Bioequivalence Study of One Tablet of Paracetamol 1000 mg... | NCT02902666

ID	Type	Description	Link
CRO-PK-15-304	Other Identifier	CROSS Research S.A., Phase I Unit

Status Module

Name	Class
Cross Research S.A.	INDUSTRY

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Paracetamol 1000 mg/codeine phosphate hemihydrate 30 mg tablet	Experimental	A single dose of the experimental drug will be administered to healthy male and female volunteers under fasting conditions before (treatment arm 1) or after (treatment arm 2) a wash-out interval of at least 7 days between the active comparator administration. Test formulation will be administered as a single dose of one paracetamol 1000 mg/codeine 30 mg tablet.	Drug: Paracetamol 1000 mg/codeine phosphate hemihydrate 30 mg tablet
paracetamol 500mg/codeine phosphate hemihydrate 30mg 2 tablets	Active Comparator	A single dose of active comparator will be administered to healthy male and female volunteers under fasting conditions before (treatment arm 2) or after (treatment arm 1) a wash-out interval of at least 7 days between the experimental drug administration. Reference formulation will be administered as a single dose of two 500 mg/30 mg tablets.	Drug: Paracetamol 500 mg/codeine phosphate hemihydrate 30 mg tablet

Name	Type	Description	Arm Group Labels	Other Names
Paracetamol 1000 mg/codeine phosphate hemihydrate 30 mg tablet	Drug		Paracetamol 1000 mg/codeine phosphate hemihydrate 30 mg tablet

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Cmax of both paracetamol and codeine after administration of one tablet of a new paracetamol 1000 mg/codeine 30 mg formulation vs. two tablets of the marketed reference Co-efferalgan® 500 mg/30 mg (dose normalisation will be applied for codeine).	Maximum plasma concentration (μg/ml)	0 (pre-dose), 5 min, 10 min, 20 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24 and 36 hours post-dose
AUC(0-t) of both paracetamol and codeine after administration of one tablet of a new paracetamol 1000 mg/codeine 30 mg formulation vs. two tablets of the marketed reference Co-efferalgan® 500 mg/30 mg (dose normalisation will be applied for codeine).	Area under the plasma concentration-time curve from administration time to the time (t) of the last measurable concentration (Ct), calculated with the linear trapezoidal method (μg*h/ml)	0 (pre-dose), 5 min, 10 min, 20 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24 and 36 hours post-dose

Secondary Outcomes

Measure	Description	Time Frame
Area under the concentration vs. time curve up to infinity (AUC(0-∞)) of paracetamol and of codeine (free base) after single dose administration of T and R (dose normalisation will be applied to AUC(0-∞), for codeine)		0 (pre-dose), 5 min, 10 min, 20 min, 30 min, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24 and 36 hours post-dose
Time to achieve Cmax (h) (Tmax) of paracetamol and of codeine (free base) after single dose administration of T and R (dose normalisation will be applied to AUC(0-∞), for codeine)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Informed consent: signed written informed consent before inclusion in the study
Sex and Age: males/females, 18-55 years old inclusive
Body Mass Index (BMI): 18.5-30 kg/m2 inclusive
Vital signs: systolic blood pressure (SBP) 100-139 mmHg, diastolic blood pressure (DBP) 50-89 mmHg, heart rate (HR) 50-90 bpm, measured after 5 min at rest in the sitting position
Full comprehension: ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to co-operate with the investigator and to comply with the requirements of the entire study
Tobacco: non-smokers or ex-smokers for at least 6 months
Contraception and fertility (females only): females of child-bearing potential must be using at least one of the following reliable methods of contraception:
1. Hormonal oral, implantable, transdermal, or injectable contraceptives for at least 2 months before the screening visit
2. A non-hormonal intrauterine device [IUD] or female condom with spermicide or contraceptive sponge with spermicide or diaphragm with spermicide or cervical cap with spermicide for at least 2 months before the screening visit
3. A male sexual partner who agrees to use a male condom with spermicide
4. A sterile sexual partner. Female participants of non-child-bearing potential or in post-menopausal status for at least 1 year will be admitted. For all female subjects, pregnancy test result must be negative at screening.

Exclusion Criteria:

Electrocardiogram (12-leads, supine position): clinically significant abnormalities
Physical findings: clinically significant abnormal physical findings which could interfere with the objectives of the study
Laboratory analyses: clinically significant abnormal laboratory values indicative of physical illness
Allergy: ascertained or presumptive hypersensitivity to the active principle (paracetamol and/or codeine) and/or formulations' ingredients or related drugs, namely non-steroidal anti-inflammatory agents and/or opioid derivatives; history of anaphylaxis to drugs or allergic reactions in general, which the investigator considers may affect the outcome of the study
Diseases: significant history of renal, hepatic, gastrointestinal, genitourinary, cardiovascular, respiratory (including allergic asthma, allergic or chronic bronchitis and other pulmonary diseases), skin, haematological, endocrine or neurological diseases that may interfere with the aim of the study
Medications: medications, including over the counter (OTC) medications and herbal remedies for 2 weeks before the start of the study. Hormonal contraceptives for females will be allowed
Investigative drug studies: participation in the evaluation of any investigational product for 3 months before this study. The 3-month interval is calculated as the time between the first calendar day of the month that follows the last visit of the previous study and the first day of the present study
Blood donation: blood donations for 3 months before this study
Drug, alcohol, caffeine: history of drug, alcohol [>1 drink/day for females and >2 drinks/day for males, defined according to the USDA Dietary Guidelines 2010], caffeine (>5 cups coffee/tea/day) abuse
Drug test: positive result at the drug test at screening or day-1
Alcohol test: positive alcohol breath test at day -1
Diet: abnormal diets (<1600 or >3500 kcal/day) or substantial changes in eating habits in the 4 weeks before this study; vegetarians
Pregnancy (females only): positive or missing pregnancy test at screening or day -1, pregnant or lactating women

ID	Term
D000082	Acetaminophen
D013607	Tablets

ID	Term
D000083	Acetanilides
D000813	Anilides
D000577	Amides
D009930	Organic Chemicals
D000814	Aniline Compounds
D000588	Amines
D004304	Dosage Forms
D004364	Pharmaceutical Preparations