Pharmacokinetics and Safety of Double-dose Dolutegravir When Used With Rifapentine for HIV-associated Tuberculosis
- Conditions
- HIV-associated Tuberculosis
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- Not specified
Inclusion Criteria:<br><br> 1. Individuals =18 years of age at study entry.<br><br> 2. Weight =40 kg.<br><br> 3. Body mass index (BMI) >18.5 kg/m2.<br><br> 4. Ability and willingness of participant or legal guardian/representative to provide<br> informed consent.<br><br> 5. Documentation of HIV-1 status.<br><br> 6. CD4+ cell count =100 cells/mm3 obtained within 30 days prior to study entry at any<br> network-approved non-US laboratory that is IQA certified.<br><br> 7. ART-naïve or not on ART for 12 consecutive weeks prior to TB diagnosis.<br><br> 8. Willingness and eligibility to start DTG-based ART at 6 weeks, with a window of ±1<br> week, after starting TB treatment, with no intention to change ART for the duration<br> of the study.<br><br> 9. Documentation of pulmonary TB.<br><br> 10. Willingness to start 2HPZM/2HPM therapy for DS-TB.<br><br> 11. The following laboratory values obtained within 30 days prior to study entry:<br><br> - Absolute neutrophil count (ANC) >750 cells/mm3<br><br> - Hemoglobin =7.4 g/dL<br><br> - Platelet count =50,000/mm3<br><br> - Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase<br> [SGOT]) <2.5 X the upper limit of normal (ULN)<br><br> - Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT])<br> <2.5 x ULN<br><br> - Total bilirubin =1.5 x ULN<br><br> - Creatinine <1.3 x ULN<br><br> 12. For participants who can become pregnant, negative serum or urine pregnancy test at<br> screening within 30 days prior to entry and within 48 hours prior to entry.<br><br> 13. Participants who can become pregnant must agree not to participate in the conception<br> process and if participating in sexual activity that could lead to pregnancy, must<br> agree to use one reliable nonhormonal method of contraception.<br><br> 14. Documentation of Karnofsky performance score =50 within 30 days prior to entry.<br><br>Exclusion Criteria:<br><br> 1. Breastfeeding, pregnant, or plans to become pregnant.<br><br> 2. Known allergy/sensitivity or any hypersensitivity to components of the study drugs,<br> or their formulations.<br><br> 3. Active drug or alcohol use or dependence that, in the opinion of the site<br> investigator, would interfere with adherence to study requirements.<br><br> 4. Requirement for ongoing use of drugs that are known to have significant drug-drug<br> interactions with DTG or RPT.<br><br> 5. Known history of acute intermittent porphyria.<br><br> 6. Previous treatment for active TB disease.<br><br> 7. More than 5 days of treatment directed against active TB for the current TB episode<br> preceding study entry.<br><br> 8. At the time of study entry, documentation of an M. tuberculosis isolate from the<br> current or previous treatment episode known to be resistant to RIF or INH.<br><br> 9. Known history of prolonged QT syndrome.<br><br> 10. Known cirrhosis, a history of decompensated liver disease (ascites, hepatic<br> encephalopathy, or esophageal varices).<br><br> 11. Documentation of severe opportunistic infections, in the opinion of the site<br> investigator, within 3 months of study entry.<br><br> 12. Documentation of severe extra-pulmonary TB (e.g., meningitis, osteomyelitis,<br> disseminated TB) at the time of screening.<br><br> 13. Acute gout at the time of screening.
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Model-simulated 5th percentile and corresponding 95% confidence interval of DTG minimum concentrations (Cmin) at 50 mg BID when co-administered with daily RPT 1200 mg plus HZM
- Secondary Outcome Measures
Name Time Method DTG minimum concentration (Cmin);DTG minimum concentration (Cmax);DTG area under the concentration-time curve (AUC0-24);Number of participants who experience Grade 3 or higher AEs;Number of participants who have a diagnosis of rifamycin hypersensitivity;Number of participants who experience ALT =3xULN with symptoms/jaundice or ALT =5xULN;Number of participants who prematurely discontinue study drugs DTG and/or RPT;Proportion of participants with HIV-1 viral load below 50 copies/mL