Clinical Evaluation of Adjusted Doses of Darunavir/Ritonavir With Rifampicin in HIV-infected Volunteers

• Status: Terminated
• Trial end date: 2018-11-22
• Target enrollment: 0
• Participant gender: All

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 without rifampicin.

3. Twenty-eight volunteers will be enrolled for a target of 24 participants completing the study.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Cape Town
• Collaborators: Desmond Tutu HIV Centre; Wits Reproductive Health and HIV Institute
• Treatments: Darunavir; Rifampin; Ritonavir

Criteria

Inclusion Criteria

• 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

• 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