None listed
Conditions
Brief summary
This study is designed as a Phase I study designed to determine and compare the pharmacokinetic profile of the combined use of a nasal spray of xylometazoline hydrochloride (1mg/mL) with fixed-dose combination tablet of Paracetamol (Acetaminophen) & Ibuprofen, with that of the individual components of xylometazoline hydrochloride and Paracetamol (Acetaminophen) & Ibuprofen. This study will include 30 healthy volunteers and will be conducted under fasting conditions.
Interventions
Each participant will be randomly allocated to receive a single dose of each of the intervention treatments, and the comparator treatment under fasting conditions in a three-way crossover sequence:
Intervention Treatments:
Treatment A: Paracetamol 500 mg & Ibuprofen 150mg Film-Coated Tablets (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 + 300mg ibuprofen) will be administer
Each participant will be randomly allocated to receive a single dose of each of the intervention treatments, and the comparator treatment under fasting conditions in a three-way crossover sequence: Intervention Treatments: Treatment A: Paracetamol 500 mg & Ibuprofen 150mg Film-Coated Tablets (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 + 300mg ibuprofen) will be administered orally with 240 mL of water. Treatment B: Xylometazoline hydrochloride (1 mg/mL; 0.138 mL per spray; 0.138 mL of 1mg/mL xylometazoline hydrochloride will give a calculated dose of 0.138 mg of xylometazoline hydrochloride per spray). Administration: One spray per nostril, a total of two sprays will be administered as a single dose (total of 0.276 mL of xylometazoline hydrochloride delivered, total calculated dose of 0.276 mg of xylometazoline hydrochloride). 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 each separated by a washout period of at least 7 days between two consecutive periods and a subsequent 7 days of final follow-up period.
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 have used 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
Study contra-indications • 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. • Have a history of allergic reactions to acetaminophen, ibuprofen and xylometazoline hydrochloride • 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 at least 14 days or have used over-the-counter drugs or 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 to engage 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 to consume 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). • Any acute intranasal problems (e.g. common cold, acute hayfever) within 2 weeks of the first study drug administration or a history of nasal pathology, surgery or disorders (particularly hayfever, rhinitis or nasal polyps) which may possibly affect intranasal drug absorption. NSAID and/or Acetaminophen Contra-Indications • 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 30ml/min) • Women during third trimester of pregnancy. 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. Xylometazoline Hydrochloride Contra-Indications • Contraindicated for patients with hypersensitivity to the active substance(s) or to any of the excipients. • Like other vasoconstrictors Xylometazoline HCl nasal spray 1 mg/ml should not be used after trans-sphenoidal hypophysectomy or surgery exposing the dura mater. • Xylometazoline should be avoided in patients with narrow angle glaucoma • Xylometazoline should be avoided in patients with chronic nasal inflammation with very dry nasal passages.
Outcome results
None listed