- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01660477
Drug-drug Interaction Study Between Lopinavir/Ritonavir and Isavuconazole
A Phase 1, Open-Label, Parallel Study to Evaluate the Effect of Multiple Doses of Isavuconazole on the Pharmacokinetics of Multiple Doses of Lopinavir/Ritonavir and the Effects of Lopinavir/Ritonavir on the Pharmacokinetics of Multiple Doses of Isavuconazole in Healthy Adult Subjects
The purpose of this two part study is to assess the effect of multiple doses of isavuconazole on the pharmacokinetics of multiple doses of lopinavir/ritonavir and the effect of multiple doses of lopinavir/ritonavir on the pharmacokinetics of isavuconazole.
Part 1 of the study includes 12 subjects randomized to receive either isavuconazole alone or isavuconazole in combination with lopinavir/ritonavir. The purpose of Part 1 is to evaluate safety and tolerability and to establish the effect of multiple doses of lopinavir/ritonavir on isavuconazole.
Part 2, if initiated, includes 54 subjects randomized to receive isavuconazole alone, lopinavir/ritonavir alone, or isavuconazole in combination with lopinavir/ritonavir.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
California
-
Glendale, California, United States, 91206
- PAREXEL International
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- The subject has a body weight of at least 45 kg and has a body mass index (BMI) of 18 to 32 kg/m2, inclusive
- Results for aspartate aminotransferase (AST) and alanine aminotransferase (ALT), total bilirubin, lipase, amylase, glucose and triglycerides must be within the normal range
- The female subject agrees to sexual abstinence, or is surgically sterile, postmenopausal (defined as at least 2 years at Screening without menses), or using a medically acceptable double barrier method (e.g. spermicide and diaphragm, or spermicide and condom) to prevent pregnancy and agrees to continue using this method from Screening until 3 weeks after the follow-up visit at the end of the study; and is not lactating or pregnant as documented by negative pregnancy tests at Screening and Day -1
- The male subject agrees to sexual abstinence, is surgically sterile, or is using a medically acceptable method to prevent pregnancy and agrees to continue using this method from Screening until 3 weeks after the follow-up visit at the end of the study
Exclusion Criteria:
- The subject has a history of unexplained syncope, cardiac arrest, unexplained cardiac arrhythmia or torsade de pointes, structural heart disease, or family history of Long QT syndrome (suggested by sudden death of a close relative at a young age due to possible or probable cardiac causes)
- The subject has a history of pancreatitis
- The subject has a positive result for hepatitis C antibodies, hepatitis B surface antigen at Screening or is known to be positive for human immunodeficiency virus (HIV)
- The subject has a known or suspected allergy to any of the components of the trial products including lopinavir/ritonavir or the azole class of compounds, or a history of multiple and/or severe allergies to drugs or foods (as judged by the investigator), or a history of severe anaphylactic reactions- - The subject is a smoker (any use of tobacco or nicotine containing products) within 6 months prior to Screening
- The subject has had treatment with prescription drugs or complementary and alternative medicines within 14 days prior to Day -1, or over-the-counter medications within 1 week prior to Day -1, with the exception of acetaminophen up to 2 g/day
- The subject has a recent history (within the last 2 years) of drug or alcohol abuse, as defined by the investigator, or a positive drug and/or alcohol screen
- The subject has participated in a previous isavuconazole study
Study Plan
How is the study designed?
Design Details
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Arm 1: isavuconazole only
Isavuconazole three times per day (TID) on Days 1-2, and once daily (QD) on Days 3 thru 13
|
oral
Other Names:
|
Experimental: Arm 2 : LPV/RTV only
Lopinavir/ritonavir (LPV/RTV) twice daily (BID) on Days 1-12 and once on Day 13
|
oral
Other Names:
|
Experimental: Arm 3: isavuconazole and LPV/RTV
Isavuconazole three times per day (TID) on Days 1-2, and once daily (QD) on Days 3 thru 13 in combination with lopinavir/ritonavir twice daily (BID) on Days 1-13
|
oral
Other Names:
oral
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pharmacokinetic (PK) for isavuconazole: AUCtau
Time Frame: Part 1, Day 13: predose, 0.5, 1, 2, 3, 4, 6, 8,10,12,16, and 24 hours post-dose
|
(Arms 1 and 3) Area under the concentration time curve during the during time interval between consecutive dosing (AUCtau) (tau=24)
|
Part 1, Day 13: predose, 0.5, 1, 2, 3, 4, 6, 8,10,12,16, and 24 hours post-dose
|
Pharmacokinetic (PK) profile for isavuconazole: AUC tau and Cmax
Time Frame: Part 2, Day 13: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hours post dose
|
(Arms 2 and 3) Maximum concentration (Cmax)
|
Part 2, Day 13: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hours post dose
|
Pharmacokinetic (PK) profile for lopinavir/ritonavir: AUC tau and Cmax
Time Frame: Part 2, Day 13: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours post dose
|
(Arms 2 and 3) AUC during time interval between consecutive dosing (AUCtau) (tau=12)
|
Part 2, Day 13: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours post dose
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
PK for isavuconazole (in plasma): trough concentration (Ctrough)
Time Frame: Parts 1 and 2, Days 3, 5, 7, 9 and 11: pre-dose
|
(Arms 1 and 3)
|
Parts 1 and 2, Days 3, 5, 7, 9 and 11: pre-dose
|
PK profile for isavuconazole (in plasma): Cmax, tmax
Time Frame: Parts 1 and 2, Day 13: predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12,16, and 24 hours post-dose
|
(Arms 1 and 3) Time to attain Cmax (tmax)
|
Parts 1 and 2, Day 13: predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12,16, and 24 hours post-dose
|
PK for lopinavir/ritonavir (in plasma): trough concentration (Ctrough)
Time Frame: Part 2, Days 3, 5, 7, 9 and 11: pre-dose
|
(Arms 2 and 3)
|
Part 2, Days 3, 5, 7, 9 and 11: pre-dose
|
PK for lopinavir/ritonavir (in plasma): tmax
Time Frame: Part 2, Day 13: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours post dose
|
(Arms 2 and 3)
|
Part 2, Day 13: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours post dose
|
Safety and tolerability of isavuconazole alone and in combination with lopinavir (LPV) and ritonavir (RTV) assessed by recording of adverse events, physical examination, clinical laboratory evaluation, electrocardiograms (ECGs) and vital signs
Time Frame: Part 1, Days 1 - 20 ± 2
|
Part 1, Days 1 - 20 ± 2
|
Collaborators and Investigators
Collaborators
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
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
- Protease Inhibitors
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 Enzyme Inhibitors
- Antifungal Agents
- HIV Protease Inhibitors
- Viral Protease Inhibitors
- Ritonavir
- Lopinavir
- Isavuconazole
Other Study ID Numbers
- 9766-CL-0035
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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