Multiple Dose Comparison of the Effect of Two Dose Combinations of Tipranavir/Ritonavir (TPV/RTV), on the Pharmacokinetic Characteristics of Efavirenz (Sustiva®) in Healthy Adult Volunteers

NCT02253823 | Completed Phase 1

• 1 other identifier: 1182.41
• Study Type: interventional
• Target: 68
• Locations: 0 countries
• Sites: N/A

Brief Summary

The objective of this study was to characterize the effects of two dose combinations of tipranavir/ritonavir (TPV 500 mg/RTV 100 mg and TPV 750 mg/RTV 200 mg), administered daily and BID, on the pharmacokinetics of efavirenz (EFV), 600 mg daily

Conditions

Healthy

Outcome Measures

Primary Outcomes (5)

• Cmax (Maximum measured concentration of the analyte in plasma)

  up to 24 hours after drug administration

• AUC 0-12 (Area under the plasma concentration time curve from 0-12 hours)

  up to 12 hours after drug administration

• Cp12h (observed drug concentration in plasma at 12 hours)

  up to 12 hours after drug administration

• AUC 0-24 (Area under the plasma concentration time curve from 0-24 hours)

  up to 24 hours after drug administration

• Cp24h (observed drug concentration in plasma at 24 hours)

  up to 24 hours after drug administration

Secondary Outcomes (6)

• CL/F (Apparent clearance of the analyte in plasma following extravascular administration)

  up to 24 hours after drug administration

• V (Volume of distribution)

  up to 24 hours after drug administration

• Tmax (Time from dosing to the maximum concentration of the analyte in plasma)

  up to 24 hours after drug administration

• t½ (Terminal half-life of the analyte in plasma)

  up to 24 hours after drug administration

• Number of subjects with adverse events

  up to 43 days

Study Arms (2)

TPV+RTV - low dose

EXPERIMENTAL

Drug: EFV; Drug: TPV/RTV - low dose

TPV+RTV - high dose

EXPERIMENTAL

Drug: EFV; Drug: TPV/RTV - high dose

Interventions

EFV DRUG

TPV+RTV - high dose; TPV+RTV - low dose

TPV/RTV - low dose DRUG

TPV+RTV - low dose

TPV/RTV - high dose DRUG

TPV+RTV - high dose

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
• Ability to swallow numerous large capsules without difficulty
• Reasonable probability for completion of the study
• A Body Mass Index (BMI) between 18 and 35 kg/m2
• Acceptable laboratory values that indicate adequate baseline organ function are required at the time of screening. Laboratory values are considered to be acceptable if severity ≤ Grade 1 based on the Adult AIDS Clinical Trial Group (ACTG) Division of Acquired Immunodeficiency Syndrome (of the National Institute of Allergy and Infectious Diseases / National Institutes of Health) (DAIDS) Grading Scale. All abnormal laboratory values \> Grade 1 (e.g., creatine phosphokinase (CPK), amylase, triglycerides) are subject to approval by the Boehringer Ingelheim Pharmaceuticals, Inc. (BIPI) clinical monitor
• Acceptable medical history, physical examination, ECG, and Chest X-ray are required prior to entering the study
• Willingness to abstain from alcohol for 48 hours prior to Study Day 0 and abstain from alcohol for the duration of the study. In addition, Cabernet Sauvignon must not have been ingested within 15 days prior to Day 0 (Visit 2)
• Willingness to abstain from ingesting grapefruit and grapefruit juice within 15 days of Day 0, Visit 2 and for the duration of the study
• Willingness to abstain from ingesting Seville oranges, 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 PK sampling days \[Visit 3 (Days 1-6), Visit 4 (Days 12-15), Visit 5 (Days 20-21 and Visit 6 (Day 22)\]
• Willingness 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
• Negative for Hepatitis B surface antigen and Hepatitis C

You may not qualify if:

• Female subjects who are of reproductive potential who:
• Have a positive serum B-human chronic gonadotropin (HCG) at Visit 1 or,
• Have not been using a barrier contraceptive method for at least 3 months prior to Visit 3 (Day 1), or
• Are not willing to use a reliable method of double-barrier contraception (such as diaphragm with spermicidal cream/jelly or condoms with spermicidal foam) during the trial and 30 days after completion/termination or,
• Are breast-feeding
• Participation in another trial with an investigational medicine for 30 days prior to Day 0 (Visit 2)
• Use of any known enzyme altering drug (such as phenothiazines, cimetidine, barbiturates, ketoconazole, fluconazole, rifampin, steroids, and herbal medications within 30 days prior to Day 0 (Visit 2) or during the trial
• Ingestion of grapefruit, grapefruit juice, and Cabernet Sauvignon within 15 days prior to Day 0 (Visit 2)
• Ingestion of Seville oranges, 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 (PK) sampling days \[Visit 3 (Days 1-6), Visit 4 (Days 12-15), Visit 5 (Days 20-21 and Visit 6 (Day 22)\]
• Administration of antibiotics within 10 days prior to Day 0 (Visit 2) or during the trial
• Inability to comply with investigator's instructions
• History of central nervous system (CNS), gastrointestinal, hepatic, or renal disorders within the past 60 days. Subjects were excluded for these disorders greater than sixty days, if in the opinion of the investigator, the subject did not qualify as a healthy volunteer
• History of alcohol abuse
• Excessive cigarettes smoking defined as greater than 10 cigarettes per day
• Blood or plasma donations within 30 days prior to Day 0 (Visit 2)

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 25, 2014
• First Posted: October 1, 2014
• Study Start: December 1, 2001
• Primary Completion: March 1, 2002
• Last Updated: October 1, 2014

Record last verified: 2014-09