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

HIV Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02229760
• Other study ID #: 1182.109
• Status: Terminated
• Phase: Phase 1/Phase 2
• First received: August 28, 2014
• Last updated: August 28, 2014
• Start date: August 2006

Study information

• Verified date: August 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. primary completion date: September 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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 Design

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Tipranavir capsules

• Ritonavir capsules

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AUC0-12h (Area under curve) of intracellular ZDV-TP		Up to 12 hours after drug administration	No
Primary	AUC0-12h (Area under curve) of carbovir-TP		Up to 12 hours after drug administration	No
Secondary	Number of patients with clinical significant findings in vital sings		Up to 14 days after last drug administration	No
Secondary	Number of patients with clinical significant findings in physical examinations		Up to 14 days after last drug administration	No
Secondary	Number of patients with clinical significant findings in laboratory measurements		Up to 14 days after last drug administration	No
Secondary	Concentration of Zidovudine (ZDV) in plasma		Up to 14 days after drug administration	No
Secondary	Concentration of Abacavir (ABC) in plasma		Up to 14 days after drug administration	No
Secondary	Concentration of Tipranavir (TPV) in plasma		Up to 14 days after drug administration	No
Secondary	Concentration of ritonavir in plasma		Up to 14 days after drug administration	No
Secondary	Cmax (Maximum observed concentration)		Up to 14 days after drug administration	No
Secondary	Cp12h (Trough plasma concentration)		Up to 14 days after drug administration	No
Secondary	AUC0-12h (Area under curve)		Up to 14 days after drug administration	No
Secondary	Number of patients with adverse events		Up to 14 days after last drug adminnistration	No
Secondary	Percentage of patients with viral load (VL) <50		Up to 14 days after last drug adminnistration	No

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