None listed
Conditions
Brief summary
This study is a Phase I study designed to determine and compare the pharmacokinetic profile of the combined use of diphenhydramine hydrochloride with fixed-dose combination tablet of Paracetamol (Acetaminophen) & Ibuprofen, with that of the individual components of diphenhydramine hydrochloride and Paracetamol (Acetaminophen) & Ibuprofen. This study will include 30 healthy volunteers and will be conducted under fasting conditions.
Interventions
Each participant will receive each of the interventions (Treatment A and B), and the comparator (Treatment C) treatment under fasting conditions in a three-way cross over sequence. The sequence in which the participants receives each treatment will be randomly allocated.
Participants will check-in to the Study Centre the evening prior to study drug administration and will stay for the duration of the Study Period (at least 12 hours after dosing).
Intervention Treatments:
Treatment A:
Parace
Each participant will receive each of the interventions (Treatment A and B), and the comparator (Treatment C) treatment under fasting conditions in a three-way cross over sequence. The sequence in which the participants receives each treatment will be randomly allocated. Participants will check-in to the Study Centre the evening prior to study drug administration and will stay for the duration of the Study Period (at least 12 hours after dosing). Intervention Treatments: Treatment A: Paracetamol 500mg plus Ibuprofen 150mg fixed-dose combination film-coated tablet (500 mg acetaminophen + 150 mg ibuprofen per film coated tablet). Administration: Two tablets (given at the same time) as a single dose (total dose 1000 mg acetaminophen + 300 mg ibuprofen) will be administered orally with 240 mL of water. Treatment B: Diphenhydramine hydrochloride (50 mg diphenhydramine hydrochloride per tablet). Administration: One tablet will be administered orally with 240 mL of water. Participants will be fasted for at least 10 hours overnight before dosing and for 4 hours after dosing. Water will be restricted for 1 hour pre-dose and 1 hour post-dose (with the exception of water administered as part of dosing) The test product will be administered under the site staff's supervision and the exact dosing time will be documented. There will be three study periods so that each participant will receive each of the interventions (Treatment A and B) and the comparator (Treatment C). Each study period will be separated by a washout period of at least 7 days between two consecutive periods. Once the participant completes the final period (Period 3), there is a follow-up period lasting for 7 days.
Sponsors
AFT Pharmaceuticals Ltd
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
A participant will be eligible for inclusion in this study only if all of the following criteria are met: • Male or female subjects aged between 18 and 50 years, inclusive, on the day of consent. • Voluntarily provide written informed consent before the initiation of any study-related procedures. • Have a Body Mass Index (BMI) between 18.5 and 30.0 kg/m2. • Have no significant disease (asthma, peptic or gastric ulcer, sinusitis, pharyngitis, gastrointestinal disease, pulmonary disease, renal disorder (impaired renal function), hepatic disorder (impaired hepatic function), cardiovascular disorder, neurological disease such as epilepsy, haematological disorders or diabetes, psychiatric, infective, dermatologic or immunological disorders) as determined by medical history, physical examination and laboratory tests. • Have negative HIV and hepatitis B & C test results. • Be able and willing to abstain from caffeine-containing beverages (e.g. coffee, soda, energy drinks or tea), caffeine-containing food (e.g. chocolate), and alcohol for at least 24 hours prior to study drug administration until the last study sample is collected in each period. • Be able and willing to abstain from any food or beverages containing grapefruit for at least 7 days prior to study drug administration until the last study sample is collected in each period. • Be able and willing to abstain from prescription drugs (not including oral contraceptives and the study medication) within at least 14 days or over-the-counter drugs within at least 7 days before the start of each study phase and during the study. • Be able and willing to abstain from vitamins taken for nutritional purposes for at least 2 days prior to study drug administration until the last study sample is collected in each period. • Be able and willing to abstain from smoking throughout the whole duration of the study. • Have a medically acceptable normal 12-lead ECG (No QTc Prolongation).
Exclusion criteria
Participants will not be eligible for inclusion in this study if any of the following criteria are met: Study contra-indications: • Female who is pregnant or nursing (not applicable for male subjects). • Female of childbearing potential who is 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 is 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 drugs of abuse during screening. • Have a history of allergic reactions to acetaminophen, ibuprofen and diphenhydramine hydrochloride • Unwilling to abstain from smoking throughout the whole duration of the study • Unable and refuse to abstain the use of prescription drugs (not including oral contraceptives and the study medication) within at least 14 days or over-the-counter drugs within at least 7 days before the start of each study phase and during the study. • Unable and refuse to abstain the use of vitamins for nutritional purposes within at least 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 at least 7 days or caffeine containing foods or beverages within at least 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 any clinically significant results from laboratory tests, however, ALP, urea and creatinine will be accepted if below reference range, total protein and albumin will be accepted if above reference range after being evaluated by the physician as clinically not significant. Haematology tests with deviation of more than 5% of the reference limits. Laboratory tests are performed not longer than two weeks before the initiation of the clinical study. • Be on a special diet (for example is vegetarian). • Unable and refuse to abstain from engaging in strenuous exercise within at least 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 C) 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 from consuming any beverages or food containing alcohol for at least 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). • Subject has a difficulty fasting or consuming standard meals. NSAID and/or Acetaminophen, Ibuprofen Contra-Indications or Exclusion Criteria: • Have known hypersensitivity reaction to acetaminophen, ibuprofen, other NSAIDs or any other ingredients in the product. • Have severe heart and renal failure (glomerular filtration below 30 ml/min) Acetaminophen: • Have active alcoholism as chronic excessive alcohol ingestion may predispose patients to acetaminophen hepatoxicity. Ibuprofen : • Have experienced asthma, urticaria, or allergic- type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactic-like reactions to NSAIDs. • Have active gastrointestinal bleeding or peptic ulceration. Use of ibuprofen is contraindicated during the third trimester of pregnancy. • Have taken other products containing ibuprofen, aspirin, salicylates or with any other anti-inflammatory medicines. Diphenhydramine hydrochloride Contra-Indications or Exclusion Criteria • Have hypersensitivity to diphenhydramine or any other component. • Have severe hepatic, renal or respiratory insufficiency. • Angle-closure glaucoma • Bladder neck obstruction • Urinary retention • Chronic Bronchitis • Stenosing peptic ulcer • Pyloroduodenal obstruction • Symptomatic prostatic hypertrophy • Porphyria • Asthma • Epilepsy
Outcome results
None listed