NCT02251223

Brief Summary

Primary: Sequentially determine the effects of three dose combinations of tipranavir (TPV) / ritonavir (RTV) (administered b.i.d.), TPV 1250 mg/RTV 100 mg vs. TPV 750 mg/RTV 100 mg vs. TPV 250 mg/RTV 200 mg on the steady-state pharmacokinetics of zidovudine, lamivudine, stavudine, didanosine, abacavir, nevirapine and efavirenz at approved doses. The three treatment groups will be enrolled sequentially starting with the highest tipranavir dosage group first and ending with the lowest tipranavir dosage group. Secondary: A) To assess the effects of zidovudine, lamivudine, stavudine, didanosine, abacavir, nevirapine, and efavirenz on the pharmacokinetics of tipranavir/ritonavir compared to historical controls. B) To assess the safety of three tipranavir/ritonavir combinations when used in combination with protocol defined antiretrovirals.

Trial Health

100
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
208

participants targeted

Target at P75+ for phase_1 hiv-infections

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 1, 2001

Completed
1 year until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2002

Completed
12.7 years until next milestone

First Submitted

Initial submission to the registry

September 25, 2014

Completed
4 days until next milestone

First Posted

Study publicly available on registry

September 29, 2014

Completed
Last Updated

September 29, 2014

Status Verified

September 1, 2014

Enrollment Period

1 year

First QC Date

September 25, 2014

Last Update Submit

September 25, 2014

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (3)

  • Change in trough plasma concentration (Cmin,ss) for non-nucleoside reverse transcriptase inhibitor (NNRTI)

    stratified by substance

    baseline, up to day 23

  • Change in area under plasma concentration-time curve over dosing interval (AUC0-τ) for nucleoside reverse transcriptase inhibitor (NRTI)

    stratified by substance

    baseline, up to day 22

  • Change in area under plasma concentration-time curve from 0 to 12 hours for didanosine (ddI)

    baseline, up to day 22

Secondary Outcomes (10)

  • Cmin,ss

    up to day 23

  • AUC0-τ

    up to day 23

  • Maximum plasma concentration (Cmax)

    up to day 23

  • Time of maximum plasma concentration (Tmax)

    up to day 23

  • Oral clearance (Cl/F)

    up to day 23

  • +5 more secondary outcomes

Study Arms (3)

TPV/r low dose

EXPERIMENTAL
Drug: Tipranavir low doseDrug: Ritonavir high dose

TPV/r medium dose

EXPERIMENTAL
Drug: Tipranavir medium doseDrug: Ritonavir low dose

TPV/r high dose

EXPERIMENTAL
Drug: Tipranavir high doseDrug: Ritonavir low dose

Interventions

Tipranavir low doseDRUG
TPV/r low dose
Tipranavir medium doseDRUG
TPV/r medium dose
Tipranavir high doseDRUG
TPV/r high dose
Ritonavir low doseDRUG
TPV/r high doseTPV/r medium dose
Ritonavir high doseDRUG
TPV/r low dose

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Signed informed consent prior to trial participation
  • Between 18 and 75 years of age inclusive
  • Female subjects of child bearing potential are required to use a barrier contraceptive method for at least 12 weeks prior to administration of study medication, during study medication administration, and for 28 days after the end of the study
  • Ability to swallow capsules without difficulty
  • A Body Mass Index (BMI) between 11 and 50 kg/m2
  • Reasonable probability for completion of the study
  • Acceptable screening laboratory values. All laboratory values ≤ Grade I (e.g., creatine phosphokinase (CPK), amylase, triglycerides) are permissible if documentation of stability for 2 months or more is available. Abnormalities \> Grade I are subject to approval by BI clinical monitor or designee
  • Acceptable medical history, physical examination, ECG, and chest X-ray prior to entering the treatment phase of the study
  • Willingness to abstain from alcohol from Day -2 to Day 23
  • Willingness to abstain from ingesting grapefruit, grapefruit juice, Seville oranges or orange marmalade from Day -2 to Day 23
  • Negative urine drug screen for drugs of abuse. Subjects on methadone or equivalent narcotic maintenance programs will be permitted to enter the study
  • Documented HIV-1 RNA load (by PCR) at screening of ≤20,000 copies/mL for at least twelve weeks. Acceptable documentation would include laboratory data, a letter or a verbal report from another provider noted in the subject records.
  • Stable doses of approved NRTIs and NNRTIs 2 for a minimum of twelve weeks prior to study Day 0. Subjects on efavirenz must be able to tolerate daily morning (8:00 a.m.) dosing starting at screening period and for 22 days of the study. Subjects receiving bid ddI must be willing to accept a change to the once a day delayed release (EC) formulation

You may not qualify if:

  • Female subjects who:
  • have a positive serum pregnancy test at Screening Period Day -14 to -7
  • are breast feeding
  • Receipt of any other investigational medicine for 30 days prior to Day 0
  • Receipt of any known cytochrome P450 3A4 (CYP3A4) altering drug i.e. phenothiazines, cimetidine, barbiturates, ketoconazole, fluconazole, rifampin, steroids and herbal medications for 30 days prior to Day 0. No antibiotics permitted within 10 days prior to Day 0
  • Ingestion of grapefruit, grapefruit juice, Seville oranges or orange marmalade within 2 days of study entry (Day 0)
  • Blood or plasma donations (\>100 ml total) for research or altruistic reasons within 30 days prior to Day 0
  • Seated systolic blood pressure either \<100 mm Hg or \>150 mm Hg; resting heart rate either \<50 beats/minute or \>90 beats/minute
  • History of any illness, including malabsorption, irregular food intake or gastrointestinal intolerance, or allergy that, in the opinion of the investigator, might confound the results of the study or pose additional risk in administering TPV/RTV
  • Any acute illness within 2 weeks prior to Day 0
  • Subjects who are currently taking any over-the-counter drug within 7 days prior to Day 0, or who are currently taking any prescription drug that, in the opinion of the investigator (in consultation with the BI medical monitor and/or pharmacokineticist), might interfere with either the absorption, distribution or metabolism of the TPV/RTV
  • Hypersensitivity to TPV, RTV or sulfonamide containing drugs
  • Using the adherence diary, subject has less than 100% documented adherence for the last 14 doses (7 days) of baseline antiretroviral medications prior to Day 0. Subjects has less than 100% adherence for the last 7 doses (7 days) of efavirenz and ddI (delayed release) prior to Day 0

Contact the study team to confirm eligibility.

Sponsors & Collaborators

MeSH Terms

Conditions

HIV Infections

Interventions

tipranavirRitonavir

Condition Hierarchy (Ancestors)

Blood-Borne InfectionsCommunicable DiseasesInfectionsSexually Transmitted Diseases, ViralSexually Transmitted DiseasesLentivirus InfectionsRetroviridae InfectionsRNA Virus InfectionsVirus DiseasesGenital DiseasesUrogenital DiseasesImmunologic Deficiency SyndromesImmune System Diseases

Intervention Hierarchy (Ancestors)

ThiazolesSulfur CompoundsOrganic ChemicalsAzolesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 25, 2014

First Posted

September 29, 2014

Study Start

February 1, 2001

Primary Completion

February 1, 2002

Last Updated

September 29, 2014

Record last verified: 2014-09