Interaction Between High Dose Rifampicine and Efavirenz in Pulmonary Tuberculosis and HIV Co-infection

NCT01986543 | Unknown Phase 2 DMC

• 1 other identifier: ANRS 12292 RIFAVIRENZ
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 1

Brief Summary

We propose a first interaction study between efavirenz (EFV) and R20mg/Kg taking into consideration the absence of data about R induction at this dose. Due to an important inter-patient variability of the CYP2B6 polymorphism, the EFV pharmacokinetic (Pk) will be compared in same patients with and without TB treatment. The main objective is to compare the Pk parameters of EFV in HIV-TB co-infected patients, with and without TB treatment, using R at 10 and 20mg/Kg/day and EFV at 600 and 800mg/day.

Conditions

Tuberculosis; HIV

Keywords

Pharmacokinetic

Outcome Measures

Primary Outcomes (2)

• Efavirenz through concentration before drug intake (Cmin); maximal concentration (Cmax); time to achieve the Cmax (Tmax) and area under the curve of concentrations vs time at steady state during a 24-hour dosing interval (AUC0-24)

  Week 8

• Efavirenz Cmin; Cmax; Tmax; AUC0-24

  Week 28

Secondary Outcomes (5)

• Pharmacokinetic parameters of R and H (Cmin, Cmax and AUC0-24)

  Week 2

• Pharmacokinetic parameters of R and H (Cmin, Cmax and AUC0-24)

  Week 8

• Mycobacterium tuberculosis culture of sputum

  week 8

• Plasma HIV-1 RNA

  week 28

• Grade 3 and 4 adverse events

  0-28 weeks

Study Arms (3)

Arm 1

EXPERIMENTAL

8 weeks R20mg/Kg + HZE and efavirenz 600mg

Drug: drug administration

Arm 2

EXPERIMENTAL

8 weeks R20mg/Kg + HZE and efavirenz 800mg

Drug: drug administration

Standard arm

ACTIVE COMPARATOR

8 weeks R10mg/Kg + HZE and efavirenz 600mg

Drug: drug administration

Interventions

drug administration DRUG

Arm 1; Arm 2; Standard arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged of 18 years or more
• Diagnosis of new pulmonary tuberculosis confirmed by a XpertMTB/RIF test
• Positive HIV antibody test, naïve of ART with CD4 cell count between 50 and 250cells/mm3
• For women of childbearing age, to have a negative urine test for pregnancy on the day of enrolment and to accept to take a barrier contraception during the period of the trial
• Participants well enough to receive ambulatory treatment
• Weight \> 45Kg
• Home address readily accessible
• Participants providing informed consent to participate in the trial

You may not qualify if:

• Rifampicin drug resistance based on the XpertMTB/RIF result confirmed by the GenotypeMTBDRplus assay
• Concomitant opportunistic infection requiring additional infectious medication
• Karnofsky score \<80%
• ALAT or bilirubin \> 5.0 x ULN (hepatitis grade 3 or 4)
• Haemoglobin \< 7.5g/dL (grade 3 or 4)
• Grade 4 clinical sign or biological result according to the ANRS for grading the intensity of adverse events
• Patient not able to give his informed consent or is unlikely or unable to cooperate with sampling procedures
• Patient suffering of psychiatric illness, which may prevent follow-up according to the protocol
• Patients receiving or requiring medications that may interfere with study drugs

Sponsors & Collaborators

• ANRS, Emerging Infectious Diseases: lead

Study Sites (1)

Mbarara Research Base

Mbarara PO Box 1956, Mbarara, Uganda

Location

MeSH Terms

Conditions

Tuberculosis

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• BONNET Maryline, MD

  Epicentre MSF

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2013
• First Posted: November 18, 2013
• Study Start: December 1, 2013
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2017
• Last Updated: July 11, 2017

Record last verified: 2017-07

Locations

UG (1)