Bioequivalence Study Between Lamivudine Formulations in the Form of Coated Tablet of 150 mg in Healthy Volunteers

HIV INFECTIONS Clinical Trial

Official title:

Bioequivalence Study Between Lamivudine Formulations in the Form of Coated Tablet 150 mg (Test) and EPIVIR of Glaxosmithkline in Healthy Volunteers of Both Genders in Fasting Condition

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02604004
• Other study ID #: NUD_04_12
• Status: Completed
• Phase: Phase 1
• First received: November 5, 2015
• Last updated: November 10, 2015
• Start date: April 2013
• Est. completion date: December 2013

Study information

• Verified date: November 2015
• Source: Universidade Federal de Pernambuco
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

The objective of this research is to check whether the test drug (lamivudine in the form of coated tablet 150 mg) achieves plasma levels equivalent to those obtained from the EPIVIR in the form of coated tablet 150 mg GlaxoSmithKline administered to 28 volunteers of both genres under fasting condition.

Description:

It is an open, randomized, crossover 2x2, single dose, with the administration of medicine with 28 healthy volunteers, adults aged 18-50 years, of both genders (14 males and 14 females). Of the 28 volunteers planned in the study protocol to start, gave up one (woman) before the start of Phase I. So the study was initiated and completed with the participation of 27 volunteers. The volunteers were in hospital for a period of approximately 36 hours in each stage.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• Considered healthy after undergoing a clinical evaluation;

• Agree freely and sign the Recruitment and Informed Consent Term, after all the content of the protocol was clear before any procedure;

• Present the body mass index greater than 19 and less than 30.

Exclusion Criteria:

• Results of laboratory tests outside the range considered normal, unless they were considered clinically irrelevant;

• Allergic to lamivudine or any other drug;

• Positive outcome of the pre-admission pregnancy test;

• Regular medication within four (4) weeks prior to the start of the study or use of any medication to present interaction with lamivudine one week before the start of the study;

• Use abusive alcoholic beverage;

• Use of illicit drugs and tobacco;

• History of liver disease, renal, pulmonary, gastrointestinal, epileptic, hematologic or psychiatric; hypo- or hypertension of any cause that required pharmacological treatment; myocardial infarction, angina and / or heart failure;

Study Design

Allocation: Randomized, Endpoint Classification: Bio-equivalence Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• HIV INFECTIONS

Intervention

Drug:
• Epivir ® tablet 150-mg single dose (drug reference)
Bioequivalence lamivudine 150 mg tablets fasting condition
• Lamivudine 150-mg tablet single dose (drug test)
Bioequivalence lamivudine 150 mg tablets fasting condition

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Universidade Federal de Pernambuco

References & Publications (22)

ANVISA. "Guia para planejamento e realização da etapa estatística de estudos de Biodisponibilidade relativa / Bioequivalência". RE Nº. 898, de 29 de maio de 2003.

ANVISA. Manual de Boas Práticas em Biodisponibilidade/ Bioequivalência. Volume I. Agência Nacional de Vigilância Sanitária. Brasília: ANVISA, 2002.

ANVISA. Resolução RE nº 1170, de 19 de abril de 2006. "Guia para provas de biodisponibilidade relativa/ bioequivalência de medicamentos". ANVISA-MS, Brasília.

ANVISA. Resolução RE nº 899, de 29 de maio de 2003. "Guia para validação de métodos analíticos e bioanalíticos". ANVISA-MS, Brasília.

Bigos KL, Pollock BG, Stankevich BA, Bies RR. Sex differences in the pharmacokinetics and pharmacodynamics of antidepressants: an updated review. Gend Med. 2009 Dec;6(4):522-43. doi: 10.1016/j.genm.2009.12.004. Review. — View Citation

Center for Drug Evaluation and Research, US Food and Drug Administration. Guidance for Industry: Bioavailability and Bioequivalence Studies for Orally Administered Drug Products-General Considerations [COER Web site). http://www.fda.gov/cder/guidance/5356

EMEA (European Agency for the Evaluation of Medicinal Products). CPMP (Committee for Propietary Medicinal Products). Note for guidance on the investigation of bioavailability and bioequivalence. London, July 2001.

FLOCKHART D. A. Drug interactions: Cytochrome P450 drug interaction table. Indiana School of Medicine. 2007. http://medicine.iupui.edu/clinpharm/ddis/ table.asp. Accessed December 1, 2009.

Goodman & Gilman's The Pharmacologic Basis of Therapeutics - 11th Ed. (2006)

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http://www4.anvisa.gov.br/base/visadoc/BM/BM[25676-1-0].PDF acessado em 13/10/2011.

Johnson MA, Moore KH, Yuen GJ, Bye A, Pakes GE. Clinical pharmacokinetics of lamivudine. Clin Pharmacokinet. 1999 Jan;36(1):41-66. Review. — View Citation

Kano EK, dos Reis Serra CH, Koono EE, Andrade SS, Porta V. Determination of lamivudine in human plasma by HPLC and its use in bioequivalence studies. Int J Pharm. 2005 Jun 13;297(1-2):73-9. Epub 2005 Apr 26. — View Citation

Martindale The Complete Drug Reference - Thirty-sixth edition (2009).

Narang VS, Lulla A, Malhotra G, Purandare S. Pharmacokinetic profiling and bioequivalence evaluation of 2 lamivudine tablet formulations after single oral administration in healthy human Indian volunteers. J Acquir Immune Defic Syndr. 2005 Apr 15;38(5):56 — View Citation

Ofotokun I, Chuck SK, Hitti JE. Antiretroviral pharmacokinetic profile: a review of sex differences. Gend Med. 2007 Jun;4(2):106-19. Review. — View Citation

Perry CM, Faulds D. Lamivudine. A review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy in the management of HIV infection. Drugs. 1997 Apr;53(4):657-80. Review. — View Citation

Pluda JM, Cooley TP, Montaner JS, Shay LE, Reinhalter NE, Warthan SN, Ruedy J, Hirst HM, Vicary CA, Quinn JB, et al. A phase I/II study of 2'-deoxy-3'-thiacytidine (lamivudine) in patients with advanced human immunodeficiency virus infection. J Infect Dis — View Citation

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van Leeuwen R, Katlama C, Kitchen V, Boucher CA, Tubiana R, McBride M, Ingrand D, Weber J, Hill A, McDade H, et al. Evaluation of safety and efficacy of 3TC (lamivudine) in patients with asymptomatic or mildly symptomatic human immunodeficiency virus infe — View Citation

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* Note: There are 22 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AUClast	Area under the Plasma concentration-time curve from time Zero to last time (AUCinf) of lamivudine in plasma.	Up to 36 hours	No
Secondary	Cmax	Maximum concentration (Cmax) of lamivudine in plasma.	Up to 36 hours	No
Secondary	Tmax	Time for Maximum concentration (Tmax) of lamivudine in plasma.	Up to 36 hours	No
Secondary	T1/2	Terminal half-time of lamivudine in plasma.	Up to 72 hours	No
Secondary	AUCinf	Area under the Plasma concentration-time curve from time Zero to infinity (AUCinf) of lamivudine in plasma.	Up to 36 hours	No