Clinical trial NCT02582996: Cefalium® Compared to Tylenol® in the Treatment of Migraine Attacks
Official title: National, Phase III, Multicenter, Randomized, Open, Parallel, to Evaluate the Efficacy, Safety and Superiority of Cefalium® Compared to the Tylenol® in the Treatment of Migraine Attacks
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE3
Conditions: Migraine
Keywords: Headache
Aura
Migraine
Moderate to Severe
Lead sponsor: Ache Laboratorios Farmaceuticos S.A.
Sponsor class: INDUSTRY
First posted: 2015-10-21
Enrollment: 336
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: National clinical trials, phase III, randomized, open, parallel, study of superiority, in which three hundred thirty-six (336) participants of both sexes, aged between 18 and 65 years will be randomly allocated to one of two treatment groups. The Group 01 will use Cefalium® and group 02 will use Tylenol®.

Detailed description: Cefalium® is a combination of Caffeine + Paracetamol + dihydroergotamine mesylate + metoclopramide hydrochloride. The dihydroergotamine mesylate interacts with the serotonergic, dopaminergic and noradrenergic receptors, but it's mechanism is not totally known. The caffeine presents mechanisms that are not totally clear, but it may relieves the pain by activating of the central noradenosine pathway (pain suppressing system). The Metoclopramide hydrochloride presents an anti-emetic action and prokinetic action in the gastrointestinal tract.One of its properties is the inhibition of nausea and vomiting triggered by drugs such as ergotamine.Paracetamol, also called acetaminophen is an effective agent analgesic and antipyretic with weak anti-inflammatory activity.

Eligibility criteria: Inclusion Criteria:

* Subjects of both gender;
* Age older or equal to 18 and younger than 66 years if they have symptoms of migraine headache before 50 years of age;
* Presence of migraine headache with or without aura symptoms, at least 03 months prior to the study, the criteria defined by International Classification of Headache Disorders(ICHD)-II, 2004 (IHS International Headache Society) - Annex I;
* Subjects which are experiencing 2-6 migraine attacks per month with mild to moderate pain intensity in the last 3 months prior to screening visit;
* Participants which are able to distinguish migraine attacks to any other type of headache;
* Ability to understand and consent to participate in this clinical research, expressed by signing the Informed Consent Form (ICF).

Exclusion Criteria:

* Any clinical finding (clinical evaluation / physical) that is interpreted by the Investigator as a risk to the subject in the clinical trial;
* Subjects which had recent episodes of headache, with frequency equal or higher than 15 daily episodes per month, 3 months prior to the screening visit;
* Subjects with headache history defined by the ICHD-II criteria, 2004 IHS (International Headache Society) rated as:

  * Typical aura with non-migraine headache;
  * Typical aura without headache;
  * Familial Hemiplegic Migraine (FHM);
  * Sporadic Hemiplegic Migraine;
  * Basilar type Migraine;
* Any laboratorial finding that the Investigator consider a risk to subject of the study;
* Hypersensitivity to the drug components used during the study;
* Women in pregnancy or nursing period;
* Women in reproductive age who do not agree to use contraception acceptable \[oral contraceptives, injectable contraceptives, intrauterine device (IUD), hormonal implants, barrier methods, hormonal patch and tubal ligation\]; other than surgically sterile (bilateral oophorectomy or hysterectomy), postmenopausal for at least one (01) years or sexual abstinence;
* Inability to understand and answer to the functional categorical scale of the study, diary of symptoms, and not having accompanying to assist him/her;
* History of abuse, according to the principal investigator, of the alcohol, opioids, barbiturates, benzodiazepines and illicit drugs in the last 02 years, or abuse of drugs for headache including ergotamines or narcotics in the last 03 months;
* Subjects with prolonged hypotension, shock, sepsis, pheochromocytoma, hemorrhage, mechanical obstruction or perforation of the gastrointestinal tract
* Participants with glucose-6-phosphate dehydrogenase(G6PD) deficiency due to increased risk of hemolysis associated with the use of paracetamol;
* Subjects with history of epilepsy or presence of psychiatric illness of any kind, in the opinion of the investigator, that may interfere with adherence to treatment;
* Subjects with a malignant disease less than five years, or for more than five years, but without documentation about the remission/cure. As example: melanoma, leukemia, lymphoma, myeloproliferative diseases and renal cell carcinoma of any length should be excluded. Exceptions: Participants with basal cell skin cancers, squamous cell, and cervical cancer in situ may be eligible;
* Subjects which uses a preventive treatment and changed the dose in the last 02 weeks before the screening visit (V0);
* Subjects with hepatic or renal failure;
* Subjects that has participated in clinical trial protocols in the last twelve (12) months (National Board of Health- Resolution 251 of 07 August 1997, Part III, sub-item J), unless the investigator considers that there may be a direct benefit to it;
* Subjects who are in prohibited medication as described in item 10.2 of the Protocol.

Primary outcomes:
measure: Pain relief of Cefalium® compared to Tylenol®
timeFrame: 2 hours
Secondary outcomes:
measure: Pain decrease after use of investigational product, without a rescue medication
timeFrame: Up to 4 hours
measure: Pain decrease after use of the investigational product, without a rescue medication
timeFrame: 4 hours
measure: Pain relief maintenance during the period 4-24 hours after use of investigational product
timeFrame: Up to 24 hours
measure: Nausea/vomiting Symptoms Free
timeFrame: Up to 4 hours
measure: Photophobia/Phonophobia Symptoms Free
timeFrame: Up to 4 hours
measure: Need of a rescue medication
timeFrame: Up to 24 hours
Other outcomes:
measure: Variation in laboratory exams ratings
timeFrame: From baseline visit until 30 days after the end of the treatment
measure: Variation in clinical exams ratings
timeFrame: From baseline visit until 30 days after the end of the treatment
measure: Variation in physical exams ratings
timeFrame: From baseline visit until 30 days after the end of the treatment
measure: Participants with adverse events
timeFrame: From baseline visit until 30 days after the end of the treatment
Locations:
city: Salvador
country: Brazil
facility: Centro de Pesquisa Clínica - CPEC / Associação Obras Sociais Irmã Dulce
state: Bahia
city: Porto Alegre
country: Brazil
facility: Centro de Pesquisa Clínica Hospital São Lucas da PUCRS
state: Rio Grande Do Sul
city: São Paulo
country: Brazil
facility: Centro de Desenvolvimento em Estudos Clínicos Brasil - CDEC Brasil
city: São Paulo
country: Brazil
facility: Cepic - Centro Paulista de Investigação Clínica
city: São Paulo
country: Brazil
facility: CPCLIN - Centro de Pesquisas Clinicas Ltda
city: São Paulo
country: Brazil
facility: Universidade Federal de São Paulo - Núcleo de Gestão de Pesquisa/HU/FAP
Study officials:
affiliation: Federal University of São Paulo
name: Thais Villa
role: PRINCIPAL_INVESTIGATOR
References: