Tipranavir Dose-response Study Using a Prototype Self-emulsifying Drug Delivery System (SEDDS) Formulation in Treatment-naive HIV-1 Infected Patients Report on the Post-study Option, a Treatment of Triple Therapy With Delavirdine, ZDV and 3TC Without Tipranavir

Study Overview
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Brief Summary
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To investigate the safety of a standard triple therapy regimen of delavirdine (DLV), zidovudine (ZDV), and lamivudine (3TC) following 14 days of experimental treatment with regimens of tipranavir (TPV) with and without ritonavir (RTV)

Official Title
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Tipranavir (PNU-140690): A Fourteen Day Dose-response Study Using a Prototype Self-emulsifying Drug Delivery System (SEDDS) Formulation in Treatment-naive HIV-1 Infected Patients. Report on the Post-study Option, a 46-week Treatment Period of Triple Therapy With Delavirdine, ZDV and 3TC Without Tipranavir

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Tipranavir (TPV)
* Drug: Ritonavir (RTV)
* Drug: Delavirdine (DLV)
* Drug: Zidovudine (ZDV)
* Drug: Lamivudine (3TC)
* Drug: Stavudine (d4T)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV-1 RNA ≥ 5,000 copies/mL by Roche Amplicor assay CD4 cell count ≥ 50 cells/mm3 Karnofsky performance status ≥ 80 Age ≥ 13 years Screening laboratory values indicative of adequate baseline organ function, Grade 0 or 1 for laboratory values based on the ACTG toxicity scale grade. Selected stable [2 months or longer] Grade 2 laboratory abnormalities were subject to sponsor's approval Acceptable medical history and physical examination Agreement to use a barrier contraceptive method for at least 1 month prior to the administration of the study medication, during the study, and for 30 days after the end of the study Signed informed consent To enter the post-study option, patients have to have completed the 14-day tipranavir phase of the trial Exclusion Criteria: Previous treatment with any antiretroviral drugs for more than 2 weeks Clinically significant, active and/or acute (onset within the prior month) medical problems including opportunistic infections, such as active cryptococcosis, Pneumocystis carinii pneumonia (PCP), herpes zoster, histoplasmosis or cytomegalovirus (CMV) , or non-opportunistic diseases including, but not limited to, progressive multifocal leukoencephalopathy, lymphoma, or malignancy requiring systemic therapy History of clinically significant nervous system or muscle diseases, seizure disorder, or psychiatric disorder that might impair compliance with the study Receipt of any known enzyme-inducing drugs including rifabutin, rifampin, carbamazepine, dexamethasone, phenobarbital, phenytoin, sulfamidine, sulfinpyrazone, or troleandomycin within 30 days prior to participation in the study Receipt of any investigational medication within 30 days prior to participation in the study Receipt of oral contraceptives within 30 days prior to participation in the study Pregnancy or lactation (serum ß-human chorionic gonadotropin (ß-HCG) test negative at second screen visit of the tipranavir phase of trial) Evidence of active substance abuse that, in the investigator's opinion, could affect study adherence In the investigator's judgment, inability to comply with the protocol requirements for reasons other than those specified above

Ages Eligible for Study
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Minimum Age: 13 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment of HIV- infected patients<br>14 days treatment with tipranavir, ritonavir, then 46 weeks of triple- treatment with delavirdine, zidovudine and lamivudine (stavudine for patients intolerant of zidovudine) | Drug: Tipranavir (TPV)<br> <br> Drug: Ritonavir (RTV)<br> <br> Drug: Delavirdine (DLV)<br> <br> Drug: Zidovudine (ZDV)<br> <br> Drug: Lamivudine (3TC)<br> <br> Drug: Stavudine (d4T)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with treatment-emergent adverse events |  | Up to 46 weeks | 
| Number of patients with drug-related adverse events |  | Up to 46 weeks | 
| Number of patients with AIDS clinical trials group (ACTG) grade 3 or 4 toxicity |  | Up to 46 weeks | 
| Number of patients with a treatment toxicity leading to study discontinuation |  | Up to 46 weeks | 
| Number of patients with serious treatment-emergent adverse events |  | Up to 46 weeks | 
| Number of patients with changes in laboratory parameters | Only lab values associated with metabolic disorders | Up to 46 weeks |