HIV/AIDSPhase 4NCT04431518
Pharmacokinetics of JULUCA in Hemodialysis
A Phase 4 study testing JULUCA 50Mg-25Mg Tablet in people with HIV/AIDS and ESRD, run by Indiana University at 1 site in United States.
Trial summary
This study will compare the pharmacokinetics of the component drugs in JULUCA, and HIV combination treatment pill, in HIV-negative patients who require hemodialysis with those with normal renal function. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- What is being tested?
- JULUCA 50Mg-25Mg Tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Apr 2021to 31 Jul 2023
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Negative HIV antibody testing at screening.
- For the ESRD requiring HD study group: ESRD requiring chronic hemodialysis for at least 6 months at an established center (not home dialysis).
- NOTE: The approximate date that hemodialysis was initiated should be reported, if known.
- For the normal renal function group: Estimated CrCl (using the Cockcroft-Gault equation) at screening ≥75mL/min.
- Availability of alternative venous access (not used for dialysis) for the purpose of PK sampling.
- The following laboratory values obtained within 30 days prior to study entry (obtained either at screening or done as part of routine clinical care):
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- AST (SGOT) and ALT (SGPT) less than or equal to ULN
- Total bilirubin less than or equal to 1.5 x ULN
- Hemoglobin greater than or equal to 8.0 mg/dL
- A negative serum pregnancy test result at screening for all women of reproductive potential who have not reached menopause or undergone hysterectomy, bilateral oophorectomy, or tubal ligation.
- Males and females, age 18-65 years.
- Ability and willingness of participant or legal guardian/representative to provide written informed consent.
Who cannot join
- Known allergy or hypersensitivity to either dolutegravir or rilpivirine
- Use of peritoneal dialysis.
- Serious illnesses, other than ESRD, requiring systemic treatment and/or hospitalization within 30 days prior to the Screening Visit.
- Known liver cirrhosis, unstable liver disease (presence of ascites, encephalopathy, coagulopathy, esophageal/gastric varices), Child-Pugh Class A, B, or C, or known biliary abnormalities (except for known Gilbert's syndrome or asymptomatic gallstones).
- Hepatitis B surface antigen or hepatitis C antibody with detectable RNA at screening.
- Known gastrointestinal disease that may lead to poor absorption of the study drugs.
Show all 25Show fewer
- Known hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption.
- Any of the following gastrointestinal signs or symptoms of Grade ≥ 2 within 7 days prior to the Screening Visit or during study drug administration prior to the Intensive PK Study Visit:
- nausea
- vomiting
- diarrhea
- abdominal pain
- Use of any of the following within 30 days of initiating study drug:
- Medications known to appreciably inhibit or induce CYP3A enzymes, P-glycoprotein, or UGT1A1 or UGT1A4 enzymes (e.g., anticonvulsants such as carbamazepine, phenytoin, oxacarbamazepine; antimycobacterials such as rifampin, rifabutin and rifapentine; antifungal agents such as ketoconazole, fluconazole and itraconazole; verapamil, clarithromycin, erythromycin)
- St. John's Wort, echinacea, grapefruits or grapefruit juice, garlic supplements, ginseng, golden seal, and milk thistle
- Cancer chemotherapeutic agents
- Investigational agents
- Immunomodulators, including systemic steroids greater than or equal to 100 mg/day of prednisone (Note: Topical and inhaled corticosteroids are allowed.)
- Dofetilide
- Positive pre-study drug screen. Drugs that will be screened for include amphetamines, barbiturates, cocaine and phencyclidine (PCP). Active injected drug users will be excluded from this study.
- Use of proton pump inhibitors within 7 days of initiating study drug (H2 blockers are permitted).
- Pregnancy and/or breast-feeding.
- Moderate to severe depression, defined as a PHQ-9 ≥ 10 at Screening.
- Significant change (i.e., more than a 50% change) in tobacco smoking habit within 6 weeks prior to the Screening Visit. Participants who have recently stopped smoking should have stopped smoking more than 6 weeks prior to the Screening Visit. Participants who have recently started smoking should have started more than 6 weeks prior to the Screening Visit.
- QTc interval greater than 500 msec at Screening.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Steady-State Pharmacokinetics (PK) of Dolutegravir/Rilpivirine Fixed Dose Combination (FDC) in Patients With End Stage Renal Disease (ESRD) Requiring Hemodialysis (HD)
This study will compare the pharmacokinetics of the component drugs in JULUCA, and HIV combination treatment pill, in HIV-negative patients who require hemodialysis with those with normal renal function.
Read the detailed description
The pharmacokinetics (PK) of dolutegravir (DTG) and rilpivirine (RPV), the components of JULUCA, in patients with end stage renal disease (ESRD) requiring hemodialysis (HD) have not previously been adequately studied. It is possible that the PK of these drugs are affected by renal failure which may then compromise effectiveness and safety. This trial will rigorously assess the plasma PK and protein-binding of these two drugs in 10 HIV-negative patients requiring hemodialysis with 10 matched persons with normal renal function. All participants will receive JULUCA for up to 14 days and then undergo a 24 hour intensive PK evaluation.
- Being tested
- JULUCA 50Mg-25Mg Tablet
- Keywords
- HIV, ESRD, Hemodialysis, Pharmacokinetics
- Medical subject headings
- Acquired Immunodeficiency Syndrome, Kidney Failure, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
JULUCA 50Mg-25Mg TabletDrug
One dose of JULUCA will be taken daily for up to 14 days
| Study group | Role | What they receive |
|---|---|---|
| Hemodialysis Group | Experimental | Receipt of JULUCA one pill per day up to 14 days Receives: Drug: JULUCA 50Mg-25Mg Tablet |
| Normal Renal Function Group | Active comparator | Receipt of JULUCA one pill per day up to 14 days Receives: Drug: JULUCA 50Mg-25Mg Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dolutegravir (DTG) Ctau
Steady-state plasma Ctau for dolutegravir at the intensive study visit, which occurred between days 11 and 14
Measured: 0 to 24 hours post-dose on the intensive study visit
Rilpivirine (RPV) Ctau
Steady-state plasma Ctau for rilpivirine at the intensive study visit, which occurred between days 11 and 14
Measured: 0 to 24 hours post-dose on the intensive study visit
Secondary outcomes (3)
Safety of DTG
The attributable grade 3 or 4 adverse events associated with use of DTG will be assessed during the study. Adverse events were graded using the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events. Grade 3 indicates a severe event, and Grade 4 indicates a potentially life-threatening event.
Measured: 30 days
DTG AUC
Steady-state plasma AUC for dolutegravir at the intensive study visit, which occurred between days 11 and 14
Measured: 0 to 24 hours post-dose on the intensive study visit
DTG Cmax
Steady-state plasma Cmax for dolutegravir at the intensive study visit, which occurred between days 11 and 14
Measured: 0 to 24 hours post-dose on the intensive study visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2020
- Study start23 Apr 2021
- Primary completion31 Jul 2023
- Study completion31 Jul 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV/AIDSStudies of the same condition, open and under way.
- More trials run by Indiana UniversityThe sponsor's other registered studies.
- 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
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Matched case-control
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Indiana University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Samir K. Gupta, MD, Indiana University
- Investigators
- Samir K Gupta, MD, Principal investigator, Indiana University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04431518
- Sponsor's protocol ID
- ViiV Healthcare IIS 1837
- Status last verified
- May 2024
- First submitted
- 9 Jun 2020
- Last updated
- 5 Jun 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All IPD will provided upon request and approval by the investigators or through online data repositories such as Figshare.
Publications
Gupta SK, Friedman AN, Desta Z. The steady-state pharmacokinetics of fixed-dose combination dolutegravir+rilpivirine in hemodialysis. AIDS. 2025 Mar 15;39(4):356-361. doi: 10.1097/QAD.0000000000004071. Epub 2024 Nov 22.
PubMed 39761595
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Steady-State Pharmacokinetics (PK) of Dolutegravir/Rilpivirine Fixed Dose Combination (FDC) in Patients With End Stage Renal Disease (ESRD) Requiring Hemodialysis (HD)
- ClinicalTrials.gov ID
- NCT04431518
- Acronym / sponsor ID
- ViiV Healthcare IIS 1837
- Keywords
- HIV, ESRD, Hemodialysis, Pharmacokinetics
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Indiana UniversityUniversity, hospital or other
- Study start
- 23 Apr 2021 (actual)
- Primary completion
- 31 Jul 2023 (actual)
- Study completion
- 31 Jul 2023 (actual)
- First posted
- 16 Jun 2020 (actual)
- Results
- Posted 21 May 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will compare the pharmacokinetics of the component drugs in JULUCA, and HIV combination treatment pill, in HIV-negative patients who require hemodialysis with those with normal renal function.
Detailed description
The pharmacokinetics (PK) of dolutegravir (DTG) and rilpivirine (RPV), the components of JULUCA, in patients with end stage renal disease (ESRD) requiring hemodialysis (HD) have not previously been adequately studied. It is possible that the PK of these drugs are affected by renal failure which may then compromise effectiveness and safety. This trial will rigorously assess the plasma PK and protein-binding of these two drugs in 10 HIV-negative patients requiring hemodialysis with 10 matched persons with normal renal function. All participants will receive JULUCA for up to 14 days and then undergo a 24 hour intensive PK evaluation.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Matched case-control
| Arm | Type | Receives |
|---|---|---|
| Hemodialysis Group | Experimental | Drug: JULUCA 50Mg-25Mg TabletReceipt of JULUCA one pill per day up to 14 days |
| Normal Renal Function Group | Active comparator | Drug: JULUCA 50Mg-25Mg TabletReceipt of JULUCA one pill per day up to 14 days |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Negative HIV antibody testing at screening.
- For the ESRD requiring HD study group: ESRD requiring chronic hemodialysis for at least 6 months at an established center (not home dialysis).
- NOTE: The approximate date that hemodialysis was initiated should be reported, if known.
- For the normal renal function group: Estimated CrCl (using the Cockcroft-Gault equation) at screening ≥75mL/min.
- Availability of alternative venous access (not used for dialysis) for the purpose of PK sampling.
Key exclusion criteria (25 listed)
- Known allergy or hypersensitivity to either dolutegravir or rilpivirine
- Use of peritoneal dialysis.
- Serious illnesses, other than ESRD, requiring systemic treatment and/or hospitalization within 30 days prior to the Screening Visit.
- Known liver cirrhosis, unstable liver disease (presence of ascites, encephalopathy, coagulopathy, esophageal/gastric varices), Child-Pugh Class A, B, or C, or known biliary abnormalities (except for known Gilbert's syndrome or asymptomatic gallstones).
- Hepatitis B surface antigen or hepatitis C antibody with detectable RNA at screening.
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 |
|---|---|---|
| JULUCA 50Mg-25Mg TabletOne dose of JULUCA will be taken daily for up to 14 days | Drug | Hemodialysis Group, Normal Renal Function Group |
Primary outcome
Dolutegravir (DTG) Ctau
Time frame: 0 to 24 hours post-dose on the intensive study visit
Steady-state plasma Ctau for dolutegravir at the intensive study visit, which occurred between days 11 and 14
Rilpivirine (RPV) Ctau
Time frame: 0 to 24 hours post-dose on the intensive study visit
Steady-state plasma Ctau for rilpivirine at the intensive study visit, which occurred between days 11 and 14
3 secondary outcomes
Safety of DTG
Time frame: 30 days
DTG AUC
Time frame: 0 to 24 hours post-dose on the intensive study visit
DTG Cmax
Time frame: 0 to 24 hours post-dose on the intensive study visit
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39761595Gupta SK, Friedman AN, Desta Z. The steady-state pharmacokinetics of fixed-dose combination dolutegravir+rilpivirine in hemodialysis. AIDS. 2025 Mar 15;39(4):356-361. doi: 10.1097/QAD.0000000000004071. Epub 2024 Nov 22.
- Individual participant dataSharing planned: Yes. All IPD will provided upon request and approval by the investigators or through online data repositories such as Figshare.
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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.
Samir K Gupta, MD principal investigator
Indiana University
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 JULUCA 50Mg-25Mg Tablet in people with HIV/AIDS and ESRD, run by Indiana University at 1 site in United States.
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 12 inclusion and 25 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 5 Jun 2024. 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 States. 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?
Yes. Results are posted in the registry (first posted 21 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Dolutegravir (DTG) Ctau (time frame: 0 to 24 hours post-dose on the intensive study visit). The study lists 2 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 NCT04431518, which also lists 1 linked publication.
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 5 Jun 2024.