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

Phase 3

Completed

• Conditions: Migraine Disorders
• Interventions: Drug: Low dose ASA; Drug: High dose ASA; Drug: High dose paracetamol; Drug: Placebo; Drug: Low dose paracetamol; Drug: Caffeine

• Registration Number: NCT02183688
• Lead Sponsor: Boehringer Ingelheim

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study Start: 1998-09
• Primary Completion: 2003-01
• Status Verified: 2014-07
• Study First Submitted: 2014-07-07
• Study First Submitted QC: 2014-07-07
• Last Update Submitted: 2014-07-07
• Study First Posted: 2014-07-08
• Last Update Posted: 2014-07-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1889

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ASA + paracetamol + caffeine	Low dose ASA	-
ASA + paracetamol + caffeine	Low dose paracetamol	-
ASA + paracetamol	Low dose ASA	-
ASA	High dose ASA	-
Paracetamol	High dose paracetamol	-
Placebo	Placebo	-
ASA + paracetamol	Low dose paracetamol	-
ASA + paracetamol + caffeine	Caffeine	-
Caffeine	Caffeine	-

Primary Outcome Measures

Name	Time	Method
Calculated time to 50% pain relief, based on the pain intensity evaluated on a visual analogue scale (VAS)	30 min., 1, 2, 3 and 4 hours after administration of the study medication

Secondary Outcome Measures

Name	Time	Method
Ratio of weighted sum of pain intensity difference scores to maximum achievable sum of pain intensity differences (%SPIDweighted), evaluated on a VAS	Up to the end of the study
Pain intensity, evaluated on a VAS	30 min., 1, 2, 3 and 4 hours after administration of the study medication
Duration of headache	Up to 48 hours after onset of each headache episode
Extent of impairment of daily activities, evaluated on a 4-grade verbal scale (VRS)	Before, 30 min., 1, 2, 3 and 4 hours after administration of study drug
Percentage of patients with 50 % pain relief, evaluated on a VAS	At least 30 min., 1, 3, and 4 hours after administration of the study medication
Number of patients with adverse events	Up to the end of the study
Global assessment of tolerability by the investigator, evaluated on a 4-grade VRS	After each administration of study drug during the treatment phase
Global assessment of efficacy by the patient, evaluated on a 4-grade VRS	Within 12 hours after study drug administration
Global assessment of tolerability by the patient, evaluated on a 4-grade VRS	Within 12 hours after study drug administration