HealthyPhase 4efv600NCT01704898
Efavirenz Comparative Bioavailability
A Phase 4 study testing Efavirenz 600 Test-Stocrin 600 Reference and Stocrin 600 Reference-Efavirenz 600 Test in people with Healthy, run by Center for Clinical Pharmacology Research Bdbeq S.A. at 1 site in Uruguay.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 50 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Efavirenz 600 Test-Stocrin 600 Reference and Stocrin 600 Reference-Efavirenz 600 Test
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUruguay
- Study dates
- Apr 2013to Aug 2013
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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,
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- Non/light-smoking,
- Lab screening and EKG within the limits stipulated in the protocol.
- Healthy as determine by medical examination.
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country.
Uruguay1 site
Center for Cllinical Pharmacology Research-Bdbeq S.A.
Montevideo, Montevideo Department, 11600
About this study
Official title: Comparative Bioavailability Study of Two Efavirenz 600 mg Formulations in Healthy Volunteers.
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.
Read the 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.
- Conditions
- Healthy
- Being tested
- Efavirenz 600 Test-Stocrin 600 Reference, Stocrin 600 Reference-Efavirenz 600 Test
- Keywords
- efavirenz, bioequivalence, fasting, healthy volunteers
- Medical subject headings
- Fasting
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Efavirenz 600 Test-Stocrin 600 ReferenceDrug
Stocrin 600 Reference-Efavirenz 600 TestDrug
| Study group | Role | What they receive |
|---|---|---|
| Efavirenz 600 Test-Stocrin 600 Reference | Other | Efavirenz 600 mg will be randomly assigned. Receives: Drug: Efavirenz 600 Test-Stocrin 600 Reference |
| Stocrin 600 Reference-Efavirenz 600 Test | Other | Stocrin 600 mg will be randomly assigned. Receives: Drug: Stocrin 600 Reference-Efavirenz 600 Test |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 0 to 192 h
Maximum Concentration for efavirenz (Cmax)
The maximum concentration taken form the curve concentration vs. time for efavirenz.
Measured: 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.
Measured: 0 to infinity
Secondary outcomes (1)
Time to the Cmax for efavirenz (tmax)
It is the time elapsed from 0 time to the Cmax time for efavirenz
Measured: 0 to 192 h
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Oct 2012 (estimated)
- Study startApr 2013
- Primary completionJun 2013
- Study completionAug 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Center for Clinical Pharmacology Research Bdbeq S.A.
- Sponsor type
- University, hospital or other
- Collaborators
- University of the Republic, Uruguay
- Responsible party
- Principal investigator, Francisco E. Estevez-Carrizo, M.D., Center for Clinical Pharmacology Research Bdbeq S.A.
- Investigators
- Francisco E. Estevez, M.D., Principal investigator, Center for Clinical Pharmacology Research Bdbeq S.A.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01704898
- Sponsor's protocol ID
- bdbeq-efv600/icuvita-020
- Acronym
- efv600
- Status last verified
- Aug 2013
- First submitted
- 9 Oct 2012
- Last updated
- 14 Aug 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 20101064Mathias 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.
PubMed 17667331Frampton 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.
PubMed 16906786Marier 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.
PubMed 16625987
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparative Bioavailability Study of Two Efavirenz 600 mg Formulations in Healthy Volunteers.
- ClinicalTrials.gov ID
- NCT01704898
- Acronym / sponsor ID
- efv600 / bdbeq-efv600/icuvita-020
- Conditions
- Healthy
- Keywords
- efavirenz, bioequivalence, fasting, healthy volunteers
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Center for Clinical Pharmacology Research Bdbeq S.A.University, hospital or other
- Collaborators
- University of the Republic, Uruguay
- Study start
- Apr 2013
- Primary completion
- Jun 2013 (actual)
- Study completion
- Aug 2013 (actual)
- First posted
- 12 Oct 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Efavirenz 600 Test-Stocrin 600 Reference | Other | Drug: Efavirenz 600 Test-Stocrin 600 ReferenceEfavirenz 600 mg will be randomly assigned. |
| Stocrin 600 Reference-Efavirenz 600 Test | Other | Drug: Stocrin 600 Reference-Efavirenz 600 TestStocrin 600 mg will be randomly assigned. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Male,
- Caucasians
- Age >=18 and <=50,
- BMI>18 and BMI<30 kg/m2
- HIV-1 negative, B Hepatitis negative, C Hepatitis negative.
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 |
Primary outcome
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.
Maximum Concentration for efavirenz (Cmax)
Time frame: 0 to 192 h
The maximum concentration taken form the curve concentration vs. time for efavirenz.
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.
1 secondary outcome
Time to the Cmax for efavirenz (tmax)
Time frame: 0 to 192 h
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Aug 2013.
- Background: PubMed 20101064Kaul 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.
- Background: PubMed 17667331Mathias 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.
- Background: PubMed 16906786Frampton 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.
- Background: PubMed 16625987Marier 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Francisco E. Estevez, M.D. principal investigator
Center for Clinical Pharmacology Research Bdbeq S.A.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Efavirenz 600 Test-Stocrin 600 Reference and Stocrin 600 Reference-Efavirenz 600 Test in people with Healthy, run by Center for Clinical Pharmacology Research Bdbeq S.A. at 1 site in Uruguay.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Aug 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Uruguay. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area Under the Curve for efavirenz (AUC0-192) (time frame: 0 to 192 h). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01704898, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Aug 2013.