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Drug-drug Interaction Study Between Lopinavir/Ritonavir and Isavuconazole

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01660477
Recruitment Status : Completed
First Posted : August 8, 2012
Last Update Posted : February 23, 2015
Sponsor:
Collaborator:
Basilea Pharmaceutica International Ltd
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Pharmacokinetics of Isavuconazole Pharmacokinetics of Lopinavir/Ritonavir Healthy Volunteers Drug: Isavuconazole Drug: Lopinavir/ritonavir Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 68 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Official Title: 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
Study Start Date : June 2012
Actual Primary Completion Date : October 2012
Actual Study Completion Date : October 2012

Resource links provided by the National Library of Medicine


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
Drug: Isavuconazole
oral
Other Name: BAL8557

Experimental: Arm 2 : LPV/RTV only
Lopinavir/ritonavir (LPV/RTV) twice daily (BID) on Days 1-12 and once on Day 13
Drug: Lopinavir/ritonavir
oral
Other Name: KALETRA®

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
Drug: Isavuconazole
oral
Other Name: BAL8557

Drug: Lopinavir/ritonavir
oral
Other Name: KALETRA®




Primary Outcome Measures :
  1. 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)

  2. 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)

  3. 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)


Secondary Outcome Measures :
  1. 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)

  2. 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)

  3. 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)

  4. 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)

  5. 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 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01660477


Locations
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United States, California
Parexel International
Glendale, California, United States, 91206
Sponsors and Collaborators
Astellas Pharma Global Development, Inc.
Basilea Pharmaceutica International Ltd
Investigators
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Study Director: Medical Director Astellas Pharma Global Development
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Responsible Party: Astellas Pharma Global Development, Inc.
ClinicalTrials.gov Identifier: NCT01660477    
Other Study ID Numbers: 9766-CL-0035
First Posted: August 8, 2012    Key Record Dates
Last Update Posted: February 23, 2015
Last Verified: February 2015
Keywords provided by Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. ):
Isavuconazole
Lopinavir/ritonavir
Healthy Volunteers
BAL8557
Kaletra ®
Additional relevant MeSH terms:
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Ritonavir
Lopinavir
Isavuconazole
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Antifungal Agents