SPRING: Safety, Efficacy, Pharmacokinetics of tipRanavir/r IN Race/Gender HIV+ Patients Randomized to TDM or SoC

Boehringer Ingelheim

Status and phase: Terminated; Phase 3

Conditions: HIV Infections

Treatments: Drug: ritonavir; Drug: tipranavir; Drug: Optimized Background Regimen (OBR)

Study type: Interventional

Funder types: Industry

Identifiers

NCT00440271

EudraCT No.: 2005-005264-86

1182.98

Details and patient eligibility

About

The primary purpose of this study is to:

1. Demonstrate the safety and efficacy of tipranavir/ritonavir (TPV/r) among a racially diverse HIV+ population (males and females) who are three-class (nucleoside reverse transcriptase inhibitor (NRTI), non-nucleoside reverse transcriptase inhibitor (NNRTI), and protease inhibitor (PI)) experienced with documented resistance to more than one PI.
2. Determine pharmacokinetic data in this racially and gender diverse population.
3. Determine the potential utility of using therapeutic drug monitoring (TDM) in improving efficacy outcomes.

Enrollment: 33 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Main inclusion criteria for the study are:

1. HIV-1 infected adults, men and women at least 18 years of age.
2. 3-class (nucleoside reverse transcriptase inhibitor (NRTI), non-nucleoside reverse transcriptase inhibitor (NNRTI), and protease inhibitor (PI)) treatment-experienced (min of 3-months duration for each class) with resistance to more than one PI (on screening resistance testing). NNRTI-naïve patients who have genotypically documented NNRTI-resistance mutations on past or screening resistance testing would be eligible.
3. CD4+ T lymphocyte count >=50 cells/mm3.
4. HIV-1 viral load >=1,000 copies/mL at screening.
5. The antiretroviral (ARV) study treatment regimen must consist of TPV/r in combo with an optimized background regimen (OBR) of 2-4 agents: N(t)RTIs (NRTI or NtRTI), enfuvirtide (ENF), and/or, where available, a trial approved expanded access program (EAP) investigational agent.
6. Acceptable screening laboratory values that indicate adequate baseline organ function.
7. Acceptable medical history with a chest X-ray without evidence of active disease and an electrocardiogram (ECG) without clinically important abnormalities within one year of the study.
8. A reliable method of barrier contraception will be used by all female patients who are of childbearing potential.

Exclusion criteria

Main exclusion criteria for the study are:

1. Known hypersensitivity to the tipranavir (TPV) or ritonavir (RTV).
2. ARV medication naïve.
3. Genotypic resistance to TPV (defined as a TPV mutation score >7).
4. Patients on recent drug holiday, defined as off antiretroviral (ARV) medications for at least 7 consecutive days within the month prior to screening.
5. Prior tipranavir use.
6. Inability to adhere to the requirements of the protocol.
7. Patients with prior history of hemorrhagic stroke or intracranial aneurysm.
8. Patients with a history of ischemic stroke, neurosurgery or skull trauma within 4 weeks prior to screening.
9. History of Progressive Multifocal Leukoencephalopathy, Visceral Kaposi's Sarcoma, and/or any malignancy.
10. Any acquired immunodeficiency syndrome (AIDS) defining illness that is unresolved, symptomatic or not stable on treatment for at least 12 weeks at screening visit.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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33 participants in 2 patient groups

Standard of Care (SoC)

Other group

Description:

Standard of Care (SOC) Arm = Tipranavir/ritonavir (TPV/r) capsules taken orally at a dose of 500 mg/200 mg twice a day (BID) plus optimized background regimen (OBR). No TPV/r dose changes were permitted.

Treatment:

Drug: ritonavir

Drug: tipranavir

Drug: Optimized Background Regimen (OBR)

Therapeutic Drug Monitoring (TDM)

Other group

Description:

Therapeutic Drug Monitoring (TDM) Arm = Patients began by receiving standard of care (SOC) tipranavir/ritonavir (TPV/r) capsules orally at a dose of 500 mg/200 mg twice a day (BID) plus optimized background regimen (OBR) followed, if needed, by TPV or ritonavir (RTV) dose adjustments at Week 4, 6, 10, 14, 18, 22, 26 and 30 based on viral response, phenotypic inhibitory quotient (IQ), and TPV trough concentrations.

Treatment:

Drug: ritonavir

Drug: tipranavir

Drug: Optimized Background Regimen (OBR)