Drug-drug Interaction Study Between Lopinavir/Ritonavir and Isavuconazole

Healthy Volunteers Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01660477
• Other study ID #: 9766-CL-0035
• Status: Completed
• Phase: Phase 1
• First received: August 6, 2012
• Last updated: February 20, 2015
• Start date: June 2012
• Est. completion date: October 2012

Study information

• Verified date: February 2015
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 68
• Est. completion date: October 2012
• Est. primary completion date: October 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Healthy Volunteers
• Pharmacokinetics of Isavuconazole
• Pharmacokinetics of Lopinavir/Ritonavir

Intervention

Drug:
• Isavuconazole
oral
• Lopinavir/ritonavir
oral

Locations

Country	Name	City	State
United States	Parexel International	Glendale	California

Sponsors (2)

Lead Sponsor	Collaborator
Astellas Pharma Global Development, Inc.	Basilea Pharmaceutica International Ltd

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetic (PK) for isavuconazole: AUCtau	(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	No
Primary	Pharmacokinetic (PK) profile for isavuconazole: AUC tau and Cmax	(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	No
Primary	Pharmacokinetic (PK) profile for lopinavir/ritonavir: AUC tau and Cmax	(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	No
Secondary	PK for isavuconazole (in plasma): trough concentration (Ctrough)	(Arms 1 and 3)	Parts 1 and 2, Days 3, 5, 7, 9 and 11: pre-dose	No
Secondary	PK profile for isavuconazole (in plasma): Cmax, tmax	(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	Yes
Secondary	PK for lopinavir/ritonavir (in plasma): trough concentration (Ctrough)	(Arms 2 and 3)	Part 2, Days 3, 5, 7, 9 and 11: pre-dose	No
Secondary	PK for lopinavir/ritonavir (in plasma): tmax	(Arms 2 and 3)	Part 2, Day 13: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours post dose	No
Secondary	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		Part 1, Days 1 - 20 ± 2	No