PK of JULUCA in Hemodialysis
PK of JULUCA in Hemodialysis
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.
The pharmacokinetics of dolutegravir and rilpivirine, the components of JULUCA, in patients
 with end stage renal disease requiring hemodialysis 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.
Inclusion Criteria:

 1. Negative HIV antibody testing at screening.

 2. 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 >90mL/min.

 3. Availability of alternative venous access (not used for dialysis) for the purpose of
 PK sampling.

 4. The following laboratory values obtained within 30 days prior to study entry (obtained
 either at screening or done as part of routine clinical care):

 -  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

 5. 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.

 6. Males and females, age 18-65 years.

 7. Ability and willingness of participant or legal guardian/representative to provide
 written informed consent.

 Exclusion Criteria:

 1. Known allergy or hypersensitivity to either dolutegravir or rilpivirine

 2. Use of peritoneal dialysis.

 3. Serious illnesses, other than ESRD, requiring systemic treatment and/or
 hospitalization within 30 days prior to the Screening Visit.

 4. 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).

 5. Hepatitis B surface antigen or hepatitis C antibody with detectable RNA at screening.

 6. Known gastrointestinal disease that may lead to poor absorption of the study drugs.

 7. Known hereditary problems of galactose intolerance, total lactase deficiency, or
 glucose-galactose malabsorption.

 8. 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

 9. 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.

 10. Use of proton pump inhibitors within 7 days of initiating study drug (H2 blockers are
 permitted).

 11. Pregnancy and/or breast-feeding.

 12. Moderate to severe depression, defined as a PHQ-9 ≥ 10 at Screening.

 13. 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.

 14. QTc interval greater than 480 msec at Screening.