Acetylsalicylic Acid (ASA) + Paracetamol + Caffeine Combination Compared With ASA + Paracetamol as Well as ASA, Paracetamol, and Caffeine in Headache Patients

Boehringer Ingelheim

Status and phase: Completed; Phase 3

Conditions: Migraine Disorders

Treatments: Drug: High dose ASA; Drug: Low dose paracetamol; Drug: Low dose ASA; Drug: High dose paracetamol; Drug: Placebo; Drug: Caffeine

Study type: Interventional

Funder types: Industry

Identifiers

NCT02183688

155.8

Details and patient eligibility

About

To confirm the combination rationale for the combination of ASA + paracetamol + caffeine compared with the combination of ASA + paracetamol and the individual substances ASA, paracetamol, caffeine, and placebo administered orally to headache patients for two headache episodes

Enrollment: 1,889 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Female or male out-patients aged between 18 and 65 years

2. Diagnosis: Headache

   1. Tension type headache according to international headache society (IHS) Headache Classification 2.1 (2.1.1 and 2.1.2) and/or
   2. Migraine according to IHS Headache Classification 1.1, 1.2.1 or
   3. Either a) or b), but cannot be distinctly classified

3. The patient normally treats his/her headache successfully with non-prescription analgesics

4. He/She has been suffering from headache for 12 months at least

5. The headache first occurred before the age of 50 years

6. During the previous three months, the patient has suffered from headache twice a month at least

7. Informed consent according to §§ 40, 41 of the german medicines act and Good Clinical Practice (GCP)

8. The patient seems likely to comply

Exclusion criteria

1. The patient treats his/her headache with prescription-only analgesics or migraine remedies

2. The patient requires higher single doses of non-prescription analgesics to treat his/her headache than indicated in the patient information leaflet (e.g. more than 2 tablets of Thomapyrin tablets)

3. The patient normally treats his/her headache with non-prescription analgesics in effervescent tablet form

4. The patient normally takes his/her non-prescription analgesics immediately at the onset of the first signs of a headache episode

5. Headache occurs on more than 10 days per month

6. The typical, untreated headache normally lasts less than 4 hours without treatment

7. Women with a close association between the occurrence of headache and menstruation (menstrual migraine)

8. Concomitant treatment with prescription-only and/or non-prescription analgesics

9. Previous or concomitant treatment with antidepressants or antipsychotic medicines (previous treatment = within the previous 4 weeks)

10. Previous or concomitant treatment with anti-rheumatic or anti-inflammatory drugs that may influence the headache symptoms (previous treatment = within the previous 4 days)

11. Treatment of concomitant illnesses with drugs containing ASA (above a daily dose of 100 mg per day), paracetamol or caffeine (e.g. for feverish common cold, etc.)

12. Migraine prophylaxis or administration of drugs, indicated for any other reasons that influence headache symptoms, e.g.

    Propanolol, Metoprolol, Flunarizine, Cyclandelate, Valproic acid, Serotonin antagonists (pizotifen, methysergide, lisuride), Ergotamine, Dihydroergotamine, Benzodiazepines, Magnesium, Monoamine oxidase inhibitors

13. Concomitant treatments with anti-emetics

14. Drug abuse connected with the headache (defined as the administration of analgesics or other drugs for the treatment of acute headache on more than 10 days per month)

15. Alcohol or drug abuse as defined by diagnostic and statistical manual of mental disorders (DSM-IV)

16. Pregnancy and lactation

17. Gastrointestinal ulcers

18. Pathologically increased bleeding tendency

19. Glucose-6-phosphate dehydrogenase deficiency

20. Hypersensitivity to paracetamol, caffeine, ASA, salicylates, and other anti-inflammatory/anti-rheumatic agents or other allergenic substances that are relevant to the clinical trial

21. Bronchial asthma

22. Concomitant treatment with anticoagulants (e.g. coumarin derivates, heparin)

23. Clinically relevant chronic or recurrent gastrointestinal symptoms

24. Clinically relevant liver disorders

25. Clinically relevant pre-existing renal damage

26. Gilbert's syndrome

27. Not successfully treated hyperthyroidism

28. Simultaneous participation in another clinical trial

29. Participation in another clinical trial within 4 weeks of entering this study

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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1,889 participants in 6 patient groups, including a placebo group

ASA + paracetamol + caffeine

Experimental group

Treatment:

Drug: Caffeine

Drug: Low dose ASA

Drug: Low dose paracetamol

ASA + paracetamol

Active Comparator group

Treatment:

Drug: Low dose ASA

Drug: Low dose paracetamol

ASA

Active Comparator group

Treatment:

Drug: High dose ASA

Paracetamol

Active Comparator group

Treatment:

Drug: High dose paracetamol

Caffeine

Active Comparator group

Treatment:

Drug: Caffeine

Placebo

Placebo Comparator group

Treatment:

Drug: Placebo