Acute Treatment Trial in Adult Subjects With Migraines

• Sponsor: Biohaven Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03872453
• Collaborator: (none)
• Enrollment: 2,154
• Locations: 82
• Arms: 4
• Actual Duration (Months): 7.6
• Patients Per Site: 26.3
• Patients Per Site Per Month: 3.5

Study Details

Study Description

Brief Summary

This study will evaluate the safety and efficacy of three different intranasal dose levels of BHV-3500, relative to placebo, in the acute treatment of moderate to severe migraine.

Condition or Disease	Intervention/Treatment	Phase
Migraine	Drug: BHV3500 (zavegepant) 10mg; Drug: BHV3500 (zavegepant) 20mg; Drug: BHV3500 (zavegepant) 5mg; Drug: BHV3500 (zavegepant) matching placebo; Device: Intranasal Aptar Pharma Unit Dose System	Phase 2/Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 2154 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Masking Description: Double-blind to Sponsor, Investigator and Subject
• Primary Purpose: Treatment
• Official Title: BHV3500-201: Phase II/III: Double-Blind, Randomized, Placebo Controlled, Dose-Ranging Trial of BHV-3500 for the Acute Treatment of Migraine
• Actual Study Start Date: Mar 25, 2019
• Actual Primary Completion Date: Oct 31, 2019
• Actual Study Completion Date: Nov 11, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm 1 - BHV-3500 (zavegepant) 5 mg One dose of 5 mg	Drug: BHV3500 (zavegepant) 5mg; one dose; Device: Intranasal Aptar Pharma Unit Dose System; one dose intranasal device
Active Comparator: Arm 2 - BHV-3500 (zavegepant) 10mg One dose of 10 mg	Drug: BHV3500 (zavegepant) 10mg; one dose; Device: Intranasal Aptar Pharma Unit Dose System; one dose intranasal device
Active Comparator: Arm 3 - BHV-3500 (zavegepant) 20mg One dose of 20mg	Drug: BHV3500 (zavegepant) 20mg; one dose; Device: Intranasal Aptar Pharma Unit Dose System; one dose intranasal device
Placebo Comparator: Arm 4 - Matching BHV-3500 (zavegepant) Placebo One dose of placebo	Drug: BHV3500 (zavegepant) matching placebo; one dose; Device: Intranasal Aptar Pharma Unit Dose System; one dose intranasal device

Outcome Measures

Primary Outcome Measures

1. To evaluate the efficacy of BHV-3500 compared with placebo in the acute treatment of migraine by using a likert scale to measure pain freedom and an multiple choice question for most bothersome symptom. [2 hours post dose.]

   Freedom from Pain will be measured on a 4 point Likert scale (0=none, 1=mild, 2=moderate, 3=severe) and The MBS (nausea, phonophobia or photophobia) will measured using a binary scale (0=absent, 1=present).

Secondary Outcome Measures

1. To evaluate BHV-3500 compared to placebo on pain relief: numeric rating scale [2 hours post-dose.]

   Pain Relief as measured by a 4 point numeric rating scale (None, Mild, Moderate, Severe)

2. To evaluate the effect of BHV-3500 relative to placebo on the patients ability function normally [2 hours post-dose, according to the Functional Disability scale.]

   Subjects self-report "normal" on the functional disability scale

3. To evaluate BHV-3500 compared to placebo on the probability of requiring rescue medication. [Within 24 hours of initial treatment.]

   Measures the percent difference in needing rescue medication on BHV3500 as compared to placebo.

4. To evaluate BHV-3500 compared to placebo on freedom from photophobia. [2 hours post-dose.]

   Freedom from photophobia will be measured in a multiple choice question.

5. To evaluate BHV-3500 compared to placebo on freedom from phonophobia. [2 hours post-dose.]

   Freedom from phonophobia will be measured in a multiple choice question.

6. To evaluate BHV-3500 compared to placebo on pain relief: likert scale [60 minutes post-dose.]

   Pain relief will be measured on a likert scale measuring pain relief after 60 minutes of dosing.

7. To evaluate the effect of BHV-3500 relative to placebo on the patients ability function normally: Functional Disability scale [60 minutes post-dose according to the Functional Disability scale.]

   The higher the score the worse the disability compared to placebo at 60 minutes.

8. To evaluate BHV-3500 compared to placebo on pain relief: likert scale [30 minutes post-dose.]

   Pain relief will be measured on a likert scale measuring pain relief after 30 minutes of dosing.

9. To evaluate the effect of BHV-3500 relative to placebo on the patients ability function normally: Functional Disability scale [30 minutes post-dose according to the Functional Disability scale.]

10. To evaluate BHV-3500 compared to placebo on sustained pain relief: likert scale [2 to 24 hours post-dose.]

    Pain relief will be measured on a likert scale measuring pain relief between 2-24 hours of dosing.

11. To evaluate BHV-3500 compared to placebo on sustained pain freedom: 4 point numeric rating scale [2 to 24 hours post-dose.]

    Sustained Pain Freedom as measured by a 4 point numeric rating scale (None, Mild, Moderate, Severe)

12. To evaluate BHV-3500 compared to placebo on sustained pain relief: likert scale [2 to 48 hours post-dose.]

    Pain relief will be measured on a likert scale measuring sustained pain relief between 2-48 hours of dosing.

13. To evaluate BHV-3500 compared to placebo on sustained pain freedom: 4 point numeric rating scale [2 to 48 hours post-dose.]

    Sustained Pain Freedom as measured by a 4 point numeric rating scale (None, Mild, Moderate, Severe)

14. To evaluate BHV-3500 compared to placebo on freedom from nausea. [2 hours post-dose.]

    Freedom from nausea will be measured in a multiple choice question.

15. To evaluate BHV-3500 compared to placebo for the incidence of pain relapse. [2 to 48 hours post-dose.]

    Pain relapse will be measured based on the lack of pain between 2-48 hours.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Subject has at least 1-year history of migraines (with or without aura), consistent with a diagnosis according to the International Classification of Headache Disorder, 3rd

Edition, Beta version [1] including the following:

1. Migraine attacks present for more than 1 year with the age of onset prior to 50 years of age

2. Migraine attacks, on average, lasting about 4-72 hours if untreated

3. Not more than 8 attacks of moderate to severe intensity per month within the last 3 months

4. At least 2 consistent migraine headache attacks of moderate or severe intensity in each of the 3 months prior to the Screening Visit and maintains this requirement during the Screening period

5. Less than 15 days with headache (migraine or non-migraine) per month in each of the 3 months prior to the Screening Visit and maintains this requirement during the Screening Period.

6. Subjects on prophylactic migraine medication are permitted to remain on therapy provided they have been on a stable dose for at least 3 months prior to screening visit and the dose is not expected to change during the course of the study.

7. Subjects with contraindications for use of triptans may be included provided they meet all other study entry criteria.

Exclusion Criteria:

Key Exclusion Criteria:

1. Subject with a history of HIV disease

2. Subject history with current evidence of uncontrolled, unstable or recently diagnosed cardiovascular disease, such as ischemic heart disease, coronary artery vasospasm, and cerebral ischemia. Subjects with Myocardial Infarction (MI), Acute Coronary Syndrome (ACS), Percutaneous Coronary Intervention (PCI), cardiac surgery, stroke or transient ischemic attack (TIA) during the 6 months prior to screening.

3. Uncontrolled hypertension (high blood pressure), or uncontrolled diabetes (however subjects can be included who have stable hypertension and/or diabetes for at least 3 months prior to being enrolled).

4. Subject has a current diagnosis of major depression, other pain syndromes, psychiatric conditions (e.g., schizophrenia), dementia, or significant neurological disorders (other than migraine) that, in the Investigator's opinion might interfere with study assessments.

5. Subject has a history of gastric, or small intestinal surgery (including Gastric Bypass, Gastric Banding, Gastric Sleeve, Gastric Balloon, etc.), or has disease that causes malabsorption.

6. The subject has a history of current or evidence of any significant and/ or unstable medical conditions (e.g., history of congenital heart disease or arrhythmia, known suspected infection, hepatitis B or C, or cancer) that, in the Investigator's opinion, would expose them to undue risk of a significant adverse event (AE) or interfere with assessments of safety or efficacy during the course of the trial.

7. History of, treatment for, or evidence of, alcohol or drug abuse within the past 12 months or subjects who have met DSM-V criteria [15] for any significant substance use disorder within the past 12 months from the date of the screening visit.

8. History of nasal surgery in the 6 months preceding the screening visit.

9. Participation in any other investigational clinical trial while participating in this clinical trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Coastal Clinical Research, Inc.	Mobile	Alabama	United States	36608
2	Elite Clinical Studies	Phoenix	Arizona	United States	85018
3	Baptist Health Center for Clinical Research	Little Rock	Arkansas	United States	72205
4	Pharmacology Research Institute	Encino	California	United States	91316
5	eStudySite	La Mesa	California	United States	91942
6	Synergy San Diego	Lemon Grove	California	United States	91945
7	Collaborative Neuroscience Network, LLC	Long Beach	California	United States	90806
8	Pharmacology Research Institute	Los Alamitos	California	United States	90720
9	Pharmacology Research Institute	Newport Beach	California	United States	92660
10	National Research Institute	Panorama City	California	United States	91402
11	Optimus Medical Group	San Francisco	California	United States	94102
12	Neurological Research Institute	Santa Monica	California	United States	90404
13	Diablo Clinical Research, Inc.	Walnut Creek	California	United States	94598
14	Denver Neurological Research, LLC	Denver	Colorado	United States	80210
15	CT Clinical Research	Cromwell	Connecticut	United States	06416
16	Ki Health Partners, LLC, dba New England Institute for Clinical Research	Stamford	Connecticut	United States	06905
17	MD Clinical	Hallandale Beach	Florida	United States	33009
18	Clinical Neuroscience Solutions, Inc.	Jacksonville	Florida	United States	32256
19	Multi-Specialty Research Associates, Inc.	Lake City	Florida	United States	32055
20	AGA Clinical Trials	Miami	Florida	United States	33012
21	Qps Mra, Llc	Miami	Florida	United States	33143
22	Clinical Neuroscience Solutions, Inc.	Orlando	Florida	United States	32801
23	Ormond Medical Arts Pharmaceutical Research Center	Ormond Beach	Florida	United States	32174
24	Meridien Research	Tampa	Florida	United States	33634
25	Premiere Research Institute	West Palm Beach	Florida	United States	33407
26	iResearch Atlanta, LLC	Decatur	Georgia	United States	30030
27	Meridian Clinical Research	Savannah	Georgia	United States	31405
28	Family Medicine Specialists/CIS	Wauconda	Illinois	United States	60084
29	Phoenix Medical Research	Prairie Village	Kansas	United States	66208
30	Crescent City Headache and Neurology Center, LLC	Chalmette	Louisiana	United States	70043
31	New Orleans Center for Clinical Research	New Orleans	Louisiana	United States	70119
32	DelRicht Research	New Orleans	Louisiana	United States	70124
33	Boston Clinical Trials	Boston	Massachusetts	United States	02131
34	Community Clinical Research Network	Marlborough	Massachusetts	United States	01752
35	Regeneris Medical	North Attleboro	Massachusetts	United States	02169
36	MedVadis Research Corporation	Watertown	Massachusetts	United States	02472
37	Michigan Head Pain & Neurological Institute	Ann Arbor	Michigan	United States	48104
38	Clinical Research Institute, Inc.	Minneapolis	Minnesota	United States	55402
39	Clinical Research Institute, Inc.	Plymouth	Minnesota	United States	55441
40	MedPharmics, LLC	Biloxi	Mississippi	United States	39531
41	Center for Pharmaceutical Research, LLC	Kansas City	Missouri	United States	64114
42	Meritas Health Neurology	North Kansas City	Missouri	United States	64116
43	Sundance Clinical Research, LLC	Saint Louis	Missouri	United States	63141
44	StudyMetrix Research	Saint Peters	Missouri	United States	63303
45	QPS Bio-Kinetic Clinical Applications, LLC	Springfield	Missouri	United States	65802
46	Clinvest Research LLC	Springfield	Missouri	United States	65810
47	Center for Emotional Fitness	Cherry Hill	New Jersey	United States	08002
48	Albuquerque Clinical Trials, Inc.	Albuquerque	New Mexico	United States	87102
49	Dent Neurosciences Research Center	Amherst	New York	United States	14226
50	Montefiore Medical Center: Headache Center	Bronx	New York	United States	10461
51	Rochester Clinical Research, Inc.	Rochester	New York	United States	14609
52	Upstate Clinical Research Associates, LLC	Williamsville	New York	United States	14221
53	PMG Research of Charlotte, LLC	Charlotte	North Carolina	United States	28209
54	Headache Wellness Center	Greensboro	North Carolina	United States	27405
55	PharmQuest	Greensboro	North Carolina	United States	27408
56	PMG Research of Raleigh, LLC	Raleigh	North Carolina	United States	27609
57	Wilmington Health, PLLC	Wilmington	North Carolina	United States	28401
58	Hometown Urgent Care and Research	Cincinnati	Ohio	United States	45215
59	Hometown Urgent Care and Research	Columbus	Ohio	United States	43214
60	Hometown Urgent Care and Research	Dayton	Ohio	United States	45424
61	Hightower Clinical	Oklahoma City	Oklahoma	United States	73134
62	Summit Research Network (Oregon) Inc.	Portland	Oregon	United States	97210
63	Oregon Center for Clinical Investigations, Inc. (OCCI, Inc.)	Salem	Oregon	United States	97301
64	Clinical Trials of South Carolina	Charleston	South Carolina	United States	29406
65	Coastal Carolina Research Center	Mount Pleasant	South Carolina	United States	29464
66	Meridian Clinical Research	Dakota Dunes	South Dakota	United States	57049
67	Alliance for Multispecialty Research/New Orleans Center for Clinical Research/Volunteer Research	Knoxville	Tennessee	United States	37920
68	Clinical Neuroscience Solutions DBA CNS Healthcare	Memphis	Tennessee	United States	38119
69	Clinical Research Associates, Inc.	Nashville	Tennessee	United States	37203
70	FutureSearch Trials of Neurology	Austin	Texas	United States	78731
71	FutureSearch Trials of Dallas	Dallas	Texas	United States	75231
72	Ventavia Research Group	Fort Worth	Texas	United States	76104
73	Texas Center for Drug Development, Inc.	Houston	Texas	United States	77081
74	Red Star Research, LLC	Lake Jackson	Texas	United States	77566
75	Advanced Pharmaceutical Development Clinical Research	Magnolia	Texas	United States	77355
76	Victorium Clinical Research	San Antonio	Texas	United States	78230
77	Dynamed Clinical Research	Tomball	Texas	United States	77375
78	Wasatch Clinical Research, LLC	Salt Lake City	Utah	United States	84107
79	Charlottesville Medical Research Center, LLC	Charlottesville	Virginia	United States	22911
80	Tidewater Integrated Medical Research	Virginia Beach	Virginia	United States	23454
81	Northwest Clinical Research	Bellevue	Washington	United States	98007
82	Clinical Investigation Specialists, Inc.	Kenosha	Wisconsin	United States	53144

Sponsors and Collaborators

• Biohaven Pharmaceuticals, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Biohaven Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT03872453
• Other Study ID Numbers: BHV3500-201
• First Posted: Mar 13, 2019
• Last Update Posted: Jul 19, 2022
• Last Verified: Sep 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes
• Keywords provided by Biohaven Pharmaceuticals, Inc.: Acute Migraine; phonophobia; photophobia; nausea
• Additional relevant MeSH terms: Migraine Disorders

Study Results

No Results Posted as of Jul 19, 2022