Non-interaction Study Between Pregabalin and Tramadol, Administered Individually or Combination, in Healthy Subjects

NCT05389150 | Completed Phase 1

• 1 other identifier: BD PT-Sil No. 97-17
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The study was carried out in the Clinical Unit and Analytical Unit of the Department of Pharmacology and Toxicology of the Faculty of Medicine of the Universidad Autónoma de Nuevo León, with the aim of comparing the bioavailability (maximum concentration and area under the curve) of an oral formulation containing Pregabalin 150 mg/Tramadol 50 mg in combination with the two oral formulations Pregabalin 150 mg or Tramadol 50 mg administered as a single dose, in healthy subjects under fasting conditions.

Conditions

Healthy

Keywords

Pharmacokinetic; Bioavailability; Fixed dose combination; Pregabalin; Tramadol; Acute Pain

Outcome Measures

Primary Outcomes (6)

• Maximum observed concentration following the treatment (Cmax)

  Evaluate the pharmacokinetics profile of the fixed dose Pregabalin/Tramadol, employing the maximum observed concentration following the treatment (Cmax), obtained graphically, from the plasma concentration profile with respect to time.

  Baseline, 0.16, 0.33, 0.50, 1.00, 1.50, 2.0, 2.5, 3.0, 3.5, 4.0, 6.0, 10.0, 14.0, 24.0 and 36.0 hours.

• The area under the curve from time zero to the last measurable concentration (AUC 0-t)

  Evaluate the fixed dose pharmacokinetics profile of Pregabalin/Tramadol, employing the area under the curve from time zero to the last measurable concentration (AUC 0-t) using the linear trapezoidal method.

  Baseline, 0.16, 0.33, 0.50, 1.00, 1.50, 2.0, 2.5, 3.0, 3.5, 4.0, 6.0, 10.0, 14.0, 24.0 and 36.0 hours.

• The area under the curve from time zero to infinity calculated (AUC 0-inf)

  Evaluate the fixed dose pharmacokinetics profile of Pregabalin/Tramadol, employing the area under the curve from time zero to infinity calculated (AUC 0-inf).

  Baseline, 0.16, 0.33, 0.50, 1.00, 1.50, 2.0, 2.5, 3.0, 3.5, 4.0, 6.0, 10.0, 14.0, 24.0 and 36.0 hours.

• Time of the maximum measured concentration (Tmax)

  Evaluate the fixed dose pharmacokinetics profile of Pregabalin/Tramadol, employing time of the maximum measured concentration (tmax), Obtained graphically, from the plasma concentration profile with respect to time.

  Baseline, 0.16, 0.33, 0.50, 1.00, 1.50, 2.0, 2.5, 3.0, 3.5, 4.0, 6.0, 10.0, 14.0, 24.0 and 36.0 hours.

• Elimination rate (Ke)

  Evaluate the fixed dose pharmacokinetics profile of Pregabalin/Tramadol, employing the elimination rate (Ke), estimated from the terminal linear portion of the plasma concentration profile with respect to time (on a semi-log scale)

  Baseline, 0.16, 0.33, 0.50, 1.00, 1.50, 2.0, 2.5, 3.0, 3.5, 4.0, 6.0, 10.0, 14.0, 24.0 and 36.0 hours.

• Half time elimination (t1/2)

  Evaluate the pharmacokinetics profile of the fixed dose Pregabalina/Tramadol, employing the half time elimination (t1/2) by the quotient of Ln(2)Ke.

  Baseline, 0.16, 0.33, 0.50, 1.00, 1.50, 2.0, 2.5, 3.0, 3.5, 4.0, 6.0, 10.0, 14.0, 24.0 and 36.0 hours.

Secondary Outcomes (2)

• Frequency of occurrence of adverse events

  6 and 19 days

• Adverse events

  6 and 19 days

Study Arms (3)

Group A: Pregabalin/ Tramadol Fixed dose

EXPERIMENTAL

Pharmaceutical Form: Tablet Dosage: 150 mg / 50 mg Administration way: oral

Drug: Fixed dose combination Pregabalin 150 mg / Tramadol 50 mg

Group B: Pregabalin (Lyrica®)

ACTIVE COMPARATOR

Pharmaceutical Form: Capsule Dosage: 150 mg Administration way: oral

Drug: Pregabalin 150mg

Group C: Tramadol (Tradol®)

ACTIVE COMPARATOR

Pharmaceutical Form: Tablet Dosage: 50 mg Administration way: oral

Drug: Tramadol 50 mg

Interventions

Fixed dose combination Pregabalin 150 mg / Tramadol 50 mg DRUG

Pregabalin/Tramadol (Laboratorios Silanes S.A. de C.V.), Pharmaceutical Form: Tablet Dosage: 150 mg / 50 mg Administration way: oral

Also known as: P/T

Group A: Pregabalin/ Tramadol Fixed dose

Pregabalin 150mg DRUG

From Pfizer S.a. de C.V. Pharmaceutical Form: Capsule Dosage: 150 mg Administration way: oral

Also known as: Preg (Lyrica®)

Group B: Pregabalin (Lyrica®)

Tramadol 50 mg DRUG

From Grünenthal de México, S.A. de C.V. Pharmaceutical Form: Capsule Dosage: 50 mg Administration way: oral

Also known as: Tram (Tradol®)

Group C: Tramadol (Tradol®)

Eligibility Criteria

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

You may qualify if:

• The subjects must have been accepted by the COFEPRIS research subjects registration database.
• Subjects without a subordinate relationship with the researchers.
• Subjects who have given informed consent in writing.
• Subjects of both genders, aged between 18 and 55 years, Mexicans. - -Subjects with no background of hypersensitivity or allergies to the drug under study or related drugs.
• Body mass index between 18 and 27 kg/m2.
• Healthy subjects, according to the results of the complete clinical history, electrocardiogram and the integration of the results of the clinical analyses, carried out in certified clinical laboratories, without alterations that require a medical intervention as a consequence.
• Subjects with negative results for immunological tests (Anti-HIV, Anti-hepatitis B and C, VDRL).
• Subjects with negative results in drug abuse screening tests: tetrahydrocannabinoids, cocaine and amphetamines.
• Negative (qualitative) pregnancy test for women of childbearing potential without bilateral tubal obstruction or hysterectomy.
• In the case of women of childbearing age, they must have a birth control method, including barrier methods, non-hormonal intrauterine device, or bilateral tubal obstruction.

You may not qualify if:

• Subjects with recent history or physical examination evidence of gastrointestinal, renal, hepatic, endocrine, respiratory, cardiovascular, dermatological, or hematological disease that could affect the pharmacokinetic study of the product in research.
• Subjects who have been exposed to drugs known as liver enzyme inducers or inhibitors or who have taken drugs potentially toxic within 30 days before the start of the study.
• Subjects who have received any medication during the 7 days before the start of the study.
• Subjects who have been hospitalized for any problem during the three months before the start of the study.
• Subjects who have been rejected by the registry database of research subjects of COFEPRIS, for having participated in a clinical study within the three months prior to the start of the study.
• Subjects who have received investigational drugs within the previous 60 days th the start of the study.
• Subjects allergic to the study drug or related drugs.
• Subjects who have ingested alcohol or drinks containing xanthines (coffee, tea, cocoa, chocolate, cola) or who have eaten charcoal-grilled food or grapefruit juice , at least 10 hours before the start of the study or who have smoked tobacco 24 hours before to the start of the internment period.
• Subjects who have donated or lost 450 mL or more of blood within the previous 60 days of the beginning of the study.
• Subjects with a history of drug and/or alcohol abuse according to the DSM-IV-TR Criteria.
• Research subjects who presents alterations in the vital signs recorded during the selection.
• Subjects who have consumed grapefruit or cranberry juice in the 10 hours prior to the study.
• Research subject with alterations of the vital signs recorded during the selection.

Sponsors & Collaborators

• Laboratorios Silanes S.A. de C.V.: lead

Study Sites (1)

Laboratorio Silanes, S.A. de C.V.

Mexico City, Mexico City, 11000, Mexico

Location

Related Publications (7)

• Patel BN, Sharma N, Sanyal M, Shrivastav PS. An accurate, rapid and sensitive determination of tramadol and its active metabolite O-desmethyltramadol in human plasma by LC-MS/MS. J Pharm Biomed Anal. 2009 Feb 20;49(2):354-66. doi: 10.1016/j.jpba.2008.10.030. Epub 2008 Nov 5.

  PMID: 19062215 BACKGROUND

• Filipe A, Almeida S, Pedroso PF, Neves R, Marques S, Sicard E, Massicotte J, Ortuno J. Single-Dose, Randomized, Open-Label, Two-Way, Crossover Bioequivalence Study of Two Formulations of Pregabalin 300 mg Hard Capsules in Healthy Volunteers Under Fasting Conditions. Drugs R D. 2015 Jun;15(2):195-201. doi: 10.1007/s40268-015-0094-8.

  PMID: 25939332 BACKGROUND

• Zhou X, Liu J. Fluorescence detection of tramadol in healthy Chinese volunteers by high-performance liquid chromatography and bioequivalence assessment. Drug Des Devel Ther. 2015 Feb 26;9:1225-31. doi: 10.2147/DDDT.S73723. eCollection 2015.

  PMID: 25750519 BACKGROUND

• Ben-Menachem E. Pregabalin pharmacology and its relevance to clinical practice. Epilepsia. 2004;45 Suppl 6:13-8. doi: 10.1111/j.0013-9580.2004.455003.x.

  PMID: 15315511 BACKGROUND

• Zareba G. Pregabalin: a new agent for the treatment of neuropathic pain. Drugs Today (Barc). 2005 Aug;41(8):509-16. doi: 10.1358/dot.2005.41.8.910482.

  PMID: 16234874 BACKGROUND

• Silva Mde F, Schramm SG, Kano EK, Mori Koono EE, Porta V, dos Reis Serra CH. Bioequivalence evaluation of single doses of two tramadol formulations: a randomized, open-label, two-period crossover study in healthy Brazilian volunteers. Clin Ther. 2010 Apr;32(4):758-65. doi: 10.1016/j.clinthera.2010.03.016.

  PMID: 20435245 BACKGROUND

• Liu P, Liang S, Wang BJ, Guo RC. Development and validation of a sensitive LC-MS method for the determination of tramadol in human plasma and urine. Eur J Drug Metab Pharmacokinet. 2009 Jul-Sep;34(3-4):185-92. doi: 10.1007/BF03191172.

  PMID: 20166437 BACKGROUND

MeSH Terms

Conditions

Acute Pain

Interventions

Tramadol; Pregabalin

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cyclohexanols; Hexanols; Fatty Alcohols; Alcohols; Organic Chemicals; Dimethylamines; Methylamines; Amines; Lipids; gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Lourdes Garza Ocaña, M.D

  Department of Pharmacology and Toxicology of the Faculty of Medicine of the U.A.N.L

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2022
• First Posted: May 25, 2022
• Study Start: January 17, 2019
• Primary Completion: February 5, 2019
• Study Completion: March 27, 2019
• Last Updated: November 13, 2024

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1)