Tipranavir/Ritonavir Low Dose Pharmacokinetics in Treatment Naive Patients

HIV Infections Clinical Trial

Official title:

A Multicenter, Randomized, Open Label, Clinical Trial to Evaluate Three Doses of Tipranavir Boosted With Ritonavir (500 mg/200 mg qd, 250 mg/100 mg Bid and 500 mg/100 mg Bid) by Assessing the Steady-state Pharmacokinetics and Short-term Efficacy and Safety in HIV-1 Positive Treatment naïve Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00530920
• Other study ID #: 1182.107
• Status: Completed
• Phase: Phase 2
• First received: September 17, 2007
• Last updated: May 27, 2014
• Start date: October 2007

Study information

• Verified date: May 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Comitato Etico Per La Sperimentazione Clinica Dei Medicinali Az. San. - Firenze
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to identify an optimal dose combination(s) of tipranavir (TPV) and ritonavir (RTV) for antiretroviral treatment naïve HIV-1 infected patients that can be used in pivotal trial by assessing the steady-state pharmacokinetics and short-term efficacy and safety

Recruitment information / eligibility

• Status: Completed
• Enrollment: 85
• Est. primary completion date: May 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Signed informed consent in accordance with GCP and local regulatory requirements prior to trial participation.

• HIV-1 infected men and non-pregnant women who are treatment naïve, with positive serology (EIA) confirmed by Western blot.

• Age > 18 and < 65 years.

• CD4 > 200 cells/mm3

• Viral load (HIV-1 mRNA viral load) > 5,000 copies/mL.

• Ability to swallow multiple large capsules without difficulty.

• Acceptable laboratory values that indicate adequate baseline organ function at screening visit.

• Laboratory values are considered to be acceptable if the severity of any parameter is = < Grade 2, based on the DAIDS/ACTG Grading Scale (see Appendix 10.2).

• Acceptable medical history, physical examination, and 12-lead ECG at screening

• Willingness to abstain from the following starting 2 weeks prior to administration of any study medication and up until the end of the study:

o Grapefruit or grapefruit juice, Seville oranges, St. John's Wort, and Milk Thistle.

• Willingness to abstain from alcohol 3 days prior to administration of any study medication up to the end of the study.

• Willingness to abstain from the following starting 3 days prior to PK sampling:

o Garlic supplements and methylxanthine containing foods or drinks (including coffee, tea, cola, energy drinks, chocolate, etc.).

• Willingness to abstain from over-the-counter herbal medications for the duration of the study.

• Willingness to abstain from any over the counter medication 7 days prior to administration of any study medication (including vitamins, minerals, dietary supplements and antacids) during the study until completion of the post study assessments.

Exclusion Criteria:

• Female patients of reproductive potential who:

• Have positive serum pregnancy test.

• Have not been using a barrier method of contraception for at least 3 months prior to participation in the study.

• Are not willing to use a reliable method of barrier contraception (such as diaphragm with spermicidal cream/jelly or condoms with spermicidal foam), during and 60 days after completion/termination of the trial.

• Are breast-feeding.

• Suspected or documented seroconversion within last 6 months

• Participation in another trial with an investigational medicine within 2 months prior to Day 0 of this study.

• Use of any pharmacological contraceptive (including oral, patch or injectable contraceptives) within 1 month prior to Day 0 and for the duration of the study.

• Use of hormone replacement therapy within 1 month prior to Day 0 and anytime during the study.

• History of acute illness within 30 days prior to Day 0.

• Have evidence of active or acute HBV or HCV.

• Alcohol or substance abuse within 1 year prior to screening or during the study.

• Patients with a history of any illness or allergy that, in the opinion of the investigator, might confound the results of the study or pose additional risk in administering TPV.

• Patients who have taken (within 7 days prior to Day 0) any over-the-counter or prescription medication that, in the opinion of the investigator in consultation with the BI clinical monitor, might interfere with absorption, distribution, or metabolism of the study medications.

• Known hypersensitivity to any ingredients of the test drug.

• Inability to adhere to the protocol.

• Genotypic resistance to tipranavir (defined as a TPV mutation score > 4).

Study Design

Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• tipranavir

• ritonavir

Locations

Country	Name	City	State
Germany	1182.107.49002 Boehringer Ingelheim Investigational Site	Berlin
Germany	1182.107.49004 Boehringer Ingelheim Investigational Site	Berlin
Germany	1182.107.49003 Boehringer Ingelheim Investigational Site	Frankfurt/Main
Germany	1182.107.49001 Boehringer Ingelheim Investigational Site	München
Italy	1182.107.39001 Boehringer Ingelheim Investigational Site	Antella (fi)
Italy	1182.107.39009 Boehringer Ingelheim Investigational Site	Bari
Italy	1182.107.39007 Boehringer Ingelheim Investigational Site	Ferrara
Italy	1182.107.39011 Boehringer Ingelheim Investigational Site	Palermo
Spain	1182.107.34001 Boehringer Ingelheim Investigational Site	Barcelona
Spain	1182.107.34002 Boehringer Ingelheim Investigational Site	Barcelona
Spain	1182.107.34003 Boehringer Ingelheim Investigational Site	L'Hospitalet de Llobregat
Spain	1182.107.34004 Boehringer Ingelheim Investigational Site	Madrid

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

Germany,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Viral Load (log10 Copies/mL) Change From Baseline (Last Observation Carried Forward (LOCF))		Baseline (Day 0) to Final (Day 14)	No
Secondary	Apparent Oral Clearance I(Cl/F) of Tipranavir	Tipranavir pharmacokinetics - Clearance (CL) is defined as the dose of a drug divided by the area-under-the-concentration-time curve (AUC), ie. CL = Dose / AUC. For extravascu-lar models the fraction of dose absorbed cannot be estimated, therefore "clear-ance" for these models is actually Cl/F where F is the fraction of the drug dose which is absorbed.	Final (Day 14)	No
Secondary	Area Under the Curve(AUC) of Tipranavir 24 h for Once Daily (QD) and AUC 12 h for Twice Daily (BID)	Tipranavir (TPV) pharmacokinetics	Final (Day 13 for QD, Day 14 for BID)	No
Secondary	Concentration-24 Hour (hr) Post Dose of Tipranavir - (Cp 24 h for QD and 12 hr Post Dose (CP 12h) for BID	TPV pharmacokinetics	Final (Day 13 for QD, Day 14 for BID)	No
Secondary	Trough Concentration (Cmin) of Tipranavir	TPV pharmacokinetics	Final (Day 13 for QD, Day 14 for BID)	No
Secondary	Maximum Concentration (Cmax) of Tipranavir	TPV pharmacokinetics	Final (Day 13 for QD, Day 14 for BID)	No
Secondary	Volume of Distribution (V/F) of Tipranavir	Tipranavir pharmacokinetics	Final (Day 14)	No
Secondary	Terminal Half-Life (t1/2) of Tipranavir	Tipranavir pharmacokinetics	Final (Day 14)	No
Secondary	Time to Cmax (Tmax) of Tipranavir	Tipranavir pharmacokinetics	Final (Day 14)	No
Secondary	AUC 24 of Ritonavir for QD and AUC 12 of Ritonavir for BID	Ritonavir pharmacokinetics	Final (Day 13 for QD, Day 14 for BID)	No
Secondary	Cp 24 h of Ritonavir for QD and CP 12 h of Ritonavir for BID	Ritonavir pharmacokinetics	Final (Day 13 for QD, Day 14 for BID)	No
Secondary	Apparent Oral Clearance I(Cl/F) of Ritonavir	Ritonavir pharmacokinetics	Final (Day 13 for QD, Day 14 for BID)	No
Secondary	Volume of Distribution (V/F) of Ritonavir	Ritonavir pharmacokinetics	Final (Day 14)	No
Secondary	Terminal Half-Life (t1/2) of Ritonavir	Ritonavir pharmacokinetics	Final (Day 14)	No
Secondary	Tmax of Ritonavir	Ritonavir pharmacokinetics	Final (Day 14)	No
Secondary	Cmax of Ritonavir	Ritonavir pharmacokinetics	Visits baseline, 5, 7, 9 and 13 or 14	No
Secondary	Clinical Abnormal Findings in Laboratory and Physical Examination		Screening through the end of the study (14 days)	Yes