Bioequivalence Study of Tramadol Hydrochloride /Paracetamol Tablets Versus Ultracet Tablets

NCT03803371 | Completed Phase 4

• 1 other identifier: B4741005
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The sponsor, Pfizer has developed a formulation of tramadol hydrochloride/ paracetamol 37.5 mg/ 325 mg (test drug) as a generic alternative to the reference listed product Ultracet®. In order to meet the requirements for registration as a generic drug, this study is being conducted to demonstrate the bioequivalence between the formulation of tramadol hydrochloride/ paracetamol 37.5 mg/ 325 mg provided by Pfizer and the reference drug tramadol hydrochloride/ paracetamol 37.5 mg/ 325 mg, available in the pharmaceutical market in Brazil (Ultracet®, Janssen Cilag Farmacêutica Ltda).

Conditions

Healthy

Outcome Measures

Primary Outcomes (2)

• Area under the tramadol and paracetamol plasma concentration-time curve from time zero to last time point (AUClast)

  Predose (0 hour), at 0.08, 0.16, 0.25, 0.33, 0.41, 0.50, 0.66, 0.83, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12, 24 and 36 hours post dose

• Maximum plasma concentrations of tramadol and paracetamol (Cmax)

  Predose (0 hour), at 0.08, 0.16, 0.25, 0.33, 0.41, 0.50, 0.66, 0.83, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12, 24 and 36 hours post dose

Secondary Outcomes (3)

• Area under the tramadol and paracetamol plasma concentration-time curve from time zero extrapolated to infinite time

  Predose (0 hour), at 0.08, 0.16, 0.25, 0.33, 0.41, 0.50, 0.66, 0.83, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12, 24 and 36 hours post dose

• Time to first occurrence of Cmax (Tmax) of tramadol and paracetamol

  Predose (0 hour), at 0.08, 0.16, 0.25, 0.33, 0.41, 0.50, 0.66, 0.83, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12, 24 and 36 hours post dose

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  Predose (0 hour), at 0.08, 0.16, 0.25, 0.33, 0.41, 0.50, 0.66, 0.83, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12, 24 and 36 hours post dose

Study Arms (2)

Tramadol hydrochloride 37.5 mg/Paracetamol 325 mg tablets

EXPERIMENTAL

Tramadol hydrochloride 37.5 mg/Paracetamol 325 mg tablets by mouth on Day 1 of period 1 or 2

Drug: Tramadol hydrochloride 37.5 mg/Paracetamol 325 mg tablets - tablet (Pfizer)

Ultracet tablet

ACTIVE COMPARATOR

Ultracet tablet (Tramadol hydrochloride 37.5 mg/Paracetamol 325 mg) by mouth on Day 1 of period 1 or 2

Drug: Ultracet Tablets

Interventions

Ultracet Tablets DRUG

Ultracet tablet (Janssen Cilag Farmacêutica Ltda) equivalent to Tramadol hydrochloride 37.5 mg/Paracetamol 325 mg

Also known as: Reference drug

Ultracet tablet

Tramadol hydrochloride 37.5 mg/Paracetamol 325 mg tablets - tablet (Pfizer) DRUG

Tramadol hydrochloride 37.5 mg/Paracetamol 325 mg tablets (Pfizer)

Also known as: Test Drug

Tramadol hydrochloride 37.5 mg/Paracetamol 325 mg tablets

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• \. Healthy female research subjects and/or male research subjects who, at the time of screening, are between the ages of 18 and 55 years, inclusive.
• Female subjects of nonchildbearing potential must meet at least 1 of the following criteria:
• Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause, and have a serum follicle stimulating hormone (FSH) level confirming the postmenopausal state;
• Have undergone a documented hysterectomy and/or bilateral oophorectomy;
• Have medically confirmed ovarian failure. All other female subjects (including female subjects with tubal ligations) are considered to be of childbearing potential.
• \. Body mass index (BMI) of 18.5 kg/m2 to 24.9 kg/m2 (the upper limit may vary up to 15% to allow subjects with a BMI from 18.5 kg/m2 to 28.6 kg/m2 to participate), and a total body weight \>50 kg (\>110 lbs).
• \. Evidence of a personally signed and dated informed consent document indicating that the research subject has been informed of all pertinent aspects of the study.
• \. Research subjects who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures

You may not qualify if:

• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).
• Clinically significant infections within the past 3 months (eg, those requiring hospitalization or parenteral antibiotics, or as judged by the Investigator), evidence of any infection within the past 7 days, history of disseminated herpes simplex infection or recurrent or disseminated herpes zoster.
• Any condition possibly affecting drug absorption (eg, gastrectomy, colon resection, etc.).
• Research subjects with a history of, or current evidence for, severe gastrointestinal narrowing (pathologic or iatrogenic).
• History of or current positive results for any of the following serological tests: hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), anti hepatitis C core antibody (HCV Ab), or human immunodeficiency virus (HIV) 1 and 2.
• Malignancy or a history of malignancy
• A positive urine drug test.
• A positive alcohol screen.
• History of regular alcohol consumption exceeding 14 drinks/week for female subjects or 21 drinks/week for male subjects \[1 drink = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor\] within 6 months before screening.
• Use of tobacco or nicotine containing products in excess of the equivalent of 5 cigarettes per day.
• Treatment with an investigational drug within 6 months or 4 or 5 half lives preceding the first dose of investigational product (whichever is longer).
• Pregnant female subjects, breastfeeding female subjects, fertile male subjects and female subjects of childbearing potential who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol from at least 14 days prior to the first dose of investigational product until at least 28 days after the last dose of investigational product.
• Use of prescription or nonprescription drugs and dietary supplements within 14 days or 5 half lives (whichever is longer) prior to the first dose of investigational product. Limited use of non prescription medications that are not believed to affect research subject safety or the overall results of the study may be permitted on a case by case basis following approval by the sponsor.
• Herbal supplements, hormonal methods of contraception (including oral and transdermal contraceptives, injectable progesterone, progestin subdermal implants, progesterone releasing intrauterine devices \[IUDs\], vaginal ring, and postcoital contraceptive methods), and hormone replacement therapy must have been discontinued at least 28 days prior to the first dose of investigational product.
• Consumption of grapefruit or grapefruit related citrus fruits (eg, Seville oranges, pomelos) or juices within 7 days prior to dosing.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

ICF - Instituto de Ciencias Farmaceuticas de Estudos e Pesquisas Ltda

Aparecida de Goiânia, Goiás, 74935-530, Brazil

Location

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Interventions

Ultracet; Tramadol; Acetaminophen; Tablets; Drug Evaluation

Intervention Hierarchy (Ancestors)

Cyclohexanols; Hexanols; Fatty Alcohols; Alcohols; Organic Chemicals; Dimethylamines; Methylamines; Amines; Lipids; Acetanilides; Anilides; Amides; Aniline Compounds; Dosage Forms; Pharmaceutical Preparations; Drug Development; Investigative Techniques; Evaluation Studies as Topic

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 2, 2019
• First Posted: January 14, 2019
• Study Start: March 26, 2019
• Primary Completion: June 28, 2019
• Study Completion: June 28, 2019
• Last Updated: July 17, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will share

Locations

BR (1)