Pharmacokinetic Interaction Study of Steady-state Tipranavir/Ritonavir (TPV/r) With Single-dose Valaciclovir (VAL) in Healthy Volunteers

• ClinicalTrials.gov Identifier: NCT02226978
• Recruitment Status: Completed
• First Posted: August 27, 2014
• Last Update Posted: August 27, 2014
• Sponsor: Boehringer Ingelheim
• Information provided by (Responsible Party): Boehringer Ingelheim

Tracking Information

• First Submitted Date: August 26, 2014
• First Posted Date: August 27, 2014
• Last Update Posted Date: August 27, 2014
• Study Start Date: February 2007
• Actual Primary Completion Date: May 2007 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 26, 2014)

• Area under the concentration-time curve of aciclovir in plasma over the time interval t0h to t12h (AUC0-12) [ Time Frame: up to 12 hours after drug administration ]
• Maximum measured concentration of aciclovir in plasma (Cmax) [ Time Frame: up to 12 hours after drug administration ]

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: August 26, 2014)

• AUC0-12 for Tipranavir (TPV) [ Time Frame: up to 12 hours after drug administration ]
• Cmax for TPV [ Time Frame: up to 12 hours after drug administration ]
• Drug concentration of TPV in plasma at 12 hours after administration (C12h) [ Time Frame: up to 12 hours after drug administration ]
• Apparent clearance of the analyte in the plasma after extravascular administration (CL/F) [ Time Frame: up to 12 hours after drug administration ]
• Apparent volume of distribution during the terminal phase λz following an extravascular dose (Vz/F) [ Time Frame: up to 12 hours after drug administration ]
• Terminal half-life of the analyte in plasma (t1/2) [ Time Frame: up to 12 hours after drug administration ]
• Number of subjects with adverse events [ Time Frame: up to 14 days after last drug administration ]
• Number of subjects with clinically significant findings in laboratory tests [ Time Frame: up to 14 days after last drug administration ]
• AUC0-12 for Ritonavir (RTV) [ Time Frame: up to 12 hours after drug administration ]
• Cmax for RTV [ Time Frame: up to 12 hours after drug administration ]
• Drug concentration of RTV in plasma at 12 hours after administration (C12h) [ Time Frame: up to 12 hours after drug administration ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Pharmacokinetic Interaction Study of Steady-state Tipranavir/Ritonavir (TPV/r) With Single-dose Valaciclovir (VAL) in Healthy Volunteers
• Official Title: An Open-label One-sequence Cross-over Pharmacokinetic Interaction Study of Steady-state Tipranavir/Ritonavir 500/200 mg With Single-dose Valaciclovir (500 mg) in Healthy Volunteers
• Brief Summary: Assessment of the interaction of tipranavir/ritonavir (TPV/RTV) and valaciclovir (VAL), a prodrug of aciclovir (ACV)
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Intervention Model: Crossover Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Healthy

Intervention

• Drug: Tipranavir
• Drug: Ritonavir
• Drug: Valaciclovir

Study Arms

Experimental: TPV/r with valaciclovir

VAL 2 days (on days 1 and 13), TPV/r 12 days (on days 2 to 13)

Interventions:

• Drug: Tipranavir
• Drug: Ritonavir
• Drug: Valaciclovir

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 26, 2014): 29
• Original Actual Enrollment: Same as current
• Study Completion Date: Not Provided
• Actual Primary Completion Date: May 2007 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Healthy male and non-pregnant, non-lactating female subjects as determined by results of screening
• Signed written informed consent in accordance with Good Clinical Practice (GCP) and local legislation
• The ability to understand and sign a written informed consent form, prior to participation in any screening procedures and willingness to comply with all study requirements
• Age >19 and <59 years (20 - 58 years inclusive)
• Weight ≥ 60 kg
• Body mass index (BMI) >18.5 and <29.9 kg/m2

Exclusion Criteria:

• Any finding of the medical examination (including blood pressure, pulse rate, and electrocardiogram) deviating from normal and of clinical relevance
• Atrioventricular (AV) block including 1°
• Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunologic, hematological, oncological or hormonal disorders
• Surgery of gastrointestinal tract (except appendectomy)
• Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
• Relevant history of orthostatic hypotension, fainting spells or blackouts
• Chronic or relevant acute infections
• History of allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator
• Known hypersensitivity to TPV, RTV, valaciclovir, aciclovir or antiretroviral drugs (marketed or experimental use as part of clinical research studies)
• Known elevated liver enzymes in past trials with any compound
• Intake of drugs with a long half-life (>24 hours) (<1 month prior to administration)
• Prescription or over the counter medications (including vitamins, minerals, herbal supplements and antacids), dietary supplements 14 days prior to study drug administration or expected during the trial)
• Participation in another trial with an investigational drug (<2 months prior to administration or expected during trial)
• Smoker with a consumption of >10 cigarettes or >3 cigars or >3 pipes/day and those who cannot keep tobacco intake constant
• Alcohol (>40 g/day for males and >20 g/day for females) and drug abuse
• Blood donation or loss >400 mL, < 3 month prior to administration
• Clinically relevant laboratory abnormalities
• Transaminases above reference values in the history
• Inability to comply with dietary regimen of study centre

For female subjects:

• Pregnancy or planning to become pregnant within 60 days of study completion
• Positive pregnancy test
• Have not been using a barrier method of contraception for at least 3 months prior to participation in the study if of childbearing potential and not surgically sterilized
• Are not willing or are unable to use a reliable method of barrier contraception (such as diaphragm with spermicidal cream/jelly or condoms with spermicidal foam), during and up to 2 months after completion/termination of the trial if of childbearing potential and not surgically sterilized
• Chronic use of oral contraception or hormone replacement containing ethinyl estradiol
• Breast-feeding

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 20 Years to 58 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT02226978
• Other Study ID Numbers: 1182.104
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Boehringer Ingelheim
• Study Sponsor: Boehringer Ingelheim
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Boehringer Ingelheim
• Verification Date: August 2014