Bioequivalence study of two oral fixed-dose combination tablets of 250 mg acetylsalicylic acid, 250 mg paracetamol and 65 mg caffeine in healthy volunteers after controlled fasting
- Conditions
- PainMigraine
- Registration Number
- DRKS00020899
- Lead Sponsor
- Dr. Pfleger Arzneimittel GmbH
- Brief Summary
Pharmacokinetics Bioequivalence of P360-tablets and Excedrin® film-coated tablets was demonstrated under fasting conditions for ASA, Paracetamol and Caffeine in healthy male and female subjects. Geometric mean ratios for AUC0-t, AUC0-inf and Cmax of all analytes were close to 100% with the 90% confidence intervals fully within the acceptance intervals (80.00%-125.00%). Safety Single oral doses of P360-tablets or Excedrin® were well tolerated
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Complete
- Sex
- All
- Target Recruitment
- 36
Main inclusion criteria:
1. The subject is healthy as determined by their medical history, a physical examination including vital signs, an electrocardiogram (ECG) and clinical laboratory testing.
2. The subject is male or female and 18 to 55 years of age inclusive, at the time of signing the informed consent.
3. The subject is able to read, write and fully understand German.
4. The subject has a body mass index (BMI) within the range of 18.5 to 30.0 kg/m2 (inclusive).
5. The subject is a non-smoker since at least 6 months as confirmed by an interview and a cotinine test at screening and on Day -2 of each period.
6. A male subject who is not vasectomized with a partner of childbearing potential must agree to refrain from fathering a child during the study and must agree to use effective contraception consisting of a combination of 2 forms of birth control (1 of which must be a barrier method) as detailed below in inclusion criterion 7, 2 days before the first dose of study medication (as appropriate), until the end of the study and refrain from donating sperm during this period.
7. A female subject is eligible if she is not pregnant (negative beta human chorionic gonadotropin [beta-hCG] test at screening and a negative urine pregnancy test on Day -2 in each period) and not breastfeeding.
8. The subject provided written informed consent prior to any clinical study-specific procedures.
1. Any history or evidence of any clinically significant cardiovascular, gastrointestinal endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, and/or other major disease or malignancy, as judged by the investigator.
2. Any clinically significant history of allergic conditions (including drug allergies, asthma, eczema, or anaphylactic reactions, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).
3. Known hypersensitivity to ASA, paracetamol, caffeine or to any of the other excipients.
4. Known hypersensitivity to salicylates or other non-steroidal anti-inflammatory drugs (NSAIDs), which have been manifested as asthma, urticaria, nasal polyps, angioedema and other allergic reactions.
5. History of gastrointestinal bleeding or perforation, related to previous NSAID therapy. Active, or history of recurrent peptic ulcer/hemorrhage (2 or more distinct episodes of proven ulceration or bleeding).
6. Difficulty in swallowing.
7. History or evidence of malabsorption or any gastrointestinal surgery except appendectomy and herniotomy.
8. History of any chronic disease which might interfere with the absorption, distribution, metabolism or excretion of the investigational medicinal product (IMP).
9. Known disorders with increased bleeding risk (e.g. periodontosis, hemorrhoids, acute gastritis, peptic ulcer), known coagulation disorders (e.g. von Willebrand´s disease, hemophilia) or known sensitivity to common causes of bleeding (e.g. nasal).
10. Febrile illness within 1 week before the first study drug administration.
11. Previous medical history of gout or reduced uric acid excretion.
12. Recently had (past 30 days) or plans to have surgery, an invasive procedure, tattoos or piercings during the trial or 2 weeks after treatment.
13. Any clinically significant laboratory findings that, in the opinion of the Investigator, would preclude inclusion in the trial; creatinine and/or liver function tests (alanine aminotransferase, aspartate aminotransferase) or total bilirubin above 1.2 x upper limit of normal (ULN) confirmed by two repeated measurements, when checked at screening.
14. Any clinically significant abnormality following the investigator’s review of the physical examination, ECG and clinical study protocol-defined clinical laboratory tests at screening or admission to the clinical unit.
15. Subjects with abnormal ECG parameters (after at least 5 minutes rest in supine position): heart rate <45 and >90 bpm, PQ interval >220 milliseconds (ms), QRS duration >120 ms, QTcF interval >450 ms at screening visit.
16. Supine systolic blood pressure (after at least 5 minutes rest in supine position) > 140 mmHg or < 100 mmHg or diastolic blood pressure > 90 mmHg or < 50 mmHg and pulse rate < 45 or > 90 beats per minute (at screening).
17. Positive alcohol or drug screen at Screening or on Day -2 of each dosing period.
18. Positive cotinine test at screening and on Day -2 of each period
19. Use of any prescribed or non-prescribed drugs (including vitamins or hormone replacement therapy, natural and herbal remedies, e.g., St. John’s Wort) in the 2 weeks or 5 half-lives, whichever is longer, prior to the first study drug administration. Oral, injectable or topical contraceptives are permitted as they are acceptable methods of contraception.
20. Intake of ASA or paracetamol or other NSAID containing these products within 2 days prior to the first study dr
Study & Design
- Study Type
- interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Area under the plasma concentration-time curve up to the last sampling time with a concentration above the limit of quantification (AUC0-tlast) and maximum plasma concentration (Cmax) of ASA, paracetamol and caffeine
- Secondary Outcome Measures
Name Time Method Area under the plasma concentration-time curve extrapolated to infinity (AUC0-inf), time to reach Cmax (tmax), terminal elimination half-life (t1/2) of ASA, paracetamol and caffeine