A single dose, randomized, open-label, three-way crossover study to assess bioequivalence of paracetamol orodispersible tablets 500 mg vs Apiretal® 100 mg/ml oral solution in healthy volunteers under fasting conditions

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Laboratorios Ern S.A.

Participant type

Healthy volunteers

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Not possible to specify

Trial duration

30 Oct 2023 → 18 Dec 2023

Decision date (initial)

2023-10-09

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Laboratorios ERN S.A.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Bioequivalence

To assess the bioequivalence of a test formulation Paracetamol orodispersible tablets 500 mg administered with or without water compared to reference formulation Apiretal® by oral solution 100 mg/ml (500 mg) means of AUC0-t, and Cmax.

Secondary objectives 1

1. To evaluate the safety and tolerability of single oral dose of paracetamol 500 mg.

Conditions and MedDRA coding

Healthy volunteers under fasting conditions

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. The subjects must meet all the following criteria at screening in order to be included in the study: 1.- Subjects of either gender (male or female) aged ≥18 and ≤50 years at the time of the enrolment. 2.- Subjects free from organic or psychic conditions. 3.- No clinically significant abnormalities in medical records and physical examination at screening. 4.- No clinically significant abnormalities in haematology, biochemistry, serology (HBsAg, HCV antibodies, HIV antibodies) and urine drug results. 5.- Vital signs (blood pressure, respiratory rate, body temperature and pulse rate) and electrocardiogram record without clinically significant abnormalities. 6.- Body weight within the range (BMI ≥ 18.5 and ≤30.0 kg/m2) expressed as weight (kg) / height (m2). 7.- Subjects must be willing to use a medically acceptable barrier method of contraception throughout the study. Hormonal contraceptives and intrauterine hormone-releasing system (IUS) are not permitted. 8.- Free acceptance to participate in the study by obtaining signed informed consent form approved by the Ethics Committee of the Hospital (CEIm).

Exclusion criteria 1

1. Subjects who fulfil or develop during the study one or more of the following criteria are NOT eligible to participate in this study: 1.- Background of allergy, idiosyncrasy or hypersensitivity to IMP or any related products (including excipients of the formulations). 2.- Heavy consumer of stimulating drinks (>5 cups of coffee, tea, chocolate or cola drinks per day). 3.- Background History of alcohol dependence or drug abuse in the last 5 years or daily consumption of alcohol > 40 gr/day for men or 24 gr/day for women.4.- Intake of any medication within 14 days prior to taking the study treatment (except for use of ibuprofen short-term symptomatic treatments, according to the investigator criteria), or intake of over-thecounter products (including natural food supplements, vitamins and medicinal plants products) within 7 days prior taking the study treatment. 5.- Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results. 6.- Positive results for abuse drugs in urine test or ethanol in breath test (Day-1). 7.- Background or clinical evidence of cardiovascular, respiratory, renal, hepatic, endocrine, gastrointestinal, haematological, neurological disease or other chronic diseases. 8.- Females with positive results from the pregnancy test or breast-feeding. 9.- Smoking within 6 months prior to the study treatment phase (Period 1, Day -1). Smokers must refrain from any tobacco usage, including smokeless tobacco, nicotine patches, electronic cigarettes, etc. at least for 6 months prior to study treatment. 10.- To have participated in another clinical trial during the 3 months prior to study start (screening visit) in which an investigational drug, medical device or a commercially available drug was tested. 11.- To have donated blood within the 4 weeks period before screening visit. 12.- Having undergone major surgery during the previous 6 months before screening visit, or have an intervention programmed during the study. 13.- Mentally or legally incapacitated at screening. 14.- Unwillingness or inability to follow the procedures outlined in the protocol. 15.- Volunteers who have difficulties in understanding the language in which the volunteer information is given. 16.- Any condition that, in the opinion of the investigator, may jeopardise the patient’s well-being or the trial conduct according to the protocol.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. · AUC0-t: Area under the plasma concentration-time curve from administration (t = 0) to the last observed concentration at time t (where t is the last time point with a measurable concentration) calculated according to the linear trapezoidal rule. · Cmax: Observed maximum plasma concentration (peak exposure).

Secondary endpoints 1

1. Secondary endpoints of bioavailability evaluated after the administration of a single dose will be: AUC0-∞, tmax, t1/2, lz, CL/F, V/F of paracetamol. Variables obtained in the safety evaluations will be also evaluated: adverse events recordings, vital signs, laboratory tests and ECG recordings.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Laboratorios Ern S.A.

Sponsor organisation

Laboratorios Ern S.A.

Address

Calle De Peru 228

City

Barcelona

Postcode

08020

Country

Spain

Scientific contact point

Organisation

Laboratorios Ern S.A.

Contact name

Francisco Jiménez Esteller

Public contact point

Organisation

Laboratorios Ern S.A.

Contact name

Francisco Jiménez Esteller

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 3 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications