HealthyPhase 1NCT02902666

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

A Phase 1 study testing Paracetamol 1000 mg/codeine phosphate hemihydrate 30 mg tablet and Paracetamol 500 mg/codeine phosphate hemihydrate 30 mg tablet in people with Healthy, run by Aziende Chimiche Riunite Angelini Francesco S.p.A.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for: Healthy
What is being tested?: Paracetamol 1000 mg/codeine phosphate hemihydrate 30 mg tablet and Paracetamol 500 mg/codeine phosphate hemihydrate 30 mg tablet
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 46 participants
Where: No sites listed yet
Study dates: Apr 2016to May 2016
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 55 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

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

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Contraception and fertility (females only): females of child-bearing potential must be using at least one of the following reliable methods of contraception:
Hormonal oral, implantable, transdermal, or injectable contraceptives for at least 2 months before the screening visit
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
A male sexual partner who agrees to use a male condom with spermicide
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.

Who cannot join

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

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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

About this study

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

Conditions: Healthy
Being tested: Paracetamol 1000 mg/codeine phosphate hemihydrate 30 mg tablet, Paracetamol 500 mg/codeine phosphate hemihydrate 30 mg tablet
Keywords: Bioequivalence, Paracetamol 1000 mg/codeine 30 mg, Co-efferalgan 500 mg/30 mg

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Paracetamol 1000 mg/codeine phosphate hemihydrate 30 mg tabletDrug
Paracetamol 500 mg/codeine phosphate hemihydrate 30 mg tabletDrug

Study groups in NCT02902666
Study group	Role	What they receive
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. Receives: 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. Receives: Drug: Paracetamol 500 mg/codeine phosphate hemihydrate 30 mg tablet

What is being measured

The primary outcome is the main question the study is designed to answer.

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)
Measured: 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)
Measured: 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 (6)

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)
Measured: 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)
Measured: 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
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)
Measured: 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
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
Measured: 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 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)
Measured: 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
Treatment-Emergent Adverse Event (TEAEs), vital signs (BP, HR), physical examinations, laboratory parameters, body weight, ECG
Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Apr 2016May 2016

First posted16 Sep 2016 (estimated)
Study startApr 2016
Primary completionMay 2016
Study completionMay 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for HealthyStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Enrolment: 46 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02902666
Sponsor's protocol ID: 044(1F)PO15313
Other IDs: CRO-PK-15-304
Status last verified: Sep 2016
First submitted: 7 Sep 2016
Last updated: 16 Sep 2016
Results posted: No
Data monitoring committee: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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Study at a glance

From the registry record, last updated by the sponsor on 16 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT02902666
Acronym / sponsor ID: 044(1F)PO15313
Conditions: Healthy
Keywords: Bioequivalence, Paracetamol 1000 mg/codeine 30 mg, Co-efferalgan 500 mg/30 mg
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 46 participants (actual)
Lead sponsor: Aziende Chimiche Riunite Angelini Francesco S.p.AIndustry (pharma, biotech, devices)
Collaborators: Cross Research S.A.
Study start: Apr 2016
Primary completion: May 2016 (actual)
Study completion: May 2016 (actual)
First posted: 16 Sep 2016 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Paracetamol 1000 mg/codeine phosphate hemihydrate 30 mg tablet	Experimental	Drug: Paracetamol 1000 mg/codeine phosphate hemihydrate 30 mg tabletA 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.
paracetamol 500mg/codeine phosphate hemihydrate 30mg 2 tablets	Active comparator	Drug: Paracetamol 500 mg/codeine phosphate hemihydrate 30 mg tabletA 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.

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (11 listed)

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

Key exclusion criteria (13 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Paracetamol 1000 mg/codeine phosphate hemihydrate 30 mg tablet	Drug	Paracetamol 1000 mg/codeine phosphate hemihydrate 30 mg tablet
Paracetamol 500 mg/codeine phosphate hemihydrate 30 mg tablet	Drug	paracetamol 500mg/codeine phosphate hemihydrate 30mg 2 tablets

Primary outcome

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)
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)

6 secondary outcomes

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
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
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
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
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
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

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 16 Sep 2016.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Milko Radicioni, MD principal investigator

Cross Research S.A.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02902666.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Sep 2016.