- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02251119
The Pharmacodynamic/Pharmacokinetic Interaction of Tipranavir and Ritonavir With Loperamide in Healthy Volunteers
September 25, 2014 updated by: Boehringer Ingelheim
The objective of the study was to determine if the co-administration of loperamide (LOP) with tipranavir (TPV), ritonavir (RTV), or TPV plus RTV (TPV/r) caused a clinically significant change in the respiratory response to carbon dioxide (CO2), defined as a 10% decrease in the area under the pharmacodynamic effect/time curve or at least a 25% decrease in at least one pharmacodynamic time point.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
24
Phase
- Phase 1
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 60 years (Adult)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Ability and willingness to give written informed consent in accordance with institutional and federal guidelines and to comply with the investigational nature of the study and the related requirements
- Healthy males or females between 18 and 60 years of age inclusive
- A body mass index (BMI) between 18 and 35 kg/m2
- Ability to perform a respiratory depression test
- Ability to swallow numerous large capsules without difficulty
- In the opinion of the investigator, a reasonable probability for completion of the study
- Acceptable laboratory values that indicated adequate baseline organ function were required at the time of screening. Laboratory values were considered to be acceptable if their severity was ≤Grade 1 based on the AIDS Clinical Trials Group Division of AIDS (DAIDS) Grading Scale. All abnormal laboratory values >Grade 1 (e.g., creatinine phosphokinase, amylase, triglycerides) were subject to approval by the clinical monitor or designee
- Acceptable medical history, physical examination, ECG, and chest x-ray were required prior to entering the study
- Willingness to abstain from alcohol from Day -2 to Day 24. In addition, red wine must not have been ingested within 14 days prior to Day 1 (Visit 2)
- Willingness to abstain from ingesting grapefruit, grapefruit juice, Seville oranges, St. John's Wort and Milk Thistle, within 14 days of Day 1 (Visit 2) and for the duration of the study
- Willingness to abstain from ingesting garlic supplements, or methylxanthine containing drinks or food (coffee, tea, cola, energy drinks, chocolate, etc) within 72 hours of pharmacokinetic (PK) sampling days (Day 1 [Visit 2], Day 9 [Visit 3], Day 21-22 [Visit 4])
- Willingness to abstain from the use of tobacco products for the duration of the study
- Nonsmoker
- Urine drug screen negative for illegal nonprescription drugs
- Negative HIV serology
- Negative serology for hepatitis B surface antigen and hepatitis C
Exclusion Criteria:
Female subjects who were of reproductive potential who:
- Had a positive serum β-human chorionic gonadotropin test at Visit 1, or
- Had not been using a barrier contraceptive method for at least 3 months prior to Visit 2 (Day 1), or
- Were not willing to use a reliable method of double-barrier contraception (such as a diaphragm with spermicidal cream/jelly or condoms with spermicidal foam) during the trial and 30 days after completion/termination of the trial, or
- Were breast-feeding
- Participation in another trial with an investigational medicine for 30 days prior to Day 1 (Visit 2)
- Ingestion of any known enzyme-altering drug listed in the protocol 30 days prior to Day 1 (Visit 2)
- Ingestion of grapefruit, grapefruit juice, St. John's Wort, Milk Thistle, Seville oranges and red wine within 14 days prior to Day 1 (Visit 2)
- Ingestion of garlic supplements or methylxanthine-containing drinks or food (coffee, tea, cola, energy drinks, chocolate, etc) within 72 hours of PK sampling days (Day 1 [Visit 2], Day 9 [Visit 3], Day 21-22 [Visit 4])
- Ingestion of antibiotics within 10 days prior to Day 1 (Visit 2)
- Inability to comply with investigator's instructions
- History of gastrointestinal, hepatic, or renal disorders within 60 days of study entry
- Recent or active alcohol abuse
- Current use of tobacco products
- Blood or plasma donations within 30 days prior to Day 1 (Visit 2)
- Seated systolic blood pressure either <100 mm Hg or >150 mm Hg; resting heart rate either <50 beats/min or >90 beats/min
- A history of any illness or allergy that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering TPV or RTV or LOP to the subject
- An acute illness within 2 weeks prior to Day 1 (Visit 2)
- Current taking of any over-the-counter drug within 7 days prior to Day 1 (Visit 2) or current taking of any prescription drug that, in the opinion of the investigator in consultation with the clinical monitor and pharmacokineticist, might interfere with either the absorption, distribution or metabolism of the test substances
- Hypersensitivity to TPV, RTV, or LOP
- Administration of any antidiarrheal agent within 7 days of Day 1 (Visit 2)
- Hypersensitivity to sulfonamide drugs
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: TPV
Administration of LOP on days 1, 9 and 22 Administration of TPV on days 4-9 Administration of TPV/RTV on days 12-22 |
|
Experimental: RTV
Administration of LOP on days 1, 9 and 22 Administration of RTV on days 4-9 Administration of TPV/RTV on days 12-22 |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum decrease in the percentage baseline CO2 response slope
Time Frame: up to 6 hours on days 1, 9 and 22
|
rebreathing test
|
up to 6 hours on days 1, 9 and 22
|
Zero-to-six hour area under the curve for the percentage baseline CO2 response slope profile
Time Frame: up to 6 hours on days 1, 9 and 22
|
up to 6 hours on days 1, 9 and 22
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in the ratio between the diameter of the iris and pupil
Time Frame: Pupillary resonse to loperamide
|
up to 6 hours on days 1, 9 and 22
|
Pupillary resonse to loperamide
|
Maximum plasma concentration
Time Frame: up to 75 h after drug administration
|
up to 75 h after drug administration
|
|
Minimum plasma concentration
Time Frame: up to 75 h after drug administration
|
up to 75 h after drug administration
|
|
Time to reach peak or maximum concentration
Time Frame: up to 75 h after drug administration
|
up to 75 h after drug administration
|
|
Terminal half life
Time Frame: up to 75 h after drug administration
|
up to 75 h after drug administration
|
|
Oral clearance
Time Frame: up to 75 h after drug administration
|
up to 75 h after drug administration
|
|
Area under the plasma concentration time curve
Time Frame: up to 75 h after drug administration
|
up to 75 h after drug administration
|
|
Number of subjects with adverse events
Time Frame: up to day 24
|
up to day 24
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
July 1, 2002
Primary Completion (Actual)
January 1, 2003
Study Registration Dates
First Submitted
September 25, 2014
First Submitted That Met QC Criteria
September 25, 2014
First Posted (Estimate)
September 29, 2014
Study Record Updates
Last Update Posted (Estimate)
September 29, 2014
Last Update Submitted That Met QC Criteria
September 25, 2014
Last Verified
September 1, 2014
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- Anti-HIV Agents
- Anti-Retroviral Agents
- Gastrointestinal Agents
- Protease Inhibitors
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 Enzyme Inhibitors
- HIV Protease Inhibitors
- Viral Protease Inhibitors
- Ritonavir
- Tipranavir
- Loperamide
- Antidiarrheals
Other Study ID Numbers
- 1182.55
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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