Study of Tipranavir and Ritonavir on the Pharmacokinetic Characteristics of Methadone Administered in Healthy Volunteers

NCT02245451 | Completed Phase 1

• 1 other identifier: 1182.26
• Study Type: interventional
• Target: 15
• Locations: 0 countries
• Sites: N/A

Brief Summary

The primary objective of this study is to characterise the effects of tipranavir 500 mg and ritonavir 200 mg (TPV/r; given twice daily) at steady-state on the pharmacokinetics of methadone administered as a single dose in healthy adult volunteers

Conditions

Healthy

Outcome Measures

Primary Outcomes (5)

• Area under the concentration-time curve for 0 to 24 hours (AUC0-24h) of methadone

  up to 24 hours after drug administration

• Maximum concentration (Cmax)

  up to 24 hours after drug administration

• Concentration at 6 hours (C6h) of methadone

  6 hours after drug administration

• Area under the concentration-time curve for 0 to 12 hours (AUC0-12h) of tipranavir and ritonavir

  up to 12 hours after drug administration

• concentration at 12 hours (C12h) of tipranavir and ritonavir

  12 hours after drug administration

Secondary Outcomes (9)

• mean residence time (MRT)

  up to 24 hours after drug administration

• apparent terminal half-life (t½)

  up to 24 hours after drug administration

• time to maximum concentration (Tmax)

  up to 24 hours after drug administration

• oral clearance (CL/F)

  up to 24 hours after drug administration

• apparent volume of distribution during the terminal elimination phase divided by the bioavailability factor (Vz/F)

  up to 24 hours after drug administration

Study Arms (1)

TPV/r with methadone

EXPERIMENTAL

Drug: Tipranavir; Drug: Ritonavir; Drug: Methadone

Interventions

Tipranavir DRUG

TPV/r with methadone

Ritonavir DRUG

TPV/r with methadone

Methadone DRUG

TPV/r with methadone

Eligibility Criteria

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

You may qualify if:

• Male or female healthy volunteers aged at least 18 to 60 years.
• Clinically normal medical history.
• Clinically normal findings on physical examination.
• Clinically normal laboratory values.
• A Body Mass Index \>18.5 and \<30 kg/m2.
• Able to swallow large capsules without difficulty.
• Capable of comprehending and communicating effectively with the investigator and staff and of providing written informed consent in accordance with ethics committee and regulatory guidelines.
• Willing to stay in the study centre for the duration of the study.
• Willing to abstain from ingesting substances during the study which may alter plasma study drug levels by interaction with the cytochrome P450 system.
• Willing to abstain from alcohol for 48 hours prior to Visit 1 and for the duration of the study. In addition, Cabernet Sauvignon must not have been ingested within 15 days prior to Visit 1.
• Willing to abstain from ingesting grapefruit and grapefruit juice for 15 days before Visit 1 and for the duration of the study.
• Willing to abstain from ingesting Seville oranges, strawberries or strawberry extract, garlic supplements, St. John's Wort, Milk Thistle, or methylxanthine-containing drinks or food (coffee, tea, cola, energy drinks, chocolate, etc) for 72 hours before the pharmacokinetic sampling days.
• Willing to abstain from use of tobacco products for the duration of the study.
• Urine drug screen negative for illegal non-prescription drugs.
• Negative HIV serology.

You may not qualify if:

• Any clinically significant disease. (A significant disease was defined as a disease which in the opinion of the investigator may either have put the subject at risk because of participation in the study or a disease which may have influenced the results of the study or the subject's ability to participate in the study.)
• Clinically significant abnormal baseline haematology, blood chemistry or urinalysis findings.
• Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholesterol, triglyceride or glucose greater than the upper limit of normal at Visit 1.
• Treatment with prohibited medications in the thirty days before the study or during the study or ingestion of drugs of abuse.
• Treatment with any investigational drug within 90 days of the first dose of study medication.
• Inability to adhere to the requirements of the protocol (including active substance abuse) as assessed by the investigator.
• Prior tipranavir use.
• Ingestion of any known enzyme altering drug (such as phenothiazines, cimetidine, barbiturates, ketoconazole, fluconazole, clarithromycin, rifampin, steroids, and herbal medications) for thirty days prior to Visit 1.
• Ingestion of grapefruit, grapefruit juice, and Cabernet Sauvignon within fifteen days prior to Visit 1.
• Ingestion of Seville oranges, strawberries or strawberry extract, garlic supplements, St. John's Wort, Milk Thistle, or methylxanthine-containing drinks or food (coffee, tea, cola, energy drinks, chocolate, etc) within 72 hours of pharmacokinetics sampling days.
• Treatment with prescription medicines within thirty days prior to Visit 1.
• History of gastrointestinal, hepatic, or renal disorders within 60 days prior to Visit 1.
• Any history of alcohol or drug abuse.
• Current use of cigarettes defined as greater than 10 cigarettes per day or rolling/pipe tobacco equivalent.
• Blood or plasma donations within 90 days prior to Visit 1

Sponsors & Collaborators

• Boehringer Ingelheim: lead

MeSH Terms

Interventions

tipranavir; Ritonavir; Methadone

Intervention Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2014
• First Posted: September 19, 2014
• Study Start: January 1, 2005
• Primary Completion: February 1, 2005
• Last Updated: September 19, 2014

Record last verified: 2014-09