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Efavirenz Comparative Bioavailability (efv600)

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ClinicalTrials.gov Identifier: NCT01704898
Recruitment Status : Completed
First Posted : October 12, 2012
Last Update Posted : August 14, 2013
Sponsor:
Collaborator:
University of the Republic, Uruguay
Information provided by (Responsible Party):
Francisco E. Estevez-Carrizo, M.D., Center for Clinical Pharmacology Research Bdbeq S.A.

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.

Condition or disease Intervention/treatment Phase
Healthy Drug: Efavirenz 600 Test-Stocrin 600 Reference Drug: Stocrin 600 Reference-Efavirenz 600 Test Phase 4

Detailed Description:

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (Investigator)
Primary Purpose: Treatment
Official Title: Comparative Bioavailability Study of Two Efavirenz 600 mg Formulations in Healthy Volunteers.
Study Start Date : April 2013
Actual Primary Completion Date : June 2013
Actual Study Completion Date : August 2013

Resource links provided by the National Library of Medicine

Drug Information available for: Efavirenz

Arm Intervention/treatment
Efavirenz 600 Test-Stocrin 600 Reference
Efavirenz 600 mg will be randomly assigned.
Drug: Efavirenz 600 Test-Stocrin 600 Reference
Stocrin 600 Reference-Efavirenz 600 Test
Stocrin 600 mg will be randomly assigned.
Drug: Stocrin 600 Reference-Efavirenz 600 Test



Primary Outcome Measures :
  1. Area Under the Curve for efavirenz (AUC0-192) [ Time Frame: 0 to 192 h ]
    The area under the concentration-time curve (AUC0-192) for efavirenz in a time frame of 8 days.

  2. Maximum Concentration for efavirenz (Cmax) [ Time Frame: 0 to 192 h ]
    The maximum concentration taken form the curve concentration vs. time for efavirenz.

  3. Area Under the Curve 0 to infinity for efavirenz (AUC0-inf) [ Time Frame: 0 to infinity ]
    Area under the concentration-time curve from time 0 to infinity for efavirenz.


Secondary Outcome Measures :
  1. Time to the Cmax for efavirenz (tmax) [ Time Frame: 0 to 192 h ]
    It is the time elapsed from 0 time to the Cmax time for efavirenz


Other Outcome Measures:
  1. First order elimination rate constant for efavirenz (Ke) [ Time Frame: 0 to 192 h ]
    It is the firs order efavirenz elimination rate constant, calculated from the final elimination phase of the curve concentration vs. time.

  2. Elimination Half Life (T1/2e) [ Time Frame: 0-92 h ]
    This outcome measures the rate of drug elimination form the body.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01704898


Locations
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Uruguay
Center for Cllinical Pharmacology Research-Bdbeq S.A.
Montevideo, Uruguay, 11600
Sponsors and Collaborators
Center for Clinical Pharmacology Research Bdbeq S.A.
University of the Republic, Uruguay
Investigators
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Principal Investigator: Francisco E. Estevez, M.D. Center for Clinical Pharmacology Research Bdbeq S.A.

Publications:
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Responsible Party: Francisco E. Estevez-Carrizo, M.D., Chief Medical Officer, Center for Clinical Pharmacology Research Bdbeq S.A.
ClinicalTrials.gov Identifier: NCT01704898     History of Changes
Other Study ID Numbers: bdbeq-efv600/icuvita-020
First Posted: October 12, 2012    Key Record Dates
Last Update Posted: August 14, 2013
Last Verified: August 2013
Keywords provided by Francisco E. Estevez-Carrizo, M.D., Center for Clinical Pharmacology Research Bdbeq S.A.:
efavirenz
bioequivalence
fasting
healthy volunteers
Additional relevant MeSH terms:
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Efavirenz
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP2C9 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 CYP2C19 Inhibitors
Cytochrome P-450 CYP2B6 Inducers
Cytochrome P-450 Enzyme Inducers
Cytochrome P-450 CYP3A Inducers