The Pharmacodynamic/Pharmacokinetic Interaction of Tipranavir and Ritonavir With Loperamide in Healthy Volunteers

NCT02251119 | Completed Phase 1

• 1 other identifier: 1182.55
• Study Type: interventional
• Target: 24
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (2)

• Maximum decrease in the percentage baseline CO2 response slope

  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

  up to 6 hours on days 1, 9 and 22

Secondary Outcomes (8)

• Change in the ratio between the diameter of the iris and pupil

  Pupillary resonse to loperamide

• Maximum plasma concentration

  up to 75 h after drug administration

• Minimum plasma concentration

  up to 75 h after drug administration

• Time to reach peak or maximum concentration

  up to 75 h after drug administration

• Terminal half life

  up to 75 h after drug administration

Study Arms (2)

TPV

EXPERIMENTAL

Administration of LOP on days 1, 9 and 22 Administration of TPV on days 4-9 Administration of TPV/RTV on days 12-22

Drug: Tipranavir; Drug: Ritonavir; Drug: Loperamide

RTV

EXPERIMENTAL

Administration of LOP on days 1, 9 and 22 Administration of RTV on days 4-9 Administration of TPV/RTV on days 12-22

Drug: Tipranavir; Drug: Ritonavir; Drug: Loperamide

Interventions

Tipranavir DRUG

RTV; TPV

Ritonavir DRUG

RTV; TPV

Loperamide DRUG

RTV; TPV

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Boehringer Ingelheim: lead

MeSH Terms

Interventions

tipranavir; Ritonavir; Loperamide

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperidines

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• 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: July 1, 2002
• Primary Completion: January 1, 2003
• Last Updated: September 29, 2014

Record last verified: 2014-09