Pharmacokinetic study of two orally formulated combinations of acetaminophen and ibuprofen (Maxigesic Rapid vs Maxigesic 325) in healthy volunteers under fasting conditions

• Register: ANZCTR
• Last refreshed on: 14 January 2019
• Main ID: ACTRN12618000782235
• Date of registration: 09/05/2018
• Prospective Registration: No
• Primary sponsor: AFT Pharmaceuticals Ltd.
• Public title: Pharmacokinetic study of two orally formulated combinations of acetaminophen and ibuprofen (Maxigesic Rapid vs Maxigesic 325) in healthy volunteers under fasting conditions
• Scientific title: Randomized, single dose, two-way crossover Open Label Study to Evaluate and compare the Pharmacokinetic parameters of 325 mg Acetaminophen and 97.5mg Ibuprofen film coated tablet, after an oral administration of 30 healthy adults under fasting conditions.
• Date of first enrolment: 04/04/2018
• Target sample size: 30
• Recruitment status: Completed
• URL: https://anzctr.org.au/ACTRN12618000782235.aspx
• Study type: Interventional
• Study design: Purpose: Treatment; Allocation: Randomised controlled trial; Masking: Open (masking not used);Assignment: Crossover;Type of endpoint: Bio-equivalence;
• Phase: Phase 1

Countries of recruitment

Jordan

Contacts

• Name: Dr Jennifer Zhang

• Name: Dr Jennifer Zhang

Key inclusion & exclusion criteria

Inclusion criteria: Healthy subjects, males and females aged 18 to 50 years of age. Females must be sterile or using adequate contraception. Participants must not have taken any prescription medications for at least 14 days or over-the-counter medications and herbal remedies for at least 7 days before the start of each study phase and for the duration of the study, with the exception of oral contraceptives and the study medication.
All subjects must be deemed healthy on the basis of a medical history, physical exam (including vital signs and 12-lead ECG recording), urinalysis, and blood biochemical, serological and haematological examinations.
Exclusion criteria: Female who are pregnant or nursing (not applicable for male subjects).
Female of childbearing potential who are unwilling to take adequate contraceptive precautions, i.e., a hormonal contraceptive, an intrauterine device, double-barrier method, or abstinence. A woman of childbearing potential is defined as any female who is less than 2 years post-menopausal or has not undergone a partial or total hysterectomy or surgical sterilisation, e.g. bilateral tubal ligation, bilateral oophorectomy (not applicable for male subjects).
Female of childbearing potential who are unwilling to undergo a urine pregnancy test (not applicable for male subjects).
Have an alcohol intake in excess of 14 units per week for females and 21 units per week for males.
Have a history of drug abuse or positive test results for drug abuse during screening.
Unwilling to abstain from smoking throughout the whole duration of the study
Unable and refuse to abstain the used prescription drugs (not including oral contraceptives and the study medication) within 14 days prior to study drug administration or have used over-the-counter drugs or herbal products within 7 days prior to study drug administration and during the study.
Unable and refuse to abstain the use of vitamins for nutritional purposes within 2 days prior to study drug administration until the last study sample is collected in each period.
Unable and refuse to abstain to consume grapefruit containing foods or beverages within 7 days or caffeine containing foods or beverages within 24 hours prior to study drug administration until the last study sample is collected in each period.
Currently, or in last 80 days, participating in a clinical trial involving another study drug.
Have donated blood or blood products within 60 days prior to study drug administration.
Have a clinically significant abnormal laboratory test (as determined by the Principal Investigator), Hb, PCV and RBC indices (MCV, MCH and MCHC) tests which deviated outside the 5% of reference range or laboratory results of liver or kidney function tests (creatinine, urea and ALP will be accepted if below reference range, total protein and albumin accepted if above reference range) are outside the reference range.
Be on a special diet (for example is vegetarian).
Unable and refuse to abstain to engage in strenuous exercise within 24 hours prior to study drug administration until the last sample is collected in each study period.
Have at screening examination a pulse outside the normal range of (60-100 beat per minute) or a body temperature outside the normal range of (35.0-37.2 oC) or a respiratory rate outside the normal range of (14-20 breath per minute) or a sitting blood pressure less than 100/60 mm Hg or more than or equal to 140/90 mm Hg.
Unable and refuse to abstain to consume any beverages or food containing alcohol for 24 hours prior to study drug administration until the last study sample is collected in each period.
Have a history of difficulties in swallowing or any gastrointestinal disease which could affect the drug absorption.
Suffering from any other diseases or condition which, in the opinion of the investigator, means that it would not be in the participant’s best interests to participate in this study.
Subject is a heavy smoker (more than 10 cigarettes per day).
Acute infection within one week preceding study drug administration.
Have any history of allergy or hypersensitivity to ibuprofen, aspirin or other NSAID.


Age minimum: 18 Years
Age maximum: 50 Years
Gender: Both males and females

Health Condition(s) or Problem(s) studied

Pain relief ;
Pain relief

Anaesthesiology - Pain management

Intervention(s)

Maxigesic® Rapid (Treatment A)- Acetaminophen 325 mg and Ibuprofen 97.5mg
Single Dose: Oral administration of three film coated tablets with 240 ml of water under fasting conditions (subjects will be fasted-abstain from all liquids and food except water for at least 10 hours overnight before dosing and for 4 hours after dosing)
The dose will be taken under the supervision of the site study staff and the dosing time will be recorded on the site source document
The washout period is at least 3 days between the two treatment periods.

Primary Outcome(s)

To evaluate and compare the pharmacokinetic parameters (Cmax, AUC0-t, AUC0-inf, Tmax, Kel and t1/2el) between test and reference products under fasting conditions[Blood samples (14) were collected before dose (0.00) and at 5 minutes (0.083 hours), 15 minutes (0.25 hours), 30 minutes (0.50 hours), 45 minutes (0.75 hours) and 1.00, 1.25, 1.50, 2.00, 3.00, 6.00, 8.00, 10.00 and 12.00 hours post dose. The total volume of blood draws did not exceed 420 ml.]

Secondary Outcome(s)

To compare the safety and tolerability of test and reference products under fasting conditions.
An acute safety evaluation will be performed during each study period by recording spontaneously reported adverse events and by clinical assessments, including measurements of vital signs (blood pressure, heart rate, respiratory rate) and body temperature.
These measurements will be done at screening as well as prior, during and after each dosing period.
Vital signs will be measured pre-dose and approximately at 0.50, 1.00, 1.50, 2.00, 3.00, 4.00, 6.00 and 12.00 hours after study drug administration. Body temperature will be measured before dosing and approximately at the following times after dosing: 4th and 12th hour. Vital signs may be taken at other times if deemed necessary.
At screening and at the end of each study period an additional blood sample will be taken for haematology, biochemistry and serological assessment (only in screening).
Known NSAID adverse effects (i.e. GI ulceration, indigestion/stomach pain, GI bleeding, bronchospasm, water retention, renal failure, skin reactions and thromboembolic events), and known adverse effects of acetaminophen (i.e. clinical evidence of hepatotoxicity) will be compared between groups.
Adverse events will continue to be assessed up to 7 days after the last dose of the study medication by spontaneous reporting and at a final follow-up phone call.[Safety will be evaluated during each study period and for 7 days following study drug administation ]

Secondary ID(s)

Not applicable

Source(s) of Monetary Support

AFT Pharmaceuticals Ltd

Ethics review

Status: Approved
Approval date:
Contact:

IRB of IPRC (International Pharmaceutical Research Center)

Results

• Results available: Yes
• Date Posted: 20/12/2018
• Date Completed: 17/04/2018