Clinical trial NCT04066023: 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
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Cluster Headache
Keywords: Episodic cluster headache
Chronic cluster headache
Lead sponsor: Zosano Pharma Corporation
Sponsor class: INDUSTRY
First posted: 2019-08-22
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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)
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Subjects Who Achieve Pain Relief
timeFrame: 15 minutes
measure: Percentage of Subjects Who Achieve Sustained Pain Relief
timeFrame: 15 minutes to 60 minutes
Secondary outcomes:
measure: Percentage of Subjects That Achieve Pain Relief
timeFrame: 5 minutes
measure: Percentage of Subjects That Achieve Sustained Pain Relief
timeFrame: 5 minutes to 60 minutes
measure: Percentage of Subjects That Achieve Pain Freedom
timeFrame: 10 minutes
measure: Percentage of Subjects That Achieve Sustained Pain Freedom
timeFrame: 15 to 60 minutes
measure: Percentage of Subjects Able to Perform Their Usual Daily Activities as Assessed by the Subject
timeFrame: within 20 minutes
measure: Percentage of Subjects That Achieve Pain Relief
timeFrame: 10 minutes
measure: Percentage of Subjects That Achieve Pain Relief
timeFrame: 20 minutes
measure: Percentage of Subjects That Achieve Sustained Pain Relief
timeFrame: 10 minutes to 60 minutes
measure: Percentage of Subjects That Achieve Pain Freedom
timeFrame: 20 minutes
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Keck Medicine of USC
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Santa Monica
country: United States
facility: California Medical Clinic for Headache
state: California
city: Stamford
country: United States
facility: KI Health Partners LLC DBA New England Institute for Clinical Research
state: Connecticut
city: Atlanta
country: United States
facility: Atlanta Headache Specialists
state: Georgia
city: Worcester
country: United States
facility: New England Regional Headache Center, Inc.
state: Massachusetts
city: Las Vegas
country: United States
facility: Nevada Headache Institute
state: Nevada
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Amherst
country: United States
facility: Dent Neuro Institute, Buffalo
state: New York
city: Philadelphia
country: United States
facility: Jefferson Headache Center
state: Pennsylvania
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center- Neurology Clinic
state: Texas
city: McLean
country: United States
facility: Medstar Georgetown University Hospital at McLean
state: Virginia
Study officials:
affiliation: Zosano Pharma Corporation
name: Don Kellerman, PharmD
role: STUDY_DIRECTOR
References: