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Bioequivalence Study of One Tablet of Paracetamol 1000 mg + Codeine 30 mg vs. Two Tablets of Paracetamol 500 mg + Codeine 30 mg

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ClinicalTrials.gov Identifier: NCT02902666
Recruitment Status : Completed
First Posted : September 16, 2016
Last Update Posted : September 16, 2016
Sponsor:
Collaborator:
Cross Research S.A.
Information provided by (Responsible Party):
Aziende Chimiche Riunite Angelini Francesco S.p.A

Brief Summary:
The purpose of this study is to evaluate the bioequivalence of a new paracetamol 1000 mg/codeine 30 mg formulation vs. the marketed reference Co-efferalgan® 500 mg/30 mg in terms of rate and extent of absorption, when administered as single oral dose (one tablet of the new A.C.R.A.F. formulation vs. two tablets of the reference formulation Co-efferalgan®) to healthy male and female volunteers, under fasting conditions, in two consecutive study periods.

Condition or disease Intervention/treatment Phase
Healthy Drug: Paracetamol 1000 mg/codeine phosphate hemihydrate 30 mg tablet Drug: Paracetamol 500 mg/codeine phosphate hemihydrate 30 mg tablet Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 46 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Official Title: A Single Dose Bioequivalence Study of Test Product (One Tablet of Paracetamol 1000 mg + Codeine 30 mg, Manufactured by A.C.R.A.F. S.p.A.) vs. Two Tablets of the Reference Product (Paracetamol 500 mg + Codeine 30 mg) in Healthy Volunteers
Study Start Date : April 2016
Actual Primary Completion Date : May 2016
Actual Study Completion Date : May 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Paracetamol 1000 mg/codeine phosphate hemihydrate 30 mg tablet

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
Active Comparator: paracetamol 500mg/codeine phosphate hemihydrate 30mg 2 tablets
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



Primary Outcome Measures :
  1. 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). [ Time Frame: 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 ]
    Maximum plasma concentration (μg/ml)

  2. 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). [ Time Frame: 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 ]
    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)


Secondary Outcome Measures :
  1. 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) [ Time Frame: 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 ]
  2. 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) [ Time Frame: 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 ]
  3. Terminal half-life, calculated, if feasible, as ln2/λz [h] (t1/2,z) 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) [ Time Frame: 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 ]
  4. Apparent First Order Terminal Rate Constant (λz) of paracetamol and of codeine (free base) after single dose administration of T and R (dose normalisation w [ Time Frame: 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 ]
  5. Time Until First Nonzero Concentration (tlag) 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) [ Time Frame: 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 ]
  6. Treatment-Emergent Adverse Event (TEAEs), vital signs (BP, HR), physical examinations, laboratory parameters, body weight, ECG [ Time Frame: 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 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Informed consent: signed written informed consent before inclusion in the study
  2. Sex and Age: males/females, 18-55 years old inclusive
  3. Body Mass Index (BMI): 18.5-30 kg/m2 inclusive
  4. 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
  5. 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
  6. Tobacco: non-smokers or ex-smokers for at least 6 months
  7. 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:

  1. Electrocardiogram (12-leads, supine position): clinically significant abnormalities
  2. Physical findings: clinically significant abnormal physical findings which could interfere with the objectives of the study
  3. Laboratory analyses: clinically significant abnormal laboratory values indicative of physical illness
  4. 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
  5. 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
  6. 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
  7. 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
  8. Blood donation: blood donations for 3 months before this study
  9. 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
  10. Drug test: positive result at the drug test at screening or day-1
  11. Alcohol test: positive alcohol breath test at day -1
  12. Diet: abnormal diets (<1600 or >3500 kcal/day) or substantial changes in eating habits in the 4 weeks before this study; vegetarians
  13. Pregnancy (females only): positive or missing pregnancy test at screening or day -1, pregnant or lactating women

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02902666


Sponsors and Collaborators
Aziende Chimiche Riunite Angelini Francesco S.p.A
Cross Research S.A.
Investigators
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Principal Investigator: Milko Radicioni, MD Cross Research S.A.

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Responsible Party: Aziende Chimiche Riunite Angelini Francesco S.p.A
ClinicalTrials.gov Identifier: NCT02902666     History of Changes
Other Study ID Numbers: 044(1F)PO15313
CRO-PK-15-304 ( Other Identifier: CROSS Research S.A., Phase I Unit )
First Posted: September 16, 2016    Key Record Dates
Last Update Posted: September 16, 2016
Last Verified: September 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Aziende Chimiche Riunite Angelini Francesco S.p.A:
Bioequivalence
Paracetamol 1000 mg/codeine 30 mg
Co-efferalgan 500 mg/30 mg
Additional relevant MeSH terms:
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Acetaminophen
Codeine
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Antipyretics
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Antitussive Agents
Respiratory System Agents