonstrate electromagnetic compatibility (EMC), electrical safety, and thermal safety. 2. Appropriate verification, validation, and hazard analysis must be performed on the device software and firmware. 3. The elements of the device that contact the patient must be assessed to be biocompatible. 4. Non-clinical testing data must demonstrate that the device performs as intended under anticipated conditions of use. This includes full characterization of the magnetic pulse output and resulting magnetic field map. This also includes characterization of the sound level of the device during use. 5. Clinical testing must demonstrate that the device is safe and effective for treating headache in the indicated patient population. 6. The physician and patient labeling must include the following: a. A summary of the clinical performance testing, including any adverse events and complications. b. The intended use population in terms of the types of headaches appropriate for use with the device. c. Information on how to report adverse events and device malfunctions. d. A diagram or picture depicting the proper placement of the device on the user.

Predicate Devices

• SpringTMS (K140094)

Submission Summary (Full Text)

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Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized caduceus symbol, which is often associated with healthcare. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the symbol.

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

June 26, 2017

eNeura Inc. c/o Larry W. Getlin Consultant 715 North Pastoria Avenue Sunnyvale, California 94085

Re: K162797

Trade/Device Name: Spring TMS Regulation Number: 21 CFR 882.5808 Regulation Name: Transcranial Magnetic Stimulator For Headache Regulatory Class: Class II Product Code: OKP Dated: October 1, 2016 Received: October 4, 2016

Dear Larry Getlin:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA), You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices. good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting (reporting of medical devicerelated adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Division of Industry and Consumer Education at its toll-free number [phone] or [phone] or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number [phone] or [phone] or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely,

William J. Heetderks -S 2017.06.26 13:17:30 -04'00'

for Carlos L. Peña, PhD, MS Director Division of Neurological and Physical Medicine Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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# Indications for Use Statement

DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

# Indications for Use

510(K) Number (if known)

K162797

Device Name

## eNeura, Inc.- SpringTMS®

° Indications for Use (Describe)

The eNeura Inc. SpringTMS® is indicated for the acute and prophylactic treatment of migraine headache.

Type of Use (Select one or both, as applicable) > Prescription Use (Part 21 CFR 801 Subpart D)

Over-The-Counter Use (21 CFR 801 Subpart C)

### PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON A SEPARATE PAGE IF NEEDED.

FOR FDA USE ONLY Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)

Form Approved: OMB No. 0910-0120 Expiration Date: January 31, 2017 See PRA Statement below.

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## 7. Premarket Notification 510(k) Summary

This summary of 510(k) safety and effectiveness information is submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

### 510(k) Number: K162797

#### Applicant Information: 7.1.

| Date Prepared: | May 25, 2017 |
|----------------------|---------------------------------------------------------------|
| Applicant Name: | eNeura, Inc. |
| Address: | 715 North Pastoria Avenue<br>Sunnyvale, CA 94085<br>U.S.A. |
| Phone: | 408-245-6500 |
| FAX: | 408-245-6424 |
| Contact Person: | Larry W. Getlin, Regulatory Consultant<br>[e-mail]. |
| Mobile Number: | [phone] |
| Alternative Contact: | Michael A Daniel, Consultant<br>[e-mail] |
| Mobile Number: | [phone] |

#### 7.2. Device Information:

| Device Trade Name: | SpringTMS® |
|---------------------------|--------------------------------------------------------|
| Classification Name(s): | Transcranial magnetic stimulator for migraine headache |
| Product Code/ Regulation: | OKP / 21 CFR§882.5808 |
| Classification: | Class II |

#### 7.3. Predicate Device:

SpringTMS®

#### 7.4. Subject Device Description

The SpringTMS® is a portable, hand-held device that is designed and intended to deliver a brief single pulse of magnetic energy at 0.9 Tesla to the back of the head to induce an electrical current in a portion of the brain called the occipital cortex to stop or lessen the effects of migraine headaches. Since a single pulse of magnetic stimulation is emitted, this method of stimulation is called single pulse transcranial magnetic stimulation or sTMS. The SpringTMS is indicated for the acute treatment and prevention of migraine headache. The device is designed for patient use where treatments are self-administered and can be delivered in a variety of settings including the home or office. The device is intended for prescription use only.

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#### 7.5. Intended Use / Indications for Use

The eNeura® Spring TMS® is designed and intended to deliver brief duration, pulsed, magnetic fields that are externally directed at spatially discrete regions of the brain to induce electric currents in the brain (Product Code OKP).

The eNeura Inc. SpringTMS® is indicated for the acute and prophylactic treatment of migraine headache.

#### 7.6. Predicate and Subject Device Comparison Chart

### Comparison to Predicate and Reference Device:

| | Subject Device | Predicate Device | Comparison to predicate<br>device |
|-------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------|
| Device Name | SpringTMS | SpringTMS | Same |
| Manufacturer | eNeura Inc. | eNeura Inc. | Same |
| 510(k) # | Not Assigned | K140094 | N/A |
| Regulation<br>Number | 21 CFR§882.5808 | 21 CFR§882.5808 | Same |
| Class | Class II | Class II | Same |
| Device<br>Class/Name | Transcranial magnetic<br>stimulator | Transcranial magnetic<br>stimulator | Same |
| Product Code | OKP | OKP | Same |
| Fundamental<br>scientific<br>technology | Portable, hand-held device<br>that is designed and intended<br>to deliver a brief single pulse<br>of magnetic energy at 0.9<br>Tesla to the back of the head<br>to induce an electrical<br>current in a portion of the<br>brain called the occipital<br>cortex to stop or lessen the<br>effects of migraine<br>headaches. | Portable, hand-held device<br>that is designed and intended<br>to deliver a brief single pulse<br>of magnetic energy at 0.9<br>Tesla to the back of the head<br>to induce an electrical<br>current in a portion of the<br>brain called the occipital<br>cortex to stop or lessen the<br>effects of migraine<br>headaches. | Same |
| Intended Use<br>(From<br>Product Code<br>Description) | Intended to deliver<br>externally directed, pulsed,<br>magnetic fields to induce<br>electric currents in spatially<br>discrete regions of the brains<br>of patients with migraine<br>headache. | Intended to deliver<br>externally directed, pulsed,<br>magnetic fields to induce<br>electric currents in spatially<br>discrete regions of the brains<br>of patients with migraine<br>headache. | Same |

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| | Subject Device | Predicate Device | Comparison to predicate device |
|--------------------|----------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------|
| Indication for Use | Indications for Use:<br>• The eNeura Inc.<br>SpringTMS® is indicated<br>for the acute and<br>prophylactic treatment of<br>migraine headache. | Indications for Use:<br>• The acute treatment of<br>pain associated with<br>migraine headache with<br>aura. | ADDITIONAL<br>INDICATIONS SUPPORTED<br>BY CLINICAL DATA<br>PROVIDED IN THIS<br>SUBMISSION. |

Table 7.1. Comparison between subject and predicate devices.

#### 7.7. Testing Completed

In addition to previously completed in vitro and in vivo testing (reference K140094), eNeura completed a prospective, multicenter, observational, clinical study demonstrating device safety and effectiveness in treating and preventing and migraine headaches.

| Test Device | eNeura SpringTMS® Device | |
|-----------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Study Design | A prospective, non-randomized, single arm, multi-center observational<br>study designed to evaluate the use of the SpringTMS system in<br>reducing the frequency of headache days against a performance goal. | |
| Number of<br>Patients | A total of 263 subjects were consented between December 2014 and<br>March 2016. 229 of these subjects completed a Baseline Diary and 220<br>were confirmed by the sites to be eligible for participation. There were<br>217 subjects that were assigned Spring TMS devices and these subjects<br>comprise the Safety Data Set. There were 179 subjects who began<br>treatment and completed a Month 1 treatment Diary, but 47 of these<br>subjects did not meet the definition of a Migraine Headache Day<br>(minimum requirement of at least 4 days with moderate to severe<br>headache pain for at least 4 hours at baseline). Thus 132 of these subjects<br>complied with the protocol requirements based upon headache day<br>definition. This was the Full-Analysis Data Set (FAS) described below.<br>There were 117 of these subjects that went on to finish treatment and<br>completed both baseline and Month 3 diaries. This was the Completed<br>Cases data set (CC). Of these subjects 95 complied with the protocol<br>instructions regarding use of the device. This was the per Protocol (PP)<br>data set. | |
| Number of Sites | Seven (7) | |
| Duration of Trial | Each provisionally enrolled subject was followed for 1 month (28±5<br>days) to establish a baseline number of headache days (HD) and<br>confirm final eligibility and then each confirmed enrolled patient was<br>followed for 3 consecutive months (12±1 weeks) of treatment followed<br>by a final assessment. | |
| Treatment | Patients were instructed to treat daily using the following protocol: | |
| Regimen | 1. From the start, treat with 4 Pulses each morning and evening:<br>2 consecutive pulses wait 15 minutes and repeat the 2<br>consecutive pulses. | |
| | 2. Additionally, the patient may treat an acute attack with:<br>3 sequential pulses (early) at the onset of migraine pain<br>Wait 15 minutes, if needed treat with additional 3 pulses<br>Wait 15 minutes, if needed treat with additional 3 pulses<br>Patients may rescue with acute medication 30 minutes after the first<br>three pulses are delivered. | |
| Performance Goal | The originally proposed performance goal for the primary endpoint,<br>representing the mean reduction in headache days for a controlled<br>study, assumed an approximate 80% chronic headache population and<br>was PGMD = -5.3 days. | |
| | This performance goal was amended ahead of un-blinding and the<br>final analysis to PGD=-0.633 in order to reflect the actual population of<br>~20% chronic and ~80% episodic enrollment. | |
| Primary<br>Effectiveness<br>Endpoint | Mean reduction in headache days over a 28-day period at 12±1 weeks<br>(i.e., weeks 9 through 12 from start of treatment period). The null and<br>alternative hypotheses for this endpoint are: | |
| | H0: $μ$ T ≥ PGMD versus Ha: $μ$ T < PGD | |
| | PGD = - 0.633 days. | |
| | where $μ$ T is the mean reduction in migraine headache days from<br>baseline at 12±1 weeks in the treated population and PGD is the<br>Performance Goal. | |
| | Headache day is defined as ≥4 hours of headache pain which at any<br>time reaches moderate or severe intensity. | |
| Secondary<br>Effectiveness<br>Endpoints | 1. The percentage of subjects who had at least a 50% reduction in<br>headache days | |
| | 2. The reduction from baseline in the days of medications use to<br>acutely treat migraine headaches | |
| | 3. The reduction from baseline in the HIT6 impact questionnaire | |
| | 4. The reduction from baseline in the days with headache for more<br>than 4 hours with any pain intensity | |
| | 5. Migraine is defined as >4 hours of headache pain which at any<br>time reached moderate or severe intensity. | |
| Primary Safety<br>Endpoint | The proportion of patients experiencing any adverse event in aggregate<br>and by event. | |
| Inclusion Criteria | 1. Patients 18 to 65 years of age; | |
| | 2. Patients able to understand and communicate in English; | |
| | 3. Migraine with or without aura; | |
| | 4. 4-25 headache days per month (confirmed by 1-month baseline<br>diary, minimum of 5 complete headache-free days/month); | |
| Exclusion Criteria | 5. Understand and willing to provide diary and survey data.<br>Subjects will be excluded from participating in this trial if they meet any of the following criteria | |
| | 1. Severe co-existing disease having a life expectancy of less than 1 year; | |
| | 2. Currently involved in any other investigational clinical trials that have not completed their primary endpoint or that may interfere with the SpringTMS study results; | |
| | 3. Mental impairment or other conditions which may not allow the subject to understand the nature, significance and scope of the study and to cooperate with follow-up requirements; | |
| | 4. Known drug and/or alcohol addiction or use of illicit substances; | |
| | 5. Patients with epilepsy or history of seizure; | |
| | 6. Severe active major depression or major psychiatric illness; | |
| | 7. Concurrent use of other neurostimulation devices (Cefaly®, TENS, implantable devices); | |
| | 8. Use of Botox® within past 4 months; | |
| | 9. Extracranial nerve block (e.g. occipital, supraorbital) within past 3 months; | |
| | 10. Use of Cefaly for prevention within past month; | |
| | 11. Patients with metal containing implants as follows: | |
| | The SpringTMS may <b>not</b> be used in patients who have metals, conductive materials, or metal-containing implants in their head, neck or upper body. Patients with implants that are affected by a magnetic field should not use the SpringTMS. Examples of such implants include: | |
| | ● Aneurysm clips or coils<br>● Cochlear implants<br>● Cerebral spinal fluid shunts<br>● Bullets or pellets lodged in the head or upper body<br>● Filters<br>● Electrodes | ● Radioactive seeds<br>● Magnetically programmable shunt valves<br>● Stents<br>● Metal plates, screws, staples or sutures in skull, neck, shoulders, arms or hands<br>● Metallic artificial heart valves<br>● Facial tattoos with metallic ink |
| | Dental implants, fillings, or other dental appliances are okay and are not affected by the device. | |
| | Note: although not explicitly excluded, safety and effectiveness have not been established in pregnant women. Please defer to the judgment of the investigator when considering the eligibility of this population. | |
| Final Enrollment Decision | 1. Satisfactory completion of Baseline Patient Diary (~80% or 22 out of 28 days) | |
| Subject Demographics | 106 Female / 132 Total (80.3% Female)<br>Age (Range 16-65 years, Mean 42.8 years) | |

7.8. Clinical Summary

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| | Baseline # of migraine days/month (Range 4-21 days,<br>Mean 9.06 days, Median 9.0 days) | | | |
|----------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------|--------------------|---------------------------------------------------------------------------------|
| Primary Safety<br>Endpoint results | Approximately 29% of the 217 subjects included in the Safety Dataset reported<br>experiencing at least one adverse event in this study. No subject had events that could be<br>determined to be serious adverse events. None of the events required treatment. Adverse<br>events as described below are the same as those reported in previous studies. | | | |
| | Adverse Events Reported in the ESPOUSE Study (greater than 2%) |…