The Pharmacokinetics and Safety of IDV/r With NRTIs in HIV/TB co-Infected Patients Receiving Rifampicin - Full Text View

Sponsored by:	The HIV Netherlands Australia Thailand Research Collaboration
Information provided by:	The HIV Netherlands Australia Thailand Research Collaboration
ClinicalTrials.gov Identifier:	NCT00411996

Purpose

We believe that there is a strong rationale for the study of IDV/r 600/100 bid as a boosted-PI combination that, in the presence of RMP, is able to produce a satisfactory PK profile associated with adequate antiretroviral potency, tolerability and efficacy.

Condition	Intervention	Phase
HIV Infections Tuberculosis	Drug: indinavir/ritonavir	Phase I Phase II

MedlinePlus related topics: AIDS Tuberculosis

Drug Information available for: Rifampin Indinavir Ritonavir Indinavir Sulfate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Pharmacokinetics Study
Official Title:	The Pharmacokinetics and Safety of Ritonavir-Boosted Indinavir 600/100mg Bid Combined With NRTIs in ARV naïve HIV/TB co-Infected Patients Receiving Rifampicin Containing Anti-Tuberculosis Therapy

Further study details as provided by The HIV Netherlands Australia Thailand Research Collaboration:

Primary Outcome Measures:

pharmacokinetics of ritonavir-boosted indinavir 600/100mg bid in combination with rifampicin-containing anti-TB therapy. [ Time Frame: 2 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

safety of ritonavir-boosted indinavir 600/100mg bid in combination with rifampicin-containing anti-TB therapy [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
efficacy of ritonavir-boosted indinavir 600/100mg bid in combination with rifampicin-containing anti-TB therapy [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
the prevalence of immune recovery syndrome of TB and other HIV-related conditions after ritonavir-boosted indinavir 600/100mg bid [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	20
Study Start Date:	December 2006
Estimated Study Completion Date:	June 2009
Estimated Primary Completion Date:	October 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator IDV/r 600/100 mg + rifampicin	Drug: indinavir/ritonavir IDV/r 600/100 mg BID + rifampicin OD for at least 2 weeks

Detailed Description:

The fixed-dose combination of d4T+3TC+NVP (GPOvir) has been widely used in Thailand since June 2002. The prevalence of NNRTI resistance has increased since 2005. Efavirenz-based antiretroviral therapy (ART) is preferred in patients with TB/HIV receiving rifampin-containing TB regimens. However, efavirenz cannot be used in the context of NNRTI failure, intolerance or toxicity. The optimal ART in populations receiving rifampicin remains unknown.

Rifabutin, which is recommended in combination with a boosted protease inhibitor (PI/r) is expensive and not available in Thailand and other developing countries. Ritonavir-boosted indinavir (IDV/r) is potent and the cheapest boosted PI available in Thailand. If IDV/r in combination with rifampin demonstrates suitable pharmacokinetics and is well tolerated, this regimen might prove useful and could be widely implemented. However, high rates of gastrointestinal and renal toxicity have been demonstrated in Thai patients receiving standard doses of IDV/r 800/100 BID. We believe that there is a strong rationale to study if IDV/r 600/100 BID in combination with rifampin is able to produce a satisfactory pharmacokinetic profile, with antiretroviral potency, tolerability and efficacy.

Eligibility

Ages Eligible for Study:	18 Years to 60 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Confirmed HIV positive after voluntary counselling and testing
Aged between 18 and 60 years of age
Antiretroviral treatment naive
CD4+ cell count of <200 cells/mm3 at the time of TB diagnosis
ALT <5 times ULN
Serum creatinine <1.4 mg/dl
Haemoglobin >8 mg/L
TB diagnosis; either probable (clinical symptoms plus chest x-ray and response to anti-TB medication) or definitive( sputum AFB culture confirmed) and receiving or planning to receive rifampicin-containing anti-TB therapy for at least a 2 week period before the initiation of ART
No other active OI (CDC class C event)
Able to provide written informed consent

Exclusion Criteria:

Current use of steroids and other immunosuppressive agents
Current use of any prohibited medications related to compliance and drug pharmacokinetics
Patients with current alcohol or illicit substance use that in the opinion of the site Principal Investigator would conflict with any aspect of the conduct of the trial.
Previous exposure to nevirapine monotherapy
Unlikely to be able to remain in follow-up for the protocol defined period
Patients with proven or suspected acute hepatitis. Patients with chronic viral hepatitis are eligible provided ALT, AST < 5 x ULN.
Karnofsky performance score <30%

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00411996

Contacts

Contact: Anchalee Avihingsanon, MD	+66 2 2557334-5 ext 107	anchalee.a@hivnat.org
Contact: Kiat Ruxrungtham, MD	+ 66 2 2557334-5	rkiat@chula.ac.th

Locations

Thailand
HIV-NAT Thai Red Cross AIDS Research Center	Recruiting
Bangkok, Thailand, 10330
Contact: Anchalee Avihingsanon, MD + 66 2 2557334-5 ext 107 anchalee.a@hivnat.org
Contact: Kiat Ruxrungtham, MD +66 2 2557334-5 rkiat@chula.ac.th
Principal Investigator: Kiat Ruxrungtham, MD

Sponsors and Collaborators

The HIV Netherlands Australia Thailand Research Collaboration

Investigators

Principal Investigator:

Kiat Ruxrungtham, MD

HIV-NAT, Thai Red Cross AIDS Research Center

More Information

Additional Information:

The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT) This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	HIV-NAT ( Kiat Ruxrungtham )
Study ID Numbers:	HIV-NAT 044
Study First Received:	December 14, 2006
Last Updated:	March 13, 2008
ClinicalTrials.gov Identifier:	NCT00411996 History of Changes
Health Authority:	Thailand: Food and Drug Administration

Keywords provided by The HIV Netherlands Australia Thailand Research Collaboration:

indinavir/ritonavir
HIV/TB
rifampicin
PK and efficacy of IDV/RTV 600/100 mg BID with rifampicin
Treatment Naive

Study placed in the following topic categories:

Bacterial Infections
HIV Protease Inhibitors
Sexually Transmitted Diseases, Viral
Anti-HIV Agents
Indinavir
Acquired Immunodeficiency Syndrome
Antiviral Agents
Immunologic Deficiency Syndromes
Protease Inhibitors
Virus Diseases
Anti-Bacterial Agents

Rifampin
Gram-Positive Bacterial Infections
Anti-Retroviral Agents
HIV Infections
Ritonavir
Sexually Transmitted Diseases
Mycobacterium Infections
Tuberculosis
Antitubercular Agents
Retroviridae Infections

Additional relevant MeSH terms:

Bacterial Infections
Anti-Infective Agents
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Indinavir
Infection
Rifampin
Anti-Bacterial Agents
Gram-Positive Bacterial Infections
Anti-Retroviral Agents
Therapeutic Uses
Tuberculosis
Retroviridae Infections
Nucleic Acid Synthesis Inhibitors

HIV Protease Inhibitors
RNA Virus Infections
Anti-HIV Agents
Immune System Diseases
Acquired Immunodeficiency Syndrome
Enzyme Inhibitors
Antiviral Agents
Immunologic Deficiency Syndromes
Actinomycetales Infections
Pharmacologic Actions
Protease Inhibitors
Antibiotics, Antitubercular
Virus Diseases
HIV Infections
Ritonavir

ClinicalTrials.gov processed this record on May 06, 2009