HIVPhase 1NCT02499874
SSAT063- Pharmacokinetics of Efavirenz 400 mg Once Daily During Pregnancy in HIV-1 Infected Women
A Phase 1 study testing Efavirenz, tenofovir /emtricitabine and tenofovir/lamivudine in people with HIV, run by St Stephens Aids Trust at 1 site in United Kingdom.
Trial summary
The purpose of the study is to measure the drug levels in your blood and to find out whether a reduced dose (400mg) of the anti-HIV medication Efavirenz is safe when taken during pregnancy. The study will recruit HIV infected women who take Efavirenz as part of their anti-hiv treatment and who are pregnant. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- HIV
- What is being tested?
- Efavirenz, tenofovir /emtricitabine and tenofovir/lamivudine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Aug 2015to 5 Oct 2017
- Phase
- Phase 1
- 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 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Evidence of a personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study.
- HIV-1-infected pregnant female, stable on two nucleos/tide analogues (tenofovir/emtricitabine or tenofovir/lamivudine or zidovudine/lamivudine) and efavirenz 600mg once daily for more than 12 weeks and willing to take efavirenz 400 mg once daily at gestational age of 28 weeks +/- 3 weeks.
- Undetectable viral load (by local assay).
- CD4 count > 100 cells/mm3.
- Aged between 18 to 45 years, inclusive.
Who cannot join
- Viral load ≥ 50 copies/mL (or detectable by local assay).
- Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG or clinical laboratory determinations.
- Positive blood screen for chronic hepatitis C (if available locally) or hepatitis B.
- Current or recent (within 3 months) gastrointestinal disease.
- Clinically relevant alcohol or drug use (positive urine drug screen) or history of alcohol or drug use considered by the Investigator to be sufficient to hinder compliance with treatment, follow-up procedures or evaluation of adverse events.
- Exposure to any investigational drug or placebo within 3 months prior to first dose of study drug.
- Use of any other drugs, including over-the-counter medications and herbal preparations, within two weeks prior to first dose of study drug, unless approved/prescribed by the Principal Investigator as known not to interact with study drugs.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
St Stephen's Centre, Chelsea and Westminster Hospital
London
About this study
Official title: Pharmacokinetics of EFV 400mg Once Daily During Pregnancy in HIV+ Women
The purpose of the study is to measure the drug levels in your blood and to find out whether a reduced dose (400mg) of the anti-HIV medication Efavirenz is safe when taken during pregnancy.
The study will recruit HIV infected women who take Efavirenz as part of their anti-hiv treatment and who are pregnant.
Read more
Efavirenz has been shown to be safe in pregnancy and at the standard dose that everybody takes of 600mg once a day, it shows levels that are enough to treat HIV and give birth to a HIV negative baby.
Efavirenz at a dose of 400mg once daily works against HIV too but this dose has not been given to HIV positive pregnant women.
People with HIV may benefit from using a dose of efavirenz of 400mg instead of 600mg, as lower drug doses could have fewer side effects and be tolerated better.
Dose reduction would also make the drug cheaper. This would allow more people to be treated and free up money for other important work in the fight against HIV such as education and prevention programs.
However, it is not known whether 400mg of Efavirenz works as well as 600mg of Efavirenz during pregnancy and this is why the investigators are conducting this study, which aims to measure the amount of Efavirenz 400mg in HIV pregnant women's bodies when they are taking 400mg of Efavirenz once a day.
Read the detailed description
Protocol Number: SSAT 063
EudraCT Number: 2014-002615-42
Name of Investigational Product: Sustiva
Name of active ingredients: Efavirenz
Study title:Pharmacokinetics of Efavirenz 400mg once daily during pregnancy in HIV-1 infected women
Name of Non Investigational Medicinal Product:
Two nucleoside reverse transcriptase inhibitors (tenofovir/ emtricitabine or tenofovir/lamivudine or zidovudine/lamivudine)
Phase of study: Phase I
Objectives: The objectives of this study are:
- Primary -To investigate the pharmacokinetics of Efavirenz 400mg during pregnancy.
- Secondary
- To investigate the safety and tolerability of Efavirenz 400mg during pregnancy.
- To investigate the association between genetic polymorphisms in drug disposition genes and drug exposure.
Study design: Two centre, approximately 18 weeks (excluding screening and follow up), open label, single treatment arm, pharmacokinetic study.
Indication: HIV in pregnancy
Methodology: Measurements of steady state pharmacokinetic profiles of efavirenz during the third trimester of pregnancy and 6 weeks postpartum in HIV-infected women on tenofovir/emtricitabine or tenofovir/lamivudine or zidovudine/lamivudine plus Efavirenz 400mg once daily.
Planned sample size: The primary endpoint will be the comparison of efavirenz Ctrough during the third trimester of pregnancy versus postpartum. The efavirenz Ctrough from each patient will be compared between the two phases using geometric mean ratios (log10 transformed data). For this sequential design, a sample size of 25 patients would provide at least 80% power to detect a decrease in efavirenz Ctrough of 20% during the third trimester of pregnancy, compared to the postpartum phase.
Up to 35 individuals may be screened to achieve 25 women completing all PK phases.
Summary of eligibility criteria:
Pregnant HIV-infected women with:
- Undetectable viral load
- CD4 count > 100 cells/mm3
- Stable on tenofovir/emtricitabine or tenofovir/lamivudine or zidovudine/lamivudine plus Efavirenz 600mg once daily for more than 12 weeks
Number of study centres: Two (London, UK and Kampala, Uganda)
Duration of treatment: Approximately 18 weeks: approximately four weeks prior to week 32 of pregnancy and up to 6 weeks postpartum (excluding screening and follow up visits)
Dose and route of administration: All subjects will be administered oral efavirenz 400mg together with the rest of the oral antiretroviral combination (tenofovir 245mg/emtricitabine 200mg or tenofovir 245mg/lamivudine 300mg or lamivudine 300mg/zidovudine 600mg) throughout the study period.
Criteria for evaluation: Pharmacokinetic parameters of efavirenz will be evaluated during the third trimester (gestational age week 32 +/- 3 weeks) and 6 weeks (+/- 4 weeks) postpartum.
Safety and tolerability of medications will also be assessed by questions, physical examination and laboratory parameters. These will be performed at regular intervals during the drug study.
At delivery, if possible, a cord blood sample will be taken and at the same time a blood sample from the mother will be taken.
Primary Endpoint:
Pharmacokinetics of efavirenz 400mg during pregnancy.
Secondary End point:
- Safety and tolerability of efavirenz 400mg during pregnancy.
- Association between genetic polymorphisms in drug disposition genes and drug exposure.
- Conditions
- HIV
- Being tested
- Efavirenz, tenofovir /emtricitabine, tenofovir/lamivudine, lamivudine/zidovudine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EfavirenzDrug
Also called Sustiva
oral Efavirenz 400mg
tenofovir /emtricitabineDrug
tenofovir 245 mg/emtricitabine 200mg
tenofovir/lamivudineDrug
tenofovir 245mg/lamivudine 300mg
lamivudine/zidovudineDrug
lamivudine 300mg/zidovudine 600mg
| Study group | Role | What they receive |
|---|---|---|
| Single treatment arm | Experimental | All subjects will be administered oral Efavirenz 400mg together with the rest of the oral antiretroviral combination (tenofovir 245 mg/emtricitabine 200mg or tenofovir 245mg/lamivudine 300mg or lamivudine 300mg/zidovudine 600mg) throughout the study period Receives: Drug: Efavirenz; Drug: tenofovir /emtricitabine; Drug: tenofovir/lamivudine; Drug: lamivudine/zidovudine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetics (AUC and Ctrough) of Efavirenz 400mg during pregnancy and postpartum.
The pharmacokinetic parameters calculated for efavirenz will be trough concentration (Ctrough), defined as the concentration at 24 hours after the observed drug dose, the maximum observed plasma concentration (Cmax), elimination half-life (t1/2), time point at Cmax (Tmax), and total drug exposure, expressed as the area under the plasma concentration-time curve from 0-24 hours after dosing (AUC0-24h). Efavirenz pharmacokinetic parameters measure during the third trimester of pregnancy and postpartum will be compared by calculating geometric mean ratios and 90% confidence intervals.
Measured: 24 weeks
Secondary outcomes (2)
Safety and tolerability (based on physical examination, laboratory tests and the DIVISION OF AIDS (DAIDS) table for granding the severity of adult and and the pediatric adverse events of Efavirenz 400mg during pregnancy and postpartum
Safety and tolerability of medications will also be assessed by questions, physical examination and laboratory parameters. These will be performed at regular intervals during the drug study.
Measured: 24 weeks
Association between polymorphisms in drug disposition genes and exposure in order to understand whether polymorphism of certain genes encoding for efavirenz metabolic enzymes are behind differences in efavirenz pharmacokinetics between people
candidate gene approach will be utilised to examine loci of interest. This procedure will provide potentially important information on genetic influences on plasma drug concentrations and give insight into how to improve the management of HIV-infected patients by individualising therapy. These studies will not be powered for genetic associations but will enable us to build a data base of genotype-phenotype. Prospective genetic studies would need to be planned based on these preliminary data.
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2015 (estimated)
- Study startAug 2015
- Primary completion5 Oct 2017
- Study completion5 Oct 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIVStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- St Stephens Aids Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Mylan Inc.
- Responsible party
- Sponsor
- Investigators
- Marta Boffito, MBBS,MD,PhD, Principal investigator, St. Stephen's AIDS TrustMohammed Lamorde, MBBS, Principal investigator, Infectious Diseases Institute (IDI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02499874
- Sponsor's protocol ID
- SSAT063
- Status last verified
- Oct 2017
- First submitted
- 7 Jul 2015
- Last updated
- 20 Oct 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetics of EFV 400mg Once Daily During Pregnancy in HIV+ Women
- ClinicalTrials.gov ID
- NCT02499874
- Acronym / sponsor ID
- SSAT063
- Conditions
- HIV
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- St Stephens Aids TrustUniversity, hospital or other
- Collaborators
- Mylan Inc.
- Study start
- Aug 2015
- Primary completion
- 5 Oct 2017 (actual)
- Study completion
- 5 Oct 2017 (actual)
- First posted
- 16 Jul 2015 (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 purpose of the study is to measure the drug levels in your blood and to find out whether a reduced dose (400mg) of the anti-HIV medication Efavirenz is safe when taken during pregnancy.
The study will recruit HIV infected women who take Efavirenz as part of their anti-hiv treatment and who are pregnant.
Efavirenz has been shown to be safe in pregnancy and at the standard dose that everybody takes of 600mg once a day, it shows levels that are enough to treat HIV and give birth to a HIV negative baby.
Efavirenz at a dose of 400mg once daily works against HIV too but this dose has not been given to HIV positive pregnant women.
People with HIV may benefit from using a dose of efavirenz of 400mg instead of 600mg, as lower drug doses could have fewer side effects and be tolerated better.
Dose reduction would also make the drug cheaper. This would allow more people to be treated and free up money for other important work in the fight against HIV such as education and prevention programs.
However, it is not known whether 400mg of Efavirenz works as well as 600mg of Efavirenz during pregnancy and this is why the investigators are conducting this study, which aims to measure the amount of Efavirenz 400mg in HIV pregnant women's bodies when they are taking 400mg of Efavirenz once a day.
Detailed description
Protocol Number: SSAT 063
EudraCT Number: 2014-002615-42
Name of Investigational Product: Sustiva
Name of active ingredients: Efavirenz
Study title:Pharmacokinetics of Efavirenz 400mg once daily during pregnancy in HIV-1 infected women
Name of Non Investigational Medicinal Product:
Two nucleoside reverse transcriptase inhibitors (tenofovir/ emtricitabine or tenofovir/lamivudine or zidovudine/lamivudine)
Phase of study: Phase I
Objectives: The objectives of this study are:
- Primary -To investigate the pharmacokinetics of Efavirenz 400mg during pregnancy.
- Secondary
- To investigate the safety and tolerability of Efavirenz 400mg during pregnancy.
- To investigate the association between genetic polymorphisms in drug disposition genes and drug exposure.
Study design: Two centre, approximately 18 weeks (excluding screening and follow up), open label, single treatment arm, pharmacokinetic study.
Indication: HIV in pregnancy
Methodology: Measurements of steady state pharmacokinetic profiles of efavirenz during the third trimester of pregnancy and 6 weeks postpartum in HIV-infected women on tenofovir/emtricitabine or tenofovir/lamivudine or zidovudine/lamivudine plus Efavirenz 400mg once daily.
Planned sample size: The primary endpoint will be the comparison of efavirenz Ctrough during the third trimester of pregnancy versus postpartum. The efavirenz Ctrough from each patient will be compared between the two phases using geometric mean ratios (log10 transformed data). For this sequential design, a sample size of 25 patients would provide at least 80% power to detect a decrease in efavirenz Ctrough of 20% during the third trimester of pregnancy, compared to the postpartum phase.
Up to 35 individuals may be screened to achieve 25 women completing all PK phases.
Summary of eligibility criteria:
Pregnant HIV-infected women with:
- Undetectable viral load
- CD4 count > 100 cells/mm3
- Stable on tenofovir/emtricitabine or tenofovir/lamivudine or zidovudine/lamivudine plus Efavirenz 600mg once daily for more than 12 weeks
Number of study centres: Two (London, UK and Kampala, Uganda)
Duration of treatment: Approximately 18 weeks: approximately four weeks prior to week 32 of pregnancy and up to 6 weeks postpartum (excluding screening and follow up visits)
Dose and route of administration: All subjects will be administered oral efavirenz 400mg together with the rest of the oral antiretroviral combination (tenofovir 245mg/emtricitabine 200mg or tenofovir 245mg/lamivudine 300mg or lamivudine 300mg/zidovudine 600mg) throughout the study period.
Criteria for evaluation: Pharmacokinetic parameters of efavirenz will be evaluated during the third trimester (gestational age week 32 +/- 3 weeks) and 6 weeks (+/- 4 weeks) postpartum.
Safety and tolerability of medications will also be assessed by questions, physical examination and laboratory parameters. These will be performed at regular intervals during the drug study.
At delivery, if possible, a cord blood sample will be taken and at the same time a blood sample from the mother will be taken.
Primary Endpoint:
Pharmacokinetics of efavirenz 400mg during pregnancy.
Secondary End point:
- Safety and tolerability of efavirenz 400mg during pregnancy.
- Association between genetic polymorphisms in drug disposition genes and drug exposure.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single treatment arm | Experimental | Drug: Efavirenz, Drug: tenofovir /emtricitabine, Drug: tenofovir/lamivudine, Drug: lamivudine/zidovudineAll subjects will be administered oral Efavirenz 400mg together with the rest of the oral antiretroviral combination (tenofovir 245 mg/emtricitabine 200mg or tenofovir 245mg/lamivudine 300mg or lamivudine 300mg/zidovudine 600mg) throughout the study period |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Evidence of a personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study.
- HIV-1-infected pregnant female, stable on two nucleos/tide analogues (tenofovir/emtricitabine or tenofovir/lamivudine or zidovudine/lamivudine) and efavirenz 600mg once daily for more than 12 weeks and willing to take efavirenz 400 mg once daily at gestational age of 28 weeks +/- 3 weeks.
- Undetectable viral load (by local assay).
- CD4 count > 100 cells/mm3.
- Aged between 18 to 45 years, inclusive.
Key exclusion criteria (7 listed)
- Viral load ≥ 50 copies/mL (or detectable by local assay).
- Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG or clinical laboratory determinations.
- Positive blood screen for chronic hepatitis C (if available locally) or hepatitis B.
- Current or recent (within 3 months) gastrointestinal disease.
- Clinically relevant alcohol or drug use (positive urine drug screen) or history of alcohol or drug use considered by the Investigator to be sufficient to hinder compliance with treatment, follow-up procedures or evaluation of adverse events.
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 |
|---|---|---|
| EfavirenzAlso: Sustivaoral Efavirenz 400mg | Drug | Single treatment arm |
| tenofovir /emtricitabinetenofovir 245 mg/emtricitabine 200mg | Drug | Single treatment arm |
| tenofovir/lamivudinetenofovir 245mg/lamivudine 300mg | Drug | Single treatment arm |
| lamivudine/zidovudinelamivudine 300mg/zidovudine 600mg | Drug | Single treatment arm |
Primary outcome
Pharmacokinetics (AUC and Ctrough) of Efavirenz 400mg during pregnancy and postpartum.
Time frame: 24 weeks
The pharmacokinetic parameters calculated for efavirenz will be trough concentration (Ctrough), defined as the concentration at 24 hours after the observed drug dose, the maximum observed plasma concentration (Cmax), elimination half-life (t1/2), time point at Cmax (Tmax), and total drug exposure, expressed as the area under the plasma concentration-time curve from 0-24 hours after dosing (AUC0-24h). Efavirenz pharmacokinetic parameters measure during the third trimester of pregnancy and postpartum will be compared by calculating geometric mean ratios and 90% confidence intervals.
2 secondary outcomes
Safety and tolerability (based on physical examination, laboratory tests and the DIVISION OF AIDS (DAIDS) table for granding the severity of adult and and the pediatric adverse events of Efavirenz 400mg during pregnancy and postpartum
Time frame: 24 weeks
Association between polymorphisms in drug disposition genes and exposure in order to understand whether polymorphism of certain genes encoding for efavirenz metabolic enzymes are behind differences in efavirenz pharmacokinetics between people
Time frame: 24 weeks
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 20 Oct 2017.
- UNAIDS is the leading advocate for worldwide action against HIV/AIDS. It promotes partnerships among and between other UN agencies, governments, corporations, media, sports and religious organizations, community-based groupsLink provided by the sponsor.
- BHIVA (the British HIV Association) is an organisation that represents healthcare professionals working in HIV in the UK. Its guidelines set out the medical and other care people living with HIV can expect to receive in the UKLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for HIV
Not yet recruiting
HealthMpowerment Korea: Pilot Testing the Cultural Adaptation of a Digital HIV Intervention for Men Who Have Sex With Men in South Korea
HIV Infections, HIV Prevention and Care
Not yet recruiting
Prescribe to Prevent HIV: A Hybrid Trial Helping Addiction Clinics Prevent HIV & Infections Through Safer Drug Use Support
People Who Use Opioids/People With Opioid Use Disorder (OUD)
Recruiting
Evaluating the Impact of Using the B-OK Bottles for HIV and ART Literacy in South Africa
HIV, HIV Treatment
Recruiting
Trial Phase: Syndemic Adapted Medly Uganda
Mental Health
RecruitingObservational study
Olfactory Function and Model-Based Behavior in People Living With HIV and SUD
HIV, Substance Use Disorder
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.
Marta Boffito, MBBS,MD,PhD principal investigator
St. Stephen's AIDS Trust
Mohammed Lamorde, MBBS principal investigator
Infectious Diseases Institute (IDI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Efavirenz, tenofovir /emtricitabine and tenofovir/lamivudine in people with HIV, run by St Stephens Aids Trust at 1 site in United Kingdom.
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 5 inclusion and 7 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 20 Oct 2017. 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 United Kingdom. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Pharmacokinetics (AUC and Ctrough) of Efavirenz 400mg during pregnancy and postpartum. (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 20 Oct 2017.