Efavirenz Comparative Bioavailability

NCT01704898 | Completed Phase 4

• 1 other identifier: bdbeq-efv600/icuvita-020
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study is to determine the average bioequivalence of a generic efavirenz 600 mg tablet (test formulation)compared with Stocrin(R) 600 mg tablets (Reference formulation).The study is designed as an open label, randomized, crossover, 2-treatments, 2-period, 2-sequence, single dose pharmacokinetic study conducted in healthy volunteers. Subjects will be randomized to receive generic efavirenz 600 (Test formulation) or Stocrin(R) 600 tablets (Reference formulation)on study day 1 (period 1). Subjects will undergo a 24 hour intensive pharmacokinetic evaluation after ingesting a single dose of either the Test or Reference formulation. Subjects will provide additional pharmacokinetic samples 36, 48, 72, 120 and 192 hours postdose, respectively. Subjects will complete a wash out period from day 8 to day 28 during wich no study drug will be ingested. On day 29 subjects will ingest either the Test or the Reference formulation (opposite to the formulation received on period 1). All subjects undergo another 24 hour intensive pharmacokinetic evaluation and pharmacokinetics samples on days 36, 48, 72, 120, 192 pos dose, respectively. Adverse events and and concomitant medication will be documented throughout the study.

Conditions

Healthy

Keywords

efavirenz; bioequivalence; fasting; healthy volunteers

Outcome Measures

Primary Outcomes (3)

• Area Under the Curve for efavirenz (AUC0-192)

  The area under the concentration-time curve (AUC0-192) for efavirenz in a time frame of 8 days.

  0 to 192 h

• Maximum Concentration for efavirenz (Cmax)

  The maximum concentration taken form the curve concentration vs. time for efavirenz.

  0 to 192 h

• Area Under the Curve 0 to infinity for efavirenz (AUC0-inf)

  Area under the concentration-time curve from time 0 to infinity for efavirenz.

  0 to infinity

Secondary Outcomes (1)

• Time to the Cmax for efavirenz (tmax)

  0 to 192 h

Other Outcomes (2)

• First order elimination rate constant for efavirenz (Ke)

  0 to 192 h

• Elimination Half Life (T1/2e)

  0-92 h

Study Arms (2)

Efavirenz 600 Test-Stocrin 600 Reference

OTHER

Efavirenz 600 mg will be randomly assigned.

Drug: Efavirenz 600 Test-Stocrin 600 Reference

Stocrin 600 Reference-Efavirenz 600 Test

OTHER

Stocrin 600 mg will be randomly assigned.

Drug: Stocrin 600 Reference-Efavirenz 600 Test

Interventions

Efavirenz 600 Test-Stocrin 600 Reference DRUG

Efavirenz 600 Test-Stocrin 600 Reference

Stocrin 600 Reference-Efavirenz 600 Test DRUG

Stocrin 600 Reference-Efavirenz 600 Test

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male,
• Caucasians
• Age \>=18 and \<=50,
• BMI\>18 and BMI\<30 kg/m2
• HIV-1 negative, B Hepatitis negative, C Hepatitis negative.
• Able to give consent,
• Non/light-smoking,
• Lab screening and EKG within the limits stipulated in the protocol.
• Healthy as determine by medical examination.

You may not qualify if:

• Subjects with any current or past history of psychiatric disorder.
• Subjects receiving any prescription or over-the-counter product.
• Subjects using any form of recreational drug.
• Subjects who has eaten grapefruit or drunk grapefruit juice during the last 15 days before administration of study drug.
• Subjects who had had xanthine containing beverages (mate, coffee, tea, chocolate, etc.) during 48 ours previous to study drug administration.
• Subjects with history of hepatic disease, renal disease, GI diseases, chronic infectious disease, heart disease, lung disease, neurologic disease, endocrine disease, etc.
• Subjects suffering any acute disease at screening or check-in.
• Alanine S. Transaminase(AST)/Alanine L. Transaminase(ALT) \> 3 times upper limit of normal (ULN).
• Bilirubin \> 2.5 times ULN.
• Amylase \> 2 times ULN.
• Absolute Neutrophil Count \<1000/mL.
• Hgb \< 9.0 g/dl.
• Platelets \> 50.000 cell/mm3,
• Serum Creatinine \> 2.5 mg/dl

Sponsors & Collaborators

• Center for Clinical Pharmacology Research Bdbeq S.A.: lead
• University of the Republic, Uruguay: collaborator

Study Sites (1)

Center for Cllinical Pharmacology Research-Bdbeq S.A.

Montevideo, Montevideo Department, 11600, Uruguay

Location

Related Publications (4)

• Kaul S, Ji P, Lu M, Nguyen KL, Shangguan T, Grasela D. Bioavailability in healthy adults of efavirenz capsule contents mixed with a small amount of food. Am J Health Syst Pharm. 2010 Feb 1;67(3):217-22. doi: 10.2146/ajhp090327.

  PMID: 20101064 BACKGROUND

• Mathias AA, Hinkle J, Menning M, Hui J, Kaul S, Kearney BP; Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate Single-Tablet Regimen Development Team. Bioequivalence of efavirenz/emtricitabine/tenofovir disoproxil fumarate single-tablet regimen. J Acquir Immune Defic Syndr. 2007 Oct 1;46(2):167-73. doi: 10.1097/QAI.0b013e3181427835.

  PMID: 17667331 BACKGROUND

• Frampton JE, Croom KF. Efavirenz/emtricitabine/tenofovir disoproxil fumarate: triple combination tablet. Drugs. 2006;66(11):1501-12; discussion 1513-4. doi: 10.2165/00003495-200666110-00012.

  PMID: 16906786 BACKGROUND

• Marier JF, Morin I, Al-Numani D, Stiles M, Morelli G, Tippabhotla SK, Vijan T, Singla AK, Garg M, Di Marco M, Monif T. Comparative bioavailability of a generic capsule formulation of the reverse transcriptase inhibitor efavirenz and the innovator product. Int J Clin Pharmacol Ther. 2006 Apr;44(4):180-4. doi: 10.5414/cpp44180.

  PMID: 16625987 BACKGROUND

MeSH Terms

Conditions

Fasting

Condition Hierarchy (Ancestors)

Feeding Behavior; Behavior

Study Officials

• Francisco E. Estevez, M.D.

  Center for Clinical Pharmacology Research Bdbeq S.A.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Medical Officer

Study Record Dates

• First Submitted: October 9, 2012
• First Posted: October 12, 2012
• Study Start: April 1, 2013
• Primary Completion: June 1, 2013
• Study Completion: August 1, 2013
• Last Updated: August 14, 2013

Record last verified: 2013-08

Locations

UR (1)