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Double-Blind Comparison of the Efficacy and Safety of C213 to Placebo for the Acute Treatment of Cluster Headaches

Primary Purpose

Cluster Headache

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
C213 Microneedle System
Placebo
Sponsored by
Zosano Pharma Corporation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cluster Headache focused on measuring Episodic cluster headache, Chronic cluster headache

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Able to provide written informed consent
  2. Women or men 18 to 65 years of age
  3. Greater than 1-year history of episodic or chronic cluster headache with onset prior to 50 years of age. Diagnosis must comply with ICHD-3 (International Headache Society (IHS) diagnostic criteria). Diagnostic criteria must include a history of at least 5 attacks not attributed to any other disorder that include all of the following criteria:

    1. Severe or very severe unilateral orbital, supraorbital and/or temporal pain lasting 45-180 minutes (average, when untreated)
    2. Either or both of the following:

      1. At least one of the following symptoms or signs, ipsilateral to the pain:

        1. Conjunctival injection and/or lacrimation
        2. Nasal congestion and/or rhinorrhea
        3. Eyelid edema
        4. Forehead and facial sweating
        5. Miosis and or/ptosis
      2. A sense of restlessness or agitation
    3. Attacks have a frequency between one every other day and eight per day for more than half of the time when the disorder is active.
    4. Not better accounted for by another International Classification of Headache Disorders (ICHD) diagnosis
  4. Cluster history during the 12-month period prior to the screening visit must include:

    1. At least 1 cluster period
    2. Averaging 2-6 headaches per day
    3. Lasting at least 7 days
  5. Subject can distinguish cluster headaches from other headaches (i.e., migraine and tension-type headaches)
  6. Women of child-bearing potential must not be pregnant, must agree to avoid pregnancy during the trial, and must use one of the following or be surgically sterilized: intrauterine device, or a hormonal contraceptive
  7. Able to understand the operation of the electronic diary and able to apply the demo study drug patch correctly.

Exclusion Criteria:

  1. Contraindications to triptans
  2. Use of any prohibited concomitant medications within 30 days of screening
  3. History of hemiplegic migraine or migraine with brainstem aura
  4. Participation in another investigational trial within 30 days or 5 half-lives of investigational product (whichever is longer).
  5. Previous M207/C213 exposure in a clinical trial
  6. Subject has other significant pain problems that might confound the study assessments in the opinion of the investigator
  7. Diagnosis of any malignant disease (other than adequately treated or excised non-metastatic basal cell carcinoma or squamous cell carcinoma of the skin) within the 5 years prior to screening
  8. History of unstable psychiatric illness requiring medication or hospitalization in the 12 months prior to study initiation
  9. Subjects who have a known allergy or sensitivity to zolmitriptan or its derivatives or formulations
  10. Subjects who have a known allergy or sensitivity to adhesions
  11. Subjects who have skin lesions or tattoos covering the entire potential area(s) of C213 application
  12. Woman who are pregnant, breast-feeding or plan a pregnancy during this study
  13. Clinically significant liver disease [Alanine Aminotransferase (ALT) > 150 U/L; Aspartate Aminotransferase (AST) > 130 U/L or bilirubin > 2x ULN]
  14. Clinically significant kidney disease (eGFR < 60 ml/min / 1.73 m² or to creatinine > 1.5 x ULN)
  15. Subject has clinically significant ECG findings, defined by:

    1. ischemic changes (defined as > 1mm of down-sloping ST segment depression in at least two contiguous leads)
    2. Q-waves in at least two contiguous leads
    3. clinically significant intra-ventricular conduction abnormalities (left bundle branch block or Wolf-Parkinson-White syndrome)
    4. clinically significant arrhythmias (e.g., current atrial fibrillation)
  16. History of coronary artery disease (CAD), coronary vasospasm (including Prinzmetal's angina), aortic aneurysm, peripheral vascular disease or other ischemic diseases (e.g., ischemic bowel syndrome or Raynaud's syndrome)
  17. Three or more of the following CAD risk factors:

    1. Current tobacco use
    2. Hypertension (systolic BP > 140 or diastolic BP > 90) or receiving anti-hypertensive medication for treatment of hypertension
    3. Hyperlipidemia - LDL > 159 mg/dL and/or HDL < 40 mg/dL (or on prescribed anti-cholesterol treatment)
    4. Family history of premature coronary artery disease (CAD) (< 55 years of age in male first-degree relatives or < 65 years of age in female first degree relatives)
    5. Diabetes mellitus
  18. History of cerebral vascular accident (CVA), transient ischemic attacks (TIA), or seizures
  19. History of concurrent illness that requires hospitalization within 30 days prior to study initiation
  20. Any other household member currently participating in a C213 study or relative of site staff member
  21. Any reason to believe that compliance with the study requirements and completion of evaluations required for this study will not be possible
  22. Any language barrier that, in the opinion of the Investigator, would preclude communication and compliance with the study requirements
  23. History or current abuse of or dependence on alcohol or drugs that would interfere with the results or adherence to study requirements
  24. Any positive drug screens for phencyclidine (PCP), 3,4-methylenedioxy-methamphetamine (MDMA) (ecstasy), cocaine, and/or meth/amphetamine(s)
  25. Current or planned use of hallucinogens (e.g. psilocybin) during the trial
  26. Any clinically relevant abnormal findings in the physical exam, vital signs or laboratory tests that, in the opinion of the Investigator, may put the subject at risk

Sites / Locations

  • Keck Medicine of USC
  • Stanford University
  • California Medical Clinic for Headache
  • KI Health Partners LLC DBA New England Institute for Clinical Research
  • Atlanta Headache Specialists
  • New England Regional Headache Center, Inc.
  • Nevada Headache Institute
  • Dartmouth Hitchcock Medical Center
  • Dent Neuro Institute, Buffalo
  • Jefferson Headache Center
  • University of Texas Southwestern Medical Center- Neurology Clinic
  • Medstar Georgetown University Hospital at McLean

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

C213 1.9 mg

C213 3.8mg

Placebo

Arm Description

C213, 1.9 mg administered as one 1.9 mg patch and one placebo patch

C213 3.8 mg administered as two 1.9 mg patches

Placebo microneedle system administered as two placebo patches

Outcomes

Primary Outcome Measures

Percentage of Subjects Who Achieve Pain Relief
Pain relief is defined by a decrease in pain from severe to mild or none without the use of acute rescue medication.
Percentage of Subjects Who Achieve Sustained Pain Relief
Sustained pain relief requires a pain rating of mild or none at each timepoint from 15 minutes to 60 minutes without the use of acute rescue medication.

Secondary Outcome Measures

Percentage of Subjects That Achieve Pain Relief
Pain relief is defined by a decrease in pain from severe to mild or none without the use of acute rescue medication.
Percentage of Subjects That Achieve Sustained Pain Relief
Sustained pain relief requires a pain rating of mild or none at each timepoint within the time frame without the use of acute rescue medication.
Percentage of Subjects That Achieve Pain Freedom
Pain freedom is defined by a decrease in pain from severe to none without the use of acute rescue medication.
Percentage of Subjects That Achieve Sustained Pain Freedom
Sustained pain freedom requires a pain rating of none at each timepoint within the time frame without the use of acute rescue medication.
Percentage of Subjects Able to Perform Their Usual Daily Activities as Assessed by the Subject
Whether or not subjects were able to perform their usual daily activities was assessed by subject responses (Yes or No) in the electronic diary (eDiary) to the question, "Do you feel able to perform your usual daily activities?" If a subject responded "Yes" but had used a rescue medication, the subject was considered as not being able to perform the usual daily activities.
Percentage of Subjects That Achieve Pain Relief
Pain relief is defined by a decrease in pain from severe to mild or none without the use of acute rescue medication
Percentage of Subjects That Achieve Pain Relief
Pain relief is defined by a decrease in pain from severe to mild or none without the use of acute rescue medication.
Percentage of Subjects That Achieve Sustained Pain Relief
Sustained pain relief requires a pain rating of mild or none at each timepoint within the time frame without the use of acute rescue medication.
Percentage of Subjects That Achieve Pain Freedom
Pain freedom is defined by a decrease in pain from severe to none without the use of acute rescue medication.

Full Information

First Posted
August 19, 2019
Last Updated
May 17, 2022
Sponsor
Zosano Pharma Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT04066023
Brief Title
Double-Blind Comparison of the Efficacy and Safety of C213 to Placebo for the Acute Treatment of Cluster Headaches
Official Title
Randomized, Double-Blind, Multi-Center, Parallel-Group Comparison of the Efficacy and Safety of the C213 (Zolmitriptan Microneedle System) to Placebo for the Acute Treatment of Cluster Headaches
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Completed
Study Start Date
October 3, 2019 (Actual)
Primary Completion Date
April 14, 2021 (Actual)
Study Completion Date
April 14, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Zosano Pharma Corporation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a double-blind, placebo-controlled study. Subjects who meet the entry criteria will be randomized o receive one of three blinded treatments [C213 1.9 mg patch and placebo patch; C213 3.8 mg (1.9 mg x 2 patches), two placebo patches] on Day 1 and will have up to 48 weeks to confirm and treat a cluster headache. Subjects will self-administer the patches and respond to questions in the electronic diary (eDiary) until 1-hour post treatment administration.
Detailed Description
This is a randomized, double-blinded, placebo-controlled study. Approximately 120 subjects who meet the entry criteria will be randomized 1:1:1 to receive one of three blinded treatments [C213 1.9 mg patch and placebo patch; C213 3.8 mg (1.9 mg x 2 patches), two placebo patches]. Qualified subjects will randomize to the double-blind treatment period at Day 1 and will have up to 48 weeks to confirm and treat a cluster headache. Using the eDiary to confirm they are experiencing a cluster headache, subjects will self-administer the patches and continue to respond to questions in the eDiary until 1-hour post treatment administration.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cluster Headache
Keywords
Episodic cluster headache, Chronic cluster headache

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Qualified subjects are assigned to received a single administration of one of three blinded treatment assignments (one of two dose levels or placebo)
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
All subjects, care providers, investigator, and outcomes assessors are blinded to randomized treatment assignment. Study drugs are blinded and identical in appearance.
Allocation
Randomized
Enrollment
42 (Actual)

8. Arms, Groups, and Interventions

Arm Title
C213 1.9 mg
Arm Type
Experimental
Arm Description
C213, 1.9 mg administered as one 1.9 mg patch and one placebo patch
Arm Title
C213 3.8mg
Arm Type
Experimental
Arm Description
C213 3.8 mg administered as two 1.9 mg patches
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo microneedle system administered as two placebo patches
Intervention Type
Drug
Intervention Name(s)
C213 Microneedle System
Other Intervention Name(s)
Zolmitriptan Microneedle System
Intervention Description
The C213 System is a proprietary disposable patch and a reusable applicator. The zolmitriptan-coated titanium microneedle array (3 cm^2 array) is attached to a 5 cm^2 adhesive patch.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
ZP Placebo
Intervention Description
The C213 System is a proprietary disposable patch and a reusable applicator. The placebo patch is a single use, 3 cm^2 Placebo (intracutaneous microneedle) system that contains no active ingredients.
Primary Outcome Measure Information:
Title
Percentage of Subjects Who Achieve Pain Relief
Description
Pain relief is defined by a decrease in pain from severe to mild or none without the use of acute rescue medication.
Time Frame
15 minutes
Title
Percentage of Subjects Who Achieve Sustained Pain Relief
Description
Sustained pain relief requires a pain rating of mild or none at each timepoint from 15 minutes to 60 minutes without the use of acute rescue medication.
Time Frame
15 minutes to 60 minutes
Secondary Outcome Measure Information:
Title
Percentage of Subjects That Achieve Pain Relief
Description
Pain relief is defined by a decrease in pain from severe to mild or none without the use of acute rescue medication.
Time Frame
5 minutes
Title
Percentage of Subjects That Achieve Sustained Pain Relief
Description
Sustained pain relief requires a pain rating of mild or none at each timepoint within the time frame without the use of acute rescue medication.
Time Frame
5 minutes to 60 minutes
Title
Percentage of Subjects That Achieve Pain Freedom
Description
Pain freedom is defined by a decrease in pain from severe to none without the use of acute rescue medication.
Time Frame
10 minutes
Title
Percentage of Subjects That Achieve Sustained Pain Freedom
Description
Sustained pain freedom requires a pain rating of none at each timepoint within the time frame without the use of acute rescue medication.
Time Frame
15 to 60 minutes
Title
Percentage of Subjects Able to Perform Their Usual Daily Activities as Assessed by the Subject
Description
Whether or not subjects were able to perform their usual daily activities was assessed by subject responses (Yes or No) in the electronic diary (eDiary) to the question, "Do you feel able to perform your usual daily activities?" If a subject responded "Yes" but had used a rescue medication, the subject was considered as not being able to perform the usual daily activities.
Time Frame
within 20 minutes
Title
Percentage of Subjects That Achieve Pain Relief
Description
Pain relief is defined by a decrease in pain from severe to mild or none without the use of acute rescue medication
Time Frame
10 minutes
Title
Percentage of Subjects That Achieve Pain Relief
Description
Pain relief is defined by a decrease in pain from severe to mild or none without the use of acute rescue medication.
Time Frame
20 minutes
Title
Percentage of Subjects That Achieve Sustained Pain Relief
Description
Sustained pain relief requires a pain rating of mild or none at each timepoint within the time frame without the use of acute rescue medication.
Time Frame
10 minutes to 60 minutes
Title
Percentage of Subjects That Achieve Pain Freedom
Description
Pain freedom is defined by a decrease in pain from severe to none without the use of acute rescue medication.
Time Frame
20 minutes

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Able to provide written informed consent Women or men 18 to 65 years of age Greater than 1-year history of episodic or chronic cluster headache with onset prior to 50 years of age. Diagnosis must comply with ICHD-3 (International Headache Society (IHS) diagnostic criteria). Diagnostic criteria must include a history of at least 5 attacks not attributed to any other disorder that include all of the following criteria: Severe or very severe unilateral orbital, supraorbital and/or temporal pain lasting 45-180 minutes (average, when untreated) Either or both of the following: At least one of the following symptoms or signs, ipsilateral to the pain: Conjunctival injection and/or lacrimation Nasal congestion and/or rhinorrhea Eyelid edema Forehead and facial sweating Miosis and or/ptosis A sense of restlessness or agitation Attacks have a frequency between one every other day and eight per day for more than half of the time when the disorder is active. Not better accounted for by another International Classification of Headache Disorders (ICHD) diagnosis Cluster history during the 12-month period prior to the screening visit must include: At least 1 cluster period Averaging 2-6 headaches per day Lasting at least 7 days Subject can distinguish cluster headaches from other headaches (i.e., migraine and tension-type headaches) Women of child-bearing potential must not be pregnant, must agree to avoid pregnancy during the trial, and must use one of the following or be surgically sterilized: intrauterine device, or a hormonal contraceptive Able to understand the operation of the electronic diary and able to apply the demo study drug patch correctly. Exclusion Criteria: Contraindications to triptans Use of any prohibited concomitant medications within 30 days of screening History of hemiplegic migraine or migraine with brainstem aura Participation in another investigational trial within 30 days or 5 half-lives of investigational product (whichever is longer). Previous M207/C213 exposure in a clinical trial Subject has other significant pain problems that might confound the study assessments in the opinion of the investigator Diagnosis of any malignant disease (other than adequately treated or excised non-metastatic basal cell carcinoma or squamous cell carcinoma of the skin) within the 5 years prior to screening History of unstable psychiatric illness requiring medication or hospitalization in the 12 months prior to study initiation Subjects who have a known allergy or sensitivity to zolmitriptan or its derivatives or formulations Subjects who have a known allergy or sensitivity to adhesions Subjects who have skin lesions or tattoos covering the entire potential area(s) of C213 application Woman who are pregnant, breast-feeding or plan a pregnancy during this study Clinically significant liver disease [Alanine Aminotransferase (ALT) > 150 U/L; Aspartate Aminotransferase (AST) > 130 U/L or bilirubin > 2x ULN] Clinically significant kidney disease (eGFR < 60 ml/min / 1.73 m² or to creatinine > 1.5 x ULN) Subject has clinically significant ECG findings, defined by: ischemic changes (defined as > 1mm of down-sloping ST segment depression in at least two contiguous leads) Q-waves in at least two contiguous leads clinically significant intra-ventricular conduction abnormalities (left bundle branch block or Wolf-Parkinson-White syndrome) clinically significant arrhythmias (e.g., current atrial fibrillation) History of coronary artery disease (CAD), coronary vasospasm (including Prinzmetal's angina), aortic aneurysm, peripheral vascular disease or other ischemic diseases (e.g., ischemic bowel syndrome or Raynaud's syndrome) Three or more of the following CAD risk factors: Current tobacco use Hypertension (systolic BP > 140 or diastolic BP > 90) or receiving anti-hypertensive medication for treatment of hypertension Hyperlipidemia - LDL > 159 mg/dL and/or HDL < 40 mg/dL (or on prescribed anti-cholesterol treatment) Family history of premature coronary artery disease (CAD) (< 55 years of age in male first-degree relatives or < 65 years of age in female first degree relatives) Diabetes mellitus History of cerebral vascular accident (CVA), transient ischemic attacks (TIA), or seizures History of concurrent illness that requires hospitalization within 30 days prior to study initiation Any other household member currently participating in a C213 study or relative of site staff member Any reason to believe that compliance with the study requirements and completion of evaluations required for this study will not be possible Any language barrier that, in the opinion of the Investigator, would preclude communication and compliance with the study requirements History or current abuse of or dependence on alcohol or drugs that would interfere with the results or adherence to study requirements Any positive drug screens for phencyclidine (PCP), 3,4-methylenedioxy-methamphetamine (MDMA) (ecstasy), cocaine, and/or meth/amphetamine(s) Current or planned use of hallucinogens (e.g. psilocybin) during the trial Any clinically relevant abnormal findings in the physical exam, vital signs or laboratory tests that, in the opinion of the Investigator, may put the subject at risk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Don Kellerman, PharmD
Organizational Affiliation
Zosano Pharma Corporation
Official's Role
Study Director
Facility Information:
Facility Name
Keck Medicine of USC
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
Stanford University
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
California Medical Clinic for Headache
City
Santa Monica
State/Province
California
ZIP/Postal Code
90404
Country
United States
Facility Name
KI Health Partners LLC DBA New England Institute for Clinical Research
City
Stamford
State/Province
Connecticut
ZIP/Postal Code
06905
Country
United States
Facility Name
Atlanta Headache Specialists
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30328
Country
United States
Facility Name
New England Regional Headache Center, Inc.
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01605
Country
United States
Facility Name
Nevada Headache Institute
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89113
Country
United States
Facility Name
Dartmouth Hitchcock Medical Center
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03756
Country
United States
Facility Name
Dent Neuro Institute, Buffalo
City
Amherst
State/Province
New York
ZIP/Postal Code
14226
Country
United States
Facility Name
Jefferson Headache Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
University of Texas Southwestern Medical Center- Neurology Clinic
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
Medstar Georgetown University Hospital at McLean
City
McLean
State/Province
Virginia
ZIP/Postal Code
22101
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Double-Blind Comparison of the Efficacy and Safety of C213 to Placebo for the Acute Treatment of Cluster Headaches

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