Effects of Tipranavir/Ritonavir on the Pharmacokinetic Characteristics of Triple Drug Nucleoside and Non-nucleoside Reverse Transcriptase Inhibitor Therapy in HIV-1-infected Subjects
Primary Purpose
HIV Infections
Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Tipranavir low dose
Tipranavir medium dose
Tipranavir high dose
Ritonavir low dose
Ritonavir high dose
Sponsored by

About this trial
This is an interventional treatment trial for HIV Infections
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
TPV/r low dose
TPV/r medium dose
TPV/r high dose
Arm Description
Outcomes
Primary Outcome Measures
Change in trough plasma concentration (Cmin,ss) for non-nucleoside reverse transcriptase inhibitor (NNRTI)
stratified by substance
Change in area under plasma concentration-time curve over dosing interval (AUC0-τ) for nucleoside reverse transcriptase inhibitor (NRTI)
stratified by substance
Change in area under plasma concentration-time curve from 0 to 12 hours for didanosine (ddI)
Secondary Outcome Measures
Cmin,ss
stratified by substance
AUC0-τ
stratified by substance
Maximum plasma concentration (Cmax)
stratified by substance
Time of maximum plasma concentration (Tmax)
stratified by substance
Oral clearance (Cl/F)
stratified by substance
Apparent terminal half life (t1/2)
stratified by substance
Change in CD4 cell count
Change in HIV-1 RNA levels
Number of patients with clinically significant findings in laboratory tests
Number of patients with adverse events
Full Information
NCT ID
NCT02251223
First Posted
September 25, 2014
Last Updated
September 25, 2014
Sponsor
Boehringer Ingelheim
1. Study Identification
Unique Protocol Identification Number
NCT02251223
Brief Title
Effects of Tipranavir/Ritonavir on the Pharmacokinetic Characteristics of Triple Drug Nucleoside and Non-nucleoside Reverse Transcriptase Inhibitor Therapy in HIV-1-infected Subjects
Official Title
An Open Label Multinational Study of the Effects of Three Dose Pairs of Tipranavir/Ritonavir (b.i.d.) on the Pharmacokinetic Characteristics of Protocol -Defined, Baseline, Triple Drug Nucleoside and Non-nucleoside Reverse Transcriptase Inhibitor Therapy in HIV-1-infected Subjects.
Study Type
Interventional
2. Study Status
Record Verification Date
September 2014
Overall Recruitment Status
Completed
Study Start Date
February 2001 (undefined)
Primary Completion Date
February 2002 (Actual)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Boehringer Ingelheim
4. Oversight
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Allocation
Non-Randomized
Enrollment
208 (Actual)
8. Arms, Groups, and Interventions
Arm Title
TPV/r low dose
Arm Type
Experimental
Arm Title
TPV/r medium dose
Arm Type
Experimental
Arm Title
TPV/r high dose
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Tipranavir low dose
Intervention Type
Drug
Intervention Name(s)
Tipranavir medium dose
Intervention Type
Drug
Intervention Name(s)
Tipranavir high dose
Intervention Type
Drug
Intervention Name(s)
Ritonavir low dose
Intervention Type
Drug
Intervention Name(s)
Ritonavir high dose
Primary Outcome Measure Information:
Title
Change in trough plasma concentration (Cmin,ss) for non-nucleoside reverse transcriptase inhibitor (NNRTI)
Description
stratified by substance
Time Frame
baseline, up to day 23
Title
Change in area under plasma concentration-time curve over dosing interval (AUC0-τ) for nucleoside reverse transcriptase inhibitor (NRTI)
Description
stratified by substance
Time Frame
baseline, up to day 22
Title
Change in area under plasma concentration-time curve from 0 to 12 hours for didanosine (ddI)
Time Frame
baseline, up to day 22
Secondary Outcome Measure Information:
Title
Cmin,ss
Description
stratified by substance
Time Frame
up to day 23
Title
AUC0-τ
Description
stratified by substance
Time Frame
up to day 23
Title
Maximum plasma concentration (Cmax)
Description
stratified by substance
Time Frame
up to day 23
Title
Time of maximum plasma concentration (Tmax)
Description
stratified by substance
Time Frame
up to day 23
Title
Oral clearance (Cl/F)
Description
stratified by substance
Time Frame
up to day 23
Title
Apparent terminal half life (t1/2)
Description
stratified by substance
Time Frame
up to day 23
Title
Change in CD4 cell count
Time Frame
up to day 23
Title
Change in HIV-1 RNA levels
Time Frame
up to day 23
Title
Number of patients with clinically significant findings in laboratory tests
Time Frame
up to 25 weeks
Title
Number of patients with adverse events
Time Frame
up to 25 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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
12. IPD Sharing Statement
Links:
URL
http://trials.boehringer-ingelheim.com
Description
Related Info
Learn more about this trial
Effects of Tipranavir/Ritonavir on the Pharmacokinetic Characteristics of Triple Drug Nucleoside and Non-nucleoside Reverse Transcriptase Inhibitor Therapy in HIV-1-infected Subjects
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