Effect of Steady State TPV/r on Intracellular Concentrations of Zidovudine and Carbovir for Patients With HIV

Effect of Steady State TPV/r 500 mg/200 mg on Intracellular Concentrations of Zidovudine Triphosphate and Carbovir Triphosphate

To determine the effect of steady-state tipranavir 500 mg/ritonavir 200 mg (TPV/r) on intracellular concentrations of zidovudine triphosphate (ZDV-TP) and carbovir triphosphate (CBV-TP) and plasma viral load

Study Overview

• Status: Terminated
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Tipranavir capsules; Drug: Ritonavir capsules

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Signed informed consent before study participation
2. Age >18 and <60 years
3. Female patients of child-bearing potential who use a barrier contraceptive method for at least 12 weeks before administration of study medication, during the study and for 28 days after administration of study medication has ended and who have a negative pregnancy test result
4. Ability to swallow capsules without difficulty
5. A Body Mass Index (BMI) between 18 and 29 kg/m2
6. Reasonable probability of completing the study
7. A medical history, physical examination, and electrocardiogram (ECG) before entering the study
8. Agreement to abstain from alcohol from Day -2 to Day 24
9. Agreement to abstain from ingesting grapefruit, grapefruit juice, Seville oranges or orange marmalade from Day -2 to Day 24
10. Negative urine drug screen for drugs of abuse
11. Documented HIV-1 RNA load (by PCR) at screening of <50 copies/mL for at least 3 months and on a stable ZDV or ABC regimen for at least 6 months. Acceptable documentation included laboratory data, letter, or verbal report from another provider noted in the patient's records
12. All HIV-infected patients must be TPV naïve and must not have received a PI based regimen within 6 months of enrollment

Exclusion Criteria:

1. Female patients who had a positive serum pregnancy test during the screening period of Day -14 to Day -7 or who plan to breast-feed at time (Day 0 to 30 after TPV/r administration)
2. Use of any other investigational medicine within 30 days before Day 0
3. Use of any known CYP3A4 altering drug (i.e., phenothiazines, cimetidine, barbiturates, ketoconazole, fluconazole, rifampin, steroids and herbal medications) within 30 days before Day 0. No antibiotics were permitted within 10 days before Day 0
4. Ingestion of grapefruit, grapefruit juice, Seville oranges, or orange marmalade within 2 days of study entry (Day 0)
5. Blood or plasma donations (>100 mL total) for research or altruistic reasons within 30 days before Day 0
6. Seated systolic blood pressure either <100 mm Hg or >150 mm Hg; resting heart rate either <50 beats/minute or >90 beats/minute
7. History of any illness (including malabsorption, irregular food intake, gastrointestinal intolerance, or allergy) that, in the opinion of the investigator, might confound the results of the study or pose additional risks in administering TPV/r
8. Any acute illness within 2 weeks before Day 0
9. Patients who were currently taking any over-the-counter medication within 7 days before Day 0, or who were currently taking any prescription drug that, in the opinion of the investigator (in consultation with the BI medical monitor or pharmacokineticist), would have interfered with either the absorption, distribution, or metabolism of TPV or ritonavir
10. Hypersensitivity to TPV, ritonavir, or sulfonamide containing drugs, or antiretroviral drugs (marketed or experimental use as part of clinical research studies)
11. Sulfonamide allergy, that in the opinion of the investigator, might confound the results of the study or pose additional risks in administering TPV/r
12. Any laboratory value outside the normal reference range that is of clinical relevance at screening, according to the judgment of the investigator (i.e., aspartate aminotransferase and alanine aminotransferase levels 2.5-fold and 2.5-fold higher than the upper normal limit, respectively)
13. Based on the compliance diary, the patient had less than 100% documented compliance for 7-14 days of background Antiretroviral (ARV) (i.e., ZDV and ABC) medications before Day -5 to 0 (visit 2)
14. Use of any protease inhibitors (i.e., fosamprenavir, amprenavir, indinavir, saquinavir, lopinavir, ritonavir, atazanavir, and nelfinavir) within 6 months of enrollment
15. Patients who are co-infected with active Hepatitis B and/or C as determined by hepatitis serology.
16. Use of any anti-platelet medications (e.g. aspirin, dipyridamole, clopidogrel, or any over the counter anti-platelet medicine).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TPV/r (Tipranavir co-administered with low dose ritonavir)	Drug: Tipranavir capsules; Drug: Ritonavir capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
AUC0-12h (Area under curve) of intracellular ZDV-TP	Up to 12 hours after drug administration
AUC0-12h (Area under curve) of carbovir-TP	Up to 12 hours after drug administration

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of patients with clinical significant findings in vital sings	Up to 14 days after last drug administration
Number of patients with clinical significant findings in physical examinations	Up to 14 days after last drug administration
Number of patients with clinical significant findings in laboratory measurements	Up to 14 days after last drug administration
Concentration of Zidovudine (ZDV) in plasma	Up to 14 days after drug administration
Concentration of Abacavir (ABC) in plasma	Up to 14 days after drug administration
Concentration of Tipranavir (TPV) in plasma	Up to 14 days after drug administration
Concentration of ritonavir in plasma	Up to 14 days after drug administration
Cmax (Maximum observed concentration)	Up to 14 days after drug administration
Cp12h (Trough plasma concentration)	Up to 14 days after drug administration
AUC0-12h (Area under curve)	Up to 14 days after drug administration
Number of patients with adverse events	Up to 14 days after last drug adminnistration
Percentage of patients with viral load (VL) <50	Up to 14 days after last drug adminnistration

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: August 1, 2006
• Primary Completion (Actual): September 1, 2007

Study Registration Dates

• First Submitted: August 28, 2014
• First Submitted That Met QC Criteria: August 28, 2014
• First Posted (Estimate): September 1, 2014

Study Record Updates

• Last Update Posted (Estimate): September 1, 2014
• Last Update Submitted That Met QC Criteria: August 28, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Ritonavir; Tipranavir
• Other Study ID Numbers: 1182.109