Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| C213 1.9 mg | Experimental | C213, 1.9 mg administered as one 1.9 mg patch and one placebo patch |
|
| C213 3.8mg | Experimental | C213 3.8 mg administered as two 1.9 mg patches |
|
| Placebo | Placebo Comparator | Placebo microneedle system administered as two placebo patches |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| C213 Microneedle System | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 15 minutes |
| 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. | 15 minutes to 60 minutes |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 5 minutes |
| Percentage of Subjects That Achieve Sustained Pain Relief |
Not provided
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:
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:
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:
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:
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
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Don Kellerman, PharmD | Zosano Pharma Corporation | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Keck Medicine of USC | Los Angeles | California | 90033 | United States | ||
| Stanford University |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
A total of 51 subjects were screened at 12 investigative sites. Of the 51 screened subjects, 42 were randomized to receive either C213 1.9 mg (17 subjects), C213 3.8 mg (13), or placebo (12) and had up to 48 weeks from randomization to treat a qualifying headache. 23 subjects applied the study patch and entered the Treatment Period.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Placebo microneedle system administered as two placebo patches Placebo: 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. |
| FG001 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Apr 15, 2020 | Dec 7, 2021 |
Not provided
Qualified subjects are assigned to received a single administration of one of three blinded treatment assignments (one of two dose levels or placebo)
Not provided
Not provided
All subjects, care providers, investigator, and outcomes assessors are blinded to randomized treatment assignment. Study drugs are blinded and identical in appearance.
|
| Placebo | Drug | 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. |
|
|
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.
| 5 minutes to 60 minutes |
| 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. | 10 minutes |
| 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. | 15 to 60 minutes |
| 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. | within 20 minutes |
| 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 | 10 minutes |
| 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. | 20 minutes |
| 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. | 10 minutes to 60 minutes |
| 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. | 20 minutes |
| Palo Alto |
| California |
| 94304 |
| United States |
| California Medical Clinic for Headache | Santa Monica | California | 90404 | United States |
| KI Health Partners LLC DBA New England Institute for Clinical Research | Stamford | Connecticut | 06905 | United States |
| Atlanta Headache Specialists | Atlanta | Georgia | 30328 | United States |
| New England Regional Headache Center, Inc. | Worcester | Massachusetts | 01605 | United States |
| Nevada Headache Institute | Las Vegas | Nevada | 89113 | United States |
| Dartmouth Hitchcock Medical Center | Lebanon | New Hampshire | 03756 | United States |
| Dent Neuro Institute, Buffalo | Amherst | New York | 14226 | United States |
| Jefferson Headache Center | Philadelphia | Pennsylvania | 19107 | United States |
| University of Texas Southwestern Medical Center- Neurology Clinic | Dallas | Texas | 75390 | United States |
| Medstar Georgetown University Hospital at McLean | McLean | Virginia | 22101 | United States |
| C213 1.9 mg |
C213, 1.9 mg administered as one 1.9 mg patch and one placebo patch C213 Microneedle System: 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. |
| FG002 | C213 3.8mg | C213 3.8 mg administered as two 1.9 mg patches C213 Microneedle System: 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. |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Safety Population
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Placebo microneedle system administered as two placebo patches Placebo: 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. |
| BG001 | C213 1.9 mg | C213, 1.9 mg administered as one 1.9 mg patch and one placebo patch C213 Microneedle System: 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. |
| BG002 | C213 3.8mg | C213 3.8 mg administered as two 1.9 mg patches C213 Microneedle System: 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. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
| ||||||||||||||||
| Weight | Mean | Standard Deviation | kilograms |
| |||||||||||||||
| Height | Mean | Standard Deviation | centimeters |
| |||||||||||||||
| BMI | Mean | Standard Deviation | kg/m^2 |
| |||||||||||||||
| Nicotine User | Count of Participants | Participants |
| ||||||||||||||||
| Current Alcohol User | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Modified Intent-to-treat Population | Posted | Count of Participants | Participants | 15 minutes |
|
|
| ||||||||||||||||||||||||||||||||
| Primary | 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. | Modified Intent-to-treat Population | Posted | Count of Participants | Participants | 15 minutes to 60 minutes |
| ||||||||||||||||||||||||||||||||||
| Secondary | 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. | Modified Intent-to-treat Population | Posted | Count of Participants | Participants | 5 minutes |
| ||||||||||||||||||||||||||||||||||
| Secondary | 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. | Modified Intent-to-treat Population | Posted | Count of Participants | Participants | 5 minutes to 60 minutes |
| ||||||||||||||||||||||||||||||||||
| Secondary | 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. | Modified Intent-to-treat Population | Posted | Count of Participants | Participants | 10 minutes |
| ||||||||||||||||||||||||||||||||||
| Secondary | 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. | Modified Intent-to-treat Population | Posted | Count of Participants | Participants | 15 to 60 minutes |
| ||||||||||||||||||||||||||||||||||
| Secondary | 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. | Modified Intent-to-treat Population | Posted | Count of Participants | Participants | within 20 minutes |
| ||||||||||||||||||||||||||||||||||
| Secondary | 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 | Posted | Count of Participants | Participants | 10 minutes |
| |||||||||||||||||||||||||||||||||||
| Secondary | 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. | Posted | Count of Participants | Participants | 20 minutes |
| |||||||||||||||||||||||||||||||||||
| Secondary | 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. | Modified Intent-to-treat Population | Posted | Count of Participants | Participants | 10 minutes to 60 minutes |
| ||||||||||||||||||||||||||||||||||
| Secondary | 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. | Modified Intent-to-treat Population | Posted | Count of Participants | Participants | 20 minutes |
|
Treatment Emergent Adverse Events were collected for 8 days (+3 days) from patch application through the End of Study or Early Discontinuation visit, up to 48 weeks
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Placebo microneedle system administered as two placebo patches Placebo: 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. | 0 | 9 | 0 | 9 | 1 | 9 |
| EG001 | C213 1.9 mg | C213, 1.9 mg administered as one 1.9 mg patch and one placebo patch C213 Microneedle System: 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. | 0 | 9 | 0 | 9 | 4 | 9 |
| EG002 | C213 3.8mg | C213 3.8 mg administered as two 1.9 mg patches C213 Microneedle System: 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. | 0 | 7 | 0 | 7 | 2 | 7 |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Sunburn | Injury, poisoning and procedural complications | MedDRA (22.0) | Non-systematic Assessment | Mild skin erythema from sunburn on right and left upper arms |
|
| Application site erythema | General disorders | MedDRA (22.0) | Non-systematic Assessment | Application site--mild erythema on right upper arm |
|
| Application site oedema | General disorders | MedDRA (22.0) | Non-systematic Assessment | Application site--mild skin edema right upper arm |
|
| Application site bruise | General disorders | MedDRA (22.0) | Non-systematic Assessment | Left arm application site bruising |
|
| Corona virus infection | Infections and infestations | MedDRA (22.0) | Non-systematic Assessment | Coronavirus subject tested positive and was asymptomatic |
|
| Tonsillitis | Infections and infestations | MedDRA (22.0) | Non-systematic Assessment | Tonsillitis |
|
| Atrioventricular block first degree | Cardiac disorders | MedDRA (22.0) | Non-systematic Assessment | First degree atrioventricular block |
|
The COVID-19 pandemic had significant impact: Enrollment was hampered; therefore, Zosano ended the trial with 42 subjects randomized and 23 subjects who treated a Cluster attack. The study was thus underpowered to detect a difference between C213 doses and placebo. The protocol was amended to allow for feasible assessments to be done virtually and permit in home monthly pregnancy testing. The monitoring plan and Zosano Pharma vendor management plan were updated to allow for remote monitoring.
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Don Kellerman, Sr. VP, Clinical Development and Medical Affairs | Zosano Pharma Corporation | +1 (510) 745-4004 | dkellerman@zosanopharma.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 14, 2020 | Dec 7, 2021 | SAP_001.pdf |
| ID | Term |
|---|---|
| D003027 | Cluster Headache |
| ID | Term |
|---|---|
| D051303 | Trigeminal Autonomic Cephalalgias |
| D051270 | Headache Disorders, Primary |
| D020773 | Headache Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Past |
|
| Current |
|
|
|
|
|
|
|
|
|
|
|
C213 3.8 mg administered as two 1.9 mg patches
C213 Microneedle System: 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.
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
|
|
|
|