HIV InfectionsPhase 1DarifiNCT03892161
Clinical Evaluation of Adjusted Doses of Darunavir/Ritonavir With Rifampicin in HIV-infected Volunteers
A Phase 1 study testing Darunavir/ritonavir 800/100 mg tablet and Rifampicin 600mg QD tablet and DTG 50mg BD in people with HIV Infections, run by University of Cape Town at 1 site in South Africa.
Trial summary
The DaRifi study aims: 1. Develop adjusted doses of darunavir/ritonavir for use in HIV-infected patients requiring co-treatment of TB with a rifampicin-based regimen. 2. Compare the steady state pharmacokinetics of doubled doses of DRV/r with rifampicin (in once daily and 12-hourly approaches) to standard daily doses… Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- HIV Infections
- What is being tested?
- Darunavir/ritonavir 800/100 mg tablet and Rifampicin 600mg QD tablet and DTG 50mg BD
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteSouth Africa
- Study dates
- 12 Apr 2018to 22 Nov 2018
- 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 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Male or female
- Aged 18 to 60 years, inclusive
- Weighing > 38 kg
- BMI > 18.5 kg/m2
- HIV-1 infected
- HIV-1 RNA <50 copies/mL
Show all 30Show fewer
- CD4+ lymphocyte count > 200 cells/L
- C-reactive protein <10 mg/L
- Established on current ART regimen of boosted protease inhibitor plus 2 NRTIs for at least 3 months.
- Women must be postmenopausal, surgically sterile or practicing an effective birth control method (established before and maintained throughout the trial). Women who are not sexually active must agree to use an effective birth control method if they become heterosexually active during the trial.
- Understand the purpose of and procedures required for the study and having confirmed they are willing to participate in the study by signing the informed consent document.
- Exclusion criteria (volunteers meeting any of the criteria will be excluded)
- TB (confirmed or suspected)
- Any symptoms of TB - as assessed by the WHO symptom-screening algorithm: self-reported or documented weight loss, cough, night sweats or fever.
- Clinical or laboratory evidence of significantly impaired hepatic function, or documented hepatic cirrhosis
- Clinical or laboratory evidence of acute viral hepatitis
- Co-infected with HBV or HCV.
- ALT grade 2 or higher (as defined by DAIDS grading table (ALT >2.5 x ULN)
- DAIDS grade 3 or 4 laboratory abnormality
- Active (not clinically stabilized >4 weeks) AIDS defining illness (Category C conditions according to the Center for Disease Control Classification System for HIV infection) with the following exceptions:
- Stable cutaneous Kaposi's Sarcoma (no internal organ involvement other than oral lesions) that is unlikely to require any form of systemic therapy during the study.
- Estimated creatinine clearance <50 mL/min.
- Active clinically significant renal or gastro-intestinal disease.
- Any active clinically significant or life-threatening disease, medical or psychiatric condition, or findings during screening, that in the investigator's opinion would compromise the safety of the participant or the study outcome, or their ability to comply with the study procedures.
- Chronic medical requirement for any drugs that are known to affect the PK of the study drugs.
- Active drug/alcohol abuser.
- Pregnant or breastfeeding.
- Increased risks of drug side effects/hypersensitivity reactions e.g. haemophilia or history of sulfonamide allergy.
- Currently enrolled in an investigational drug study or has participated in an investigational drug study within the 4 weeks before screening.
- Unable to comply with peri-study restrictions
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
South Africa1 site
Clinical Research Centre
Cape Town, Western Cape, 7725
About this study
The DaRifi study aims:
- Develop adjusted doses of darunavir/ritonavir for use in HIV-infected patients requiring co-treatment of TB with a rifampicin-based regimen.
- Compare the steady state pharmacokinetics of doubled doses of DRV/r with rifampicin (in once daily and 12-hourly approaches) to standard daily doses without rifampicin.
- Twenty-eight volunteers will be enrolled for a target of 24 participants completing the study.
Read the detailed description
A significant barrier to the use of better tolerated antiretrovirals in many low-to-middle income countries (LMIC), where tuberculosis (TB) is endemic, is a lack of evidence to support their use in patients with TB. Access to optimal protease inhibitor (PI)-based regimens for patients with and without TB is urgent. Switching rifampicin to rifabutin, a weak inducer that does not significantly reduce PI concentrations, is recommended in high income countries for patients on boosted PIs who develop TB. However, rifabutin is not available in most LMIC where TB is typically treated with fixed dose combination tablets.
We will enrol virologically suppressed participants on a second-line DRV/r regimen without TB. Based on data from a Physiologically-Based PK model, we selected two adjusted doses of DRV/r (1600/200 mg daily and 800/100 mg 12 hourly) with RIF for comparison to plasma exposures with DRV/r 800/100 mg daily without RIF, in a cross-over design.
Baseline DRV steady state PK will be determined and RIF added for 7 days, then the dose of ritonavir will be increased to 200 mg; 7 days later the dose of DRV will be increased; after another 7 days participants will be crossed over to the alternative adjusted DRV dose.
DRV will be measured in plasma samples after observed doses at baseline and after each dose adjustment. Non-compartmental analysis will be used to estimate the PK measures. Clinical adverse events, ALT, and bilirubin will be monitored every 2 to 3 days during treatment with RIF.
- Conditions
- HIV Infections
- Being tested
- Darunavir/ritonavir 800/100 mg tablet, Rifampicin 600mg QD tablet and DTG 50mg BD
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Darunavir/ritonavir 800/100 mg tabletDrug
Standard dose DRV/r administered
Rifampicin 600mg QD tablet and DTG 50mg BDDrug
Rifampicin and DTG added
| Study group | Role | What they receive |
|---|---|---|
| Standard dose DRV/r | Experimental | Standard dose DRV/r 800/100mg without Rifampicin Receives: Drug: Darunavir/ritonavir 800/100 mg tablet |
| Standard DRV/r with Rifampicin | Experimental | Rifampicin 600mg QD will be added and darunavir/ritonavir steady state pharmacokinetic analysis will be performed. Receives: Drug: Darunavir/ritonavir 800/100 mg tablet; Drug: Rifampicin 600mg QD tablet and DTG 50mg BD |
| Boosed ritonavir 200mg | Experimental | Rifampicin 600mg QD continued with ritonavir 200mg dose doubled QD and darunavir remains 800mg QD. The darunavir/ritonavir steady state pharmacokinetic analysis will be performed and compared. Receives: Drug: Darunavir/ritonavir 800/100 mg tablet; Drug: Rifampicin 600mg QD tablet and DTG 50mg BD |
| Double dose DRV/r 1600/200mg QD | Experimental | Rifampicin 600mg QD and DTG QD continued. Double dose DRV/r QD. The darunavir/ritonavir steady state pharmacokinetic analysis will be performed and compared. Receives: Drug: Darunavir/ritonavir 800/100 mg tablet; Drug: Rifampicin 600mg QD tablet and DTG 50mg BD |
| Double dose DRV/r 800/100mg BD | Experimental | Rifampicin 600mg QD and DTG BD continued. Double dose DRV/r QD. The darunavir/ritonavir steady state pharmacokinetic analysis will be performed and compared. Receives: Drug: Darunavir/ritonavir 800/100 mg tablet; Drug: Rifampicin 600mg QD tablet and DTG 50mg BD |
What is being measured
The primary outcome is the main question the study is designed to answer.
Darunavir plasma concentrations nanogram per milliliter (ng/ml)
Darunavir plasma concentrations will be compared with rifampicin and without rifampicin.
Measured: 1 year
Secondary outcomes (1)
Alanine Transaminase (ALT) blood level (iu/L)
Clinical safety will be monitored, ALT liver enzyme tests will be evaluated every 3 days.
Measured: 1 Year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2019
- Study start12 Apr 2018
- Primary completion22 Nov 2018
- Study completion22 Nov 2018
Why it stopped: Risks to participation
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (25)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies 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
- Randomised
- Intervention model
- Crossover
- Model description
- A phase I, open-label, cross-over, single center, PK drug-drug interaction study will be conducted in 24 medically stable HIV-1 infected adults with viral suppression (viral load \<50 copies/mL).
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Cape Town
- Sponsor type
- University, hospital or other
- Collaborators
- Wits Reproductive Health and HIV Institute, Desmond Tutu HIV Centre
- Responsible party
- Principal investigator, Helen Margaret McIlleron, University of Cape Town
- Investigators
- Helen McIlleron, PhD, Principal investigator, University of Cape Town
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03892161
- Sponsor's protocol ID
- Darifi
- Acronym
- Darifi
- Status last verified
- Apr 2019
- First submitted
- 23 Apr 2018
- Last updated
- 3 Apr 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Baietto L, Calcagno A, Motta I, Baruffi K, Poretti V, Di Perri G, Bonora S, D'Avolio A. A UPLC-MS-MS method for the simultaneous quantification of first-line antituberculars in plasma and in PBMCs. J Antimicrob Chemother. 2015 Sep;70(9):2572-5. doi: 10.1093/jac/dkv148. Epub 2015 Jun 11.
PubMed 26066583Chirehwa MT, Rustomjee R, Mthiyane T, Onyebujoh P, Smith P, McIlleron H, Denti P. Model-Based Evaluation of Higher Doses of Rifampin Using a Semimechanistic Model Incorporating Autoinduction and Saturation of Hepatic Extraction. Antimicrob Agents Chemother. 2015 Nov 9;60(1):487-94. doi: 10.1128/AAC.01830-15. Print 2016 Jan.
PubMed 26552972D'Avolio A, Simiele M, Siccardi M, Baietto L, Sciandra M, Oddone V, Stefani FR, Agati S, Cusato J, Bonora S, Di Perri G. A HPLC-MS method for the simultaneous quantification of fourteen antiretroviral agents in peripheral blood mononuclear cell of HIV infected patients optimized using medium corpuscular volume evaluation. J Pharm Biomed Anal. 2011 Mar 25;54(4):779-88. doi: 10.1016/j.jpba.2010.10.011. Epub 2010 Nov 10.
PubMed 21071165Decloedt EH, McIlleron H, Smith P, Merry C, Orrell C, Maartens G. Pharmacokinetics of lopinavir in HIV-infected adults receiving rifampin with adjusted doses of lopinavir-ritonavir tablets. Antimicrob Agents Chemother. 2011 Jul;55(7):3195-200. doi: 10.1128/AAC.01598-10. Epub 2011 May 2.
PubMed 21537021Decloedt EH, Maartens G, Smith P, Merry C, Bango F, McIlleron H. The safety, effectiveness and concentrations of adjusted lopinavir/ritonavir in HIV-infected adults on rifampicin-based antitubercular therapy. PLoS One. 2012;7(3):e32173. doi: 10.1371/journal.pone.0032173. Epub 2012 Mar 7.
PubMed 22412856De Nicolo A, Bonifacio G, Boglione L, Cusato J, Pensi D, Tomasello C, Di Perri G, D'Avolio A. UHPLC-MS/MS method with automated on-line solid phase extraction for the quantification of entecavir in peripheral blood mononuclear cells of HBV+ patients. J Pharm Biomed Anal. 2016 Jan 25;118:64-69. doi: 10.1016/j.jpba.2015.10.017. Epub 2015 Oct 22.
PubMed 26517850Dooley KE, Sayre P, Borland J, Purdy E, Chen S, Song I, Peppercorn A, Everts S, Piscitelli S, Flexner C. Safety, tolerability, and pharmacokinetics of the HIV integrase inhibitor dolutegravir given twice daily with rifampin or once daily with rifabutin: results of a phase 1 study among healthy subjects. J Acquir Immune Defic Syndr. 2013 Jan 1;62(1):21-7. doi: 10.1097/QAI.0b013e318276cda9.
PubMed 23075918Haas DW, Koletar SL, Laughlin L, Kendall MA, Suckow C, Gerber JG, Zolopa AR, Bertz R, Child MJ, Hosey L, Alston-Smith B, Acosta EP; A5213 StudyTeam. Hepatotoxicity and gastrointestinal intolerance when healthy volunteers taking rifampin add twice-daily atazanavir and ritonavir. J Acquir Immune Defic Syndr. 2009 Mar 1;50(3):290-3. doi: 10.1097/QAI.0b013e318189a7df.
PubMed 19194314la Porte CJ, Colbers EP, Bertz R, Voncken DS, Wikstrom K, Boeree MJ, Koopmans PP, Hekster YA, Burger DM. Pharmacokinetics of adjusted-dose lopinavir-ritonavir combined with rifampin in healthy volunteers. Antimicrob Agents Chemother. 2004 May;48(5):1553-60. doi: 10.1128/AAC.48.5.1553-1560.2004.
PubMed 15105105L'homme RF, Nijland HM, Gras L, Aarnoutse RE, van Crevel R, Boeree M, Brinkman K, Prins JM, Juttmann JR, Burger DM. Clinical experience with the combined use of lopinavir/ritonavir and rifampicin. AIDS. 2009 Apr 27;23(7):863-5. doi: 10.1097/QAD.0b013e328329148e.
PubMed 19352137Nijland HM, L'homme RF, Rongen GA, van Uden P, van Crevel R, Boeree MJ, Aarnoutse RE, Koopmans PP, Burger DM. High incidence of adverse events in healthy volunteers receiving rifampicin and adjusted doses of lopinavir/ritonavir tablets. AIDS. 2008 May 11;22(8):931-5. doi: 10.1097/QAD.0b013e3282faa71e.
PubMed 18453852Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf
Rabie et al., Pharmacokinetics of lopinavir/ritonavir superboosting in infants and young children co-infected with HIV and TB. 7th Int WS on HIV Pediatrics 2015, Vancouver
Ren Y, Nuttall JJ, Egbers C, Eley BS, Meyers TM, Smith PJ, Maartens G, McIlleron HM. Effect of rifampicin on lopinavir pharmacokinetics in HIV-infected children with tuberculosis. J Acquir Immune Defic Syndr. 2008 Apr 15;47(5):566-9. doi: 10.1097/QAI.0b013e3181642257.
PubMed 18197120Roberts O, Khoo S, Owen A, Siccardi M. Interaction of Rifampin and Darunavir-Ritonavir or Darunavir-Cobicistat In Vitro. Antimicrob Agents Chemother. 2017 Apr 24;61(5):e01776-16. doi: 10.1128/AAC.01776-16. Print 2017 May.
PubMed 28193650
Study at a glance
From the registry record, last updated by the sponsor on 3 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Evaluation of Adjusted Doses of Darunavir/Ritonavir With Rifampicin in HIV-infected Volunteers
- ClinicalTrials.gov ID
- NCT03892161
- Acronym / sponsor ID
- Darifi / Darifi
- Conditions
- HIV Infections
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Risks to participation
- Enrolment
- 17 participants (actual)
- Lead sponsor
- University of Cape TownUniversity, hospital or other
- Collaborators
- Wits Reproductive Health and HIV Institute, Desmond Tutu HIV Centre
- Study start
- 12 Apr 2018 (actual)
- Primary completion
- 22 Nov 2018 (actual)
- Study completion
- 22 Nov 2018 (actual)
- First posted
- 27 Mar 2019 (actual)
- 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 DaRifi study aims:
- Develop adjusted doses of darunavir/ritonavir for use in HIV-infected patients requiring co-treatment of TB with a rifampicin-based regimen.
- Compare the steady state pharmacokinetics of doubled doses of DRV/r with rifampicin (in once daily and 12-hourly approaches) to standard daily doses without rifampicin.
- Twenty-eight volunteers will be enrolled for a target of 24 participants completing the study.
Detailed description
A significant barrier to the use of better tolerated antiretrovirals in many low-to-middle income countries (LMIC), where tuberculosis (TB) is endemic, is a lack of evidence to support their use in patients with TB. Access to optimal protease inhibitor (PI)-based regimens for patients with and without TB is urgent. Switching rifampicin to rifabutin, a weak inducer that does not significantly reduce PI concentrations, is recommended in high income countries for patients on boosted PIs who develop TB. However, rifabutin is not available in most LMIC where TB is typically treated with fixed dose combination tablets.
We will enrol virologically suppressed participants on a second-line DRV/r regimen without TB. Based on data from a Physiologically-Based PK model, we selected two adjusted doses of DRV/r (1600/200 mg daily and 800/100 mg 12 hourly) with RIF for comparison to plasma exposures with DRV/r 800/100 mg daily without RIF, in a cross-over design.
Baseline DRV steady state PK will be determined and RIF added for 7 days, then the dose of ritonavir will be increased to 200 mg; 7 days later the dose of DRV will be increased; after another 7 days participants will be crossed over to the alternative adjusted DRV dose.
DRV will be measured in plasma samples after observed doses at baseline and after each dose adjustment. Non-compartmental analysis will be used to estimate the PK measures. Clinical adverse events, ALT, and bilirubin will be monitored every 2 to 3 days during treatment with RIF.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 5
- Model description
- A phase I, open-label, cross-over, single center, PK drug-drug interaction study will be conducted in 24 medically stable HIV-1 infected adults with viral suppression (viral load <50 copies/mL).
| Arm | Type | Receives |
|---|---|---|
| Standard dose DRV/r | Experimental | Drug: Darunavir/ritonavir 800/100 mg tabletStandard dose DRV/r 800/100mg without Rifampicin |
| Standard DRV/r with Rifampicin | Experimental | Drug: Darunavir/ritonavir 800/100 mg tablet, Drug: Rifampicin 600mg QD tablet and DTG 50mg BDRifampicin 600mg QD will be added and darunavir/ritonavir steady state pharmacokinetic analysis will be performed. |
| Boosed ritonavir 200mg | Experimental | Drug: Darunavir/ritonavir 800/100 mg tablet, Drug: Rifampicin 600mg QD tablet and DTG 50mg BDRifampicin 600mg QD continued with ritonavir 200mg dose doubled QD and darunavir remains 800mg QD. The darunavir/ritonavir steady state pharmacokinetic analysis will be performed and compared. |
| Double dose DRV/r 1600/200mg QD | Experimental | Drug: Darunavir/ritonavir 800/100 mg tablet, Drug: Rifampicin 600mg QD tablet and DTG 50mg BDRifampicin 600mg QD and DTG QD continued. Double dose DRV/r QD. The darunavir/ritonavir steady state pharmacokinetic analysis will be performed and compared. |
| Double dose DRV/r 800/100mg BD | Experimental | Drug: Darunavir/ritonavir 800/100 mg tablet, Drug: Rifampicin 600mg QD tablet and DTG 50mg BDRifampicin 600mg QD and DTG BD continued. Double dose DRV/r QD. The darunavir/ritonavir steady state pharmacokinetic analysis will be performed and compared. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (30 listed)
- Male or female
- Aged 18 to 60 years, inclusive
- Weighing > 38 kg
- BMI > 18.5 kg/m2
- HIV-1 infected
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| Darunavir/ritonavir 800/100 mg tabletStandard dose DRV/r administered | Drug | Boosed ritonavir 200mg, Double dose DRV/r 1600/200mg QD, Double dose DRV/r 800/100mg BD, Standard DRV/r with Rifampicin, Standard dose DRV/r |
| Rifampicin 600mg QD tablet and DTG 50mg BDRifampicin and DTG added | Drug | Boosed ritonavir 200mg, Double dose DRV/r 1600/200mg QD, Double dose DRV/r 800/100mg BD, Standard DRV/r with Rifampicin |
Primary outcome
Darunavir plasma concentrations nanogram per milliliter (ng/ml)
Time frame: 1 year
Darunavir plasma concentrations will be compared with rifampicin and without rifampicin.
1 secondary outcome
Alanine Transaminase (ALT) blood level (iu/L)
Time frame: 1 Year
Results and safety
The study was stopped early (reason given: Risks to participation). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Apr 2019.
- Background: PubMed 26066583Baietto L, Calcagno A, Motta I, Baruffi K, Poretti V, Di Perri G, Bonora S, D'Avolio A. A UPLC-MS-MS method for the simultaneous quantification of first-line antituberculars in plasma and in PBMCs. J Antimicrob Chemother. 2015 Sep;70(9):2572-5. doi: 10.1093/jac/dkv148. Epub 2015 Jun 11.
- Background: PubMed 26552972Chirehwa MT, Rustomjee R, Mthiyane T, Onyebujoh P, Smith P, McIlleron H, Denti P. Model-Based Evaluation of Higher Doses of Rifampin Using a Semimechanistic Model Incorporating Autoinduction and Saturation of Hepatic Extraction. Antimicrob Agents Chemother. 2015 Nov 9;60(1):487-94. doi: 10.1128/AAC.01830-15. Print 2016 Jan.
- Background: PubMed 21071165D'Avolio A, Simiele M, Siccardi M, Baietto L, Sciandra M, Oddone V, Stefani FR, Agati S, Cusato J, Bonora S, Di Perri G. A HPLC-MS method for the simultaneous quantification of fourteen antiretroviral agents in peripheral blood mononuclear cell of HIV infected patients optimized using medium corpuscular volume evaluation. J Pharm Biomed Anal. 2011 Mar 25;54(4):779-88. doi: 10.1016/j.jpba.2010.10.011. Epub 2010 Nov 10.
- Background: PubMed 21537021Decloedt EH, McIlleron H, Smith P, Merry C, Orrell C, Maartens G. Pharmacokinetics of lopinavir in HIV-infected adults receiving rifampin with adjusted doses of lopinavir-ritonavir tablets. Antimicrob Agents Chemother. 2011 Jul;55(7):3195-200. doi: 10.1128/AAC.01598-10. Epub 2011 May 2.
- Background: PubMed 22412856Decloedt EH, Maartens G, Smith P, Merry C, Bango F, McIlleron H. The safety, effectiveness and concentrations of adjusted lopinavir/ritonavir in HIV-infected adults on rifampicin-based antitubercular therapy. PLoS One. 2012;7(3):e32173. doi: 10.1371/journal.pone.0032173. Epub 2012 Mar 7.
- Background: PubMed 26517850De Nicolo A, Bonifacio G, Boglione L, Cusato J, Pensi D, Tomasello C, Di Perri G, D'Avolio A. UHPLC-MS/MS method with automated on-line solid phase extraction for the quantification of entecavir in peripheral blood mononuclear cells of HBV+ patients. J Pharm Biomed Anal. 2016 Jan 25;118:64-69. doi: 10.1016/j.jpba.2015.10.017. Epub 2015 Oct 22.
- Background: PubMed 23075918Dooley KE, Sayre P, Borland J, Purdy E, Chen S, Song I, Peppercorn A, Everts S, Piscitelli S, Flexner C. Safety, tolerability, and pharmacokinetics of the HIV integrase inhibitor dolutegravir given twice daily with rifampin or once daily with rifabutin: results of a phase 1 study among healthy subjects. J Acquir Immune Defic Syndr. 2013 Jan 1;62(1):21-7. doi: 10.1097/QAI.0b013e318276cda9.
- Background: PubMed 19194314Haas DW, Koletar SL, Laughlin L, Kendall MA, Suckow C, Gerber JG, Zolopa AR, Bertz R, Child MJ, Hosey L, Alston-Smith B, Acosta EP; A5213 StudyTeam. Hepatotoxicity and gastrointestinal intolerance when healthy volunteers taking rifampin add twice-daily atazanavir and ritonavir. J Acquir Immune Defic Syndr. 2009 Mar 1;50(3):290-3. doi: 10.1097/QAI.0b013e318189a7df.
- Background: PubMed 15105105la Porte CJ, Colbers EP, Bertz R, Voncken DS, Wikstrom K, Boeree MJ, Koopmans PP, Hekster YA, Burger DM. Pharmacokinetics of adjusted-dose lopinavir-ritonavir combined with rifampin in healthy volunteers. Antimicrob Agents Chemother. 2004 May;48(5):1553-60. doi: 10.1128/AAC.48.5.1553-1560.2004.
- Background: PubMed 19352137L'homme RF, Nijland HM, Gras L, Aarnoutse RE, van Crevel R, Boeree M, Brinkman K, Prins JM, Juttmann JR, Burger DM. Clinical experience with the combined use of lopinavir/ritonavir and rifampicin. AIDS. 2009 Apr 27;23(7):863-5. doi: 10.1097/QAD.0b013e328329148e.
- Background: PubMed 18453852Nijland HM, L'homme RF, Rongen GA, van Uden P, van Crevel R, Boeree MJ, Aarnoutse RE, Koopmans PP, Burger DM. High incidence of adverse events in healthy volunteers receiving rifampicin and adjusted doses of lopinavir/ritonavir tablets. AIDS. 2008 May 11;22(8):931-5. doi: 10.1097/QAD.0b013e3282faa71e.
- BackgroundPanel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf
- Individual participant dataSharing planned: No
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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.
Helen McIlleron, PhD principal investigator
University of Cape Town
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 Darunavir/ritonavir 800/100 mg tablet and Rifampicin 600mg QD tablet and DTG 50mg BD in people with HIV Infections, run by University of Cape Town at 1 site in South Africa.
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 30 inclusion and 0 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: stopped early, as of the sponsor's last update on 3 Apr 2019. 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 South Africa. 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 was stopped early (reason given: Risks to participation). Results are not available in the source record.
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?
Darunavir plasma concentrations nanogram per milliliter (ng/ml) (time frame: 1 year). 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 NCT03892161, which also lists 25 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 3 Apr 2019.