R-Verapamil for the Prophylaxis of Episodic Cluster Headache

Study Overview
=================
Brief Summary
-----------------
This is a double-blinded, randomized, parallel, placebo-controlled phase 2 study to evaluate the safety and efficacy of R-verapamil in the prophylaxis of episodic cluster headache.

Detailed Description
-----------------
Approximately 30 subjects (about 15 per treatment group),will be enrolled and randomized to receive either R-verapamil or placebo for 2 weeks. The study will consist of a 1-week run-in period and a 2-week treatment period (R-verapamil or placebo). The total duration of the study for each treatment group is 3 weeks.

Official Title
-----------------
A Randomized, Placebo-Controlled, Double-Blind, Parallel-Group, Phase 2 Study to Evaluate the Safety and Efficacy of R-Verapamil in the Prophylaxis of Episodic Cluster Headache

Conditions
-----------------
Episodic Cluster Headache

Intervention / Treatment
-----------------
* Drug: R-verapamil 75 mg tablet
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy man or woman between the ages of 18 and 65 In good health as determined by medical history and medical examination Has a diagnosis of episodic cluster headache as defined by the International Classification of Headache Disorders (2nd edition) Has a lifetime prevalence of at least 2 prior cluster bouts - Subjects must experience at least 7 attacks/week during the run-in baseline period Subjects must have a typical cluster period lasting at least 1 month. Subjects must be present in active cluster period and the expected remaining duration of the cluster cycle must be at least 3 weeks from Baseline Day 1 visit Able to differentiate other headache types from cluster headaches Is using or agrees to use a medically acceptable form of contraception(female of child-bearing potential) Negative urine pregnancy test prior to study entry(female of child-bearing potential) Concomitant medication that, in the opinion of the investigator and the patient's general practitioner(GP), do not pose an unacceptable risk based upon the prescribing information for verapamil Able to understand and comply with all study requirements Written informed consent Exclusion Criteria: Women who are pregnant or lactating Subjects who, in the investigators opinion, have a history or have evidence of a medical or psychiatric condition that would expose them to an increased risk of a significant adverse event or would interfere with the assessments of efficacy and tolerability Use of any drug or having any medical condition which might interact adversely with, or interfere with the action of, the study medication The concomitant use of beta blockers The consumption of grapefruit juice Allergic to or has shown hypersensitivity to verapamil or agents similar to verapamil Abuses opioids or has a history of significant drug or alcohol abuse within the past year as determined by investigator Has participated in an investigational drug trial in the 30 days prior to the screening visit Has liver or kidney disease Has a cardiopathology contraindicating verapamil administration Subjects with previous adynamic ileus. Subjects with chronic cluster headache Use of antipsychotic, antidepressants, lithium or other prophylactic treatment less than one month prior to inclusion

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: R-verapamil 75 mg tablet<br>375 mg/day; one in the morning, two in the afternoon and two at bedtime daily | Drug: R-verapamil 75 mg tablet<br> <br> |
| Placebo Comparator: Placebo<br>one in the morning, two in the afternoon and two at bedtime daily | Drug: Placebo<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the average daily frequency of attacks |  | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the average daily frequency of attacks |  | 1 week | 
| Change in intensity of attacks |  | 2 weeks | 
| Change in duration of attacks |  | 2 weeks | 
| Change in consumption of abortive agents |  | 2 weeks | 
| Patient acceptability of treatment |  | 2 weeks | 
| Change in headache severity index |  | 2 weeks | 
| Change in Hit-6 disability score |  | 2 weeks | 
| R-verapamil and Placebo responders |  | 2 weeks |