Clinical trial NCT03213353: A Bioequivalence Study Between Two Brands of Medications to Treat Cough & Cold Symptoms
Official title: A SingleDose Rand, TwoPeriod, Crossover Bioequivalence Study Between a Combination Tablet With Paracetamol, Guaifenesin and Penylephrine HCL (Wrafton Lab Ltd, UK) and Vicks Active SymptoMax Plus, Powder for Oral Solution (Wrafton Lab Ltd, UK) in Healthy Adult Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Bioequivalence
Healthy Volunteers
Lead sponsor: Johnson & Johnson Consumer and Personal Products Worldwide
Sponsor class: INDUSTRY
First posted: 2017-07-11
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: This is a single-dose, randomized, two-period cross-over study with 72 healthy male and female volunteers. The investigational products will be given (after fasting overnight) at separate visits separated by 7 ± 3 days. Blood for pharmacokinetic analyses will be drawn pre-dose and at 5, 10, 15, 20, 25, 30, 40, 60, 75, 90, 105 minutes, as well as 2, 2.25, 3, 4, 5, 6, 8, and 12 hours after drug administration. Subjects will also be monitored to capture any adverse events that may occur. Bioequivalence will be assessed based on the single-dose pharmacokinetics of paracetamol, guaifenesin and phenylephrine, respectively


Eligibility criteria: Inclusion Criteria:

1. Subjects being verified as "Healthy": "Healthy" is defined as absence of any diseases or abnormalities on the basis of physical examination, standard clinical laboratory, and instrumental examinations performed at the screening visit.
2. Females of childbearing potential must have a negative urine pregnancy test at the baseline visit.
3. Male or non-pregnant, non-lactating female agree to the contraceptive requirements (including female partner's use of a highly effective method of birth control for at least 3 months before the study, during the study, and for 30 days after the last dose of study drug) as outlined in Section 11.6 (Note: Female subjects are not permitted to use hormonal contraceptives as per exclusion criterion 7).
4. Body Mass Index (BMI) between 18.5 and 30.0 kg/m2, inclusive, and a total body weight of at least 50.0 kg.
5. Volunteers who agree to abstain from alcohol consumption for at least 48 hours prior to dosing and until the last blood sample collection of each study period.

Exclusion Criteria:

1. Use of medications, including prescription medication, over-the-counter medication including vitamins, herbal supplements, medicinal plants (e.g., supplements containing garlic extract), and topical preparations of drugs that are systemically absorbed (e.g., steroids and non-steroid anti-inflammatory drugs) within two weeks prior to dosing.
2. Use of St. John's wort (Hypericum perforatum) within 30 days prior to dosing.
3. Depot injection or an implant of any drug within 3 months prior to dosing.
4. Abnormal results of laboratory and instrumental methods of examinations, including electrocardiogram (ECG).
5. Is hypersensitive, intolerant, or has experienced an allergic reaction to the active ingredients or excipients of drug products that will be used for the study, or has had severe allergy (e.g., anaphylaxis, angioedema) in the past.
6. Females with a positive pregnancy test and/or are breast-feeding.
7. Females, currently using hormonal contraceptives (including use less than 2 months prior to enrollment).
8. Males with a pregnant spouse or partner or males who are not willing to prevent conception in a spouse or partner.
9. History of regular alcohol consumption in the 6 months before screening, exceeding weekly limits of 10 alcohol units (2 L of wine or 5 L of beer or 0.5 L of spirits) or presence of information on alcoholism, substance, or drug abuse in medical history.
10. Alcohol consumption within 48 hours prior to dosing, positive respiratory alcohol test at screening, or inability to abstain from alcohol consumption until the last blood sample collection of each study period.
11. Volunteers who smoke more than 10 cigarettes per day or have an uncontrollable habit of chewing or inhaling nicotine products.
12. Drug addiction in history, or a positive urine test for psychoactive or narcotic substances.
13. Use of caffeine products exceeding 500 mg caffeine daily (5 cups of coffee) and the inability to abstain from caffeine products within 48 hours before dosing and prior to the last blood sample collection of each study period.
14. Use of xanthine containing products (e.g., coffee, tea, chocolate, or cola drink) within 48 hours before dosing and prior to the last blood sample collection of each study period.
15. Ingestion of food or beverages containing grapefruit, Chinese grapefruit (pomelo), or Seville oranges (including marmalade) within 10 days prior to the first dose of the investigational product and inability to stop taking these products during the study.
16. Positive test for human immunodeficiency virus (HIV) 1 or 2 antibodies, hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (anti-HCV) or syphilis (RW).
17. Heart rate \<60 or \>90 per minute at rest, or systolic blood pressure \<100 or \>130 mm Hg, or diastolic blood pressure \<70 or \>90 mm Hg.
18. Clinically significant signs and symptoms or history of respiratory, cardiovascular, gastrointestinal, dermatological, neurological, psychiatric, genitourinary, endocrinological, musculoskeletal, eye, ear, nose and throat disease, liver disorders, severe chronic kidney disease, active gastric or duodenal ulcer, benign prostate hyperplasia, phenylketonuria, hypertension, hyperthyroidism, diabetes, heart disease, aortic stenosis, tachyarrhythmia, glaucoma or phaeochromocytoma.
19. Hereditary problems of glucose-galactose malabsorption, fructose intolerance, or sucrose/isomaltase deficiency.
20. History of gastrointestinal surgery other than appendectomy.
21. Medical or surgical conditions, which might significantly interfere with the functioning of gastrointestinal tract, blood-forming organs etc.

Primary outcomes:
measure: Peak Plasma Concentration (Cmax) of paracetamol, guaifenesin and phenylephrine (total)
timeFrame: At baseline and during 12 hours after product administration
measure: The area under the plasma concentration-vs.-time curves from start of drug administration until the time of the last measurable concentration (AUCt) for paracetamol, guaifenesin and phenylephrine (total)
timeFrame: At baseline and during 12 hours after product administration
measure: The area under the concentration-vs.-time curve extrapolated to infinity (AUC∞) for paracetamol, guaifenesin and phenylephrine (total)
timeFrame: At baseline and during 12 hours after product administration
measure: The extrapolated part of AUC∞, AUCExtrap of paracetamol, guaifenesin and phenylephrine (total)
timeFrame: From 12 hours after start of drug administration until up to 96 hours
measure: The time at which the maximum plasma concentration is observed (tmax) for paracetamol, guaifenesin and phenylephrine (total)
timeFrame: At baseline and during 12 hours after product administration
measure: The half-life (t1/2) for paracetamol, guaifenesin and phenylephrine (total) in plasma
timeFrame: At baseline and during 12 hours after product administration
measure: The terminal elimination rate constant (λz) for paracetamol, guaifenesin and phenylephrine (total) in plasma
timeFrame: At baseline and during 12 hours after product administration
measure: The mean residence time (MRT) for paracetamol, guaifenesin and phenylephrine (total)
timeFrame: At baseline and during 12 hours after product administration
Secondary outcomes:
measure: Peak Plasma Concentration (Cmax) of unconjugated phenylephrine
timeFrame: At baseline and during 12 hours after product administration
measure: The area under the plasma concentration-vs.-time curves from start of drug administration until the time of the last measurable concentration (AUCt) for unconjugated phenylephrine
timeFrame: At baseline and during 12 hours after product administration
measure: The area under the concentration-vs.-time curve extrapolated to infinity (AUC∞) for unconjugated phenylephrine
timeFrame: At baseline and during 12 hours after product administration
measure: The extrapolated part of AUC∞, AUCExtrap of unconjugated phenylephrine
timeFrame: From 12 hours after start of drug administration until up to 96 hours
measure: The time at which the maximum plasma concentration is observed (tmax) for unconjugated phenylephrine
timeFrame: At baseline and during 12 hours after product administration
measure: The half-life (t1/2) for unconjugated phenylephrine in plasma
timeFrame: At baseline and during 12 hours after product administration
measure: The terminal elimination rate constant (λz) for unconjugated phenylephrine in plasma
timeFrame: At baseline and during 12 hours after product administration
measure: The mean residence time (MRT) for unconjugated phenylephrine
timeFrame: At baseline and during 12 hours after product administration
Other outcomes:
Locations:
city: Saint Petersburg
country: Russian Federation
facility: Scientific Research center Eco-Safety LLC
Study officials:
affiliation: McNeil AB
name: Elisabeth Kruse, PhD
role: STUDY_DIRECTOR
References: