Efficacy, Safety, Tolerability and Pharmacokinetics of BIBN 4096 BS Versus Placebo in the Treatment of a Single Attack of Acute Migraine Headache

A Phase II a, Double-Blind, Randomised, Group Sequential Adaptive Assignment Design Trial to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of Seven Fixed Doses of Intravenous BIBN 4096 BS Ranging From 0.1 to 10.0 mg Versus Placebo in the Treatment of a Single Attach of Acute Migraine Headache

Efficacy, Safety, Tolerability and Pharmacokinetics of BIBN 4096 BS in patients with a single acute migraine attack with or without aura

Study Overview

• Status: Completed
• Conditions: Migraine Disorders
• Intervention / Treatment: Drug: Placebo; Drug: BIBN 4096 BS

• Study Type: Interventional
• Enrollment (Actual): 126
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Man and women with an acute onset of acute migraine headache with or without aura of moderate to severe intensity
• Established diagnosis of migraine (with or without aura) according to International Headache Society (IHS) criteria for >= 1 year; age of onset <= 50 years
• Current age is 18-65 years
• Study drug treatment to begin in less than 6 hours of the onset of migraine headache which is not spontaneously improving. Time of awakening with a migraine headache is considered as time of onset provided no headache was present prior to sleep
• History of 1 to 6 migraine headaches per month for the preceding 6 months
• Ability to give written informed consent in accordance with International Committee on Harmonisation - Good Clinical Practice (ICH-GCP) and local legislation

Exclusion Criteria:

• Use of prescription and non-prescription medications for migraine prophylaxis within 2 weeks prior to treatment including Selective Serotonin Reuptake Inhibitors (SSRIs) (except fluoxetine which should have a 6 weeks washout), flunarizine (which should have a 4 week washout) and Mono-amino-oxidase-inhibitors drugs (MAOIs)
• Use of paracetamol (acetaminophen), aspirin, Non-steroidal anti-inflammatory drugs (NSAIDS), barbiturates or anti-emetics within 12 hours of taking study drug or of any 'triptan', ergotamine preparation or opiate analgesics within 48 hours prior to study drug administration or the use of analgesics > 10 days/months
• History of significant medical (i.e. coronary artery disease by history, renal failure), neurological (including epilepsy and structural brain lesions) or psychiatric disorders
• History, clinical evidence or screening or baseline electrocardiogram suggestive of cardiovascular disease including ischemic heart disease, Prinzmetal angina, coronary vasospasm, history of atherosclerotic heart disease of cardiac arrhythmia
• History of known hypertension
• History of basilar, ophthalmoplegic or hemiplegic migraine headaches or non-migraine headaches (e.g. tension-type headaches) occurring on average >= 10 days per month for the preceding 6 months
• History of treatment resistance migraine attacks defined as a lack of response to a range of commonly used acute anti-migraine compounds
• Females who are nursing or pregnant (as determined by a serum pregnancy test at screening and a urine pregnancy test at baseline) or of childbearing potential (any woman who is not at least 1 year post-menopausal or surgically sterile is considered to be of childbearing potential) and not using a medically approved method of birth control as defined by local country requirements
• Baseline systolic BP >= 160 mmHg or diastolic BP >= 100 mmHg
• Any daily intake of prescribed medication within 2 weeks prior to randomization for diseases in the investigator's judgment that would contraindicate participation in the trial
• History of Raynauds' disease
• A recent history (six months) of current evidence of alcohol or recreational drug abuse as defined by Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM- IV) (R97-1072)
• Post or present medical conditions that would keep administration of study mediation from being in the patient's best interest in the judgment of the clinical investigator
• Unwillingness or inability to comply with the protocol (e.g. the patient cannot read or write and does not have another person to assist in completing the diary; the patient cannot be followed for 1 weeks). Patients unable to give informed consent are to be excluded from participation in the trial. Patients with legally appointed custodian can not be enrolled in the trial. In case of doubt an independent psychiatrist should testify that the patient is able to give informed consent
• Use of another investigational drug within a time span of at least ten half-lives but never less than 1 month. Concurrent participation in another investigational protocol
• Prior exposure to BIBN 4096 BS

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BIBN 4096 BS - ranging dose; sequential adaptive design, allocation of verum treated patients to dose groups not fixed in advance IV infusion over 10 minutes	Drug: BIBN 4096 BS
Placebo Comparator: Placebo; IV infusion over 10 minutes	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Headache Response measured on a four-point scale	2 hours post start of infusion

Secondary Outcome Measures

Outcome Measure	Time Frame
Headache Response measured on a four-point scale	30 min, 1, 4 and 24 hours post start of infusion
Headache Free measured on a four-point scale	30 min, 1, 2, 4 and 24 hours post start of infusion
Maintenance of Headache Response measured on a four-point scale	up to 24 hours post start of infusion
Relief of associated symptoms	30 min, 1, 2, 4 and 24 hours post start of infusion
Occurence of Meaningful Relief measured by stopwatch	up to 4 hours post start of infusion
Time to Meaningful Relief measured by stopwatch	up to 4 hours post start of infusion
Clinical Disability measured on four-point scale	30 min, 1, 2, 4 and 24 hours post start of infusion
Use of rescue medication	within 24 hours post start of infusion
Time to use of rescue medication	within 24 hours post start infusion
Number of patients with adverse events	up to day 9
AUC (Area under the concentration time curve of the analyte in plasma)	up to 4 hours post start of infusion
Cmax (Maximum observed concentration of the analyte in plasma)	up to 4 hours post start of infusion
Qualified Headache Response measured on four-point scale	up to 24 hours post start of infusion
Time to sustained Headache Response	up to 24 hours post start of infusion
Worsening/Recurrence of Headache pain	2 - 24 hours post start of infusion
Tmax (Time to maximum concentration of the analyte in plasma)	up to 4 hours post start of infusion

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: February 1, 1999
• Primary Completion (Actual): December 1, 1999
• Study Completion: December 7, 2022

Study Registration Dates

• First Submitted: July 22, 2014
• First Submitted That Met QC Criteria: July 22, 2014
• First Posted (Estimate): July 23, 2014

Study Record Updates

• Last Update Posted (Estimate): July 23, 2014
• Last Update Submitted That Met QC Criteria: July 22, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Headache
• Other Study ID Numbers: 1149.2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No