Efavirenz Comparative Bioavailability

NCT ID: NCT01704898

Last Updated: 2013-08-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

12 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-04-30

Study Completion Date

2013-08-31

Brief Summary

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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.

Detailed Description

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The primary objective of this study is to determine the average bioequivalence of 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), then they will undergo a 24 hour intensive pharmacokinetic evaluation after ingesting a single dose of either the Test or Reference formulation. Additional pharmacokinetic samples 36, 48, 72, 120 and 192 hours postdose will be drawn.

Subjects will complete a wash out period form day 8 to day 28 during which no study drug will be ingested. On day 29 (period 2) they 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, will be drawn. Adverse events and concomitant medication will be documented throughout the study.

The sample size is 28 and is based on a 15% dropout rate (due to lost to follow-up, treatment discontinuation, etc.) Since the investigators are expecting four subjects not to complete the study,24 evaluable subjects are finally expected. If the discontinuation rate is greater than 15%, the investigators will continue to enroll until they get 24 evaluable subjects.

The primary endpoint is to determine average bioequivalence for Test and Reference formulation of efavirenz according to the FDA guidance on bioequivalence testing. The ratio of the Test to Reference formulation mean for efavirenz AUC0-192, AUC0-inf and Cmax and the 90% confidence interval around each mean ratio will be determined. Average bioequivalence will be met if 90% confidence interval around de AUC and Cmax mean ratios for efavirenz falls within the FDA's predefined limits of 0.80 to 1.25.

Safety will be evaluated by administering a questionnaire to the subjects during the study . This questionnaire will list the most frequent adverse effects already described for the innovator (Stocrin(R)). Safety will also be evaluated from vital signs recordings, lab tests out of the limits fixed in the study protocol and Psychiatric Evaluations during screening, in the wash out period and 15 days after the last administration of the study medication.

Conditions

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Healthy

Keywords

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efavirenz bioequivalence fasting healthy volunteers

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Investigators

Study Groups

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Efavirenz 600 Test-Stocrin 600 Reference

Efavirenz 600 mg will be randomly assigned.

Group Type OTHER

Efavirenz 600 Test-Stocrin 600 Reference

Intervention Type DRUG

Stocrin 600 Reference-Efavirenz 600 Test

Stocrin 600 mg will be randomly assigned.

Group Type OTHER

Stocrin 600 Reference-Efavirenz 600 Test

Intervention Type DRUG

Interventions

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Efavirenz 600 Test-Stocrin 600 Reference

Intervention Type DRUG

Stocrin 600 Reference-Efavirenz 600 Test

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes

Sponsors

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University of the Republic, Uruguay

OTHER

Sponsor Role collaborator

Center for Clinical Pharmacology Research Bdbeq S.A.

OTHER

Sponsor Role lead

Responsible Party

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Francisco E. Estevez-Carrizo, M.D.

Chief Medical Officer

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Francisco E. Estevez, M.D.

Role: PRINCIPAL_INVESTIGATOR

Center for Clinical Pharmacology Research Bdbeq S.A.

Locations

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Center for Cllinical Pharmacology Research-Bdbeq S.A.

Montevideo, Montevideo Department, Uruguay

Site Status

Countries

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Uruguay

References

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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.

Reference Type BACKGROUND
PMID: 20101064 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17667331 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16906786 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16625987 (View on PubMed)

Other Identifiers

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bdbeq-efv600/icuvita-020

Identifier Type: -

Identifier Source: org_study_id